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Sample records for high-risk clinically localized

  1. Chemotherapy and novel therapeutics before radical prostatectomy for high-risk clinically localized prostate cancer.

    PubMed

    Cha, Eugene K; Eastham, James A

    2015-05-01

    Although both surgery and radiation are potential curative options for men with clinically localized prostate cancer, a significant proportion of men with high-risk and locally advanced disease will demonstrate biochemical and potentially clinical progression of their disease. Neoadjuvant systemic therapy before radical prostatectomy (RP) is a logical strategy to improve treatment outcomes for men with clinically localized high-risk prostate cancer. Furthermore, delivery of chemotherapy and other systemic agents before RP affords an opportunity to explore the efficacy of these agents with pathologic end points. Neoadjuvant chemotherapy, primarily with docetaxel (with or without androgen deprivation therapy), has demonstrated feasibility and safety in men undergoing RP, but no study to date has established the efficacy of neoadjuvant chemotherapy or neoadjuvant chemohormonal therapies. Other novel agents, such as those targeting the vascular endothelial growth factor receptor, epidermal growth factor receptor, platelet-derived growth factor receptor, clusterin, and immunomodulatory therapeutics, are currently under investigation.

  2. Neoadjuvant Treatment of High-Risk, Clinically Localized Prostate Cancer Prior to Radical Prostatectomy.

    PubMed

    Pietzak, Eugene J; Eastham, James A

    2016-05-01

    Multimodal strategies combining local and systemic therapy offer the greatest chance of cure for many with men with high-risk prostate cancer who may harbor occult metastatic disease. However, no systemic therapy combined with radical prostatectomy has proven beneficial. This was in part due to a lack of effective systemic agents; however, there have been several advancements in the metastatic and castrate-resistant prostate cancer that might prove beneficial if given earlier in the natural history of the disease. For example, novel hormonal agents have recently been approved for castration-resistant prostate cancer with some early phase II neoadjuvant showing promise. Additionally, combination therapy with docetaxel-based chemohormonal has demonstrated a profound survival benefit in metastatic hormone-naïve patients and might have a role in eliminating pre-existing ADT-resistant tumor cells in the neoadjuvant setting. The Cancer and Leukemia Group B (CALGB)/Alliance 90203 trial has finished accrual and should answer the question as to whether neoadjuvant docetaxel-based chemohormonal therapy provides an advantage over prostatectomy alone. There are also several promising targeted agents and immunotherapies under investigation in phase I/II trials with the potential to provide benefit in the neoadjuvant setting. PMID:26968417

  3. Retrospective Comparison of External Beam Radiotherapy and Radical Prostatectomy in High-Risk, Clinically Localized Prostate Cancer

    SciTech Connect

    Arcangeli, Giorgio; Strigari, Lidia; Arcangeli, Stefano; Petrongari, Maria Grazia; Saracino, Biancamaria; Gomellini, Sara; Papalia, Rocco; Simone, Giuseppe; De Carli, Piero; Gallucci, Michele

    2009-11-15

    Purpose: Because of the lack of conclusive and well-conducted randomized studies, the optimal therapy for prostate tumors remains controversial. The aim of this study was to retrospectively compare the results of radical surgery vs. a conservative approach such as external beam radiotherapy (EBRT) plus androgen deprivation therapy using an intent-to-treat analysis on two pretreatment defined, concurrently treated, high-risk patient populations. Methods and Materials: Between January 2003 and December 2007, 162 patients with high-risk prostate cancer underwent an EBRT plus androgen deprivation therapy program at the RT department of our institute. In the same period, 122 patients with the same high-risk disease underwent radical prostatectomy (RP) at the urologic department of our institute. Patients with adverse pathologic factors also underwent adjuvant EBRT with or without androgen deprivation therapy. The primary endpoint was freedom from biochemical failure. Results: The two groups of high-risk patients were homogeneous in terms of freedom from biochemical failure on the basis of the clinical T stage, biopsy Gleason score, and initial prostate-specific antigen level. The median follow-up was 38.6 and 33.8 months in the EBRT and RP groups, respectively. The actuarial analysis of the freedom from biochemical failure showed a 3-year rate of 86.8% and 69.8% in the EBRT and RP group, respectively (p = .001). Multivariate analysis of the whole group revealed the initial prostate-specific antigen level and treatment type (EBRT vs. RP) as significant covariates. Conclusion: This retrospective intention-to-treat analysis showed a significantly better outcome after EBRT than after RP in patients with high-risk prostate cancer, although a well-conducted randomized comparison would be the best procedure to confirm these results.

  4. Utility of Clinical Breast Exams in Detecting Local-Regional Breast Events after Breast-Conservation in Women with a Personal History of High-risk Breast Cancer

    PubMed Central

    Neuman, Heather B.; Schumacher, Jessica R.; Francescatti, Amanda B.; Adesoye, Taiwo; SB, Edge; ES, Burnside; DJ, Vanness; M, Yu; Y, Si; D, McKellar; DP, Winchester; Greenberg, Caprice C.

    2016-01-01

    Introduction Although breast cancer follow-up guidelines emphasize the importance of clinical exams, prior studies suggest a small fraction of local-regional events occurring after breast conservation are detected by exam alone. Our objective was to examine how local-regional events are detected in a contemporary, national cohort of high-risk breast cancer survivors. Methods A stage-stratified sample of stage II/III breast cancer patients diagnosed in 2006-2007 (n=11,099) were identified from 1,217 facilities within the National Cancer Data Base. Additional data on local-regional and distant breast events, method of event detection, imaging received, and mortality was collected. We further limited the cohort to patients with breast conservation (n=4,854). Summary statistics describe local-regional event rates and detection method. Results Local-regional events were detected in 5.5% (n=265). 83% were ipsilateral or contralateral in-breast events, and 17% within ipsilateral lymph nodes. 48% of local-regional events were detected on asymptomatic breast imaging, 29% by patients, and 10% on clinical exam. Overall, 0.5% of the 4,854 patients had a local-regional event detected on exam. Exams detected a higher proportion of lymph node (8/45) compared to in-breast events (18/220). No factors were associated with method of event detection. Discussion Clinical exams, as an adjunct to screening mammography, have a modest effect on local-regional event detection. This contradicts current belief that exams are a critical adjunct to mammographic screening. These findings can help to streamline follow-up care, potentially improving follow-up efficiency and quality. PMID:27491784

  5. Radiation With or Without 6 Months of Androgen Suppression Therapy in Intermediate- and High-Risk Clinically Localized Prostate Cancer: A Postrandomization Analysis by Risk Group

    SciTech Connect

    Nguyen, Paul L.; Chen, Ming-Hui; Beard, Clair J.; Suh, W. Warren

    2010-07-15

    Purpose: Six months of androgen suppression therapy (AST) plus radiation (RT) prolongs survival vs. RT alone in men with unfavorable risk localized prostate cancer (PCa), but it is unknown if this benefit applies to all risk subgroups and, in particular, the intermediate-risk group. Methods and Materials: Among 206 men with stages T1b to T2b PCa and either a prostate-specific antigen level of >10 or a Gleason score of {>=}7 or MRI evidence of T3 disease randomized to receive 70 Gy of RT with or without 6 months of AST, Cox multivariable analysis was used to assess the impact of AST on overall survival in intermediate- and high-risk localized PCa, adjusting for age, Adult Comorbidity Evaluation 27 comorbidity score, interaction between comorbidity and treatment, and known prognostic factors. Survival estimates were compared using a two-sided log-rank test. Results: After an 8.2-year median follow-up, 74 men died. Compared to treatment with AST plus RT, treatment with RT alone was associated with an increased risk of death in intermediate-risk (adjusted hazard ratio, 3.0 [95% confidence interval, 1.3-7.2]; p = 0.01) and high-risk PCa (adjusted hazard ratio, 3.3 [95% confidence interval, 0.94-11.3]; p = 0.06). The survival benefit of adding AST was restricted to men with no or mild comorbidity in both the intermediate-risk (90.9% vs. 85.8% survival, respectively, at 7 years for AST plus RT vs. RT alone; p = 0.009) and high-risk (88.9% vs. 51.2% survival, respectively, at 7 years for AST plus RT vs. RT alone; p = 0.007) subgroups. Conclusions: In men with localized PCa who have no or mild comorbidity, adding 6 months of AST to RT was associated with improved survival for those with both intermediate-risk and high-risk disease, but in men with moderate to severe comorbidity, no benefit was observed in either risk group.

  6. Excellent Local Control From Radiation Therapy for High-Risk Neuroblastoma

    SciTech Connect

    Gatcombe, Heather G.; Marcus, R.B.; Katzenstein, Howard M.; Tighiouart, Mourad; Esiashvili, Natia

    2009-08-01

    Purpose: Local recurrence has been demonstrated in previous studies to be one of the obstacles to cure in neuroblastoma. Radiation therapy indications, optimal dose, and technique are still evolving. Here we report our experience of high-risk neuroblastoma patients who received local radiation therapy as part of their cancer management. Methods and Materials: We conducted a retrospective study of 34 high-risk neuroblastoma patients who received radiation therapy to local sites of disease from March 2001 until February 2007 at our institution as part of their multimodality therapy. Results: At a median follow-up of 33.6 months, 6 patients died of disease, 7 patients were alive with disease, and 21 patients were in clinical remission. Eleven patients relapsed, all distantly. Two patients failed locally in addition to distant sites. Both of these patients had persistent gross disease after induction chemotherapy and surgery. Our 3-year local control, event-free survival, overall survival were 94%, 66%, and 86%, respectively. Conclusion: Patients with high-risk neuroblastoma in our series achieved excellent local control. Doses of 21-24 Gy to the primary tumor site appear to be adequate for local control for patients in the setting of minimal residual disease after induction chemotherapy and surgery. Patients with significant residual disease may benefit from radiation dose escalation, and this should be evaluated in a prospective clinical trial.

  7. Smell identification in individuals at clinical high risk for schizophrenia.

    PubMed

    Gill, Kelly Elizabeth; Evans, Elizabeth; Kayser, Jürgen; Ben-David, Shelly; Messinger, Julie; Bruder, Gerard; Malaspina, Dolores; Corcoran, Cheryl Mary

    2014-12-15

    Smell identification deficits exist in schizophrenia, and may be associated with its negative symptoms. Less is known about smell identification and its clinical correlates in individuals at clinical high risk (CHR) for schizophrenia and related psychotic disorders. We examined smell identification, symptoms and IQ in 71 clinical high-risk (CHR) subjects and 36 healthy controls. Smell identification was assessed using both the 40-item University of Pennsylvania Smell Identification Test (UPSIT; Doty, R.L., Shaman, P., Kimmelman, C.P., Dann, M.S., 1984. University of Pennsylvania Smell Identification Test: a rapid quantitative olfactory function test for the clinic. Laryngoscope 94, 176-178) and its extracted 12-item Brief Smell Identification Test (Goudsmit, N., Coleman, E., Seckinger, R.A., Wolitzky, R., Stanford, A.D., Corcoran, C., Goetz, R.R., Malaspina, D., 2003. A brief smell identification test discriminates between deficit and non-deficit schizophrenia. Psychiatry Research 120, 155-164). Smell identification did not significantly differ between CHR subjects and controls. Among CHR subjects, smell identification did not predict schizophrenia (N=19; 27%) within 2 years, nor was it associated with negative or positive symptoms. This is the third prospective cohort study to examine smell identification in CHR subjects, and overall, findings are inconclusive, similar to what is found for other disorders in adolescents, such as autism spectrum, attention deficit and anxiety disorders. Smell identification deficit may not have clear utility as a marker of emergent schizophrenia and related psychotic disorders.

  8. An examination of the Clinical Impairment Assessment among women at high risk for eating disorder onset

    PubMed Central

    Vannucci, Anna; Kass, Andrea E.; Sinton, Meghan M.; Aspen, Vandana; Weisman, Hannah; Bailey, Jakki O.; Wilfley, Denise E.; Taylor, C. Barr

    2013-01-01

    Identifying measures that reliably and validly assess clinical impairment has important implications for eating disorder (ED) diagnosis and treatment. The current study examined the psychometric properties of the Clinical Impairment Assessment (CIA) in women at high risk for ED onset. Participants were 543 women (20.6 ± 2.0 years) who were classified into one of three ED categories: clinical ED, high risk for ED onset, and low risk control. Among high risk women, the CIA demonstrated high internal consistency (α = 0.93) and good convergent validity with disordered eating attitudes (rs = 0.27–0.68, ps < 0.001). Examination of the CIA’s discriminant validity revealed that CIA global scores were highest among women with a clinical ED (17.7 ± 10.7) followed by high risk women (10.6 ± 8.5) and low risk controls (3.0 ± 3.3), respectively (p < 0.001). High risk women reporting behavioral indices of ED psychopathology (objective and/or subjective binge episodes, purging behaviors, driven exercise, and ED treatment history) had higher CIA global scores than those without such indices (ps < 0.05), suggesting good criterion validity. These data establish the first norms for the CIA in a United States sample. The CIA is psychometrically sound among high risk women, and heightened levels of impairment among these individuals as compared to low risk women verify the relevance of early intervention efforts. PMID:22516320

  9. Facial emotion perception differs in young persons at genetic and clinical high-risk for psychosis.

    PubMed

    Kohler, Christian G; Richard, Jan A; Brensinger, Colleen M; Borgmann-Winter, Karin E; Conroy, Catherine G; Moberg, Paul J; Gur, Ruben C; Gur, Raquel E; Calkins, Monica E

    2014-05-15

    A large body of literature has documented facial emotion perception impairments in schizophrenia. More recently, emotion perception has been investigated in persons at genetic and clinical high-risk for psychosis. This study compared emotion perception abilities in groups of young persons with schizophrenia, clinical high-risk, genetic risk and healthy controls. Groups, ages 13-25, included 24 persons at clinical high-risk, 52 first-degree relatives at genetic risk, 91 persons with schizophrenia and 90 low risk persons who completed computerized testing of emotion recognition and differentiation. Groups differed by overall emotion recognition abilities and recognition of happy, sad, anger and fear expressions. Pairwise comparisons revealed comparable impairments in recognition of happy, angry, and fearful expressions for persons at clinical high-risk and schizophrenia, while genetic risk participants were less impaired, showing reduced recognition of fearful expressions. Groups also differed for differentiation of happy and sad expressions, but differences were mainly between schizophrenia and control groups. Emotion perception impairments are observable in young persons at-risk for psychosis. Preliminary results with clinical high-risk participants, when considered along findings in genetic risk relatives, suggest social cognition abilities to reflect pathophysiological processes involved in risk of schizophrenia. PMID:24582775

  10. Characterization of the nuclear localization signal of high risk HPV16 E2 protein

    SciTech Connect

    Klucevsek, Kristin; Wertz, Mary; Lucchi, John; Leszczynski, Anna; Moroianu, Junona . E-mail: moroianu@bc.edu

    2007-03-30

    The E2 protein of high risk human papillomavirus type 16 (HPV16) contains an amino-terminal (N) domain, a hinge (H) region and a carboxyl-terminal (C) DNA-binding domain. Using enhanced green fluorescent protein (EGFP) fusions with full length E2 and E2 domains in transfection assays in HeLa cells, we found that the C domain is responsible for the nuclear localization of E2 in vivo, whereas the N and H domains do not contain additional nuclear localization signals (NLSs). Deletion analysis of EGFP-E2 and EGFP-cE2 determined that the C domain contains an {alpha} helix cNLS that overlaps with the DNA-binding region. Mutational analysis revealed that the arginine and lysine residues in this cNLS are essential for nuclear localization of HPV16 E2. Interestingly, these basic amino acid residues are well conserved among the E2 proteins of BPV-1 and some high risk HPV types but not in the low risk HPV types, suggesting that there are differences between the NLSs and corresponding nuclear import pathways between these E2 proteins.

  11. Identification of the nuclear localization and export signals of high risk HPV16 E7 oncoprotein

    SciTech Connect

    Knapp, Alixandra A.; McManus, Patrick M.; Bockstall, Katy; Moroianu, Junona

    2009-01-05

    The E7 oncoprotein of high risk human papillomavirus type 16 (HPV16) binds and inactivates the retinoblastoma (RB) family of proteins. Our previous studies suggested that HPV16 E7 enters the nucleus via a novel Ran-dependent pathway independent of the nuclear import receptors (Angeline, M., Merle, E., and Moroianu, J. (2003). The E7 oncoprotein of high-risk human papillomavirus type 16 enters the nucleus via a nonclassical Ran-dependent pathway. Virology 317(1), 13-23.). Here, analysis of the localization of specific E7 mutants revealed that the nuclear localization of E7 is independent of its interaction with pRB or of its phosphorylation by CKII. Fluorescence microscopy analysis of enhanced green fluorescent protein (EGFP) and 2xEGFP fusions with E7 and E7 domains in HeLa cells revealed that E7 contains a novel nuclear localization signal (NLS) in the N-terminal domain (aa 1-37). Interestingly, treatment of transfected HeLa cells with two specific nuclear export inhibitors, Leptomycin B and ratjadone, changed the localization of 2xEGFP-E7{sub 38-98} from cytoplasmic to mostly nuclear. These data suggest the presence of a leucine-rich nuclear export signal (NES) and a second NLS in the C-terminal domain of E7 (aa 38-98). Mutagenesis of critical amino acids in the putative NES sequence ({sub 76}IRTLEDLLM{sub 84}) changed the localization of 2xEGFP-E7{sub 38-98} from cytoplasmic to mostly nuclear suggesting that this is a functional NES. The presence of both NLSs and an NES suggests that HPV16 E7 shuttles between the cytoplasm and nucleus which is consistent with E7 having functions in both of these cell compartments.

  12. Self-awareness of functional impairment in individuals at clinical high-risk for psychosis

    PubMed Central

    Olvet, Doreen M.; Carrión, Ricardo E.; Auther, Andrea M.; Cornblatt, Barbara A.

    2013-01-01

    Aims A major public health concern associated with schizophrenia is the long-term disability that involves an inability to function independently in the community. An individual’s self-awareness of functional impairment may be a significant factor contributing to long-term disability. In fact, subjective interpretation of one’s illness impacts treatment participation and adherence, and is linked to poor outcomes. However, it remains unclear how illness-related functional impairment is perceived by individuals prior to the onset of psychosis. This study aims to examine the relationship between clinician-based and self-report assessments of functioning, as well as the contribution of clinical symptoms to this relationship in individuals at clinical high-risk for psychosis. Methods The Sheehan Disability Scale, a self-rated instrument, was used to measure disruption in daily functioning in social and role functioning due to symptoms in a sample of 73 treatment-seeking patients at clinical high-risk for psychosis and 50 healthy controls. Results Relative to healthy controls, clinical high-risk patients self-reported significant disruptions in social and role functioning. In addition, a specific relationship emerged in that clinician-rated measures of functioning and depression were related to disability scores. Conclusions These findings suggest that clinical high-risk patients are significantly disturbed by their illness. Self-reported disruption of daily functioning was associated with clinician-rated functioning and depressive symptoms, further highlighting the impact of functional impairments on the level of distress experienced by patients in the early phases of the illness. Intervention strategies that repair functional impairment before the onset of psychosis may prevent long-term disability. PMID:23968457

  13. Youth-caregiver Agreement on Clinical High-risk Symptoms of Psychosis

    PubMed Central

    Golembo-Smith, Shana; Bachman, Peter; Senturk, Damla; Cannon, Tyrone D.; Bearden, Carrie E.

    2014-01-01

    Early identification of individuals who will go on to develop schizophrenia is a difficult endeavor. The variety of symptoms experienced by clinical high-risk youth make it difficult to identify who will eventually develop schizophrenia in the future. Efforts are being made, therefore, to more accurately identify at-risk individuals and factors that predict conversion to psychosis. As in most assessments of children and adolescents, however, both youth and parental report of symptomatology and resulting dysfunction are important to assess. The goals of the current study were to assess the extent of cross-informant agreement on the Structured Interview for Prodromal Symptoms (SIPS), a widely-used tool employed to determine clinical high-risk status. A total of 84 youth-caregiver pairs participated. Youth and caregiver raters displayed moderate overall agreement on SIPS-rated symptoms. Both youth and caregiver ratings of youth symptomatology contributed significantly to predicting conversion to psychosis. In addition, youth age and quality of youth-caregiver relationships appear to be related to cross-informant symptom ratings. Despite differences on individual SIPS domains, the majority of dyads agreed on youth clinical high-risk status. Results highlight the potential clinical utility of using caregiver informants to determine youth psychosis risk. PMID:24092494

  14. Working with Asian American Youth at Clinical High Risk for Psychosis: A Case Illustration

    PubMed Central

    Li, Huijun; Friedman-Yakoobian, Michelle; Min, Grace; Granato, Andréa Gnong; Seidman, Larry J.

    2013-01-01

    The idea of a clinical high risk (CHR) for psychosis has focused attention on early intervention to prevent or attenuate psychosis. However, many clinicians may still not be very familiar with the concept of CHR. Current studies have not allowed for an in-depth examination of the challenges and strategies of working with youth from the range of racial/ethnic minority families, Asian American families in particular. The purpose of this paper is three fold. First, we critically review Asian cultural values and beliefs about mental illness, psychosis in particular, while highlighting specific challenges that Asian American families encounter. Second, we provide a clinical case to illustrate these challenges and inform clinical practice when working with Asian youth at risk for psychosis and their families. Third, practical and easy-to-follow clinical strategies are provided. Implications for clinical practice and directions for future research are presented. PMID:23689196

  15. DNA Methylation-Guided Prediction of Clinical Failure in High-Risk Prostate Cancer

    PubMed Central

    Joniau, Steven; Lerut, Evelyne; Laenen, Annouschka; Gevaert, Thomas; Gevaert, Olivier; Spahn, Martin; Kneitz, Burkhard; Gramme, Pierre; Helleputte, Thibault; Isebaert, Sofie; Haustermans, Karin; Bollen, Mathieu

    2015-01-01

    Background Prostate cancer (PCa) is a very heterogeneous disease with respect to clinical outcome. This study explored differential DNA methylation in a priori selected genes to diagnose PCa and predict clinical failure (CF) in high-risk patients. Methods A quantitative multiplex, methylation-specific PCR assay was developed to assess promoter methylation of the APC, CCND2, GSTP1, PTGS2 and RARB genes in formalin-fixed, paraffin-embedded tissue samples from 42 patients with benign prostatic hyperplasia and radical prostatectomy specimens of patients with high-risk PCa, encompassing training and validation cohorts of 147 and 71 patients, respectively. Log-rank tests, univariate and multivariate Cox models were used to investigate the prognostic value of the DNA methylation. Results Hypermethylation of APC, CCND2, GSTP1, PTGS2 and RARB was highly cancer-specific. However, only GSTP1 methylation was significantly associated with CF in both independent high-risk PCa cohorts. Importantly, trichotomization into low, moderate and high GSTP1 methylation level subgroups was highly predictive for CF. Patients with either a low or high GSTP1 methylation level, as compared to the moderate methylation groups, were at a higher risk for CF in both the training (Hazard ratio [HR], 3.65; 95% CI, 1.65 to 8.07) and validation sets (HR, 4.27; 95% CI, 1.03 to 17.72) as well as in the combined cohort (HR, 2.74; 95% CI, 1.42 to 5.27) in multivariate analysis. Conclusions Classification of primary high-risk tumors into three subtypes based on DNA methylation can be combined with clinico-pathological parameters for a more informative risk-stratification of these PCa patients. PMID:26086362

  16. An Unusual BRCA Mutation Distribution in a High Risk Cancer Genetics Clinic

    PubMed Central

    Nelson-Moseke, Anna C.; Jeter, Joanne M.; Cui, Haiyan; Roe, Denise J.; Chambers, Setsuko K.; Laukaitis, Christina M.

    2012-01-01

    The Database of Individuals at High Risk for Breast, Ovarian, or Other Hereditary Cancers at the Arizona Cancer Center in Tucson, Arizona, assesses cancer risk factors and outcomes in patients with a family history of cancer or a known genetic mutation. We analyzed the subset of clinic probands who carry deleterious BRCA gene mutations to identify factors that could explain why mutations in BRCA2 out number those in BRCA1. Medical, family, social, ethnic and genetic mutation histories were collected from consenting patients’ electronic medical records. Differences between BRCA1 and BRCA2 probands from this database were analyzed for statistical significance and compared to published analyses.. A significantly higher proportion of our clinic probands carry mutations in BRCA2 than BRCA1, compared with previous reports of mutation prevalence. This also holds true for the Hispanic sub-group. Probands with BRCA2 mutations were significantly more likely than their BRCA1 counterparts to present to the high risk clinic without adiagnosis of cancer. Other differences between the groups were not significant. Six previously unreported BRCA2 mutations appear in our clinic population. The increased proportion of probands carrying deleterious BRCA2 mutations is likely multifactorial, but may reflect aspects of Southern Arizona’s unique ethnic heritage. PMID:23179792

  17. Improved Biochemical Outcomes With Statin Use in Patients With High-Risk Localized Prostate Cancer Treated With Radiotherapy

    SciTech Connect

    Kollmeier, Marisa A.; Katz, Matthew S.; Mak, Kimberley; Yamada, Yoshiya; Feder, David J.; Zhang Zhigang; Jia Xiaoyu; Shi Weiji; Zelefsky, Michael J.

    2011-03-01

    Purpose: To investigate the association between 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) and biochemical and survival outcomes after high-dose radiotherapy (RT) for prostate cancer. Methods and Materials: A total of 1711 men with clinical stage T1-T3 prostate cancer were treated with conformal RT to a median dose of 81 Gy during 1995-2007. Preradiotherapy medication data were available for 1681 patients. Three hundred eighty-two patients (23%) were taking a statin medication at diagnosis and throughout RT. Nine hundred forty-seven patients received a short-course of neoadjuvant and concurrent androgen-deprivation therapy (ADT) with RT. The median follow-up was 5.9 years. Results: The 5- and 8-year PSA relapse-free survival (PRFS) rates for statin patients were 89% and 80%, compared with 83% and 74% for those not taking statins (p = 0.002). In a multivariate analysis, statin use (hazard ratio [HR]0.69, p = 0.03), National Comprehensive Cancer Network (NCCN) low-risk group, and ADT use were associated with improved PRFS. Only high-risk patients in the statin group demonstrated improvement in PRFS (HR 0.52, p = 0.02). Across all groups, statin use was not associated with improved distant metastasis-free survival (DMFS) (p = 0.51). On multivariate analysis, lower NCCN risk group (p = 0.01) and ADT use (p = 0.005) predicted improved DMFS. Conclusions: Statin use during high-dose RT for clinically localized prostate cancer was associated with a significant improvement in PRFS in high-risk patients. These data suggest that statins have anticancer activity and possibly provide radiosensitization when used in conjunction with RT in the treatment of prostate cancer.

  18. Clinical and psychological telemonitoring and telecare of high risk heart failure patients.

    PubMed

    Villani, Alessandra; Malfatto, Gabriella; Compare, Angelo; Della Rosa, Francesco; Bellardita, Lara; Branzi, Giovanna; Molinari, Enrico; Parati, Gianfranco

    2014-12-01

    We conducted a trial of telemonitoring and telecare for patients with chronic heart failure leaving hospital after being treated for clinical instability. Eighty patients were randomized before hospital discharge to a usual care group (n=40: follow-up at the outpatient clinic) or to an integrated management group (n=40: patients learned to use a handheld PDA and kept in touch daily with the monitoring centre). At enrolment, the groups were similar for all clinical variables. At one-year follow-up, integrated management patients showed better adherence, reduced anxiety and depression, and lower NYHA class and plasma levels of BNP with respect to the usual care patients (e.g. NYHA class 2.1 vs 2.4, P<0.02). Mortality and hospital re-admissions for congestive heart failure were also reduced in integrated management patients (P<0.05). Integrated management was more expensive than usual care, although the cost of adverse events was 42% lower. In heart failure patients at high risk of relapse, the regular acquisition of simple clinical information and the possibility for the patient to contact the clinical staff improved drug titration, produced better psychological status and quality of life, and reduced hospitalizations for heart failure. PMID:25339632

  19. Approval of high-risk medical devices in the US: implications for clinical cardiology.

    PubMed

    Rome, Benjamin N; Kramer, Daniel B; Kesselheim, Aaron S

    2014-01-01

    Since 1976, the US Food and Drug Administration (FDA) has used the premarket approval (PMA) process to approve high-risk medical devices, including implantable cardioverter defibrillators (ICDs), coronary stents, and artificial heart valves. The PMA process is widely viewed as a rigorous evaluation of device safety and effectiveness, though recent recalls-most notably related to underperforming ICD leads-have raised concerns about whether physicians and patients should sometimes be more wary about devices approved via this pathway. The FDA must utilize a "least burdensome" approach to approve new medical devices, and many widely used device models have been approved as supplements to existing PMA-approved devices with limited clinical testing. A recent Supreme Court ruling has made it difficult for patients harmed by unsafe PMA-approved devices to seek damages in court. Cardiologists who utilize high-risk medical devices should be aware that FDA approval of new devices relies on variable levels of evidence and does not necessarily indicate improved effectiveness over existing models. Clinician and patient engagement in postmarket surveillance and comparative effectiveness research remains imperative. PMID:24760423

  20. Approval of high-risk medical devices in the US: implications for clinical cardiology.

    PubMed

    Rome, Benjamin N; Kramer, Daniel B; Kesselheim, Aaron S

    2014-01-01

    Since 1976, the US Food and Drug Administration (FDA) has used the premarket approval (PMA) process to approve high-risk medical devices, including implantable cardioverter defibrillators (ICDs), coronary stents, and artificial heart valves. The PMA process is widely viewed as a rigorous evaluation of device safety and effectiveness, though recent recalls-most notably related to underperforming ICD leads-have raised concerns about whether physicians and patients should sometimes be more wary about devices approved via this pathway. The FDA must utilize a "least burdensome" approach to approve new medical devices, and many widely used device models have been approved as supplements to existing PMA-approved devices with limited clinical testing. A recent Supreme Court ruling has made it difficult for patients harmed by unsafe PMA-approved devices to seek damages in court. Cardiologists who utilize high-risk medical devices should be aware that FDA approval of new devices relies on variable levels of evidence and does not necessarily indicate improved effectiveness over existing models. Clinician and patient engagement in postmarket surveillance and comparative effectiveness research remains imperative.

  1. Coping Styles of Individuals at Clinical High Risk for Developing Psychosis

    PubMed Central

    Jalbrzikowski, Maria; Sugar, Catherine A.; Zinberg, Jamie; Bachman, Peter; Cannon, Tyrone D.; Bearden, Carrie E.

    2012-01-01

    Aim There is a wealth of evidence suggesting that patients with schizophrenia tend to respond to life stressors using less effective coping skills, which are in turn related to poor outcome. However, the contribution of coping strategies to outcome in youth at clinical high risk (CHR) for developing psychosis has not been investigated. Methods This longitudinal study followed CHR youth over a twelve-month period, using the Brief COPE questionnaire. CHR subjects (n=88) were compared at baseline to a healthy control sample (n=53), and then mixed models were used to explore the relationship of coping strategies to clinical and psychosocial outcomes in CHR subjects over time (n=102). Results Cross-sectional analyses revealed that, in comparison to healthy controls, CHR youth reported using more maladaptive coping strategies (p<.001) and fewer adaptive coping strategies (p<.01). Longitudinal analyses within the CHR group showed significant decreases in maladaptive coping and symptom severity over time, with corresponding improvements in social and role functioning. Adaptive coping was associated with better concurrent social functioning and less severe symptomatology (both p<.001). Over time, more maladaptive coping was associated with more severe positive and negative symptoms (both p < .005). Conclusions Youth at-risk for psychosis report using fewer adaptive and more maladaptive coping strategies relative to healthy controls. Over one year follow-up, more adaptive coping styles are associated with less severe clinical symptomatology and better social functioning. These findings suggest that teaching adaptive coping styles may be an important target for intervention in youth at high risk for psychosis. PMID:23164368

  2. fMRI investigation of response inhibition, emotion, impulsivity, and clinical high-risk behavior in adolescents

    PubMed Central

    Brown, Matthew R. G.; Benoit, James R. A.; Juhás, Michal; Dametto, Ericson; Tse, Tiffanie T.; MacKay, Marnie; Sen, Bhaskar; Carroll, Alan M.; Hodlevskyy, Oleksandr; Silverstone, Peter H.; Dolcos, Florin; Dursun, Serdar M.; Greenshaw, Andrew J.

    2015-01-01

    High-risk behavior in adolescents is associated with injury, mental health problems, and poor outcomes in later life. Improved understanding of the neurobiology of high-risk behavior and impulsivity shows promise for informing clinical treatment and prevention as well as policy to better address high-risk behavior. We recruited 21 adolescents (age 14–17) with a wide range of high-risk behavior tendencies, including medically high-risk participants recruited from psychiatric clinics. Risk tendencies were assessed using the Adolescent Risk Behavior Screen (ARBS). ARBS risk scores correlated highly (0.78) with impulsivity scores from the Barratt Impulsivity scale (BIS). Participants underwent 4.7 Tesla functional magnetic resonance imaging (fMRI) while performing an emotional Go/NoGo task. This task presented an aversive or neutral distractor image simultaneously with each Go or NoGo stimulus. Risk behavior and impulsivity tendencies exhibited similar but not identical associations with fMRI activation patterns in prefrontal brain regions. We interpret these results as reflecting differences in response inhibition, emotional stimulus processing, and emotion regulation in relation to participant risk behavior tendencies and impulsivity levels. The results are consistent with high impulsivity playing an important role in determining high risk tendencies in this sample containing clinically high-risk adolescents. PMID:26483645

  3. The Recidivism Patterns of Previously Deported Aliens Released from a Local Jail: Are They High-Risk Offenders?

    ERIC Educational Resources Information Center

    Hickman, Laura J.; Suttorp, Marika J.

    2010-01-01

    Previously deported aliens are a group about which numerous claims are made but very few facts are known. Using data on male deportable aliens released from a local jail, the study sought to test the ubiquitous claim that they pose a high risk of recidivism. Using multiple measures of recidivism and propensity score weighting to account for…

  4. The Subjective Experience of Youths at Clinical High Risk for Psychosis: A Qualitative Study

    PubMed Central

    Ben-David, Shelly; Birnbaum, Michael; Eilenberg, Mara; DeVylder, Jordan; Gill, Kelly; Schienle, Jessica; Azimov, Neyra; Lukens, Ellen P.; Davidson, Larry; Corcoran, Cheryl Mary

    2015-01-01

    Objective Understanding the experience of individuals across stages of schizophrenia is important for development of services to promote recovery. As yet, little is known about the experience of individuals who exhibit prodromal symptoms of schizophrenia. Methods Audiotaped interviews were conducted with 27 participants at clinical high risk (CHR) for psychosis (15 males; 12 females; mean age 21; ethnically diverse). Phenomenological qualitative research techniques of coding, consensus, and comparison were used. Results Emergent themes differed by gender. Themes for males were feeling abnormal or “broken”; focus on going “crazy”; fantasy and escapism; and alienation and despair, with a desire for relationships. Themes for females were psychotic illness in family members; personal trauma; struggle with intimate relationships; and career and personal development. Conclusions The finding of relative social engagement and future-orientation of females identified as at risk for psychosis is novel, and has implications for outreach and treatment. PMID:25179420

  5. Pilot Clinical Trial of Indocyanine Green Fluorescence-Augmented Colonoscopy in High Risk Patients.

    PubMed

    Sheth, Rahul A; Heidari, Pedram; Woods, Kevin; Chung, Daniel; Chan, Andrew T; Mahmood, Umar

    2016-01-01

    White light colonoscopy is the current gold standard for early detection and treatment of colorectal cancer, but emerging data suggest that this approach is inherently limited. Even the most experienced colonoscopists, under optimal conditions, miss at least 15-25% of adenomas. There is an unmet clinical need for an adjunctive modality to white light colonoscopy with improved lesion detection and characterization. Optical molecular imaging with exogenously administered organic fluorochromes is a burgeoning imaging modality poised to advance the capabilities of colonoscopy. In this proof-of-principle clinical trial, we investigated the ability of a custom-designed fluorescent colonoscope and indocyanine green, a clinically approved fluorescent blood pool imaging agent, to visualize polyps in high risk patients with polyposis syndromes or known distal colonic masses. We demonstrate (1) the successful performance of real-time, wide-field fluorescence endoscopy using off-the-shelf equipment, (2) the ability of this system to identify polyps as small as 1 mm, and (3) the potential for fluorescence imaging signal intensity to differentiate between neoplastic and benign polyps. PMID:26989406

  6. Prediction of Functional Outcome in Individuals at Clinical High Risk for Psychosis

    PubMed Central

    Carrión, Ricardo E.; McLaughlin, Danielle; Goldberg, Terry E.; Auther, Andrea M.; Olsen, Ruth H.; Olvet, Doreen M.; Correll, Christoph U.; Cornblatt, Barbara A.

    2014-01-01

    Importance A major public health concern associated with schizophrenia and psychotic disorders is the long-term disability that involves impaired cognition, lack of social support, and an inability to function independently in the community. A critical goal of early detection and intervention studies in psychosis is therefore to understand the factors leading to this often profound impairment. Objective To develop a predictive model of functional (social and role) outcome in a clinical high-risk sample for psychosis. Design Prospective, naturalistic, longitudinal 3- to 5-year follow-up study. Setting The Recognition and Prevention Program in New York, a research clinic located in the Zucker Hillside Hospital in New York. Participants One hundred one treatment-seeking patients at clinical high risk for psychosis. Ninety-two (91%) were followed up prospectively for a mean (SD) of 3 (1.6) years. Intervention Neurocognitive and clinical assessment. Main Outcomes and Measures The primary outcome variables were social and role functioning at the last follow-up visit. Results Poor social outcome was predicted by reduced processing speed (odds ratio [OR], 1.38; 95% CI, 1.050-1.823; P = .02), impaired social functioning at baseline (OR, 1.85; 95% CI, 1.258-2.732; P = .002), and total disorganized symptoms (OR, 5.06; 95% CI, 1.548-16.527; P = .007). Reduced performance on tests for verbal memory (OR, 1.74; 95% CI, 1.169-2.594; P = .006), role functioning at baseline (OR, 1.34; 95% CI, 1.053-1.711; P = .02), and motor disturbances (OR, 1.77; 95% CI, 1.060-2.969; P = .03) predicted role outcome. The areas under the curve for the social and role prediction models were 0.824 (95% CI, 0.736-0.913; P < .001) and 0.77 (95% CI, 0.68-0.87; P < .001), respectively, demonstrating a high discriminative ability. In addition, poor functional outcomes were not entirely dependent on the development of psychosis, because 40.3% and 45.5% of nonconverters at clinical high risk had poor social

  7. Noninvasive prenatal testing in routine clinical practice for a high-risk population

    PubMed Central

    Qi, Guijie; Yi, Jianping; Han, Baosheng; Liu, Heng; Guo, Wanru; Shi, Chong; Yin, Lirong

    2016-01-01

    Abstract This study aimed to summarize the effects of noninvasive prenatal testing (NIPT) on aneuploidy among high-risk participants in Tangshan Maternal and Children Health Hospital. NIPT or invasive prenatal diagnosis was recommended to patients with a high risk of fetal aneuploidy from February 2013 to February 2014. Patients who exhibited eligibility and applied for NIPT from January 2012 to January 2013 were included in a comparison group. The rates of patients who underwent invasive testing, declined to undergo further testing, and manifested trisomies 21, 18, and 13 were compared between two groups. Follow-up data were obtained from the participants who underwent NIPT from 2013 to 2014. A total of 7223 patients (3018 and 4205 individuals before and after NIPT) were eligible for analysis. After NIPT was introduced in 2013 to 2014, 727 patients (17.3%) underwent invasive testing, 2828 preferred NIPT (67.3%), and 650 declined to undergo further testing (15.5%). A total of 34 cases of trisomies 21, 18, and 13 (0.8%) were found. In 2012 to 2013, 565 patients (18.7%) underwent invasive testing and 2453 declined to undergo further testing (81.3%). A total of 7 cases of trisomies 21, 18, and 13 were documented (0.2%). Of these cases, 24 were found from NIPT and 10 cases were found from invasive testing. The number of participants who declined to undergo further testing significantly decreased after NIPT was introduced (81.3% vs. 15.5%, P < 0.001). The sensitivity and specificity of NIPT for trisomies 21, 18, and 13 were 100% and 99.9%, respectively. The detection rates of NIPT for trisomies 21, 18, and 13 also significantly increased (0.2% vs. 0.8%, P < 0.001). By contrast, the overall rates of invasive testing remained unchanged (18.7% vs. 17.3%, P = 0.12). The positive predictive values of NIPT for trisomies 21, 18, and 13 were 100%, 83.3%, and 50.0%, respectively. The false positive rates of NIPT were 0% and 0.04%. With NIPT implementation in clinical

  8. Dosimetric comparison of axilla and groin radiotherapy techniques for high-risk and locally advanced skin cancer

    PubMed Central

    Mattes, Malcolm D.; Zhou, Ying; Berry, Sean L.; Barker, Christopher A.

    2016-01-01

    Purpose: Radiation therapy targeting axilla and groin lymph nodes improves regional disease control in locally advanced and high-risk skin cancers. However, trials generally used conventional two-dimensional radiotherapy (2D-RT), contributing towards relatively high rates of side effects from treatment. The goal of this study is to determine if three-dimensional conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), or volumetric-modulated arc therapy (VMAT) may improve radiation delivery to the target while avoiding organs at risk in the clinical context of skin cancer regional nodal irradiation. Materials and Methods: Twenty patients with locally advanced/high-risk skin cancers underwent computed tomography simulation. The relevant axilla or groin planning target volumes and organs at risk were delineated using standard definitions. Paired t-tests were used to compare the mean values of several dose-volumetric parameters for each of the 4 techniques. Results: In the axilla, the largest improvement for 3D-CRT compared to 2D-RT was for homogeneity index (13.9 vs. 54.3), at the expense of higher lung V20 (28.0% vs. 12.6%). In the groin, the largest improvements for 3D-CRT compared to 2D-RT were for anorectum Dmax (13.6 vs. 38.9 Gy), bowel D200cc (7.3 vs. 23.1 Gy), femur D50 (34.6 vs. 57.2 Gy), and genitalia Dmax (37.6 vs. 51.1 Gy). IMRT had further improvements compared to 3D-CRT for humerus Dmean (16.9 vs. 22.4 Gy), brachial plexus D5 (57.4 vs. 61.3 Gy), bladder D5 (26.8 vs. 36.5 Gy), and femur D50 (18.7 vs. 34.6 Gy). Fewer differences were observed between IMRT and VMAT. Conclusion: Compared to 2D-RT and 3D-CRT, IMRT and VMAT had dosimetric advantages in the treatment of nodal regions of skin cancer patients. PMID:27306779

  9. Assessing depression in youth at clinical high risk for psychosis: a comparison of three measures

    PubMed Central

    DeVylder, Jordan; Yang, Lawrence; Harkavy-Friedman, Jill; Azimov, Neyra; Walder, Deborah; Corcoran, Cheryl

    2014-01-01

    Depressive symptoms are prevalent among individuals at clinical high-risk (CHR) for psychosis. Prior studies have used the Beck Depression Inventory (BDI), Hamilton Depression Rating Scale (HDRS), and the “dysphoric mood” item of the Scale of Prodromal Symptoms (SOPS) to assess depressive symptoms in CHR samples. We compared the psychometric properties of these instruments in a CHR cohort, to support the selection of appropriate depressive symptoms measures in future studies and in clinical settings. Internal consistency was assessed using Cronbach’s alpha. Construct validity was assessed through correlations with SOPS items that were expected or not expected to be related to depressive symptoms. Criterion validity was assessed by comparing scores between patients with and without a major depressive disorder diagnosis. We hypothesized based on the schizophrenia literature that the BDI would have superior internal consistency and discriminant validity compared to the HDRS, and that all three measures would show convergent validity and criterion validity. The BDI demonstrated superior internal consistency and construct validity in this at-risk sample. The BDI and HDRS differentiated patients with major depressive disorder, but SOPS dysphoria did not. This has implications for the choice of depression measures in future CHR studies and for the interpretation of past findings. PMID:24370335

  10. Use of primary high-risk human papillomavirus testing for cervical cancer screening: interim clinical guidance.

    PubMed

    Huh, Warner K; Ault, Kevin A; Chelmow, David; Davey, Diane D; Goulart, Robert A; Garcia, Francisco A; Kinney, Walter K; Massad, L Stewart; Mayeaux, Edward J; Saslow, Debbie; Schiffman, Mark; Wentzensen, Nicolas; Lawson, Herschel W; Einstein, Mark H

    2015-04-01

    In 2011, the American Cancer Society, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology updated screening guidelines for the early detection of cervical cancer and its precursors. Recommended screening strategies were cytology or cotesting (cytology in combination with high-risk HPV (hrHPV) testing). These guidelines also addressed the use of hrHPV testing alone as a primary screening approach, which was not recommended for use at that time. There is now a growing body of evidence for screening with primary hrHPV testing, including a prospective US-based registration study. Thirteen experts including representatives from the Society of Gynecologic Oncology, American Society for Colposcopy and Cervical Pathology, American College of Obstetricians and Gynecologists, American Cancer Society, American Society of Cytopathology, College of American Pathologists, and the American Society for Clinical Pathology, convened to provide interim guidance for primary hrHPV screening. This guidance panel was specifically triggered by an application to the FDA for a currently marketed HPV test to be labeled for the additional indication of primary cervical cancer screening. Guidance was based on literature review and review of data from the FDA registration study, supplemented by expert opinion. This document aims to provide information for health care providers who are interested in primary hrHPV testing and an overview of the potential advantages and disadvantages of this strategy for screening as well as to highlight areas in need of further investigation.

  11. Reciprocal social behavior in youths with psychotic illness and those at clinical high risk

    PubMed Central

    Jalbrzikowski, Maria; Krasileva, Kate E.; Marvin, Sarah; Zinberg, Jamie; Andaya, Angielette; Bachman, Peter; Cannon, Tyrone D.; Bearden, Carrie E.

    2015-01-01

    Youths at clinical high risk (CHR) for psychosis typically exhibit significant social dysfunction. However, the specific social behaviors associated with psychosis risk have not been well characterized. We administer the Social Responsiveness Scale (SRS), a measure of autistic traits that examines reciprocal social behavior, to the parents of 117 adolescents (61 CHR individuals, 20 age-matched adolescents with a psychotic disorder [AOP], and 36 healthy controls) participating in a longitudinal study of psychosis risk. AOP and CHR individuals have significantly elevated SRS scores relative to healthy controls, indicating more severe social deficits. Mean scores for AOP and CHR youths are typical of scores obtained in individuals with high functioning autism (Constantino & Gruber, 2005). SRS scores are significantly associated with concurrent real-world social functioning in both clinical groups. Finally, baseline SRS scores significantly predict social functioning at follow-up (an average of 7.2 months later) in CHR individuals, over and above baseline social functioning measures ( p < .009). These findings provide novel information regarding impairments in domains critical for adolescent social development, because CHR individuals and those with overt psychosis show marked deficits in reciprocal social behavior. Further, the SRS predicts subsequent real-world social functioning in CHR youth, suggesting that this measure may be useful for identifying targets of treatment in psychosocial interventions. PMID:24229557

  12. Susceptibility of high-risk human papillomavirus type 16 to clinical disinfectants

    PubMed Central

    Meyers, Jordan; Ryndock, Eric; Conway, Michael J.; Meyers, Craig; Robison, Richard

    2014-01-01

    Objectives Little to nothing is known about human papillomavirus (HPV) susceptibility to disinfection. HPV is estimated to be among the most common sexually transmitted diseases in humans. HPV is also the causative agent of cervical cancers and other anogenital cancers and is responsible for a significant portion of oropharyngeal cancers. While sexual transmission is well documented, vertical and non-sexual transmission may also be important. Methods Using recombinant HPV16 particles (quasivirions) and authentic HPV16 grown in three-dimensional organotypic human epithelial culture, we tested the susceptibility of high-risk HPV to clinical disinfectants. Infectious viral particles were incubated with 11 common clinical disinfectants, appropriate neutralizers were added to inactivate the disinfectant and solutions were filter centrifuged. Changes in the infectivity titres of the disinfectant-treated virus were measured compared with untreated virus. Results HPV16 is a highly resistant virus; more so than other non-enveloped viruses previously tested. The HPV16 quasivirions showed similar resistance to native virions, except for being susceptible to isopropanol, the triple phenolic and the lower concentration peracetic acid-silver (PAA-silver)-based disinfectant. Authentic virus and quasivirus were resistant to glutaraldehyde and ortho-phthalaldehyde and susceptible to hypochlorite and the higher concentration PAA-silver-based disinfectant. Conclusions We present the first disinfectant susceptibility data on HPV16 native virions, which show that commonly used clinical disinfectants, including those used as sterilants in medical and dental healthcare facilities, have no effect on HPV16 infectivity. Policy changes concerning disinfectant use are needed. The unusually high resistance of HPV16 to disinfection supports other data suggesting the possibility of fomite or non-sexual transmission of HPV16. PMID:24500190

  13. Fractionated total lymphoid irradiation as preparative immunosuppression in high risk renal transplantation: clinical and immunological studies

    SciTech Connect

    Najarian, J.S.; Ferguson, R.M.; Sutherland, D.E.; Slavin, S.; Kim, T.; Kersey, J.; Simmons, R.S.

    1982-10-01

    Twenty-two patients at high risk to reject renal allografts have been treated with fractionated total lymphoid irradiation (FTLI) prior to transplantation of primary (2), secondary (16) or teritary (4) renal allografts. All patients undergoing retransplantation had rapidly rejected previous grafts. At 24 months following transplantation, 72% of grafts were functioning in the TLI group compared with a 38% graft function in an historical control group of recipients receiving secondary or tertiary grafts and treated with conventional immunosuppression. Important variables in determining success of transplantation following fractionated TLI include the dose of TLI, the interval from radiation to transplantation, and maintenance, post-transplant immunosuppressive therapy. Optimal results were achieved with 2500 rads delivered in 100 rad fractions followed by transplantation within two weeks, and a tapering prednisone schedule and maintenance azathioprine post-transplantation. Seventeen patients had significant complications of the radiation treatment and there was one death, prior to transplantation, associated with pneumonitis. In vitro assessment of immune function demonstrated marked peripheral T cell depletion and loss of in vitro responsiveness to mitogen and allogeneic stimulation following FTLI. The administration of donor bone marrow at the time of transplantation did not produce chimerism. The results suggest that when properly utilized FTLI can produce effective adjunctive immunosuppression for clinical transplantation.

  14. N100 Repetition Suppression Indexes Neuroplastic Defects in Clinical High Risk and Psychotic Youth.

    PubMed

    Gonzalez-Heydrich, Joseph; Enlow, Michelle Bosquet; D'Angelo, Eugene; Seidman, Larry J; Gumlak, Sarah; Kim, April; Woodberry, Kristen A; Rober, Ashley; Tembulkar, Sahil; O'Donnell, Kyle; Hamoda, Hesham M; Kimball, Kara; Rotenberg, Alexander; Oberman, Lindsay M; Pascual-Leone, Alvaro; Keshavan, Matcheri S; Duffy, Frank H

    2016-01-01

    Highly penetrant mutations leading to schizophrenia are enriched for genes coding for N-methyl-D-aspartate receptor signaling complex (NMDAR-SC), implicating plasticity defects in the disease's pathogenesis. The importance of plasticity in neurodevelopment implies a role for therapies that target these mechanisms in early life to prevent schizophrenia. Testing such therapies requires noninvasive methods that can assess engagement of target mechanisms. The auditory N100 is an obligatory cortical response whose amplitude decreases with tone repetition. This adaptation may index the health of plasticity mechanisms required for normal development. We exposed participants aged 5 to 17 years with psychosis (n = 22), at clinical high risk (CHR) for psychosis (n = 29), and healthy controls (n = 17) to an auditory tone repeated 450 times and measured N100 adaptation (mean amplitude during first 150 tones - mean amplitude during last 150 tones). N100 adaptation was reduced in CHR and psychosis, particularly among participants <13 years old. Initial N100 blunting partially accounted for differences. Decreased change in the N100 amplitude with tone repetition may be a useful marker of defects in neuroplastic mechanisms measurable early in life. PMID:26881109

  15. Meta-cognition is associated with cortical thickness in youth at clinical high risk of psychosis.

    PubMed

    Buchy, Lisa; Stowkowy, Jacque; MacMaster, Frank P; Nyman, Karissa; Addington, Jean

    2015-09-30

    Meta-cognition is compromised in people with schizophrenia and people at clinical high risk (CHR) of psychosis. In the current work in a CHR sample, we hypothesized that meta-cognitive functions would correlate with cortical thickness in five brain regions implicated in the pathogenesis of psychosis: inferior and middle frontal cortices, anterior cingulate cortex, superior temporal cortex and insula. Secondly, we hypothesized that similar neural systems would underlie different meta-cognitive functions. Narratives were gathered for 29 youth at CHR of psychosis using a semi-structured interview. Four meta-cognitive functions within the narratives were measured with the Meta-cognition Assessment Scale and regressed on cortical thickness from our a priori regions of interest using FreeSurfer. Mapping statistics from our a priori regions of interest revealed that meta-cognition functions were associated with cortical thickness in inferior and middle frontal gyri, superior temporal cortex and insula. The distribution of cortical thickness was partially similar across the four MAS items. Results confirm our hypothesis that cortical thickness is significantly associated with meta-cognition in brain regions that consistently show gray matter reductions across the schizophrenia spectrum. Evidence for thickness covariation in a variety of regions suggests partial dependence in the neural architecture underlying various meta-cognitive functions in CHR.

  16. Clinical efficacy and safety of arbekacin for high-risk infections in patients with hematological malignancies.

    PubMed

    Miura, Katsuhiro; Nakagawa, Masaru; Takahashi, Hiromichi; Uchino, Yoshihito; Kodaira, Hitomi; Iriyama, Noriyoshi; Sakagami, Masashi; Ohtake, Shimon; Kobayashi, Sumiko; Hojo, Atsuko; Kurita, Daisuke; Kobayashi, Yujin; Kusuda, Machiko; Hirabayashi, Yukio; Hatta, Yoshihiro; Takei, Masami

    2016-03-01

    We performed a clinical trial to investigate the efficacy and safety of arbekacin (ABK), a unique aminoglycoside with activity against methicillin-resistant Staphylococcus aureus (MRSA), in patients with hematological malignancies complicated by high-risk infections. ABK was administered intravenously at a dose of approximately 5 mg/kg with various broad-spectrum β-lactams, followed by therapeutic drug monitoring (TDM). A total of 54 febrile or infectious episodes were registered, and TDM was performed in 44 (81%) cases. The absolute neutrophil count was below 500/μl in 49 (91%) cases, and cytotoxic chemotherapy was being administered in 47 (87%) cases. Before initiation of ABK, 52 (96%) patients had received fluoroquinolones (n = 37) and/or broad-spectrum β-lactams (n = 34). There were 10 cases of documented infections including one of MRSA pneumonia, and 44 cases of febrile neutropenia. The efficacy at the end of treatment was 80% for all patients, and efficacy was significantly higher in patients attaining maximum concentrations ≥ 16 µg/ml or receiving TDM-guided dose-adjustment of ABK (n = 19, 95 vs. 71%, P = 0.039). Renal toxicity was observed in six cases (11%) but was generally acceptable. This study demonstrated that TDM-guided ABK administration may be applicable under limited conditions for patients with hematological malignancies.

  17. Relation between cannabis use and subcortical volumes in people at clinical high risk of psychosis.

    PubMed

    Buchy, Lisa; Mathalon, Daniel H; Cannon, Tyrone D; Cadenhead, Kristin S; Cornblatt, Barbara A; McGlashan, Thomas H; Perkins, Diana O; Seidman, Larry J; Tsuang, Ming T; Walker, Elaine F; Woods, Scott W; Bearden, Carrie E; Addington, Jean

    2016-08-30

    Among people at genetic risk of schizophrenia, those who use cannabis show smaller thalamic and hippocampal volumes. We evaluated this relationship in people at clinical high risk (CHR) of psychosis. The Alcohol and Drug Use Scale was used to identify 132 CHR cannabis users, the majority of whom were non-dependent cannabis users, 387 CHR non-users, and 204 healthy control non-users, and all participants completed magnetic resonance imaging scans. Volumes of the thalamus, hippocampus and amygdala were extracted with FreeSurfer, and compared across groups. Comparing all CHR participants with healthy control participants revealed no significant differences in volumes of any ROI. However, when comparing CHR users to CHR non-users, a significant ROI×Cannabis group effect emerged: CHR users showed significantly smaller amygdala compared to CHR non-users. However, when limiting analysis to CHR subjects who reported using alcohol at a 'use without impairment' severity level, the amygdala effect was non-significant; rather, smaller hippocampal volumes were seen in CHR cannabis users compared to non-users. Controlling statistically for effects of alcohol and tobacco use rendered all results non-significant. These results highlight the importance of controlling for residual confounding effects of other substance use when examining the relationship between cannabis use and neural structure. PMID:27289213

  18. N100 Repetition Suppression Indexes Neuroplastic Defects in Clinical High Risk and Psychotic Youth.

    PubMed

    Gonzalez-Heydrich, Joseph; Enlow, Michelle Bosquet; D'Angelo, Eugene; Seidman, Larry J; Gumlak, Sarah; Kim, April; Woodberry, Kristen A; Rober, Ashley; Tembulkar, Sahil; O'Donnell, Kyle; Hamoda, Hesham M; Kimball, Kara; Rotenberg, Alexander; Oberman, Lindsay M; Pascual-Leone, Alvaro; Keshavan, Matcheri S; Duffy, Frank H

    2016-01-01

    Highly penetrant mutations leading to schizophrenia are enriched for genes coding for N-methyl-D-aspartate receptor signaling complex (NMDAR-SC), implicating plasticity defects in the disease's pathogenesis. The importance of plasticity in neurodevelopment implies a role for therapies that target these mechanisms in early life to prevent schizophrenia. Testing such therapies requires noninvasive methods that can assess engagement of target mechanisms. The auditory N100 is an obligatory cortical response whose amplitude decreases with tone repetition. This adaptation may index the health of plasticity mechanisms required for normal development. We exposed participants aged 5 to 17 years with psychosis (n = 22), at clinical high risk (CHR) for psychosis (n = 29), and healthy controls (n = 17) to an auditory tone repeated 450 times and measured N100 adaptation (mean amplitude during first 150 tones - mean amplitude during last 150 tones). N100 adaptation was reduced in CHR and psychosis, particularly among participants <13 years old. Initial N100 blunting partially accounted for differences. Decreased change in the N100 amplitude with tone repetition may be a useful marker of defects in neuroplastic mechanisms measurable early in life.

  19. N100 Repetition Suppression Indexes Neuroplastic Defects in Clinical High Risk and Psychotic Youth

    PubMed Central

    Gonzalez-Heydrich, Joseph; Bosquet Enlow, Michelle; D'Angelo, Eugene; Seidman, Larry J.; Gumlak, Sarah; Kim, April; Woodberry, Kristen A.; Rober, Ashley; Tembulkar, Sahil; O'Donnell, Kyle; Hamoda, Hesham M.; Kimball, Kara; Rotenberg, Alexander; Oberman, Lindsay M.; Pascual-Leone, Alvaro; Keshavan, Matcheri S.; Duffy, Frank H.

    2016-01-01

    Highly penetrant mutations leading to schizophrenia are enriched for genes coding for N-methyl-D-aspartate receptor signaling complex (NMDAR-SC), implicating plasticity defects in the disease's pathogenesis. The importance of plasticity in neurodevelopment implies a role for therapies that target these mechanisms in early life to prevent schizophrenia. Testing such therapies requires noninvasive methods that can assess engagement of target mechanisms. The auditory N100 is an obligatory cortical response whose amplitude decreases with tone repetition. This adaptation may index the health of plasticity mechanisms required for normal development. We exposed participants aged 5 to 17 years with psychosis (n = 22), at clinical high risk (CHR) for psychosis (n = 29), and healthy controls (n = 17) to an auditory tone repeated 450 times and measured N100 adaptation (mean amplitude during first 150 tones − mean amplitude during last 150 tones). N100 adaptation was reduced in CHR and psychosis, particularly among participants <13 years old. Initial N100 blunting partially accounted for differences. Decreased change in the N100 amplitude with tone repetition may be a useful marker of defects in neuroplastic mechanisms measurable early in life. PMID:26881109

  20. Neuropsychological Profiles in Individuals at Clinical High Risk for Psychosis: Relationship to Psychosis and Intelligence

    PubMed Central

    Woodberry, Kristen A.; Seidman, Larry J.; Giuliano, Anthony J.; Verdi, Mary B.; Cook, William L.; McFarlane, William R.

    2010-01-01

    Background Characterizing neuropsychological (NP) functioning of individuals at clinical high risk (CHR) for psychosis may be useful for prediction of psychosis and understanding functional outcome. The degree to which NP impairments are associated with general cognitive ability and/or later emergence of full psychosis in CHR samples requires study with well-matched controls. Methods We assessed NP functioning across eight cognitive domains in a sample of 73 CHR youth, 13 of whom developed psychotic-level symptoms after baseline assessment, and 34 healthy comparison (HC) subjects. Groups were matched on age, sex, ethnicity, handedness, subject and parent grade attainment, and median family income, and were comparable on WRAT-3 Reading, an estimate of premorbid IQ. Profile analysis was used to examine group differences and the role of IQ in profile shape. Results The CHR sample demonstrated a significant difference in overall magnitude of NP impairment but only a small and nearly significant difference in profile shape, primarily due to a large impairment in olfactory identification. Individuals who subsequently developed psychotic-level symptoms demonstrated large impairments in verbal IQ, verbal memory and olfactory identification comparable in magnitude to first episode samples. Conclusions CHR status may be associated with moderate generalized cognitive impairments marked by some degree of selective impairment in olfaction and verbal memory. Impairments were greatest in those who later developed psychotic symptoms. Future study of olfaction in CHR samples may enhance early detection and specification of neurodevelopmental mechanisms of risk. PMID:20692125

  1. Change in Neuropsychological Functioning over One Year in Youth at Clinical High Risk for Psychosis

    PubMed Central

    Woodberry, Kristen A.; McFarlane, William R.; Giuliano, Anthony J.; Verdi, Mary B.; Cook, William L.; Faraone, Stephen V.; Seidman, Larry J.

    2013-01-01

    Schizophrenia and related psychotic disorders are associated with significant neuropsychological (NP) impairments. Yet the onset and developmental evolution of these impairments remains incompletely characterized. This study examined NP functioning over one year in a sample of youth at clinical high risk (CHR) for psychosis participating in a treatment study. We assessed functioning across six cognitive domains at two time points in a sample of 53 CHR and 32 healthy comparison (HC) subjects. Linear regression of HC one-year scores was used to predict one-year performance for CHR from baseline scores and relevant demographic variables. We used raw scores and MANOVAs of the standardized residuals to test for progressive impairment over time. NP functioning of CHR at one year fell significantly below predicted levels. Effects were largest and most consistent for a failure of normative improvement on tests of executive function. CHR who reached the highest positive symptom rating (6, severe and psychotic) on the Structured Interview of Prodromal Syndromes after the baseline assessment (n = 10/53) demonstrated a particularly large (d= −1.89), although non-significant, discrepancy between observed and predicted one-year verbal memory test performance. Findings suggest that, although much of the cognitive impairment associated with psychosis is present prior to the full expression of the psychotic syndrome, some progressive NP impairments may accompany risk for psychosis and be greatest for those who develop psychotic level symptoms. PMID:23434505

  2. Use of primary high-risk human papillomavirus testing for cervical cancer screening: interim clinical guidance.

    PubMed

    Huh, Warner K; Ault, Kevin A; Chelmow, David; Davey, Diane D; Goulart, Robert A; Garcia, Francisco A R; Kinney, Walter K; Massad, L Stewart; Mayeaux, Edward J; Saslow, Debbie; Schiffman, Mark; Wentzensen, Nicolas; Lawson, Herschel W; Einstein, Mark H

    2015-02-01

    In 2011, the American Cancer Society, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology updated screening guidelines for the early detection of cervical cancer and its precursors. Recommended screening strategies were cytology or cotesting (cytology in combination with high-risk human papillomavirus [hrHPV] testing). These guidelines also addressed the use of hrHPV testing alone as a primary screening approach, which was not recommended for use at that time. There is now a growing body of evidence for screening with primary hrHPV testing, including a prospective U.S.-based registration study. Thirteen experts, including representatives from the Society of Gynecologic Oncology, the American Society for Colposcopy and Cervical Pathology, the American College of Obstetricians and Gynecologists, the American Cancer Society, the American Society of Cytopathology, the College of American Pathologists, and the American Society for Clinical Pathology, convened to provide interim guidance for primary hrHPV screening. This guidance panel was specifically triggered by an application to the U.S. Food and Drug Administration (FDA) for a currently marketed HPV test to be labeled for the additional indication of primary cervical cancer screening. Guidance was based on literature review and review of data from the FDA registration study, supplemented by expert opinion. This document aims to provide information for health care providers who are interested in primary hrHPV testing and an overview of the potential advantages and disadvantages of this strategy for screening as well as to highlight areas in need of further investigation.

  3. Altered relationships between age and functional brain activation in adolescents at clinical high risk for psychosis

    PubMed Central

    Karlsgodt, Katherine H.; van Erp, Theo G.M.; Bearden, Carrie E.; Cannon, Tyrone D.

    2014-01-01

    Schizophrenia is considered a neurodevelopmental disorder, but whether the adolescent period, proximal to onset, is associated with aberrant development in individuals at clinical high risk (CHR) for psychosis is incompletely understood. While abnormal gray and white matter development has been observed, alterations in functional neuroimaging (fMRI) parameters during adolescence as related to conversion to psychosis have not yet been investigated. Twenty CHR individuals and 19 typically developing controls (TDC), (ages 14-21), were recruited from the Center for Assessment and Prevention of Prodromal States (CAPPS) at UCLA. Participants performed a Sternberg-style verbal working memory (WMem) task during fMRI and data were analyzed using a cross-sectional design to test the hypothesis that there is a deviant developmental trajectory in WMem associated neural circuitry in those at risk for psychosis. Eight of the CHR adolescents converted to psychosis within 2 years of initial assessment. A voxel-wise regression examining the relationship between age and activation revealed a significant group-by-age interaction. TDC showed a negative association between age and functional activation in the WMem circuitry while CHR adolescents showed a positive association. Moreover, CHR patients who later converted to overt psychosis showed a distinct pattern of abnormal age-associated activation in the frontal cortex relative to controls, while non-converters showed a more diffuse posterior pattern. Finding that age related variation in baseline patterns of neural activity differentiate individuals who subsequently convert to psychosis from healthy subjects suggests that these differences are likely to be clinically relevant. PMID:24144510

  4. Altered relationships between age and functional brain activation in adolescents at clinical high risk for psychosis.

    PubMed

    Karlsgodt, Katherine H; van Erp, Theo G M; Bearden, Carrie E; Cannon, Tyrone D

    2014-01-30

    Schizophrenia is considered a neurodevelopmental disorder, but whether the adolescent period, proximal to onset, is associated with aberrant development in individuals at clinical high risk (CHR) for psychosis is incompletely understood. While abnormal gray and white matter development has been observed, alterations in functional neuroimaging (fMRI) parameters during adolescence as related to conversion to psychosis have not yet been investigated. Twenty CHR individuals and 19 typically developing controls (TDC), (ages 14-21), were recruited from the Center for Assessment and Prevention of Prodromal States (CAPPS) at UCLA. Participants performed a Sternberg-style verbal working memory (WMem) task during fMRI and data were analyzed using a cross-sectional design to test the hypothesis that there is a deviant developmental trajectory in WMem associated neural circuitry in those at risk for psychosis. Eight of the CHR adolescents converted to psychosis within 2 years of initial assessment. A voxel-wise regression examining the relationship between age and activation revealed a significant group-by-age interaction. TDC showed a negative association between age and functional activation in the WMem circuitry while CHR adolescents showed a positive association. Moreover, CHR patients who later converted to overt psychosis showed a distinct pattern of abnormal age-associated activation in the frontal cortex relative to controls, while non-converters showed a more diffuse posterior pattern. Finding that age related variation in baseline patterns of neural activity differentiate individuals who subsequently convert to psychosis from healthy subjects suggests that these differences are likely to be clinically relevant. PMID:24144510

  5. Mapping Patterns of Ipsilateral Supraclavicular Nodal Metastases in Breast Cancer: Rethinking the Clinical Target Volume for High-risk Patients

    SciTech Connect

    Jing, Hao; Wang, Shu-Lian; Li, Jing; Xue, Mei; Xiong, Zu-Kun; Jin, Jing; Wang, Wei-Hu; Song, Yong-Wen; Liu, Yue-Ping; Ren, Hua; Fang, Hui; Yu, Zi-Hao; Liu, Xin-Fan; Li, Ye-Xiong

    2015-10-01

    Purpose: To map the location of metastatic supraclavicular (SCV) lymph nodes (LNMs) in breast cancer patients with SCV node involvement and determine whether and where the radiation therapy clinical target volume (CTV) of this region could be modified in high-risk subsets. Methods and Materials: Fifty-five patients with metastatic SCV LNMs were eligible for geographic mapping and atlas coverage analysis. All LNMs and their epicenters were registered proportionally by referencing the surrounding landmarks onto simulation computed tomography images of a standard patient. CTVs based on selected SCV atlases, including the one by the Radiation Therapy Oncology Group (RTOG) were contoured. A modified SCV CTV was tried and shown to have better involved-node coverage and thus theoretically improved prophylaxis in this setting. Results: A total of 50 (91%) and 45 (81.8%) patients had LNMs in the medial and lateral SCV subregions, respectively. Also, 36 patients (65.5%) had LNMs located at the junction of the jugular-subclavian veins. All nodes were covered in only 25.5% to 41.8% of patients by different atlases. The RTOG atlas covered all nodes in 25.5% of patients. Stratified by the nodes in all the patients as a whole, 49.2% to 81.3% were covered, and the RTOG atlas covered 62.6%. The lateral and posterior borders were the most overlooked locations. Modification by extending the borders to natural anatomic barriers allowed the new CTV to cover all the nodes in 81.8% of patients and encompass 96.1% of all the nodes. Conclusions: According to the distribution of SCV LNMs, the extent of existing atlases might not be adequate for potential metastatic sites in certain groups of patients. The extension of the lateral and posterior CTV borders in high-risk or recurrent patients might be a reasonable approach for increasing coverage. However, additional data in more homogeneous populations with localized disease are needed before routine application.

  6. Specificity of Incident Diagnostic Outcomes in Patients at Clinical High Risk for Psychosis

    PubMed Central

    Webb, Jadon R.; Addington, Jean; Perkins, Diana O.; Bearden, Carrie E.; Cadenhead, Kristin S.; Cannon, Tyrone D.; Cornblatt, Barbara A.; Heinssen, Robert K.; Seidman, Larry J.; Tarbox, Sarah I.; Tsuang, Ming T.; Walker, Elaine F.; McGlashan, Thomas H.; Woods, Scott W.

    2015-01-01

    It is not well established whether the incident outcomes of the clinical high-risk (CHR) syndrome for psychosis are diagnostically specific for psychosis or whether CHR patients also are at elevated risk for a variety of nonpsychotic disorders. We collected 2 samples (NAPLS-1, PREDICT) that contained CHR patients and a control group who responded to CHR recruitment efforts but did not meet CHR criteria on interview (help-seeking comparison patients [HSC]). Incident diagnostic outcomes were defined as the occurrence of a SIPS-defined psychosis or a structured interview diagnosis from 1 of 3 nonpsychotic Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) groups (anxiety, bipolar, or nonbipolar mood disorder), when no diagnosis in that group was present at baseline. Logistic regression revealed that the CHR vs HSC effect did not vary significantly across study for any emergent diagnostic outcome; data from the 2 studies were therefore combined. CHR (n = 271) vs HSC (n = 171) emergent outcomes were: psychosis 19.6% vs 1.8%, bipolar disorders 1.1% vs 1.2%, nonbipolar mood disorders 4.4% vs 5.3%, and anxiety disorders 5.2% vs 5.3%. The main effect of CHR vs HSC was statistically significant (OR = 13.8, 95% CI 4.2–45.0, df = 1, P < .001) for emergent psychosis but not for any emergent nonpsychotic disorder. Sensitivity analyses confirmed these findings. Within the CHR group emergent psychosis was significantly more likely than each nonpsychotic DSM-IV emergent disorder, and within the HSC group emergent psychosis was significantly less likely than most emergent nonpsychotic disorders. The CHR syndrome is specific as a marker for research on predictors and mechanisms of developing psychosis. PMID:26272875

  7. The Validation and Clinical Implementation of BRCAplus: A Comprehensive High-Risk Breast Cancer Diagnostic Assay

    PubMed Central

    Chong, Hansook Kim; Wang, Tao; Lu, Hsiao-Mei; Seidler, Sara; Lu, Hong; Keiles, Steven; Chao, Elizabeth C.; Stuenkel, A. J.; Li, Xiang; Elliott, Aaron M.

    2014-01-01

    Breast cancer is the most commonly diagnosed cancer in women, with 10% of disease attributed to hereditary factors. Although BRCA1 and BRCA2 account for a high percentage of hereditary cases, there are more than 25 susceptibility genes that differentially impact the risk for breast cancer. Traditionally, germline testing for breast cancer was performed by Sanger dideoxy terminator sequencing in a reflexive manner, beginning with BRCA1 and BRCA2. The introduction of next-generation sequencing (NGS) has enabled the simultaneous testing of all genes implicated in breast cancer resulting in diagnostic labs offering large, comprehensive gene panels. However, some physicians prefer to only test for those genes in which established surveillance and treatment protocol exists. The NGS based BRCAplus test utilizes a custom tiled PCR based target enrichment design and bioinformatics pipeline coupled with array comparative genomic hybridization (aCGH) to identify mutations in the six high-risk genes: BRCA1, BRCA2, PTEN, TP53, CDH1, and STK11. Validation of the assay with 250 previously characterized samples resulted in 100% detection of 3,025 known variants and analytical specificity of 99.99%. Analysis of the clinical performance of the first 3,000 BRCAplus samples referred for testing revealed an average coverage greater than 9,000X per target base pair resulting in excellent specificity and the sensitivity to detect low level mosaicism and allele-drop out. The unique design of the assay enabled the detection of pathogenic mutations missed by previous testing. With the abundance of NGS diagnostic tests being released, it is essential that clinicians understand the advantages and limitations of different test designs. PMID:24830819

  8. A Comparison of Community and Clinic Baby Showers to Promote Safe Sleep for Populations at High Risk for Infant Mortality.

    PubMed

    Ahlers-Schmidt, Carolyn R; Schunn, Christy; Lopez, Venessa; Kraus, Stacey; Blackmon, Sheila; Dempsey, Millicent; Sollo, Natalie

    2016-01-01

    Community baby showers have provided education and free portable cribs to promote safe sleep for high-risk infants. We evaluated knowledge gained at these showers and the effectiveness of holding baby showers at a primary care clinic as an alternative to traditional community venues. Participants at the community venue were more likely to exhibit risk factors associated with unsafe sleep and to report an unsafe sleep location for their infant without the provided portable crib. Following the showers, both groups showed improvement in knowledge and intentions regarding safe sleep. However, to connect with the highest risk groups, showers held at community venues appeared to be preferable to those held at high-risk clinics. PMID:27335991

  9. A Comparison of Community and Clinic Baby Showers to Promote Safe Sleep for Populations at High Risk for Infant Mortality

    PubMed Central

    Ahlers-Schmidt, Carolyn R.; Schunn, Christy; Lopez, Venessa; Kraus, Stacey; Blackmon, Sheila; Dempsey, Millicent; Sollo, Natalie

    2016-01-01

    Community baby showers have provided education and free portable cribs to promote safe sleep for high-risk infants. We evaluated knowledge gained at these showers and the effectiveness of holding baby showers at a primary care clinic as an alternative to traditional community venues. Participants at the community venue were more likely to exhibit risk factors associated with unsafe sleep and to report an unsafe sleep location for their infant without the provided portable crib. Following the showers, both groups showed improvement in knowledge and intentions regarding safe sleep. However, to connect with the highest risk groups, showers held at community venues appeared to be preferable to those held at high-risk clinics. PMID:27335991

  10. Local anaesthetic thoracoscopy for intractable pneumothorax in a high-risk patient.

    PubMed

    Yutaka, Yojiro; Katakura, Hiromichi; Kaneda, Shohei; Yamanaka, Akira

    2012-08-01

    The management of high-operative-risk patients with a pneumothorax is complicated. The case of a 79-year old man with an intractable secondary pneumothorax, who had taken oral steroids to control asthma, is presented. Since the patient could not tolerate general anaesthesia because of poor cardiac function, thoracoscopic surgery was performed under local anaesthesia. A successful lung fistula closure was achieved and the continuous air leakage disappeared immediately after the surgery. PMID:22527089

  11. Effects of relaxation on depression levels in women with high-risk pregnancies: a randomised clinical trial 1

    PubMed Central

    de Araújo, Wanda Scherrer; Romero, Walckiria Garcia; Zandonade, Eliana; Amorim, Maria Helena Costa

    2016-01-01

    ABSTRACT Objective: to analyse the effects of relaxation as a nursing intervention on the depression levels of hospitalised women with high-risk pregnancies. Methods: a randomised clinical trial realised in a reference centre for high-risk pregnancies. The sample consisted of 50 women with high-risk pregnancies (25 in the control group and 25 in the intervention group). The Benson relaxation technique was applied to the intervention group for five days. Control variables were collected using a predesigned form, and the signs and symptoms of depression were evaluated using the Edinburgh Postnatal Depression Scale (EPDS). The Statistical Package for Social Sciences (SPSS), version 20.0, was used with a significance level of 5%. The Wilcoxon and paired t-tests were used to evaluate depression levels between two timepoints. Using categorical data, the McNemar test was used to analyse differences in depression severity before and after the intervention. Results: depression levels decreased in the intervention group five days after the relaxation technique was applied (4.5 ± 3, p<0.05) compared with the levels at the first timepoint (10.3±5.9). Conclusion: as a nursing intervention, relaxation was effective in decreasing the symptoms of depression in hospitalised women with high-risk pregnancies. PMID:27627126

  12. Impact of catheter fragmentation followed by local intrapulmonary thrombolysis in acute high risk pulmonary embolism as primary therapy

    PubMed Central

    Mohan, Bishav; Aslam, Naved; Kumar Mehra, Anil; Takkar Chhabra, Shibba; Wander, Praneet; Tandon, Rohit; Singh Wander, Gurpreet

    2014-01-01

    Background Pulmonary embolism (PE) with more than 50% compromise of pulmonary circulation results significant right ventricular (RV) afterload leading to progressive RV failure, systemic hypotension and shock. Prompt restoration of thrombolysis, surgical embolectomy, or percutaneous mechanical thrombectomy (PMT) prevents progressive hemodynamic decline. We report our single center experience in high risk PE patients treated with standard pigtail catheter mechanical fragmentation followed by intrapulmonary thrombolysis as a primary therapy. Methods 50 consecutive patients with diagnosis of high risk PE defined as having shock index >1 with angiographic evidence of >50% pulmonary arterial occlusion are included in the present study. All patients underwent emergent cardiac catheterization. After ensuring flow across pulmonary artery with mechanical breakdown of embolus by rotating 5F pigtail catheter; bolus dose of urokinase (4400 IU/kg) followed by infusion for 24 h was given in the thrombus. Hemodynamic parameters were recorded and follow up pulmonary angiogram was done. Clinical and echo follow up was done for one year. Results Pigtail rotational mechanical thrombectomy restored antegrade flow in all patients. The mean pulmonary artery pressure, Miller score, Shock index decreased significantly from 41 ± 8 mmHg, 20 ± 5, 1.32 ± 0.3 to 24.52 ± 6.89, 5.35 ± 2.16, 0.79 ± 0.21 respectively (p < 0.0001). In-hospital major complications were seen in 4 patients. There was a statistically significant reduction of PA pressures from 62 ± 11 mmHg to 23±6 mmHg on follow up. Conclusions Rapid reperfusion of pulmonary arteries with mechanical fragmentation by pigtail catheter followed by intrapulmonary thrombolysis results in excellent immediate and intermediate term outcomes in patients presenting with high risk pulmonary embolism. PMID:24973834

  13. Social dysfunction predicts two years clinical outcome in people at ultra high risk for psychosis.

    PubMed

    Fusar-Poli, P; Byrne, M; Valmaggia, L; Day, F; Tabraham, P; Johns, L; McGuire, P

    2010-04-01

    The experience of a first psychotic episode is associated with a marked impairment in psychosocial functioning. However, the decline may be already evident in the pre-psychotic phases and play a significant role in the etiopathology of the disease onset. A sample of subjects at ultra high clinical risk for psychosis ("At Risk Mental State", ARMS, n=152) was compared with a demographically-matched general population (n=98,072) on different measures of psychosocial functioning. The proportion of subjects with an ARMS living in communal establishments or living at home with their parents was significantly higher than that of the local population (p<0.001). Subjects with an ARMS showed also higher rates of unemployment as compared to the general population (p<0.001). GAF scores at baseline were significantly lower in unemployed ARMS as compared to students and employed ARMS (p=0.002). ARMS subjects living in communal establishments presented higher rates of co-morbid psychiatric conditions (p=0.007) and lower GAF scores at baseline (p=0.017). Finally, baseline unemployment and living in a communal establishment were associated with an increased risk of developing a psychotic episode within the following two years (p<0.05). We concluded that the "At Risk Mental State" is a clinical condition which is characterized by marked psychosocial impairment and by an increased vulnerability to psychosis. Unemployment at the first contact with the prodromal service may be a risk factor for the development of a psychotic episode. PMID:19836755

  14. Clinical high-risk designation does not predict excess fetal-maternal hemorrhage.

    PubMed

    Ness, P M; Baldwin, M L; Niebyl, J R

    1987-01-01

    During a 5-year period, an enzyme-linked antiglobulin test was used to screen and quantitate fetal-maternal hemorrhage in 789 consecutive D-negative mothers who were delivered of D-positive babies. Six hundred seventy-two patients (85.2%) had no detectable fetal-maternal hemorrhage, and 117 patients (14.8%) had a detectable fetal-maternal hemorrhage. Eight of the 789 (1%) had a fetal-maternal hemorrhage greater than 30 ml and required more than one vial of Rh immune globulin. Two patients with fetal-maternal hemorrhage of 29 and 30 ml also received additional Rh immune globulin. Each case was reviewed for the presence of high-risk features that are thought to predict patients at risk for fetal-maternal hemorrhage. Patients having a cesarean section or complicated vaginal delivery were considered to be in a group at high risk for fetal-maternal hemorrhage, while those with a spontaneous vaginal delivery were considered not to be at risk for fetal-maternal hemorrhage. Thirty-two of 237 patients (13.5%) in the risk group and 82 of 552 patients (15.3%) in the group not at risk had detectable fetal-maternal hemorrhage. The incidence of fetal-maternal hemorrhage for these two groups was not statistically different (p greater than 0.50 by chi 2 analysis). If only patients in the risk group had been screened for fetal-maternal hemorrhage, then five of 10 (50%) who required more than one vial of Rh immune globulin would have been undertreated and at risk for developing anti-D antibodies. In addition, newborn birth weight, Apgar scores, and hematocrits were examined for 13 cases of fetal-maternal hemorrhage of greater than or equal to 21 ml, and none of these characteristics could be used to predict patients at risk for fetal-maternal hemorrhage. Therefore, no maternal or newborn characteristics could be identified that would reliably predict patients at risk for fetal-maternal hemorrhage. We conclude that all D-negative patients with D-positive babies should continue to be

  15. High-risk angina patient. Identification by clinical features, hospital course, electrocardiography and technetium-99m stannous pyrophosphate scintigraphy

    SciTech Connect

    Olson, H.G.; Lyons, K.P.; Aronow, W.S.; Stinson, P.J.; Kuperus, J.; Waters, H.J.

    1981-10-01

    We evaluated 193 consecutive unstable angina patients by clinical features, hospital course and electrocardiography. All patients were managed medically. Of the 193 patients, 150 (78%) had a technetium-99m pyrophosphate (Tc-PYP) myocardial scintigram after hospitalization. Of these, 49 (33%) had positive scintigrams. At a follow-up of 24.9 +/- 10.8 months after hospitalization, 16 of 49 patients (33%) with positive scintigrams died from cardiac causes, compared with six of 101 patients (6%) with negative scintigrams (p less than 0.001). Of 49 patients with positive scintigrams, 11 (22%) had had nonfatal myocardial infarction at follow-up, compared with seven of 101 patients (7%) with negative scintigrams (p less than 0.01). Age, duration of clinical coronary artery disease, continuing angina during hospitalization, ischemic ECG, cardiomegaly and a history of heart failure also correlated with cardiac death at follow-up. Ischemic ECG and a history of angina with a crescendo pattern also correlated with nonfatal infarction at follow-up. Patients with continuing angina, an ischemic ECG and a positive scintigram constituted a high-risk unstable angina subgroup with a survival rate of 58% at 6 months, 47% at 12 months and 42% at 24 and 36 months. We conclude that the assessment of clinical features, hospital course, ECG and Tc-PYP scintigraphy may be useful in identifying high-risk unstable angina patients.

  16. High-risk angina patient: identification by clinical features, hospital course, electrocardiography, and technetium-99m stannous pyrophosphate scintigraphy

    SciTech Connect

    Olson, H.G.; Lyons, K.P.; Aronow, W.S.; Stinson, P.J.; Kuperus, J.; Waters, H.J.

    1981-10-01

    We evaluated 193 consecutive unstable angina patients by clinical features, hospital course and electrocardiography. All patients were managed medically. Of the 193 patients, 150 (78%) had a technetium-99m pyrophosphate (Tc-PYP) myocardial scintigram after hospitalization. Of these, 49 (33%) had positive scintigrams. At a follow-up of 24.9 +- 10.8 months after hospitalization, 16 of 49 patients (33%) with positive scintigrams died from cardiac causes, compared with six of 101 patients (6%) with negative scintigrams (p < 0.001). Of 49 patients with positive scintigrams, 11 (22%) had had nonfatal myocardial infarction at follow-up, compared with seven of 101 patients (7%) with negative scintigrams (p < 0.01). Age, duration of clinical coronary artery disease, continuing angina during hospitalization, ischemic ECG, cardiomegaly and a history of heart failure also correlated with cardiac death at follow-up. Ischemic ECG and a history of angina with a crescendo pattern also correlated with nonfatal infarction at follow-up. Patients with continuing angina, an ischemic ECG and a positive scintigram constituted a high-risk unstable angina subgroup, with a survival rate of 58% at 6 months, 47% at 12 months and 42% at 24 and 36 months. We conclude that the assessment of clinical features, hospital course, ECG and Tc-PYP scintigraphy may be useful in identifying high-risk unstable angina patients.

  17. The influence of number of high risk factors on clinical outcomes in patients with early-stage cervical cancer after radical hysterectomy and adjuvant chemoradiation

    PubMed Central

    Lim, Soyi; Lee, Seok-Ho; Park, Chan-Yong

    2016-01-01

    Objective The purpose of this study was to evaluate the prognosis according to the number of high risk factors in patients with high risk factors after radical hysterectomy and adjuvant chemoradiation therapy for early stage cervical cancer. Methods Clinicopathological variables and clinical outcomes of patients with FIGO (International Federation of Gynecology and Obstetrics) stage IB1 to IIA cervical cancer who had one or more high risk factors after radical hysterectomy and adjuvant chemoradiation therapy were retrospectively analyzed. Patients were divided into two groups according to the number of high risk factors (group 1, single high risk factor; group 2, two or more high risk factors). Results A total of 93 patients were enrolled in the present study. Forty nine out of 93 (52.7%) patients had a single high risk factor, and 44 (47.3%) had two or more high risk factors. Statistically significant differences in stage and stromal invasion were observed between group 1 and group 2. However, age, histology, tumor size, and lymphovascular space invasion did not differ significantly between the groups. Distant recurrence occurred more frequently in group 2, and the probability of recurrence and death was higher in group 2. Conclusion Patients with two or more high risk factors had worse prognosis in early stage cervical cancer. For these patients, consideration of new strategies to improve survival may be worthwhile. Conduct of further clinical trials is warranted for development of adjuvant treatment strategies individualized to each risk group. PMID:27200308

  18. Trauma history characteristics associated with mental states at clinical high risk for psychosis

    PubMed Central

    Russo, Debra A.; Stochl, Jan; Painter, Michelle; Dobler, Veronika; Jackson, Erica; Jones, Peter B.; Perez, Jesus

    2014-01-01

    Traumatic experiences have been positively associated with both severity of attenuated psychotic symptoms in individuals at high risk (HR) for psychosis and transitions into psychotic disorders. Our aim was to determine what characteristics of the trauma history are more likely to be associated with individuals at HR. The Trauma History Screen (THS) was used to enable emphasis on number and perceived intensity of adverse life events and age at trauma exposure. Sixty help-seeking individuals who met HR criteria were compared to a random sample of 60 healthy volunteers. Both groups were aged 16–35 and resided in the same geographical location. HR participants experienced their first trauma at an earlier age, continued to experience trauma at younger developmental stages, especially during early/mid adolescence and were exposed to a high number of traumas. They were more depressed and anxious, but did not experience more distress in relation to trauma. Both incidences of trauma and age at which trauma occurred were the most likely predictors of becoming HR. This work emphasises the importance of assessing trauma characteristics in HR individuals to enable differentiation between psychotic-like experiences that may reflect dissociative responses to trauma and genuine prodromal psychotic presentations. PMID:25200190

  19. Prevalence and predictors of Lymphogranuloma venereum in a high risk population attending a STD outpatients clinic in Italy

    PubMed Central

    2014-01-01

    Background We evaluated LGV prevalence and predictors in a high risk population attending a STI Outpatients Clinic in the North of Italy. Methods A total of 108 patients (99 MSM and 9 women), with a history of unsafe anal sexual intercourses, were enrolled. Anorectal swabs and urine samples were tested for Chlamydia trachomatis (CT) DNA detection by Versant CT/GC DNA 1.0 Assay (Siemens Healthcare Diagnostics Terrytown, USA). RFLP analysis was used for CT molecular typing. Results L2 CT genotype was identified in 13/108 (12%) rectal swabs. All LGV cases were from MSM, declaring high-risk sexual behaviour and complaining anorectal symptoms. Patients first attending the STI Outpatient Clinic received a significant earlier LGV diagnosis than those first seeking care from general practitioners or gastroenterologists (P = 0.0046). LGV prevalence and characteristics found in our population are in agreement with international reports. Statistical analysis showed that LGV positive patients were older (P = 0.0008) and presented more STIs (P = 0.0023) than LGV negative ones, in particular due to syphilis (P < 0.001), HIV (P < 0.001) and HBV (P = 0.001). Multivariate logistic regression analysis revealed that HIV and syphilis infections are strong risk factors for LGV presence (respectively, P = 0.001 and P = 0.010). Conclusions Even if our results do not provide sufficient evidence to recommend routine screening of anorectal swabs in high-risk population, they strongly suggest to perform CT NAAT tests and genotyping on rectal specimens in presence of ulcerative proctitis in HIV and/or syphilis-positive MSM. In this context, CT DNA detection by Versant CT/GC DNA 1.0 Assay, followed by RFLP analysis for molecular typing demonstrated to be an excellent diagnostic algorithm for LGV identification. PMID:24716676

  20. Women at high risk of breast cancer: Molecular characteristics, clinical presentation and management.

    PubMed

    Kleibl, Zdenek; Kristensen, Vessela N

    2016-08-01

    The presence of breast cancer in any first-degree female relative in general nearly doubles the risk for a proband and the risk gradually increases with the number of affected relatives. Current advances in molecular oncology and oncogenetics may enable the identification of high-risk individuals with breast-cancer predisposition. The best-known forms of hereditary breast cancer (HBC) are caused by mutations in the high-penetrance genes BRCA1 and BRCA2. Other genes, including PTEN, TP53, STK11/LKB1, CDH1, PALB2, CHEK2, ATM, MRE11, RAD50, NBS1, BRIP1, FANCA, FANCC, FANCM, RAD51, RAD51B, RAD51C, RAD51D, and XRCC2 have been described as high- or moderate-penetrance breast cancer-susceptibility genes. The majority of breast cancer-susceptibility genes code for tumor suppressor proteins that are involved in critical processes of DNA repair pathways. This is of particular importance for those women who, due to their increased risk of breast cancer, may be subjected to more frequent screening but due to their repair deficiency might be at the risk of developing radiation-induced malignancies. It has been proven that cancers arising from the most frequent BRCA1 gene mutation carriers differ significantly from the sporadic disease of age-matched controls in their histopathological appearances and molecular characteristics. The increased depth of mutation detection brought by next-generation sequencing and a better understanding of the mechanisms through which these mutations cause the disease will bring novel insights in terms of oncological prevention, diagnostics, and therapeutic options for HBC patients.

  1. Women at high risk of breast cancer: Molecular characteristics, clinical presentation and management.

    PubMed

    Kleibl, Zdenek; Kristensen, Vessela N

    2016-08-01

    The presence of breast cancer in any first-degree female relative in general nearly doubles the risk for a proband and the risk gradually increases with the number of affected relatives. Current advances in molecular oncology and oncogenetics may enable the identification of high-risk individuals with breast-cancer predisposition. The best-known forms of hereditary breast cancer (HBC) are caused by mutations in the high-penetrance genes BRCA1 and BRCA2. Other genes, including PTEN, TP53, STK11/LKB1, CDH1, PALB2, CHEK2, ATM, MRE11, RAD50, NBS1, BRIP1, FANCA, FANCC, FANCM, RAD51, RAD51B, RAD51C, RAD51D, and XRCC2 have been described as high- or moderate-penetrance breast cancer-susceptibility genes. The majority of breast cancer-susceptibility genes code for tumor suppressor proteins that are involved in critical processes of DNA repair pathways. This is of particular importance for those women who, due to their increased risk of breast cancer, may be subjected to more frequent screening but due to their repair deficiency might be at the risk of developing radiation-induced malignancies. It has been proven that cancers arising from the most frequent BRCA1 gene mutation carriers differ significantly from the sporadic disease of age-matched controls in their histopathological appearances and molecular characteristics. The increased depth of mutation detection brought by next-generation sequencing and a better understanding of the mechanisms through which these mutations cause the disease will bring novel insights in terms of oncological prevention, diagnostics, and therapeutic options for HBC patients. PMID:27318168

  2. Increasing the clinical efficacy of NK and antibody-mediated cancer immunotherapy: potential predictors of successful clinical outcome based on observations in high-risk neuroblastoma.

    PubMed

    Koehn, Tony A; Trimble, Lori L; Alderson, Kory L; Erbe, Amy K; McDowell, Kimberly A; Grzywacz, Bartosz; Hank, Jacquelyn A; Sondel, Paul M

    2012-01-01

    Disease recurrence is frequent in high-risk neuroblastoma (NBL) patients even after multi-modality aggressive treatment [a combination of chemotherapy, surgical resection, local radiation therapy, autologous stem cell transplantation, and cis-retinoic acid (CRA)]. Recent clinical studies have explored the use of monoclonal antibodies (mAbs) that bind to disialoganglioside (GD(2)), highly expressed in NBL, as a means to enable immune effector cells to destroy NBL cells via antibody-dependent cell-mediated cytotoxicity (ADCC). Preclinical data indicate that ADCC can be more effective when appropriate effector cells are activated by cytokines. Clinical studies have pursued this by administering anti-GD(2) mAb in combination with ADCC-enhancing cytokines (IL2 and GM-CSF), a regimen that has demonstrated improved cancer-free survival. More recently, early clinical studies have used a fusion protein that consists of the anti-GD(2) mAb directly linked to IL2, and anti-tumor responses were seen in the Phase II setting. Analyses of genes that code for receptors that influence ADCC activity and natural killer (NK) cell function [Fc receptor (FcR), killer immunoglublin-like receptor (KIR), and KIR-ligand (KIR-L)] suggest patients with anti-tumor activity are more likely to have certain genotype profiles. Further analyses will need to be conducted to determine whether these genotypes can be used as predictive markers for favorable therapeutic outcome. In this review, we discuss factors that affect response to mAb-based tumor therapies such as hu14.18-IL2. Many of our observations have been made in the context of NBL; however, we will also include some observations made with mAbs targeting other tumor types that are consistent with results in NBL. Therefore, we hypothesize that the NBL observations discussed here may also be relevant to mAb therapy for other cancers, in which ADCC is known to play a role.

  3. Contributions of Early Cortical Processing and Reading Ability to Functional Status in Individuals at Clinical High Risk for Psychosis

    PubMed Central

    Carrión, Ricardo E.; Cornblatt, Barbara A.; McLaughlin, Danielle; Chang, Jeremy; Auther, Andrea M.; Olsen, Ruth H.; Javitt, Daniel C.

    2015-01-01

    Background There is a growing recognition that individuals at clinical high risk need intervention for functional impairments, along with emerging psychosis, as the majority of clinical high risk (CHR) individuals show persistent deficits in social and role functioning regardless of transition to psychosis. Recent studies have demonstrated reduced reading ability as a potential cause of functional disability in schizophrenia, related to underlying deficits in generation of mismatch negativity (MMN). The present study extends these findings to subjects at CHR. Methods The sample consisted of 34 CHR individuals and 33 healthy comparisons subjects (CNTLs) from the Recognition and Prevention (RAP) Program at the Zucker Hillside Hospital in New York. At baseline, reading measures were collected, along with MMN to pitch, duration, and intensity deviants, and measures of neurocognition, and social and role (academic/work) functioning. Results CHR subjects showed impairments in reading ability, neurocognition, and MMN generation, relative to CNTLs. Lower-amplitude MMN responses were correlated with worse reading ability, slower processing speed, and poorer social and role functioning. However, when entered into a simultaneous regression, only reduced responses to deviance in sound duration and volume predicted poor social and role functioning, respectively. Conclusions Deficits in reading ability exist even prior to illness onset in schizophrenia and may represent a decline in performance from prior abilities. As in schizophrenia, deficits are related to impaired MMN generation, suggesting specific contributions of sensory-level impairment to neurocognitive processes related to social and role function. PMID:25728833

  4. Feasibility and Clinical Outcomes of Peripheral Drug-Coated Balloon in High-Risk Patients with Femoropopliteal Disease

    PubMed Central

    Huang, Hsuan-Li; Juang, Jyh-Ming Jimmy; Chou, Hsin-Hua; Tsao, Chueh-Yung; Wu, Tien-Yu; Ko, Yu-Lin

    2015-01-01

    Background Clinical outcomes of the drug-coated balloon (DCB) procedure in high-risk patients with femoropopliteal (FP) disease have not been investigated sufficiently. Methods This retrospective, single-center study analyzed 87 patients (39% dialysis) and 97 affected legs (64% critical limb ischemia [CLI]) that underwent DCB for symptomatic FP disease from March 2013 to September 2014. Risk stratification was based on FeDCLIP (female, diabetes, dialysis, CLI, lesion length >150 mm and poor runoff) score. The DCB outcomes among the different risk groups were compared and factors predicting restenosis were analyzed during follow-up. Results Most of study participants (84%) were moderate to high-risk patients. The procedural success rate was 100% and the 30-day major adverse vascular event rate was 2.1%. The mean lesion length was 178 ± 106 mm and the mean follow-up time was 428 ± 145 (range 50–782) days. The binary restenosis-free and clinically driven target lesion revascularization (CD-TLR)-free rates at 12 months were 77.5% and 84.3%, respectively, for all participants. No significant differences were observed in 1-year binary restenosis and CD-TLR rates in the low-, moderate-, and high-risk groups (60%, 84%, and 73%: p = 0.396; 78%, 89%, and 80%: p = 0.635, respectively). In multivariate analysis, lesion length >150 mm (Hazard ratio [HR]: 8.00, 95% confidence interval (CI) 1.12 to 55.6, p = 0.038) and Rutherford class 6 (HR: 7.09, 95% CI, 1.15 to 43.5, p = 0.034) were identified as independent predictors of binary restenosis. Conclusions Despite general comorbidities and advanced limb ischemia, 1-year outcomes of DCB in high-risk patients with FP disease were effective. The DCB procedure holds promise to improve vessel patency; however, lesion length >150 mm and major tissue loss were independent predictors for binary restenosis after the treatment. PMID:26599128

  5. Clinically important improvement in function is common in people with or at high risk of knee OA: the MOST study

    PubMed Central

    White, Daniel K.; Keysor, Julie J.; LaValley, Michael P.; Lewis, Cora E.; Torner, James C.; Nevitt, Michael C.; Felson, David T.

    2010-01-01

    To calculate the frequency of clinically important improvement in function over 30 months and identify risk factors in people who have or are at risk of knee OA. Subjects were from MOST, a longitudinal study of persons with or at high risk of knee OA. We defined Minimal Clinically Important Improvement (MCII) with WOMAC physical function using three different methods. Baseline risk factors tested for improvement included age, gender, educational attainment, presence of radiographic knee OA (ROA), the number of comorbidities, Body Mass Index (BMI), knee pain, walking speed, isokinetic knee extensor strength, depressive symptoms, physical activity, and medication usage. We used logistic regression to evaluate the association of baseline risk factors with MCII. Of the 1801 subjects (age= 63, BMI= 31, 63% female), most had mild limitations in baseline function (WOMAC = 19 +/− 11). Regardless how defined, a substantial percentage of subjects (24%–39%) reached MCII at 30 months. Compared to their counterparts, people with MCII were less likely to have ROA and to use medications, and were more likely to have a lower BMI, less knee pain, a faster walking speed, more knee strength, and fewer depressive symptoms. After adjustment, MCII was 40% to 50% less likely in those with ROA, and 1.9 to 2.0 times more likely in those walking 1.0 m/s faster than counterparts. Clinically important improvement is frequent in people with or at high risk of knee OA. The absence of ROA and a faster walking speed appear to be associated with clinically important improvements. PMID:20395640

  6. Ethical, Legal, and Clinical Considerations when Disclosing a High-Risk Syndrome for Psychosis.

    PubMed

    Mittal, Vijay A; Dean, Derek J; Mittal, Jyoti; Saks, Elyn R

    2015-10-01

    There are complex considerations when planning to disclose an attenuated psychosis syndrome (APS) diagnosis. In this review, we evaluate ethical, legal, and clinical perspectives as well as caveats related to full, non- and partial disclosure strategies, discuss societal implications, and provide clinical suggestions. Each of the disclosure strategies is associated with benefits as well as costs/considerations. Full disclosure promotes autonomy, allows for the clearest psychoeducation about additional risk factors, helps to clarify and/or correct previous diagnoses/treatments, facilitates early intervention and bolsters communication between providers but there are important considerations involving heritability, comorbidity, culture, and stigma. Non-disclosure advances nonmaleficence by limiting stigma and stress (which may inadvertently exacerbate the condition), and confusion (related to the rapidly evolving diagnosis) in a sensitive developmental period but is complicated by varying patient preferences and the possibility that, as new treatments without adverse effects become available, the risk with false positives no longer justifies the accompanying loss of autonomy. Partial disclosure balances ethical considerations by focusing on symptoms instead of labels, but evidence that laypersons may interpret this information as a pseudo-diagnosis and that symptoms alone also contribute to stigma limits the efficacy of this approach. In addition, there are notable societal considerations relating to disclosure involving conservatorship, the reach of insurance companies, and discrimination. We advocate a hybrid approach to disclosure and recommend future research aimed at understanding the effects of stigma on clinical course and a renewed focus on those help-seeking cases that do not transition but remain clinically relevant.

  7. Expressive writing for high-risk drug dependent patients in a primary care clinic: A pilot study

    PubMed Central

    Baikie, Karen A; Wilhelm, Kay; Johnson, Beverley; Boskovic, Mary; Wedgwood, Lucinda; Finch, Adam; Huon, Gail

    2006-01-01

    Background Previous research has shown that expressive writing is beneficial in terms of both physical and emotional health outcomes. This study aimed to investigate the effectiveness and acceptability of a brief expressive writing intervention for high-risk drug dependent patients in a primary care clinic, and to determine the relationship between linguistic features of writing and health outcomes. Methods Participants completed four 15-minute expressive writing tasks over a week, in which they described their thoughts and feelings about a recent stressful event. Self-report measures of physical (SF-12) and psychological health (DASS-21) were administered at baseline and at a two-week follow-up. Fifty-three participants were recruited and 14 (26%) completed all measures. Results No statistically significant benefits in physical or psychological health were found, although all outcomes changed in the direction of improvement. The intervention was well-received and was rated as beneficial by participants. The use of more positive emotion words in writing was associated with improvements in depression and stress, and flexibility in first person pronoun use was associated with improvements in anxiety. Increasing use of cognitive process words was associated with worsening depressive mood. Conclusion Although no significant benefits in physical and psychological health were found, improvements in psychological wellbeing were associated with certain writing styles and expressive writing was deemed acceptable by high-risk drug dependent patients. Given the difficulties in implementing psychosocial interventions in this population, further research using a larger sample is warranted. PMID:17112389

  8. Use of primary high-risk human papillomavirus testing for cervical cancer screening: interim clinical guidance.

    PubMed

    Huh, Warner K; Ault, Kevin A; Chelmow, David; Davey, Diane D; Goulart, Robert A; Garcia, Francisco A R; Kinney, Walter K; Massad, L Stewart; Mayeaux, Edward J; Saslow, Debbie; Schiffman, Mark; Wentzensen, Nicolas; Lawson, Herschel W; Einstein, Mark H

    2015-02-01

    In 2011, the American Cancer Society, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology updated screening guidelines for the early detection of cervical cancer and its precursors. Recommended screening strategies were cytology and cotesting (cytology in combination with hrHPV testing). These guidelines also addressed the use of hrHPV testing alone as a primary screening approach, which was not recommended for use at that time. There is now a growing body of evidence for screening with primary hrHPV testing, including a prospective US-based registration study. Thirteen experts including representatives from the Society of Gynecologic Oncology, American Society for Colposcopy and Cervical Pathology, American College of Obstetricians and Gynecologists, American Cancer Society, American Society of Cytopathology, College of American Pathologists, and the American Society for Clinical Pathology, convened to provide interim guidance for primary hrHPV screening. This guidance panel was specifically triggered by an application to the FDA for a currently marketed HPV test to be labeled for the additional indication of primary cervical cancer screening. Guidance was based on literature review and review of data from the FDA registration study, supplemented by expert opinion. This document aims to provide information for healthcare providers who are interested in primary hrHPV testing and an overview of the potential advantages and disadvantages of this strategy for screening as well as to highlight areas in need of further investigation.

  9. Long-term results of adjuvant imatinib mesylate in localized, high-risk, primary gastrointestinal stromal tumor (GIST): ACOSOG Z9000 (Alliance) intergroup phase 2 trial

    PubMed Central

    DeMatteo, Ronald P.; Ballman, Karla V.; Antonescu, Cristina R.; Corless, Christopher; Kolesnikova, Violetta; von Mehren, Margaret; McCarter, Martin D.; Norton, Jeffrey; Maki, Robert G.; Pisters, Peter W.T.; Demetri, George D.; Brennan, Murray F.; Owzar, Kouros

    2014-01-01

    Objective To conduct the first adjuvant trial of imatinib mesylate for treatment of gastrointestinal stromal tumor (GIST). Summary Background Data GIST is the most common sarcoma. While surgical resection has been the mainstay of therapy for localized, primary GIST, postoperative tumor recurrence is common. The KIT proto-oncogene or, less frequently, platelet-derived growth factor receptor alpha (PDGFRA) is mutated in GIST; the gene products of both are inhibited by imatinib mesylate. Methods This was a phase II, intergroup trial led by the American College of Surgeons Oncology Group (ACOSOG), registered at ClinicalTrials.gov as NCT00025246. From 09/2001 to 09/2003, we accrued 106 patients who had undergone complete gross tumor removal but were deemed at high risk for recurrence. Patients were prescribed imatinib 400 mg/day for 1 year and followed with serial radiologic evaluation. The primary endpoint was overall survival (OS). Results After a median follow-up of 7.7 years, the 1-, 3-, and 5-year OS rate was 99, 97, and 83%, which compared favorably with a historical 5 year OS rate of 35%. The 1-, 3-, and 5-year RFS rate was 96, 60, and 40%. On univariable analysis, age and mitotic rate were associated with OS. On multivariable analysis, the RFS rate was lower with increasing tumor size, small bowel site, KIT exon 9 mutation, high mitotic rate, and older age. Conclusion Adjuvant imatinib in patients with primary GIST who are at high risk of recurrence prolongs OS compared to that of historical controls. Optimal duration of adjuvant therapy remains undefined. (NCT00025246) PMID:23860199

  10. Predicting the onset of psychosis in patients at clinical high risk: practical guide to probabilistic prognostic reasoning.

    PubMed

    Fusar-Poli, P; Schultze-Lutter, F

    2016-02-01

    Prediction of psychosis in patients at clinical high risk (CHR) has become a mainstream focus of clinical and research interest worldwide. When using CHR instruments for clinical purposes, the predicted outcome is but only a probability; and, consequently, any therapeutic action following the assessment is based on probabilistic prognostic reasoning. Yet, probabilistic reasoning makes considerable demands on the clinicians. We provide here a scholarly practical guide summarising the key concepts to support clinicians with probabilistic prognostic reasoning in the CHR state. We review risk or cumulative incidence of psychosis in, person-time rate of psychosis, Kaplan-Meier estimates of psychosis risk, measures of prognostic accuracy, sensitivity and specificity in receiver operator characteristic curves, positive and negative predictive values, Bayes' theorem, likelihood ratios, potentials and limits of real-life applications of prognostic probabilistic reasoning in the CHR state. Understanding basic measures used for prognostic probabilistic reasoning is a prerequisite for successfully implementing the early detection and prevention of psychosis in clinical practice. Future refinement of these measures for CHR patients may actually influence risk management, especially as regards initiating or withholding treatment.

  11. Screening schizotypal personality disorder for detection of clinical high risk of psychosis in Chinese mental health services.

    PubMed

    Zhang, TianHong; Li, HuiJun; Tang, YingYing; Li, Hui; Zheng, LiNa; Guo, Qian; Zhao, ShanShan; Zhuo, KaiMing; Qian, ZhenYing; Wang, LanLan; Dai, YunFei; Chow, Annabelle; Li, ChunBo; Jiang, KaiDa; Wang, JiJun; Xiao, ZePing

    2015-08-30

    Schizotypal personality disorder (SPD) is viewed as a marker of prodromal psychosis. However, information regarding genetic risk (e.g. SPD) is often overlooked in the identification process. This study assessed whether SPD screening questionnaire help the prodromal psychosis (also widely applied "clinical high risk" (CHR) for clinical sample) detection in Chinese mental health service. This work also examined whether SPD had higher frequency in genetic risk population and CHR subjects. Two wave studies concerning the SPD identification was used for analysis. Wave 1 survey: 3075 subjects were assessed by Personality Diagnostic Questionnaire for SPD (PDQ-SPD) and Structured Clinical Interview for DSM-IV Axis II (SCID-II). Wave 2 survey: 2113 subjects screened with the prodromal questionnaire -brief version (PQ-B), PDQ-SPD, and interviewed by Structured Interview for Prodromal Symptoms (SIPS). Subjects with family history of mental disorders or with psychosis reported significantly higher scores in SPD. Receiver operating characteristic curves suggested that PDQ-SPD had moderate sensitivity and specificity for identifying CHR subjects. There was significant higher on SPD features in subjects with early stage (Course less than 1 year) of psychosis. Identifying SPD may be useful in early detection of psychosis especially in detecting the genetic risk syndromes and can be integrated with existing prodromal screen tools to improve its efficiency.

  12. Clinical validation of the Abbott RealTime High Risk HPV assay according to the guidelines for human papillomavirus DNA test requirements for cervical screening.

    PubMed

    Hesselink, A T; Meijer, C J L M; Poljak, M; Berkhof, J; van Kemenade, F J; van der Salm, M L; Bogaarts, M; Snijders, P J F; Heideman, D A M

    2013-07-01

    This study showed that the Abbott RealTime High Risk HPV assay fulfilled cross-sectional clinical equivalence and reproducibility criteria of international consensus guidelines, which indicates that this assay can be considered clinically validated for cervical cancer screening purposes.

  13. Emotional and behavioral symptomatology reported by help-seeking youth at clinical high-risk for psychosis.

    PubMed

    Thompson, Elizabeth; Kline, Emily; Ellman, Lauren M; Mittal, Vijay; Reeves, Gloria M; Schiffman, Jason

    2015-03-01

    Subthreshold psychosis-like experiences are typically the focus of psychosis-risk screening as they are associated with a greater propensity for future illness. Potentially prodromal individuals identified as being at clinical high-risk (CHR), however, report a variety of distressing and impairing mental health symptoms in addition to subthreshold psychosis symptoms, indicating that this population is of clinical interest regardless of whether or not they develop psychosis. In the current study, 90 young people (12-21) seeking mental health services completed the Behavior Assessment System for Children, Second Edition (BASC-2), a broad-range checklist of emotional and behavioral concerns and adaptive skills, followed by the Structured Interview for Psychosis-risk Syndromes to assess psychosis risk. Those who met criteria for CHR (n=35) reported elevated scores across several BASC-2 scales including depression, attention problems, locus of control, and sense of inadequacy compared to help-seeking youth without CHR (n=55). Most of these scales were also elevated compared to general population norms. Further, the CHR group had significantly lower scores on two adaptive scales, self-reliance and relations with parents, indicating more impairment in these domains. Results indicate that young people at CHR experience more pervasive and/or more severe symptomatology across several domains of clinical significance compared to a similar group of help-seeking youth not at CHR. Results from this study aid in the understanding of symptom correlates of CHR status beyond attenuated symptoms that can provide clinical information relevant for treatment. PMID:25638728

  14. Test and treat: the early experiences in a clinic serving women at high risk of HIV infection in Kampala.

    PubMed

    Mbonye, Martin; Seeley, Janet; Nalugya, Ruth; Kiwanuka, Thadeus; Bagiire, Daniel; Mugyenyi, Michelle; Namale, Gertrude; Mayanja, Yunia; Kamali, Anatoli

    2016-01-01

    At the end of 2013, the Government of Uganda issued guidance recommending provision of Anti-Retroviral Treatment (ART) to HIV-positive people in key populations, including female sex workers, regardless of CD4 cell count. We describe the implementation of this new guidance in a clinic serving women at high risk of HIV infection in Kampala. Between July and December 2015, we conducted repeat in-depth interviews with 15 women attending the clinic after the change in guidelines, to explore their perceptions regarding prompt ART initiation. The sample included some women who were HIV-negative and women who had both started and deferred ART. We conducted a data-led thematic analysis of the material from the interviews. A total of 257 of 445 eligible women had started ART; others were undecided or had not returned to the clinic after receiving the new information. Participants recounted varying experiences with the provision of prompt treatment. At an individual level, a history of treatment for opportunistic infections and other illnesses, coupled with relatively poor health, encouraged some to initiate ART promptly. However, knowledge of friends/relatives already on ART who had experienced side effects caused others to delay starting, fearing the same experience for themselves. A number of women questioned why they should start treatment when they were not sick. Situational factors such as work and residence (with many sharing single rooms) caused discomfort among newly diagnosed women who feared disclosure and stigma that would result from taking ART when they were not ill. Alcohol consumption and irregular working hours affected perceptions of future adherence, making prompt ART harder to embrace for some. Our findings show the challenges that influence the delay of treatment initiation, and/or the decision to defer receiving information on ART, with implications for the success of the test and treat programmes and guidelines. PMID:27421050

  15. Evaluating the relationship between cannabis use and IQ in youth and young adults at clinical high risk of psychosis.

    PubMed

    Buchy, Lisa; Seidman, Larry J; Cadenhead, Kristin S; Cannon, Tyrone D; Cornblatt, Barbara A; McGlashan, Thomas H; Perkins, Diana O; Stone, William; Tsuang, Ming T; Walker, Elaine F; Woods, Scott W; Bearden, Carrie E; Mathalon, Daniel H; Addington, Jean

    2015-12-30

    Among people with psychosis, those with a history of cannabis use show better cognitive performance than those who are cannabis naïve. It is unknown whether this pattern is present in youth at clinical high risk (CHR) of psychosis. We evaluated relationships between IQ and cannabis use while controlling for use of other substances known to impact cognition in 678 CHR and 263 healthy control (HC) participants. IQ was estimated using the Vocabulary and Block Design subtests of the Wechsler Abbreviated Scale of Intelligence. Drug and alcohol use severity and frequency were assessed with the Alcohol and Drug Use Scale, and we inquired participants' age at first use. CHR were further separated into early and late age at onset of cannabis use sub-groups, and low-, moderate- and high-frequency sub-groups. No significant differences in IQ emerged between CHR or HC cannabis users vs. non-users, or between use frequency groups. CHR late-onset users showed significantly higher IQ than CHR early-onset users. Age at onset of cannabis use was significantly and positively correlated with IQ in CHR only. Results suggest that age at onset of cannabis may be a more important factor for IQ than use current use or use frequency in CHR.

  16. Evaluating the relationship between cannabis use and IQ in youth and young adults at clinical high risk of psychosis.

    PubMed

    Buchy, Lisa; Seidman, Larry J; Cadenhead, Kristin S; Cannon, Tyrone D; Cornblatt, Barbara A; McGlashan, Thomas H; Perkins, Diana O; Stone, William; Tsuang, Ming T; Walker, Elaine F; Woods, Scott W; Bearden, Carrie E; Mathalon, Daniel H; Addington, Jean

    2015-12-30

    Among people with psychosis, those with a history of cannabis use show better cognitive performance than those who are cannabis naïve. It is unknown whether this pattern is present in youth at clinical high risk (CHR) of psychosis. We evaluated relationships between IQ and cannabis use while controlling for use of other substances known to impact cognition in 678 CHR and 263 healthy control (HC) participants. IQ was estimated using the Vocabulary and Block Design subtests of the Wechsler Abbreviated Scale of Intelligence. Drug and alcohol use severity and frequency were assessed with the Alcohol and Drug Use Scale, and we inquired participants' age at first use. CHR were further separated into early and late age at onset of cannabis use sub-groups, and low-, moderate- and high-frequency sub-groups. No significant differences in IQ emerged between CHR or HC cannabis users vs. non-users, or between use frequency groups. CHR late-onset users showed significantly higher IQ than CHR early-onset users. Age at onset of cannabis use was significantly and positively correlated with IQ in CHR only. Results suggest that age at onset of cannabis may be a more important factor for IQ than use current use or use frequency in CHR. PMID:26626949

  17. Clinical impact of the NKp30/B7-H6 axis in high-risk neuroblastoma patients.

    PubMed

    Semeraro, Michaela; Rusakiewicz, Sylvie; Minard-Colin, Véronique; Delahaye, Nicolas F; Enot, David; Vély, Frédéric; Marabelle, Aurélien; Papoular, Benjamin; Piperoglou, Christelle; Ponzoni, Mirco; Perri, Patrizia; Tchirkov, Andrei; Matta, Jessica; Lapierre, Valérie; Shekarian, Tala; Valsesia-Wittmann, Sandrine; Commo, Frédéric; Prada, Nicole; Poirier-Colame, Vichnou; Bressac, Brigitte; Cotteret, Sophie; Brugieres, Laurence; Farace, Françoise; Chaput, Nathalie; Kroemer, Guido; Valteau-Couanet, Dominique; Zitvogel, Laurence

    2015-04-15

    The immunosurveillance mechanisms governing high-risk neuroblastoma (HR-NB), a major pediatric malignancy, have been elusive. We identify a potential role for natural killer (NK) cells, in particular the interaction between the NK receptor NKp30 and its ligand, B7-H6, in the metastatic progression and survival of HR-NB after myeloablative multimodal chemotherapy and stem cell transplantation. NB cells expressing the NKp30 ligand B7-H6 stimulated NK cells in an NKp30-dependent manner. Serum concentration of soluble B7-H6 correlated with the down-regulation of NKp30, bone marrow metastases, and chemoresistance, and soluble B7-H6 contained in the serum of HR-NB patients inhibited NK cell functions in vitro. The expression of distinct NKp30 isoforms affecting the polarization of NK cell functions correlated with 10-year event-free survival in three independent cohorts of HR-NB in remission from metastases after induction chemotherapy (n = 196, P < 0.001), adding prognostic value to known risk factors such as N-Myc amplification and age >18 months. We conclude that the interaction between NKp30 and B7-H6 may contribute to the fate of NB patients and that both the expression of NKp30 isoforms on circulating NK cells and the concentration of soluble B7-H6 in the serum may be clinically useful as biomarkers for risk stratification. PMID:25877893

  18. Clinical application of dichotic multiple-stimulus auditory steady-state responses in high-risk newborns and young children.

    PubMed

    Luts, Heleen; Desloovere, Christian; Wouters, Jan

    2006-01-01

    Experience with dichotic multiple-stimulus auditory steady-state responses (ASSRs) in clinical practice is described. ASSR thresholds were assessed in a sample of 60 high-risk newborns and young children between birth and 4 years of age. Amplitudes and signal-to-noise ratios (SNRs) of the ASSR were compared between normal-hearing infants and adults. Age-related changes within a group of infants younger than 3 months of age were investigated. A comparison was made between ASSR, the click-evoked auditory brainstem response and behavioral hearing thresholds in infants with a wide range of hearing threshold levels. Mean ASSR thresholds for normal-hearing infants at an average corrected age of 12 days were 42 +/- 10, 35 +/- 10, 32 +/- 10 and 36 +/- 9 dB SPL for 0.5, 1, 2 and 4 kHz, respectively. Compared to adults, these thresholds were elevated by on average 11 dB and SNRs were 1.7 times smaller. However, based on ASSRs, reasonably accurate estimations could be made of behavioral hearing thresholds obtained at a later age (median delay of 7 months). The predicted thresholds were in 61% of the cases within 10 dB of the corresponding behavioral thresholds, and in 83% of the cases within 15 dB. In less than 1 h, thresholds at four frequencies per ear could be obtained. The optimal age of testing is between 1 week and 3 months corrected age. The dichotic multiple-stimulus ASSR technique is a valuable extension of the clinical test battery for hearing-impaired children, as a follow-up diagnostic after the neonatal hearing screening. PMID:16219992

  19. Seasonal variation in affective and other clinical symptoms among high-risk families for bipolar disorders in an Arctic population

    PubMed Central

    Pirkola, Sami; Eriksen, Heidi A.; Partonen, Timo; Kieseppä, Tuula; Veijola, Juha; Jääskeläinen, Erika; Mylläri-Figuerola, Eeva-Maija; Salo, Paula M.; Paunio, Tiina

    2015-01-01

    Background In bipolar disorder (BD), seasonality of symptoms is common and disturbances in circadian rhythms have been reported. Objectives We identified high-penetrance families in a geographically restricted area in Northern Fennoscandia and studied the seasonal variation of clinical symptoms among BD subjects and their healthy relatives. Design We explored the clinical characteristics of subjects living in Northern Fennoscandia, with extreme annual variation in daylight. Among known indigenous high-risk families for BD, we compared the affected ones (N=16) with their healthy relatives (N=15), and also included 18 healthy non-related controls from the same geographical area. Seasonal fluctuation in clinical measures was followed up at the 4 most demarcated photoperiodic time points of the annual cycle: around the summer solstice and autumn equinox in 2013, the winter solstice in 2013/2014, and the spring equinox in 2014. In the baseline, lifetime manic symptoms [Mood Disorder Questionnaire (MDQ)] and morningness–eveningness questionnaire type (MEQ) were registered, whereas in the follow-up, depressive [Beck Depression Inventory (BDI)] and distress [General Health Questionnaire (GHQ-12)] symptoms and alcohol consumption and sleep were recorded. Results Possibly indicative or statistically significant differences in symptoms between the affected subjects and their healthy relatives were the BDI winter (13.3 vs. 2.6, t=−2.51, p=0.022) and spring scores (12.6 vs. 3.2, t=−1.97, p=0.063) and GHQ winter (4.2 vs. 0.82, t=−2.08, p=0.052) and spring scores (3.8 vs. 0.82, t=−1.97, p=0.063). Scores were higher among the affected subjects, exceeding a possibly diagnostic threshold (10 and 3) at all the time points, and without the notable seasonality which was observed among the healthy relatives. In the overall population, MDQ and MEQ scores had an inverse correlation (−0.384, significant at 0.016), indicating increased lifetime manic behaviour among “the night

  20. Emotion recognition deficits as predictors of transition in individuals at clinical high risk for schizophrenia: a neurodevelopmental perspective

    PubMed Central

    Corcoran, C. M.; Keilp, J. G.; Kayser, J.; Klim, C.; Butler, P. D.; Bruder, G. E.; Gur, R. C.; Javitt, D. C.

    2016-01-01

    Background Schizophrenia is characterized by profound and disabling deficits in the ability to recognize emotion in facial expression and tone of voice. Although these deficits are well documented in established schizophrenia using recently validated tasks, their predictive utility in at-risk populations has not been formally evaluated. Method The Penn Emotion Recognition and Discrimination tasks, and recently developed measures of auditory emotion recognition, were administered to 49 clinical high-risk subjects prospectively followed for 2 years for schizophrenia outcome, and 31 healthy controls, and a developmental cohort of 43 individuals aged 7–26 years. Deficit in emotion recognition in at-risk subjects was compared with deficit in established schizophrenia, and with normal neurocognitive growth curves from childhood to early adulthood. Results Deficits in emotion recognition significantly distinguished at-risk patients who transitioned to schizophrenia. By contrast, more general neurocognitive measures, such as attention vigilance or processing speed, were non-predictive. The best classification model for schizophrenia onset included both face emotion processing and negative symptoms, with accuracy of 96%, and area under the receiver-operating characteristic curve of 0.99. In a parallel developmental study, emotion recognition abilities were found to reach maturity prior to traditional age of risk for schizophrenia, suggesting they may serve as objective markers of early developmental insult. Conclusions Profound deficits in emotion recognition exist in at-risk patients prior to schizophrenia onset. They may serve as an index of early developmental insult, and represent an effective target for early identification and remediation. Future studies investigating emotion recognition deficits at both mechanistic and predictive levels are strongly encouraged. PMID:26040537

  1. Clinical Application of High-Dose, Image-Guided Intensity-Modulated Radiotherapy in High-Risk Prostate Cancer

    SciTech Connect

    Bayley, Andrew; Rosewall, Tara; Craig, Tim; Bristow, Rob; Chung, Peter; Gospodarowicz, Mary; Menard, Cynthia; Milosevic, Michael; Warde, Padraig; Catton, Charles

    2010-06-01

    Purpose: To report the feasibility and early toxicity of dose-escalated image-guided IMRT to the pelvic lymph nodes (LN), prostate (P), and seminal vesicles (SV). Methods and Materials: A total of 103 high-risk prostate cancer patients received two-phase, dose-escalated, image-guided IMRT with 3 years of androgen deprivation therapy. Clinical target volumes (CTVs) were delineated using computed tomography/magnetic resonance co-registration and included the prostate, portions of the SV, and the LN. Planning target volume margins (PTV) used were as follows: P (10 mm, 7 mm posteriorly), SV (10 mm), and LN (5 mm). Organs at risk (OaR) were the rectal and bladder walls, femoral heads, and large and small bowel. The IMRT was planned with an intended dose of 55.1 Gy in 29 fractions to all CTVs (Phase 1), with P+SV consecutive boost of 24.7 Gy in 13 fractions. Daily online image guidance was performed using bony landmarks and intraprostatic markers. Feasibility criteria included delivery of intended doses in 80% of patients, 95% of CTV displacements incorporated within PTV during Phase 1, and acute toxicity rate comparable to that of lower-dose pelvic techniques. Results: A total of 91 patients (88%) received the total prescription dose. All patients received at least 72 Gy. In Phase 1, 63 patients (61%) received the intended 55.1 Gy, whereas 87% of patients received at least 50 Gy. Dose reductions were caused by small bowel and rectal wall constraints. All CTVs received the planned dose in >95% of treatment fractions. There were no Radiation Therapy Oncology Group acute toxicities greater than Grade 3, although there were five incidences equivalent to Grade 3 within a median follow-up of 23 months. Conclusion: These results suggest that dose escalation to the PLN+P+SV using IMRT is feasible, with acceptable rates of acute toxicity.

  2. Safety, Correlative Markers, and Clinical Results of Adjuvant Nivolumab in Combination with Vaccine in Resected High-Risk Metastatic Melanoma

    PubMed Central

    Gibney, Geoffrey T.; Kudchadkar, Ragini R.; DeConti, Ronald C.; Thebeau, Melissa S.; Czupryn, Maria P.; Tetteh, Leticia; Eysmans, Cabell; Richards, Allison; Schell, Michael J.; Fisher, Kate J.; Horak, Christine E.; Inzunza, H. David; Yu, Bin; Martinez, Alberto J.; Younos, Ibrahim; Weber, Jeffrey S.

    2015-01-01

    Purpose The anti-programmed death-1 (PD-1) antibody nivolumab (BMS-936558) has clinical activity in patients with metastatic melanoma. Nivolumab plus vaccine was investigated as adjuvant therapy in resected stage IIIC and IV melanoma patients. Experimental Design HLA-A*0201 positive patients with HMB-45, NY-ESO-1, and/or MART-1 positive resected tumors received nivolumab (1 mg/kg, 3 mg/kg, or 10 mg/kg i.v.) with a multi-peptide vaccine (gp100, MART-1, and NY-ESO-1 with Montanide ISA 51 VG) every 2 weeks for 12 doses followed by nivolumab maintenance every 12 weeks for 8 doses. Primary objective was safety and determination of a maximum tolerated dose (MTD). Secondary objectives included relapse-free survival (RFS), overall survival (OS), and immunologic correlative studies. Results Thirty-three patients were enrolled. Median age was 47 years; 55% were male. Two patients had stage IIIC disease; 31 patients had stage IV disease. Median follow-up was 32.1 months. MTD was not reached. Most common related adverse events (>40%) were vaccine injection site reaction, fatigue, rash, pruritus, nausea, and arthralgias. Five related grade 3 adverse events [hypokalemia (1), rash (1), enteritis (1), and colitis (2)] were observed. Ten of 33 patients relapsed. Estimated median RFS was 47.1 months; median OS was not reached. Increases in CTLA-4+/CD4+, CD25+Treg/CD4+, and tetramer specific CD8+ T-cell populations were observed with treatment (P < 0.05). Trends for lower baseline myeloid-derived suppressor cell and CD25+Treg/CD4+ populations were seen in nonrelapsing patients; PD-L1 tumor status was not significantly associated with RFS. Conclusions Nivolumab with vaccine is well tolerated as adjuvant therapy and demonstrates immunologic activity with promising survival in high-risk resected melanoma, justifying further study. PMID:25524312

  3. Stress-induced dopamine response in subjects at clinical high risk for schizophrenia with and without concurrent cannabis use.

    PubMed

    Mizrahi, Romina; Kenk, Miran; Suridjan, Ivonne; Boileau, Isabelle; George, Tony P; McKenzie, Kwame; Wilson, Alan A; Houle, Sylvain; Rusjan, Pablo

    2014-05-01

    Research on the environmental risk factors for schizophrenia has focused on either psychosocial stress or drug exposure, with limited investigation of their interaction. A heightened dopaminergic stress response in patients with schizophrenia and individuals at clinical high risk (CHR) supports the dopaminergic sensitization hypothesis. Cannabis is believed to contribute to the development of schizophrenia, possibly through a cross-sensitization with stress. Twelve CHR and 12 cannabis-using CHR (CHR-CU, 11 dependent) subjects underwent [(11)C]-(+)-PHNO positron emission tomography scans, while performing a Sensorimotor Control Task (SMCT) and a stress condition (Montreal Imaging Stress task). The simplified reference tissue model was used to obtain binding potential relative to non-displaceable binding (BPND) in the whole striatum, its functional subdivisions (limbic striatum (LST), associative striatum (AST), and sensorimotor striatum (SMST)), globus pallidus (GP), and substantia nigra (SN). Changes in BPND, reflecting alterations in synaptic dopamine (DA) levels, were tested with analysis of variance. SMCT BPND was not significantly different between groups in any brain region (p>0.21). Although stress elicited a significant reduction in BPND in the CHR group, CHR-CU group exhibited an increase in BPND. Stress-induced changes in regional BPND between CHR-CU and CHR were significantly different in AST (p<0.001), LST (p=0.007), SMST (p=0.002), SN (p=0.021), and whole striatum (p=0.001), with trend level in the GP (p=0.099). All subjects experienced an increase in positive (attenuated) psychotic symptoms (p=0.001) following the stress task. Our results suggest altered DA stress reactivity in CHR subjects who concurrently use cannabis, as compared with CHR subjects. Our finding does not support the cross-sensitization hypothesis, which posits greater dopaminergic reactivity to stress in CHR cannabis users, but adds to the growing body of literature showing reduced DA

  4. Language network dysfunction as a predictor of outcome in youth at clinical high-risk for psychosis

    PubMed Central

    Sabb, Fred W.; van Erp, Theo G.M.; Hardt, Molly E.; Dapretto, Mirella; Caplan, Rochelle; Cannon, Tyrone D.; Bearden, Carrie E.

    2009-01-01

    Objectives Language processing abnormalities are a hallmark feature of schizophrenia. Yet, no study to date has investigated underlying neural networks associated with discourse processing in adolescents at clinical high risk (CHR) for developing psychosis. Methods Forty CHR youth and 24 demographically comparable healthy controls underwent functional magnetic resonance imaging while performing a naturalistic discourse processing paradigm. We assessed differences in blood oxygenation level-dependent (BOLD) activity between task conditions (Topic Maintenance vs. Reasoning) and between groups. Furthermore, we examined the association of regional brain activity with symptom severity and social outcome at follow-up, 6 to 24 months after the scan. Results Relative to controls, CHR participants showed increased neural activity in a network of language-associated brain regions, including the medial prefrontal cortex bilaterally, left inferior frontal (LIFG; BA44/45, 47) and middle temporal gyri, and the anterior cingulate (BA24&32). Further, increased activity in the superior temporal gyrus (STG), caudate, and LIFG distinguished those who subsequently developed psychosis. Within the CHR sample, severity of positive formal thought disorder at follow-up was positively correlated with signal change in the LIFG, superior frontal gyrus, and inferior/middle temporal gyri, whereas social outcome was inversely correlated with signal change in the LIFG and anterior cingulate. Conclusions These findings are consistent with a neural inefficiency hypothesis in those at greatest risk for psychosis, and additionally suggest that baseline activation differences may predict symptomatic and functional outcome. These results highlight the need to further investigate the neural systems involved in conversion to psychosis, and how language disruption changes over time in at-risk adolescents. PMID:19861234

  5. Clinical evaluation of ultrasound screening in follow-up visits of infants with cerebral palsy at high risk for developmental dysplasia of the hip

    PubMed Central

    Qiu, Aizhen; Yang, Zhongxiu; Wang, Jiping; Wang, Taotao

    2016-01-01

    The aim of the study was to assess the clinical value of ultrasound screenings for the developmental dysplasia of the hip (DDH) and explore its etiology in high-risk infants with cerebral palsy in follow-up visits. A group of 98 cases of infants at high-risk of cerebral palsy who received rehabilitation treatment between July, 2009 and July, 2010 were selected. Infants included 58 men and 40 women, aged <6 months and not lost to follow-up visits. Ultrasound (using Graf static inspection) screening of hips was performed and the infants with abnormalities were given clinical intervention, and 1- to 2-year-old infants were given outpatient follow-ups. The results were analyzed and there were 40 abnormal cases among the 98 cases of infants at high risk of cerebral palsy, including 18 cases of unstable hip joint, and 22 cases of DDH (12 cases of hip dysplasia, 3 cases of hip subluxation and 7 cases of hip dislocation). Early clinical intervention for infants with hip dysplasia and outpatient follow up for infants aged 1–2 years was carried out and had ischemic necrosis of femoral head, with the exception of 1 case of femoral detorsion that was poorly restored. In conclusion, the probability of DDH was higher in infants at high-risk of cerebral palsy compared to the normal infants. Hip ultrasound is a safe, simple, and effective screening method for these infants, which is of great clinical significance for an earlier diagnosis and treatment of DDH in infants with cerebral palsy. PMID:27698744

  6. Family history of psychosis as a predictor or protective factor of social maladjustment in a population at clinical high risk for psychosis.

    PubMed

    Poe, S Lucy; Gill, Kelly E; Brucato, Gary; Corcoran, Cheryl M; Girgis, Ragy R

    2014-11-30

    Literature suggests that social maladjustment is predictive of psychosis. We assessed 70 clinical high risk (CHR) patients for social maladjustment. There were no significant differences between patients with a positive or negative family history, suggesting that the relationship between social maladjustment and psychosis found in the recent literature may not translate to a relationship between social maladjustment and family history of psychosis in a CHR population.

  7. Clinical evaluation of ultrasound screening in follow-up visits of infants with cerebral palsy at high risk for developmental dysplasia of the hip

    PubMed Central

    Qiu, Aizhen; Yang, Zhongxiu; Wang, Jiping; Wang, Taotao

    2016-01-01

    The aim of the study was to assess the clinical value of ultrasound screenings for the developmental dysplasia of the hip (DDH) and explore its etiology in high-risk infants with cerebral palsy in follow-up visits. A group of 98 cases of infants at high-risk of cerebral palsy who received rehabilitation treatment between July, 2009 and July, 2010 were selected. Infants included 58 men and 40 women, aged <6 months and not lost to follow-up visits. Ultrasound (using Graf static inspection) screening of hips was performed and the infants with abnormalities were given clinical intervention, and 1- to 2-year-old infants were given outpatient follow-ups. The results were analyzed and there were 40 abnormal cases among the 98 cases of infants at high risk of cerebral palsy, including 18 cases of unstable hip joint, and 22 cases of DDH (12 cases of hip dysplasia, 3 cases of hip subluxation and 7 cases of hip dislocation). Early clinical intervention for infants with hip dysplasia and outpatient follow up for infants aged 1–2 years was carried out and had ischemic necrosis of femoral head, with the exception of 1 case of femoral detorsion that was poorly restored. In conclusion, the probability of DDH was higher in infants at high-risk of cerebral palsy compared to the normal infants. Hip ultrasound is a safe, simple, and effective screening method for these infants, which is of great clinical significance for an earlier diagnosis and treatment of DDH in infants with cerebral palsy.

  8. The Queensland high risk foot form (QHRFF) – is it a reliable and valid clinical research tool for foot disease?

    PubMed Central

    2014-01-01

    Background Foot disease complications, such as foot ulcers and infection, contribute to considerable morbidity and mortality. These complications are typically precipitated by “high-risk factors”, such as peripheral neuropathy and peripheral arterial disease. High-risk factors are more prevalent in specific “at risk” populations such as diabetes, kidney disease and cardiovascular disease. To the best of the authors’ knowledge a tool capturing multiple high-risk factors and foot disease complications in multiple at risk populations has yet to be tested. This study aimed to develop and test the validity and reliability of a Queensland High Risk Foot Form (QHRFF) tool. Methods The study was conducted in two phases. Phase one developed a QHRFF using an existing diabetes foot disease tool, literature searches, stakeholder groups and expert panel. Phase two tested the QHRFF for validity and reliability. Four clinicians, representing different levels of expertise, were recruited to test validity and reliability. Three cohorts of patients were recruited; one tested criterion measure reliability (n = 32), another tested criterion validity and inter-rater reliability (n = 43), and another tested intra-rater reliability (n = 19). Validity was determined using sensitivity, specificity and positive predictive values (PPV). Reliability was determined using Kappa, weighted Kappa and intra-class correlation (ICC) statistics. Results A QHRFF tool containing 46 items across seven domains was developed. Criterion measure reliability of at least moderate categories of agreement (Kappa > 0.4; ICC > 0.75) was seen in 91% (29 of 32) tested items. Criterion validity of at least moderate categories (PPV > 0.7) was seen in 83% (60 of 72) tested items. Inter- and intra-rater reliability of at least moderate categories (Kappa > 0.4; ICC > 0.75) was seen in 88% (84 of 96) and 87% (20 of 23) tested items respectively. Conclusions The QHRFF had

  9. Short-term clinicopathological outcome of neoadjuvant chemohormonal therapy comprising complete androgen blockade, followed by treatment with docetaxel and estramustine phosphate before radical prostatectomy in Japanese patients with high-risk localized prostate cancer

    PubMed Central

    2012-01-01

    Background To assess the outcome of neoadjuvant chemohormonal therapy comprising complete androgen blockade followed by treatment with docetaxel and estramustine phosphate before radical prostatectomy in Japanese patients with a high risk of localized prostate cancer (PCa). Methods Complete androgen blockade followed by 6 cycles of docetaxel (30 mg/m2) with estramustine phosphate (560 mg) were given to 18 PCa patients before radical prostatectomy. Subsequently, the clinical and pathological outcomes were analyzed. Results No patients had severe adverse events during chemohormonal therapy, and hence they were treated with radical prostatectomy. Two patients (11.1%) achieved pathological complete response. Surgical margins were negative in all patients. At a median follow-up of 18 months, 14 patients (77.8%) were disease-free without PSA recurrence. All 4 patients with PSA recurrence had pathologic T3b or T4 disease and 3 of these 4 patients had pathologic N1 disease. Conclusion We found that neoadjuvant chemohormonal therapy with complete androgen blockade followed by treatment with docetaxel and estramustine phosphate before radical prostatectomy was safe, feasible, and associated with favorable pathological outcomes in patients with a high risk of localized PCa. PMID:22214417

  10. Basal Tumor Cell Isolation and Patient-Derived Xenograft Engraftment Identify High-Risk Clinical Bladder Cancers

    PubMed Central

    Skowron, K. B.; Pitroda, S. P.; Namm, J. P.; Balogun, O.; Beckett, M. A.; Zenner, M. L.; Fayanju, O.; Huang, X.; Fernandez, C.; Zheng, W.; Qiao, G.; Chin, R.; Kron, S. J.; Khodarev, N. N.; Posner, M. C.; Steinberg, G. D.; Weichselbaum, R. R.

    2016-01-01

    Strategies to identify tumors at highest risk for treatment failure are currently under investigation for patients with bladder cancer. We demonstrate that flow cytometric detection of poorly differentiated basal tumor cells (BTCs), as defined by the co-expression of CD90, CD44 and CD49f, directly from patients with early stage tumors (T1-T2 and N0) and patient-derived xenograft (PDX) engraftment in locally advanced tumors (T3-T4 or N+) predict poor prognosis in patients with bladder cancer. Comparative transcriptomic analysis of bladder tumor cells isolated from PDXs indicates unique patterns of gene expression during bladder tumor cell differentiation. We found cell division cycle 25C (CDC25C) overexpression in poorly differentiated BTCs and determined that CDC25C expression predicts adverse survival independent of standard clinical and pathologic features in bladder cancer patients. Taken together, our findings support the utility of BTCs and bladder cancer PDX models in the discovery of novel molecular targets and predictive biomarkers for personalizing oncology care for patients. PMID:27775025

  11. Generating local scale land use/cover change scenarios: case studies of high-risk mountain areas

    NASA Astrophysics Data System (ADS)

    Malek, Žiga; Glade, Thomas; Boerboom, Luc

    2014-05-01

    The relationship between land use/cover changes and consequences to human well-being is well acknowledged and has led to higher interest of both researchers and decision makers in driving forces and consequences of such changes. For example, removal of natural vegetation cover or urban expansion resulting in new elements at risk can increase hydro-meteorological risk. This is why it is necessary to study how the land use/cover could evolve in the future. Emphasis should especially be given to areas experiencing, or expecting, high rates of socio-economic change. A suitable approach to address these changes is scenario development; it offers exploring possible futures and the corresponding environmental consequences, and aids decision-making, as it enables to analyse possible options. Scenarios provide a creative methodology to depict possible futures, resulting from existing decisions, based on different assumptions of future socio-economic development. They have been used in various disciplines and on various scales, such as flood risk and soil erosion. Several studies have simulated future scenarios of land use/cover changes at a very high success rate, however usually these approaches are tailor made for specific case study areas and fit to available data. This study presents a multi-step scenario generation framework, which can be transferable to other local scale case study areas, taking into account the case study specific consequences of land use/cover changes. Through the use of experts' and decision-makers' knowledge, we aimed to develop a framework with the following characteristics: (1) it enables development of scenarios that are plausible, (2) it can overcome data inaccessibility, (3) it can address intangible and external driving forces of land use/cover change, and (4) it ensures transferability to other local scale case study areas with different land use/cover change processes and consequences. To achieve this, a set of different methods is applied

  12. Longitudinal investigation of the relationship between family history of psychosis and affective disorders and Child Behavior Checklist ratings in clinical high-risk adolescents.

    PubMed

    Simeonova, Diana I; Lee, Frances J; Walker, Elaine F

    2015-08-01

    This is the first study to investigate whether positive family history (FH) of psychosis and affective disorders moderates the relationship between child diagnostic status and parent-reported social and behavioral problems on the Child Behavior Checklist (CBCL) in clinical high-risk adolescents. This longitudinal investigation assessed 122 participants (mean age=14.25±1.8years) from three groups (at-risk, other personality disorders, non-psychiatric controls) at baseline and one year follow-up. As predicted, there was a main effect of FH for a number of CBCL scales indicating higher scores for adolescents with positive FH. The findings also demonstrate a significant Diagnostic Status×Family History interaction for several behavioral scales providing support for FH as a concurrent and longitudinal moderator of the relationship between diagnostic status and CBCL scales. The moderating effect is present for areas of functioning associated with depression, anxiety, social adjustment, thought problems, attention problems, and aggressive behavior. The findings also indicate that both positive and negative symptoms are related to the genetic vulnerability for developing psychosis in clinical high-risk individuals, particularly those symptoms reflective of emotional, attentional, and interpersonal functioning. The present findings are novel and have significant clinical and research implications. This investigation provides a platform for future studies to clarify further the role of FH in clinical high-risk individuals and contributes to integration of this knowledge in the development of early intervention and prevention approaches in at-risk populations for the emergence of severe mental illness.

  13. Sexually transmitted infections clinics as strategic venues for targeting high risk populations for HIV research and sexual health interventions.

    PubMed

    Clatts, Michael C; Rodríguez-Díaz, Carlos E; García, Hermes; Vargas-Molina, Ricardo L; Colón-López, Vivian; Pérez-Rios, Naydi; Goldsamt, Lloyd; Jovet-Toledo, Gerardo G

    2011-09-01

    Puerto Rico has one of the highest incidence rates of HIV in the U.S. Concurrent with increases in sexually transmitted infections (STI), an increasing share of the new infections in PR are associated with sexual transmission. Much of the available research on sexual risk in PR derives from STI/HIV surveillance data. There is limited social and epidemiological research on sexual risk in PR, particularly in hidden and often hard-to-reach populations at high risk. Despite the absence of substantial resources that most epidemiological studies require, a research collaboration was initiated in 2007 between researchers in the School of Public Health at the University of Puerto Rico and the Centro Latinoamericano de Enfermedades de Transmisión Sexual (CLETS), one of the largest publicly funded centers for STI/HIV screening and treatment in the San Juan metropolitan area. Structured as a case study in the development of community-based research collaborations, this paper describes the early history and development of the project, including formative research, recruitment and training of students, and evolution in the study design that contributed to the current configuration of the ongoing "Core" study. Preliminary data are presented, highlighting data from a number of subpopulations that may contribute to our understanding of the role of behavioral risk in the STI/HIV epidemics in PR. More generally, the paper may guide the development of similar collaboration elsewhere in the Caribbean where HIV risk is increasing but where resources for research in high risk settings and groups are scarce.

  14. Clinical significance of CD81 expression by clonal plasma cells in high-risk smoldering and symptomatic multiple myeloma patients.

    PubMed

    Paiva, B; Gutiérrez, N-C; Chen, X; Vídriales, M-B; Montalbán, M-Á; Rosiñol, L; Oriol, A; Martínez-López, J; Mateos, M-V; López-Corral, L; Díaz-Rodríguez, E; Pérez, J-J; Fernández-Redondo, E; de Arriba, F; Palomera, L; Bengoechea, E; Terol, M-J; de Paz, R; Martin, A; Hernández, J; Orfao, A; Lahuerta, J-J; Bladé, J; Pandiella, A; Miguel, J-F San

    2012-08-01

    The presence of CD19 in myelomatous plasma cells (MM-PCs) correlates with adverse prognosis in multiple myeloma (MM). Although CD19 expression is upregulated by CD81, this marker has been poorly investigated and its prognostic value in MM remains unknown. We have analyzed CD81 expression by multiparameter flow cytometry in MM-PCs from 230 MM patients at diagnosis included in the Grupo Español de Mieloma (GEM)05>65 years trial as well as 56 high-risk smoldering MM (SMM). CD81 expression was detected in 45% (103/230) MM patients, and the detection of CD81(+) MM-PC was an independent prognostic factor for progression-free (hazard ratio=1.9; P=0.003) and overall survival (hazard ratio=2.0; P=0.02); this adverse impact was validated in an additional series of 325 transplant-candidate MM patients included in the GEM05 <65 years trial. Moreover, CD81(+) SMM (n=34/56, 57%) patients had a shorter time to progression to MM (P=0.02). Overall, our results show that CD81 may have a relevant role in MM pathogenesis and represent a novel adverse prognostic marker in myeloma. PMID:22333880

  15. [Comparison of clinical efficacy between decitabine combined with CAG regimen and CAG regimen alone in patients with intermediate to high-risk myelodysplastic syndromes].

    PubMed

    Zhang, Yun-Ping; Wu, Wen-Zhong; Cui, Guo-Xing

    2014-10-01

    This study was purposed to compare the clinical efficacy and adverse reactions of low-dose decitabine combined with CAG regimen (aclarubicin, Ara-C, and G-CSF) and CAG regimen alone in intermediate to high-risk myelodysplastic syndromes (MDS), and evaluate the validity and efficacy of the former regimen as new treatment method of intermediate to high-risk myelodysplastic syndromes. A total of 12 patients with intermediate (IR) to high-risk (HR) MDS treated by low-dose decitabine combined with CAG regimen and 10 patients with IR to HR MDS treated by CAG regimen alone were evaluated after treatment of 1 cycle and at least after 2 cycles. The complete remission (CR) after 1 cycle, overall remission rate (ORR), progression free survival (PFS) and overall survival (OS) between them were analyzed. The results showed that 9 patients treated by low-dose decitabine combined with CAG regimen achieved complete remission after 1 cycle, 2 patients achieved partial remission, 1 patient did not show reaction. The complete remission rate was 75.0% and overall response rate was 91.7%. The median time of disease free survival was 9 months (0-27 months). The median overall survival time was 16 months (3-28 months). 4 patients suffered from pulmonary infection after treatment and then were all cured after treatment with anti-infective therapy. The 5 patients treated by CAG regimen alone achieved complete remission,3 patients achieved partial remission, 2 patients showed non-reaction. The complete remission rate was 50.0% and overall response rate was 80.0%. The median time of disease free survival was 6 months(0-18 months). The median overall survival time was 13 months(3-31 months), 4 patients suffered from pulmonary infection, 1 patient suffered from enteric infection and 1 patient suffered from Escherichia coli septicemia after treatment, all of them becomed better after active treatment. Two groups of patients all had no serious adverse reactions, All patients could tolerate, no

  16. Reproductive health services for populations at high risk of HIV: Performance of a night clinic in Tete province, Mozambique

    PubMed Central

    2010-01-01

    Background Different models exist to provide HIV/STI services for most-at-risk populations (MARP). Along the Tete traffic corridor in Mozambique, linking Malawi and Zimbabwe, a night clinic opening between 4 and 10 PM was established targeting female sex workers (FSW) and long-distance truck drivers (LDD). The clinic offers free individual education and counselling, condoms, STI care, HIV testing, contraceptive services and outreach peer education. To evaluate this clinic model, we assessed relevance, service utilisation, efficiency and sustainability. Methods In 2007-2009, mapping and enumeration of FSW and LDD was conducted; 28 key informants were interviewed; 6 focus group discussions (FGD) were held with FSW from Mozambique and Zimbabwe, and LDD from Mozambique and Malawi. Clinic outputs and costs were analysed. Results An estimated 4,415 FSW work in the area, or 9% of women aged 15-49, and on average 66 trucks stay overnight near the clinic. Currently on average, 475 clients/month visit the clinic (43% for contraception, 24% for counselling and testing and 23% for STI care). The average clinic running cost is US$ 1408/month, mostly for human resources. All informants endorsed this clinic concept and the need to expand the services. FGD participants reported high satisfaction with the services and mentioned good reception by the health staff, short waiting times, proximity and free services as most important. Participants were in favour of expanding the range of services, the geographical coverage and the opening times. Conclusions Size of the target population, satisfaction of clients and endorsement by health policy makers justify maintaining a separate clinic for MARP. Cost-effectiveness may be enhanced by broadening the range of SRHR-HIV/AIDS services, adapting opening times, expanding geographical coverage and targeting additional MARP. Long-term sustainability remains challenging and requires private-public partnerships or continued project-based funding

  17. The experience of premature birth for fathers: the application of the Clinical Interview for Parents of High-Risk Infants (CLIP) to an Italian sample

    PubMed Central

    Candelori, Carla; Trumello, Carmen; Babore, Alessandra; Keren, Miri; Romanelli, Roberta

    2015-01-01

    Aim: The study explored fathers’ experience of premature birth during the hospitalization of their infants, analyzing levels of depressive and anxiety symptoms as compared with mothers. Moreover the Italian version of the Clinical Interview for Parents of High-Risk Infant (CLIP) was tested through confirmatory factor analysis. Methods: Couples of parents (N = 64) of preterm infants (gestational age < 37 weeks) were administered a socio-demographic questionnaire, the Edinburgh Postnatal Depression Scale, the State-Trait Anxiety Inventory and the CLIP after the admission to the Neonatal Intensive Care Unit (NICU). Results: Significant levels of anxiety and depressive symptoms and high percentages of subjects above the corresponding risk thresholds were found among fathers and mothers with higher scores among the latters. Confirmatory factor analysis of the CLIP showed an adequate structure, with better fit for mothers than for fathers. Conclusion: Results highlighted the importance for nurses and clinicians working in the NICU to consider not only the maternal difficulties but also the paternal ones, even if these are often more hidden and silent. In addition the CLIP may be considered an useful interview for research and clinical purposes to be used with parents of high-risk infants. PMID:26483712

  18. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions.

    PubMed

    Cheng, A L; Hsu, C H; Lin, J K; Hsu, M M; Ho, Y F; Shen, T S; Ko, J Y; Lin, J T; Lin, B R; Ming-Shiang, W; Yu, H S; Jee, S H; Chen, G S; Chen, T M; Chen, C A; Lai, M K; Pu, Y S; Pan, M H; Wang, Y J; Tsai, C C; Hsieh, C Y

    2001-01-01

    Curcumin (diferuloylmethane), a yellow substance from the root of the plant Curcuma longa Linn., has been demonstrated to inhibit carcinogenesis of murine skin, stomach, intestine and liver. However, the toxicology, pharmacokinetics and biologically effective dose of curcumin in humans have not been reported. This prospective phase-I study evaluated these issues of curcumin in patients with one of the following five high-risk conditions: 1) recently resected urinary bladder cancer; 2) arsenic Bowen's disease of the skin; 3) uterine cervical intraepithelial neoplasm (CIN); 4) oral leucoplakia; and 5) intestinal metaplasia of the stomach. Curcumin was taken orally for 3 months. Biopsy of the lesion sites was done immediately before and 3 months after starting curcumin treament. The starting dose was 500 mg/day. If no toxicity > or = grade II was noted in at least 3 successive patients, the dose was then escalated to another level in the order of 1,000, 2,000, 4,000, 8,000, and 12,000 mg/day. The concentration of curcumin in serum and urine was determined by high pressure liquid chromatography (HPLC). A total of 25 patients were enrolled in this study. There was no treatment-related toxicity up to 8,000 mg/day. Beyond 8,000 mg/day, the bulky volume of the drug was unacceptable to the patients. The serum concentration of curcumin usually peaked at 1 to 2 hours after oral intake of crucumin and gradually declined within 12 hours. The average peak serum concentrations after taking 4,000 mg, 6,000 mg and 8,000 mg of curcumin were 0.51 +/- 0.11 microM, 0.63 +/- 0.06 microM and 1.77 +/- 1.87 microM, respectively. Urinary excretion of curcumin was undetectable. One of 4 patients with CIN and 1 of 7 patients with oral leucoplakia proceeded to develop frank malignancies in spite of curcumin treatment. In contrast, histologic improvement of precancerous lesions was seen in 1 out of 2 patients with recently resected bladder cancer, 2 out of 7 patients of oral leucoplakia, 1 out

  19. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions.

    PubMed

    Cheng, A L; Hsu, C H; Lin, J K; Hsu, M M; Ho, Y F; Shen, T S; Ko, J Y; Lin, J T; Lin, B R; Ming-Shiang, W; Yu, H S; Jee, S H; Chen, G S; Chen, T M; Chen, C A; Lai, M K; Pu, Y S; Pan, M H; Wang, Y J; Tsai, C C; Hsieh, C Y

    2001-01-01

    Curcumin (diferuloylmethane), a yellow substance from the root of the plant Curcuma longa Linn., has been demonstrated to inhibit carcinogenesis of murine skin, stomach, intestine and liver. However, the toxicology, pharmacokinetics and biologically effective dose of curcumin in humans have not been reported. This prospective phase-I study evaluated these issues of curcumin in patients with one of the following five high-risk conditions: 1) recently resected urinary bladder cancer; 2) arsenic Bowen's disease of the skin; 3) uterine cervical intraepithelial neoplasm (CIN); 4) oral leucoplakia; and 5) intestinal metaplasia of the stomach. Curcumin was taken orally for 3 months. Biopsy of the lesion sites was done immediately before and 3 months after starting curcumin treament. The starting dose was 500 mg/day. If no toxicity > or = grade II was noted in at least 3 successive patients, the dose was then escalated to another level in the order of 1,000, 2,000, 4,000, 8,000, and 12,000 mg/day. The concentration of curcumin in serum and urine was determined by high pressure liquid chromatography (HPLC). A total of 25 patients were enrolled in this study. There was no treatment-related toxicity up to 8,000 mg/day. Beyond 8,000 mg/day, the bulky volume of the drug was unacceptable to the patients. The serum concentration of curcumin usually peaked at 1 to 2 hours after oral intake of crucumin and gradually declined within 12 hours. The average peak serum concentrations after taking 4,000 mg, 6,000 mg and 8,000 mg of curcumin were 0.51 +/- 0.11 microM, 0.63 +/- 0.06 microM and 1.77 +/- 1.87 microM, respectively. Urinary excretion of curcumin was undetectable. One of 4 patients with CIN and 1 of 7 patients with oral leucoplakia proceeded to develop frank malignancies in spite of curcumin treatment. In contrast, histologic improvement of precancerous lesions was seen in 1 out of 2 patients with recently resected bladder cancer, 2 out of 7 patients of oral leucoplakia, 1 out

  20. Clinical studies of combined photodynamic therapy using 5-fluorouracil and methyl-aminolevulinate in patients at high risk for squamous cell carcinoma

    NASA Astrophysics Data System (ADS)

    Maytin, Edward V.; Lohser, Sara; Tellez, Alejandra; Wene, Lauren; Ishak, Rim; Anand, Sanjay

    2013-03-01

    Photodynamic therapy (PDT) using aminolevulinic acid or its methyl ester, methyl-aminolevulinate (MAL), is an increasingly recognized approach for treating squamous neoplasia of the skin. Advantages of MAL-PDT include its ability to cover broad diseased areas (field treatment), and to do multiple sessions with little-to-no risk of scarring or mutagenesis. MAL-PDT is especially valuable in certain populations at high risk for skin cancer, including Caucasian patients with extensive solar damage, and organ transplant recipients (OTR) who take immunosuppressive drugs to prevent graft rejection. The latter group has a 65-200 fold increased risk of developing squamous cell carcinoma (SCC), a major cause of mortality. Therapeutic options for those patients, other than frequent surgeries, are very limited. Topical 5-Fluorouracil (5-FU), frequently prescribed in normal patients for pre-SCC of the skin, is only minimally effective in the OTR group. MAL-PDT, however, has ~40% efficacy for pre-SCC in OTR patients. Based upon our preclinical studies in mouse tumor models, which showed that preconditioning with 5-FU can drive higher accumulation of target protoporphyins (PpIX), we proposed a rational combination regimen of 5-FU and MAL-PDT in humans. A clinical trial was designed to test the hypothesis that a combination of 5-FU followed by MAL-PDT will elevate PpIX levels and achieve better clinical outcomes in high-risk OTR patients. Primary endpoints include PpIX levels and biochemical markers (p53) measured noninvasively and in skin biopsies. Lesion clearance and recurrence (via photographs and clinical exam) are secondary endpoints. Ongoing results of this clinical trial are presented.

  1. Development and Validation of a Clinic-Based Prediction Tool to Identify Female Athletes at High Risk for Anterior Cruciate Ligament Injury

    PubMed Central

    Myer, Gregory D.; Ford, Kevin R.; Khoury, Jane; Succop, Paul; Hewett, Timothy E.

    2012-01-01

    Background Prospective measures of high knee abduction moment (KAM) during landing identify female athletes at high risk for anterior cruciate ligament injury. Laboratory-based measurements demonstrate 90% accuracy in prediction of high KAM. Clinic-based prediction algorithms that employ correlates derived from laboratory-based measurements also demonstrate high accuracy for prediction of high KAM mechanics during landing. Hypotheses Clinic-based measures derived from highly predictive laboratory-based models are valid for the accurate prediction of high KAM status, and simultaneous measurements using laboratory-based and clinic-based techniques highly correlate. Study Design Cohort study (diagnosis); Level of evidence, 2. Methods One hundred female athletes (basketball, soccer, volleyball players) were tested using laboratory-based measures to confirm the validity of identified laboratory-based correlate variables to clinic-based measures included in a prediction algorithm to determine high KAM status. To analyze selected clinic-based surrogate predictors, another cohort of 20 female athletes was simultaneously tested with both clinic-based and laboratory-based measures. Results The prediction model (odds ratio: 95% confidence interval), derived from laboratory-based surrogates including (1) knee valgus motion (1.59: 1.17-2.16 cm), (2) knee flexion range of motion (0.94: 0.89°-1.00°), (3) body mass (0.98: 0.94-1.03 kg), (4) tibia length (1.55: 1.20-2.07 cm), and (5) quadriceps-to-hamstrings ratio (1.70: 0.48%-6.0%), predicted high KAM status with 84% sensitivity and 67% specificity (P < .001). Clinic-based techniques that used a calibrated physician’s scale, a standard measuring tape, standard camcorder, ImageJ software, and an isokinetic dynamometer showed high correlation (knee valgus motion, r = .87; knee flexion range of motion, r = .95; and tibia length, r = .98) to simultaneous laboratory-based measurements. Body mass and quadriceps-to-hamstrings ratio

  2. Decreases in Perceived Maternal Criticism Predict Improvement in Subthreshold Psychotic Symptoms in a Randomized Trial of Family-Focused Therapy for Individuals at Clinical High Risk for Psychosis

    PubMed Central

    O’Brien, Mary P.; Miklowitz, David J.; Cannon, Tyrone D.

    2015-01-01

    Perceived criticism (PC) is a measure of how much criticism from 1 family member “gets through” to another. PC ratings have been found to predict the course of psychotic disorders, but questions remain regarding whether psychosocial treatment can effectively decrease PC, and whether reductions in PC predict symptom improvement. In a sample of individuals at high risk for psychosis, we examined a) whether Family Focused Therapy for Clinical High-Risk (FFT-CHR), an 18-session intervention that consists of psychoeducation and training in communication and problem solving, brought about greater reductions in perceived maternal criticism, compared to a 3-session family psychoeducational intervention; and b) whether reductions in PC from baseline to 6-month reassessment predicted decreases in subthreshold positive symptoms of psychosis at 12-month follow-up. This study was conducted within a randomized controlled trial across 8 sites. The perceived criticism scale was completed by 90 families prior to treatment and by 41 families at 6-month reassessment. Evaluators, blind to treatment condition, rated subthreshold symptoms of psychosis at baseline, 6- and 12-month assessments. Perceived maternal criticism decreased from pre- to posttreatment for both treatment groups, and this change in criticism predicted decreases in subthreshold positive symptoms at 12-month follow-up. This study offers evidence that participation in structured family treatment is associated with improvement in perceptions of the family environment. Further, a brief measure of perceived criticism may be useful in predicting the future course of attenuated symptoms of psychosis for CHR youth. PMID:26168262

  3. Decreases in perceived maternal criticism predict improvement in subthreshold psychotic symptoms in a randomized trial of family-focused therapy for individuals at clinical high risk for psychosis.

    PubMed

    O'Brien, Mary P; Miklowitz, David J; Cannon, Tyrone D

    2015-12-01

    Perceived criticism (PC) is a measure of how much criticism from 1 family member "gets through" to another. PC ratings have been found to predict the course of psychotic disorders, but questions remain regarding whether psychosocial treatment can effectively decrease PC, and whether reductions in PC predict symptom improvement. In a sample of individuals at high risk for psychosis, we examined a) whether Family Focused Therapy for Clinical High-Risk (FFT-CHR), an 18-session intervention that consists of psychoeducation and training in communication and problem solving, brought about greater reductions in perceived maternal criticism, compared to a 3-session family psychoeducational intervention; and b) whether reductions in PC from baseline to 6-month reassessment predicted decreases in subthreshold positive symptoms of psychosis at 12-month follow-up. This study was conducted within a randomized controlled trial across 8 sites. The perceived criticism scale was completed by 90 families prior to treatment and by 41 families at 6-month reassessment. Evaluators, blind to treatment condition, rated subthreshold symptoms of psychosis at baseline, 6- and 12-month assessments. Perceived maternal criticism decreased from pre- to posttreatment for both treatment groups, and this change in criticism predicted decreases in subthreshold positive symptoms at 12-month follow-up. This study offers evidence that participation in structured family treatment is associated with improvement in perceptions of the family environment. Further, a brief measure of perceived criticism may be useful in predicting the future course of attenuated symptoms of psychosis for CHR youth.

  4. Sunitinib Plus Androgen Deprivation and Radiation Therapy for Patients With Localized High-Risk Prostate Cancer: Results From a Multi-institutional Phase 1 Study

    SciTech Connect

    Corn, Paul G.; Song, Danny Y.; Heath, Elisabeth; Maier, Jordan; Meyn, Raymond; Kuban, Deborah; DePetrillo, Thomas A.; Mathew, Paul

    2013-07-01

    Purpose: To evaluate the feasibility of administering sunitinib in combination with androgen deprivation therapy and external-beam intensity modulated radiation therapy (XRT) in patients with localized high-risk prostate cancer. Methods and Materials: Seventeen men with localized adenocarcinoma of the prostate with cT2c-cT4 or Gleason 8-10 or prostate-specific antigen >20 ng/mL received initial androgen deprivation (leuprolide 22.5 mg every 12 weeks plus oral bicalutamide 50 mg daily) for 4-8 weeks before oral sunitinib 12.5, 25, or 37.5 mg daily for 4 weeks as lead-in, then concurrently with and 4 weeks after XRT (75.6 Gy in 42 fractions to prostate and seminal vesicles). A 3+3 sequential dose-escalation design was used to assess the frequency of dose-limiting toxicity (DLT) and establish a maximal tolerated dose of sunitinib. Results: Sunitinib at 12.5- and 25-mg dose levels was well tolerated. The first 4 patients enrolled at 37.5 mg experienced a DLT during lead-in, and a drug interaction between sunitinib and bicalutamide was suspected. The protocol was revised and concurrent bicalutamide omitted. Of the next 3 patients enrolled at 37.5 mg, 2 of 3 receiving concurrent therapy experienced DLTs during radiation: grade 3 diarrhea and grade 3 proctitis, respectively. Only 1 of 7 patients completed sunitinib at 37.5 mg daily, whereas 3 of 3 patients (25 mg as starting dose) and 3 of 4 patients (25 mg as reduced dose) completed therapy. Conclusions: The feasibility of combined vascular endothelial growth factor receptor (VEGFR)/platelet-derived growth factor receptor (PDGFR) inhibitor therapy, androgen deprivation, and radiation therapy for prostate cancer was established. Using a daily dosing regimen with lead-in, concurrent, and post-XRT therapy, the recommended phase 2 dose of sunitinib is 25 mg daily.

  5. HPV Awareness and Willingness to HPV Vaccination among High-Risk Men attending an STI Clinic in Puerto Rico

    PubMed Central

    Colón-López, Vivian; Del Toro-Mejías, Lizbeth M.; Ortiz, Ana P.; Tortolero-Luna, Guillermo; Palefsky, Joel M.

    2013-01-01

    Objective An HPV vaccine has been approved for men aged 9 to 26 in the US for the prevention of genital warts and anal cancer. The purpose of this study is to describe 1) HPV vaccine awareness, 2) willingness to get the HPV vaccine and 3) perceived susceptibility to HPV-related cancers and genital warts among men 18–26 years old who attend an STI clinic in San Juan, Puerto Rico (PR). Methods A cross-sectional pilot study consisting of 206 HIV+/HIV− men. For purpose of this analysis, only those participants aged ≤26 years old were included in this analysis (n=46). Results None of the study participants had been vaccinated against HPV. Fewer than a third knew about the HPV vaccine (28.3%). However, more than half (76.9%) were willing to be vaccinated against HPV. Information sources about the HPV vaccine included their female sexual partners (13.0%), a female sexual partner who received the vaccine (8.7%) and a male sexual partner (2.2%). Most participants reported that the main reason that would increase their willingness to get vaccinated was if a physician recommend the vaccine (95.7%). Perceived susceptibility was low, particularly for anal and oral cancer. Conclusion This pilot study shows poor awareness of the HPV vaccine, although willingness to getting the HPV vaccine was high among those who knew about the vaccine. Future studies should try to evaluate this paradox and study in depth willingness and barriers to vaccination among male sub-groups, such as men who have sex with men (MSM). These studies should also evaluate predictors of uptake of the HPV vaccine among men in this and other STI clinics in PR, in order to develop interventions to increase male vaccination. PMID:23844472

  6. Flavopiridol administered using a pharmacologically derived schedule is associated with marked clinical efficacy in refractory, genetically high-risk chronic lymphocytic leukemia

    PubMed Central

    Byrd, John C.; Lin, Thomas S.; Dalton, James T.; Wu, Di; Phelps, Mitch A.; Fischer, Beth; Moran, Mollie; Blum, Kristie A.; Rovin, Brad; Brooker-McEldowney, Michelle; Broering, Sarah; Schaaf, Larry J.; Johnson, Amy J.; Lucas, David M.; Heerema, Nyla A.; Lozanski, Gerard; Young, Donn C.; Suarez, Jose-Ramon; Colevas, A. Dimitrios; Grever, Michael R.

    2007-01-01

    Despite promising preclinical studies with the cyclin-dependent kinase inhibitor flavopiridol in chronic lymphocytic leukemia (CLL) and other diseases, previous clinical trials with this agent have been disappointing. The discovery of differential protein binding of flavopiridol in human and bovine serum contributed to an effective pharmacokinetic-derived schedule of administration of this agent. On the basis of pharmacokinetic modeling using our in vitro results and data from a previous trial, we initiated a phase 1 study using a 30-minute loading dose followed by 4 hours of infusion administered weekly for 4 of 6 weeks in patients with refractory CLL. A group of 42 patients were enrolled on 3 cohorts (cohort 1, 30 mg/m2 loading dose followed by 30 mg/m2 4-hour infusion; cohort 2, 40 mg/m2 loading dose followed by 40 mg/m2 4-hour infusion; and cohort 3, cohort 1 dose for treatments 1 to 4, then a 30 mg/m2 loading dose followed by a 50 mg/m2 4-hour infusion). The dose-limiting toxicity using this novel schedule was hyperacute tumor lysis syndrome. Aggressive prophylaxis and exclusion of patients with leukocyte counts greater than 200 × 109/L have made this drug safe to administer at the cohort 3 dose. Of the 42 patients treated, 19 (45%) achieved a partial response with a median response duration that exceeds 12 months. Responses were noted in patients with genetically high-risk disease, including 5 (42%) of 12 patients with del(17p13.1) and 13 (72%) of 18 patients with del(11q22.3). Flavopiridol administered using this novel schedule has significant clinical activity in refractory CLL. Patients with bulky disease and high-risk genetic features have achieved durable responses, thereby justifying further study of flavopiridol in CLL and other diseases. PMID:17003373

  7. Flavopiridol administered using a pharmacologically derived schedule is associated with marked clinical efficacy in refractory, genetically high-risk chronic lymphocytic leukemia.

    PubMed

    Byrd, John C; Lin, Thomas S; Dalton, James T; Wu, Di; Phelps, Mitch A; Fischer, Beth; Moran, Mollie; Blum, Kristie A; Rovin, Brad; Brooker-McEldowney, Michelle; Broering, Sarah; Schaaf, Larry J; Johnson, Amy J; Lucas, David M; Heerema, Nyla A; Lozanski, Gerard; Young, Donn C; Suarez, Jose-Ramon; Colevas, A Dimitrios; Grever, Michael R

    2007-01-15

    Despite promising preclinical studies with the cyclin-dependent kinase inhibitor flavopiridol in chronic lymphocytic leukemia (CLL) and other diseases, previous clinical trials with this agent have been disappointing. The discovery of differential protein binding of flavopiridol in human and bovine serum contributed to an effective pharmacokinetic-derived schedule of administration of this agent. On the basis of pharmacokinetic modeling using our in vitro results and data from a previous trial, we initiated a phase 1 study using a 30-minute loading dose followed by 4 hours of infusion administered weekly for 4 of 6 weeks in patients with refractory CLL. A group of 42 patients were enrolled on 3 cohorts (cohort 1, 30 mg/m2 loading dose followed by 30 mg/m2 4-hour infusion; cohort 2, 40 mg/m2 loading dose followed by 40 mg/m2 4-hour infusion; and cohort 3, cohort 1 dose for treatments 1 to 4, then a 30 mg/m2 loading dose followed by a 50 mg/m2 4-hour infusion). The dose-limiting toxicity using this novel schedule was hyperacute tumor lysis syndrome. Aggressive prophylaxis and exclusion of patients with leukocyte counts greater than 200x10(9)/L have made this drug safe to administer at the cohort 3 dose. Of the 42 patients treated, 19 (45%) achieved a partial response with a median response duration that exceeds 12 months. Responses were noted in patients with genetically high-risk disease, including 5 (42%) of 12 patients with del(17p13.1) and 13 (72%) of 18 patients with del(11q22.3). Flavopiridol administered using this novel schedule has significant clinical activity in refractory CLL. Patients with bulky disease and high-risk genetic features have achieved durable responses, thereby justifying further study of flavopiridol in CLL and other diseases.

  8. Attitudes and compliance of clinical management after genetic testing for hereditary breast and ovarian cancer among high-risk Southern Chinese females with breast cancer history.

    PubMed

    Kwong, Ava; Chu, Annie Tsz-Wai; Wu, Christine Teen-Sum; Tse, Desiree Man-Sik

    2014-09-01

    Western studies have shown that the uptake rates of surveillance and prophylaxis may vary among BRCA mutation carriers between ethnicities. The present study is the first to investigate the behavioural impact and subjective attitudes in Southern Chinese high-risk families who had undergone BRCA1 and BRCA2 genetic testing up to 2.5 years post-testing. Individuals who had such genetic testing and have consented to participate in the prospective database of Hong Kong Hereditary Breast Cancer Family Registry were recruited and surveyed by a face-to-face or telephone interview. Sociodemographic information, genetic test results, pre- and post-testing surveillance, medical regimes, and attitudes towards the choice of clinical management were obtained by interviews and retrieval of medical records using this prospective database. 69 females with breast cancer history were recruited into the study. Twenty-nine female carriers (15 BRCA1 mutated gene-carriers and 14 BRCA2 mutated gene-carriers) and 40 non-carriers of a BRCA 1/2 mutations were interviewed. The uptake rate of high risk breast screening i.e. clinical breast examination, mammography, and breast MRI is significantly higher among female carriers (48.3 %) after knowing genetic testing results than before (p < 0.01). A strong significant relationship between any increase or decrease of ovarian ultrasound screening (OS) and genetic status is found (p < .001), with more females did OS and with a higher frequency after knowing genetic testing results among both carriers (22.7 % → 86.4 %) and non-carriers (37.5 % → 50.0 %). Among carriers, very few opted for prophylactic surgeries. The present cohort might see prophylaxis as last resort and would use traditional Chinese medicine in cancer risk management.

  9. Diagnoses and clinical features associated with high risk for unplanned readmission in vascular surgery. A cohort study

    PubMed Central

    Yiasemidou, Marina; Mavor, Andrew I.D.; Kent, Patrick J.

    2015-01-01

    Background Readmission rate is an established health quality indicator. Preventable readmissions bear an unnecessary, high cost on the healthcare system. An analysis performed by the National Centre for Health Outcomes Development (NCHOD) has demonstrated an increasing trend in emergency readmissions in the UK. Vascular surgery has been reported to have high readmission rates second only to congestive heart failure. This study aims to identify diagnoses and other clinical risk factors for high unplanned readmission rates. This may be the first step to sparing both the health care system and patients of unnecessary readmissions. Results The overall 30 day readmission rate for Leeds Vascular Institute was 8.8%. The two diagnoses with the highest readmission rates were lower limb ischaemia and diabetic foot sepsis. The readmission rate for medical reasons was overwhelmingly higher than for surgical reasons (6.5% and 2.3% respectively). The most common medical diagnoses were renal disease and COPD. The majority of the patients readmitted under the care of vascular surgery required further surgical treatment. Conclusion Vascular units should focus on holistic and multidisciplinary treatment of lower limb ischaemia and diabetic foot sepsis, in order to prevent readmissions. Furthermore, the early involvement and input of physicians in the treatment of vascular patients with renal disease and COPD may be appropriate. PMID:26005566

  10. The MARINER trial of rivaroxaban after hospital discharge for medical patients at high risk of VTE. Design, rationale, and clinical implications.

    PubMed

    Raskob, Gary E; Spyropoulos, Alex C; Zrubek, Julie; Ageno, Walter; Albers, Gregory; Elliott, C Gregory; Halperin, Jonathan; Haskell, Lloyd; Hiatt, William R; Maynard, Gregory A; Peters, Gary; Spiro, Theodore; Steg, Philippe Gabriel; Suh, Eun Young; Weitz, Jeffrey I

    2016-06-01

    Hospital-associated venous thromboembolism (VTE) is a leading cause of premature death and disability worldwide. Evidence-based guidelines recommend that anticoagulant thromboprophylaxis be given to hospitalised medical patients at risk of VTE, but suggest against routine use of thromboprophylaxis beyond the hospital stay. The MARINER study is a randomised, double-blind, placebo-controlled trial to evaluate the efficacy and safety of thromboprophylaxis using rivaroxaban, begun at hospital discharge and continued for 45 days, for preventing symptomatic VTE in high-risk medical patients. Eligible patients are identified using the International Medical Prevention Registry on Venous Thromboembolism (IMPROVE VTE) risk score, combined with a laboratory test, D-dimer. The rivaroxaban regimen is 10 mg once daily for patients with CrCl ≥ 50 ml/min, or 7.5 mg once daily for patients with CrCl ≥ 30 ml/min and < 50 ml/min. The primary efficacy outcome is the composite of symptomatic VTE (lower extremity deep-vein thrombosis and non-fatal pulmonary embolism) and VTE-related death. The principal safety outcome is major bleeding. A blinded clinical events committee adjudicates all suspected outcome events. The sample size is event-driven with an estimated total of 8,000 patients to acquire 161 primary outcome events. Study design features that distinguish MARINER from previous and ongoing thromboprophylaxis trials in medically ill patients are: (i) use of a validated risk assessment model (IMPROVE VTE) and D-dimer determination for identifying eligible patients at high risk of VTE, (ii) randomisation at the time of hospital discharge, (iii) a 45-day treatment period and (iv) restriction of the primary efficacy outcome to symptomatic VTE events.

  11. STD care: variations in clinical care associated with provider sex, patient sex, patients' self-reported symptoms or high-risk behaviors, partner STD history.

    PubMed

    St Lawrence, Janet S; Kuo, Wen-Hung; Hogben, Matthew; Montaño, Daniel E; Kasprzyk, Danuta; Phillips, William R

    2004-09-01

    Sexually transmitted diseases in the United States are frequently diagnosed by private, as well as public, physicians. However, we know little about the decision processes that physicians employ when faced with people who may or may not be infected. To address this gap, we compared physicians' responses to different patient vignettes to assess how variations in patients' presentations affect physicians' clinical behavior. We systematically varied reported symptoms, behavioral risk, partner STD, and sex of patients in 16 different vignettes, with one vignette randomly presented to each physician in a national survey. Physicians rated the likelihood of 12 clinical management actions they might take with the patient vignette presented. Responses varied with self-reported symptoms, high-risk behavior, and report of an STD infected partner such that female physicians were more attentive to sexual health, and all physicians were more likely to treat female patients aggressively, relative to their male patients. Overall behavior was broadly congruent with sound medical practice, although we discuss several caveats to this general statement.

  12. Comparison of the Ability of Different Clinical Treatment Scores to Estimate Prognosis in High-Risk Early Breast Cancer Patients: A Hellenic Cooperative Oncology Group Study

    PubMed Central

    Pliarchopoulou, Kyriaki; Wirtz, Ralph M.; Alexopoulou, Zoi; Zagouri, Flora; Veltrup, Elke; Timotheadou, Eleni; Gogas, Helen; Koutras, Angelos; Lazaridis, Georgios; Christodoulou, Christos; Pentheroudakis, George; Laskarakis, Apostolos; Arapantoni-Dadioti, Petroula; Batistatou, Anna; Sotiropoulou, Maria; Aravantinos, Gerasimos; Papakostas, Pavlos; Kosmidis, Paris; Pectasides, Dimitrios; Fountzilas, George

    2016-01-01

    Background-Aim Early breast cancer is a heterogeneous disease, and, therefore, prognostic tools have been developed to evaluate the risk for distant recurrence. In the present study, we sought to develop a risk for recurrence score (RRS) based on mRNA expression of three proliferation markers in high-risk early breast cancer patients and evaluate its ability to predict risk for relapse and death. In addition the Adjuvant! Online score (AOS) was also determined for each patient, providing a 10-year estimate of relapse and mortality risk. We then evaluated whether RRS or AOS might possibly improve the prognostic information of the clinical treatment score (CTS), a model derived from clinicopathological variables. Methods A total of 1,681 patients, enrolled in two prospective phase III trials, were treated with anthracycline-based adjuvant chemotherapy. Sufficient RNA was extracted from 875 samples followed by multiplex quantitative reverse transcription-polymerase chain reaction for assessing RACGAP1, TOP2A and Ki67 mRNA expression. The CTS, slightly modified to fit our cohort, integrated the prognostic information from age, nodal status, tumor size, histological grade and treatment. Patients were also classified to breast cancer subtypes defined by immunohistochemistry. Likelihood ratio (LR) tests and concordance indices were used to estimate the relative increase in the amount of information provided when either RRS or AOS is added to CTS. Results The optimal RRS, in terms of disease-free survival (DFS) and overall survival (OS), was based on the co-expression of two of the three evaluated genes (RACGAP1 and TOP2A). CTS was prognostic for DFS (p<0.001), while CTS, AOS and RRS were all prognostic for OS (p<0.001, p<0.001 and p = 0.036, respectively). The use of AOS in addition to CTS added prognostic information regarding DFS (LR-Δχ2 8.7, p = 0.003), however the use of RRS in addition to CTS did not. For estimating OS, the use of either AOS or RRS in addition to

  13. Prediction of transition from ultra-high risk to first-episode psychosis using a probabilistic model combining history, clinical assessment and fatty-acid biomarkers

    PubMed Central

    Clark, S R; Baune, B T; Schubert, K O; Lavoie, S; Smesny, S; Rice, S M; Schäfer, M R; Benninger, F; Feucht, M; Klier, C M; McGorry, P D; Amminger, G P

    2016-01-01

    Current criteria identifying patients with ultra-high risk of psychosis (UHR) have low specificity, and less than one-third of UHR cases experience transition to psychosis within 3 years of initial assessment. We explored whether a Bayesian probabilistic multimodal model, combining baseline historical and clinical risk factors with biomarkers (oxidative stress, cell membrane fatty acids, resting quantitative electroencephalography (qEEG)), could improve this specificity. We analyzed data of a UHR cohort (n=40) with a 1-year transition rate of 28%. Positive and negative likelihood ratios were calculated for predictor variables with statistically significant receiver operating characteristic curves (ROCs), which excluded oxidative stress markers and qEEG parameters as significant predictors of transition. We clustered significant variables into historical (history of drug use), clinical (Positive and Negative Symptoms Scale positive, negative and general scores and Global Assessment of Function) and biomarker (total omega-3, nervonic acid) groups, and calculated the post-test probability of transition for each group and for group combinations using the odds ratio form of Bayes' rule. Combination of the three variable groups vastly improved the specificity of prediction (area under ROC=0.919, sensitivity=72.73%, specificity=96.43%). In this sample, our model identified over 70% of UHR patients who transitioned within 1 year, compared with 28% identified by standard UHR criteria. The model classified 77% of cases as very high or low risk (P>0.9, <0.1) based on history and clinical assessment, suggesting that a staged approach could be most efficient, reserving fatty-acid markers for 23% of cases remaining at intermediate probability following bedside interview. PMID:27648919

  14. Prediction of transition from ultra-high risk to first-episode psychosis using a probabilistic model combining history, clinical assessment and fatty-acid biomarkers.

    PubMed

    Clark, S R; Baune, B T; Schubert, K O; Lavoie, S; Smesny, S; Rice, S M; Schäfer, M R; Benninger, F; Feucht, M; Klier, C M; McGorry, P D; Amminger, G P

    2016-01-01

    Current criteria identifying patients with ultra-high risk of psychosis (UHR) have low specificity, and less than one-third of UHR cases experience transition to psychosis within 3 years of initial assessment. We explored whether a Bayesian probabilistic multimodal model, combining baseline historical and clinical risk factors with biomarkers (oxidative stress, cell membrane fatty acids, resting quantitative electroencephalography (qEEG)), could improve this specificity. We analyzed data of a UHR cohort (n=40) with a 1-year transition rate of 28%. Positive and negative likelihood ratios were calculated for predictor variables with statistically significant receiver operating characteristic curves (ROCs), which excluded oxidative stress markers and qEEG parameters as significant predictors of transition. We clustered significant variables into historical (history of drug use), clinical (Positive and Negative Symptoms Scale positive, negative and general scores and Global Assessment of Function) and biomarker (total omega-3, nervonic acid) groups, and calculated the post-test probability of transition for each group and for group combinations using the odds ratio form of Bayes' rule. Combination of the three variable groups vastly improved the specificity of prediction (area under ROC=0.919, sensitivity=72.73%, specificity=96.43%). In this sample, our model identified over 70% of UHR patients who transitioned within 1 year, compared with 28% identified by standard UHR criteria. The model classified 77% of cases as very high or low risk (P>0.9, <0.1) based on history and clinical assessment, suggesting that a staged approach could be most efficient, reserving fatty-acid markers for 23% of cases remaining at intermediate probability following bedside interview. PMID:27648919

  15. Do sleep abnormalities and misaligned sleep/circadian rhythm patterns represent early clinical characteristics for developing psychosis in high risk populations?

    PubMed

    Zanini, Marcio; Castro, Juliana; Coelho, Fernando Morgadinho; Bittencourt, Lia; Bressan, Rodrigo A; Tufik, Sergio; Brietzke, Elisa

    2013-12-01

    Sleep architecture changes, such as slow-wave sleep (SWS) percentage variations and reductions in latency and density of rapid eye movement (REM), are found in most patients with schizophrenia and are considered to be an important part of the pathophysiology of the disorder. In addition to these sleep parameters changes, disruptions in sleep homeostasis and the sleep/circadian rhythm also occur in these patients. Sleep/circadian rhythm abnormalities negatively affect neocortical plasticity and cognition and often precede the diagnosis of the illness. Thus, it has been suggested that the sleep/circadian rhythm might be involved in the pathophysiology of psychosis. Recent advances in the identification of individuals at a high risk for developing schizophrenia allow us to investigate several neurobiological processes involved in the development of psychosis. In this article, we review the current evidence of the effects of sleep parameter abnormalities, disruptions in sleep homeostasis and misalignments of sleep circadian rhythm on the early stages of schizophrenia. In addition, we discuss the preliminary evidence of sleep and circadian rhythm abnormalities during the prodromal stages of psychosis and propose that these abnormalities can be explored as potential predictors, as an adjunct to clinical diagnosis, of developing a psychotic disorder in at risk populations.

  16. Intensive vs. Standard Post-Operative Surveillance in High-Risk Breast Cancer Patients (INSPIRE): Japan Clinical Oncology Group Study JCOG1204.

    PubMed

    Hojo, Takashi; Masuda, Norikazu; Mizutani, Tomonori; Shibata, Taro; Kinoshita, Takayuki; Tamura, Kenji; Hara, Fumikata; Fujisawa, Tomomi; Inoue, Kenichi; Saji, Shigehira; Nakamura, Kenichi; Fukuda, Haruhiko; Iwata, Hiroji

    2015-10-01

    This Phase III trial aims to determine the superiority of intensive follow-up to standard follow-up in terms of overall survival in high-risk breast cancer patients, who are expected to have recurrence rates of over 30% within 5 years after surgery. Eligible patients are randomized either to the intensive follow-up group or to the standard follow-up group; the former will undergo physical examination, bone scintigraphy, chest computed tomography, abdominal computed tomography, brain magnetic resonance imaging/computed tomography and frequent tumor marker evaluations, whereas the latter will undergo physical examination at the same frequency and tumor markers will be evaluated once a year. Mammography once a year is planned for both groups. The primary endpoint is overall survival. Patient accrual was started in November 2013. A total of 1700 patients will be enrolled for 3 years and followed up for 7 years after closure of accrual. This trial has been registered at the UMIN Clinical Trials Registry as UMIN000012429.

  17. Clinical Factors Associated with High-risk Carotid Plaque Features as Assessed by Magnetic Resonance Imaging in Patients with Established Vascular Disease (From the AIM-HIGH Study)

    PubMed Central

    Zhao, Xue-Qiao; Hatsukami, Thomas S.; Hippe, Daniel S.; Sun, Jie; Balu, Niranjan; Isquith, Daniel A.; Crouse, John R.; Anderson, Todd; Huston, John; Polissar, Nayak; O’Brien, Kevin; Yuan, Chun

    2014-01-01

    Association between clinical factors and high-risk plaque features such as thin or ruptured cap, intra-plaque hemorrhage (IPH), presence of Lipid Rich Necrotic Core (LRNC) and increased LRNC volume as assessed by Magnetic Resonance Imaging (MRI) was examined in patients with established vascular disease in AIM-HIGH. A total of 214 subjects underwent carotid MRI and had acceptable image quality for assessment of plaque burden, tissue contents and MRI-modified AHA lesion type by a Core Lab. We found that 77% of subjects had carotid plaques, 52% had lipid-containing plaques, and 11% had advanced, AHA type-VI lesions with possible surface defect, IPH or mural thrombus. Type-VI lesions were associated with older age (OR=2.6 per 5 years increase, p<0.001). After adjusting for age, these lesions were associated with history of cerebrovascular disease (OR=4.1, p=0.01), higher levels of Lipoprotein(a) (OR=2.0 per 1 SD increase, p=0.02) and larger %wall volume (%WV; OR=4.6 per 1 SD increase, p<0.001), but, were negatively associated with metabolic syndrome (OR=0.2, p=0.02). Presence of LRNC was associated with male gender (OR=3.2, p=0.02) and %WV (OR=3.8 per 1 SD, p<0.001), but, was negatively associated with diabetes (OR=0.4, p=0.02) and HDL-C levels (OR=0.7 per 1 SD, p=0.02). Increased %LRNC was associated with %WV (regression coefficient=0.36, p<0.001) and negatively associated with ApoA1 levels (regression coefficient=−0.20, p=0.03). In conclusions, older age, male gender, history of cerebrovascular disease, larger plaque burden, higher Lp(a), and lower HDL-C or ApoA1 have statistically significant associations with high-risk plaque features. Metabolic syndrome and diabetes showed negative associations in this population. PMID:25245415

  18. Potential Clinical and Economic Value of Long-Acting Preexposure Prophylaxis for South African Women at High-Risk for HIV Infection

    PubMed Central

    Walensky, Rochelle P.; Jacobsen, Margo M.; Bekker, Linda-Gail; Parker, Robert A.; Wood, Robin; Resch, Stephen C.; Horstman, N. Kaye; Freedberg, Kenneth A.; Paltiel, A. David

    2016-01-01

    Background. For young South African women at risk for human immunodeficiency virus (HIV) infection, preexposure prophylaxis (PrEP) is one of the few effective prevention options available. Long-acting injectable PrEP, which is in development, may be associated with greater adherence, compared with that for existing standard oral PrEP formulations, but its likely clinical benefits and additional costs are unknown. Methods. Using a computer simulation, we compared the following 3 PrEP strategies: no PrEP, standard PrEP (effectiveness, 62%; cost per patient, $150/year), and long-acting PrEP (effectiveness, 75%; cost per patient, $220/year) in South African women at high risk for HIV infection (incidence of HIV infection, 5%/year). We examined the sensitivity of the strategies to changes in key input parameters among several outcome measures, including deaths averted and program cost over a 5-year period; lifetime HIV infection risk, survival rate, and program cost and cost-effectiveness; and budget impact. Results. Compared with no PrEP, standard PrEP and long-acting PrEP cost $580 and $870 more per woman, respectively, and averted 15 and 16 deaths per 1000 women at high risk for infection, respectively, over 5 years. Measured on a lifetime basis, both standard PrEP and long-acting PrEP were cost saving, compared with no PrEP. Compared with standard PrEP, long-acting PrEP was very cost-effective ($150/life-year saved) except under the most pessimistic assumptions. Over 5 years, long-acting PrEP cost $1.6 billion when provided to 50% of eligible women. Conclusions. Currently available standard PrEP is a cost-saving intervention whose delivery should be expanded and optimized. Long-acting PrEP will likely be a very cost-effective improvement over standard PrEP but may require novel financing mechanisms that bring short-term fiscal planning efforts into closer alignment with longer-term societal objectives. PMID:26681778

  19. Duration of attenuated positive and negative symptoms in individuals at clinical high risk: Associations with risk of conversion to psychosis and functional outcome.

    PubMed

    Carrión, Ricardo E; Demmin, Docia; Auther, Andrea M; McLaughlin, Danielle; Olsen, Ruth; Lencz, Todd; Correll, Christoph U; Cornblatt, Barbara A

    2016-10-01

    Research in individuals at clinical high-risk (CHR) for psychosis has focused on subjects with no more than 12 months of present or worsened attenuated positive symptoms. However, the impact of long duration attenuated positive and/or negative prodromal symptoms on outcomes is unclear. Seventy-six CHR subjects with attenuated positive symptoms and at least moderate severity level negative symptoms rated on the Scale of Prodromal Symptoms (SOPS) were prospectively followed for a mean of 3.0 ± 1.6 years. Social and Role functioning was assessed with the Global Functioning: Social and Role scales. Correlations between attenuated positive and negative symptom duration and severity and conversion to psychosis and functional outcomes were analyzed. The average onset of SOPS rated negative symptoms (M = 53.24 months, SD = 48.90, median = 37.27) was approximately twelve months prior to the emergence of attenuated positive symptom (M = 40.15 months, SD = 40.33, median = 24.77, P < 0.05). More severe positive symptoms (P = 0.004), but not longer duration of positive (P = 0.412) or negative (P = 0.754) symptoms, predicted conversion to psychosis. Neither positive symptom duration (P = 0.181) nor severity (P = 0.469) predicted role or social functioning at study endpoint. Conversely, longer negative symptom duration predicted poor social functioning (P = 0.004). Overall, our findings suggest that the severity of attenuated positive symptoms at baseline may be more important than symptom duration for determining individuals at increased risk of developing psychosis. In contrast, long-standing negative symptoms may be associated with persistent social difficulties and therefore have an important position in the treatment of disability.

  20. Altered Age-Related Trajectories of Amygdala-Prefrontal Circuitry in Adolescents at Clinical High Risk for Psychosis: A Preliminary Study

    PubMed Central

    Gee, Dylan G.; Karlsgodt, Katherine H.; Bearden, Carrie E.; Lieberman, Matthew D.; Belger, Aysenil; Perkins, Diana O.; Olvet, Doreen M.; Cornblatt, Barbara A.; Constable, Todd; Woods, Scott W.; Addington, Jean; Cadenhead, Kristin S.; McGlashan, Thomas H.; Seidman, Larry J.; Tsuang, Ming T.; Walker, Elaine F.; Cannon, Tyrone D.

    2011-01-01

    Emotion processing deficits are prominent in schizophrenia and exist prior to the onset of overt psychosis. However, developmental trajectories of neural circuitry subserving emotion regulation and the role that they may play in illness onset have not yet been examined in patients at risk for psychosis. The present study employed a cross-sectional analysis to examine age-related functional activation in amygdala and prefrontal cortex, as well as functional connectivity between these regions, in adolescents at clinical high risk (CHR) for psychosis relative to typically developing adolescents. Participants (n=34) performed an emotion processing fMRI task, including emotion labeling, emotion matching, and non-emotional control conditions. Regression analyses were used to predict activation in the amygdala and ventrolateral prefrontal cortex (vlPFC) based on age, group, sex, and the interaction of age by group. CHR adolescents exhibited altered age-related variation in amygdala and vlPFC activation, relative to controls. Controls displayed decreased amygdala and increased vlPFC activation with age, while patients exhibited the opposite pattern (increased amygdala and decreased vlPFC activation), suggesting a failure of prefrontal cortex to regulate amygdala reactivity. Moreover, a psychophysiological interaction analysis revealed decreased amygdala-prefrontal functional connectivity among CHR adolescents, consistent with disrupted brain connectivity as a vulnerability factor in schizophrenia. These results suggest that the at-risk syndrome is marked by abnormal development and functional connectivity of neural systems subserving emotion regulation. Longitudinal data are needed to confirm aberrant developmental trajectories intra-individually and to examine whether these abnormalities are predictive of conversion to psychosis, and of later deficits in socioemotional functioning. PMID:22056201

  1. Family Perception and 6-Month Symptomatic and Functioning Outcomes in Young Adolescents at Clinical High Risk for Psychosis in a General Population in China

    PubMed Central

    Wang, Lu; Shi, JingYu; Chen, FaZhan; Yao, YuHong; Zhan, ChenYu; Yin, XiaoWen; Fang, XiaoYan; Wang, HaoJie; Yuan, JiaBei; Zhao, XuDong

    2015-01-01

    Background and Aims Given the difficulty of treating schizophrenia and other forms of psychosis, researchers have shifted focus to early detection and intervention of individuals at clinical high risk (CHR) for psychosis. Previous studies have shown that elements in family functioning could predict symptom outcome in CHR individuals. However, associations between self reported family functioning and symptom or functioning outcome of CHR individuals was rarely reported. Our study aimed to investigate the characteristics and the role of family functioning in the development of CHR individuals among young adolescents. Methods A sample of 32 CHR individuals was recruited from 2800 university students. The characteristics of family perception were evaluated by both Family Assessment Device (FAD) and Family cohesion and adaptability evaluation Scale II (FACES II). 6 month follow up data was available with 25 of the recruited CHR individuals. Baseline socio-demographic characteristics and family functioning were compared between CHR and control group. We also measured the associations between different dimensions of perceived family functioning and both severity of prodromal symptoms and global functioning at baseline and 6-month follow up. Results CHR individuals showed more maladaptive family functioning compared to control in nearly all of the dimensions of FAD and FACES II except for Affective Involvement. Better Problem Solving and Affective Responsiveness predicted less severe positive and negative symptoms respectively. Family cohesion and adaptability were not only correlated with the baseline severity of general symptoms, but also positively associated with the general and disorganized symptom outcome. Conclusions This study contributed preliminary evidence towards the associations between family perception and symptom outcome of CHR individuals. It also provided evidence for the importance of family interventions on CHR individuals. PMID:26394221

  2. Altered age-related trajectories of amygdala-prefrontal circuitry in adolescents at clinical high risk for psychosis: a preliminary study.

    PubMed

    Gee, Dylan G; Karlsgodt, Katherine H; van Erp, Theo G M; Bearden, Carrie E; Lieberman, Matthew D; Belger, Aysenil; Perkins, Diana O; Olvet, Doreen M; Cornblatt, Barbara A; Constable, Todd; Woods, Scott W; Addington, Jean; Cadenhead, Kristin S; McGlashan, Thomas H; Seidman, Larry J; Tsuang, Ming T; Walker, Elaine F; Cannon, Tyrone D

    2012-01-01

    Emotion processing deficits are prominent in schizophrenia and exist prior to the onset of overt psychosis. However, developmental trajectories of neural circuitry subserving emotion regulation and the role that they may play in illness onset have not yet been examined in patients at risk for psychosis. The present study employed a cross-sectional analysis to examine age-related functional activation in amygdala and prefrontal cortex, as well as functional connectivity between these regions, in adolescents at clinical high risk (CHR) for psychosis relative to typically developing adolescents. Participants (n=34) performed an emotion processing fMRI task, including emotion labeling, emotion matching, and non-emotional control conditions. Regression analyses were used to predict activation in the amygdala and ventrolateral prefrontal cortex (vlPFC) based on age, group, sex, and the interaction of age by group. CHR adolescents exhibited altered age-related variation in amygdala and vlPFC activation, relative to controls. Controls displayed decreased amygdala and increased vlPFC activation with age, while patients exhibited the opposite pattern (increased amygdala and decreased vlPFC activation), suggesting a failure of prefrontal cortex to regulate amygdala reactivity. Moreover, a psychophysiological interaction analysis revealed decreased amygdala-prefrontal functional connectivity among CHR adolescents, consistent with disrupted brain connectivity as a vulnerability factor in schizophrenia. These results suggest that the at-risk syndrome is marked by abnormal development and functional connectivity of neural systems subserving emotion regulation. Longitudinal data are needed to confirm aberrant developmental trajectories intra-individually and to examine whether these abnormalities are predictive of conversion to psychosis, and of later deficits in socioemotional functioning. PMID:22056201

  3. Theory of Mind, Emotion Recognition and Social Perception in Individuals at Clinical High Risk for Psychosis: findings from the NAPLS-2 cohort

    PubMed Central

    Barbato, Mariapaola; Liu, Lu; Cadenhead, Kristin S.; Cannon, Tyrone D.; Cornblatt, Barbara A.; McGlashan, Thomas H.; Perkins, Diana O.; Seidman, Larry J.; Tsuang, Ming T.; Walker, Elaine F.; Woods, Scott W.; Bearden, Carrie E.; Mathalon, Daniel H.; Heinssen, Robert; Addington, Jean

    2015-01-01

    Social cognition, the mental operations that underlie social interactions, is a major construct to investigate in schizophrenia. Impairments in social cognition are present before the onset of psychosis, and even in unaffected first-degree relatives, suggesting that social cognition may be a trait marker of the illness. In a large cohort of individuals at clinical high risk for psychosis (CHR) and healthy controls, three domains of social cognition (theory of mind, facial emotion recognition and social perception) were assessed to clarify which domains are impaired in this population. Six-hundred and seventy-five CHR individuals and 264 controls, who were part of the multi-site North American Prodromal Longitudinal Study, completed The Awareness of Social Inference Test, the Penn Emotion Recognition task, the Penn Emotion Differentiation task, and the Relationship Across Domains, measures of theory of mind, facial emotion recognition, and social perception, respectively. Social cognition was not related to positive and negative symptom severity, but was associated with age and IQ. CHR individuals demonstrated poorer performance on all measures of social cognition. However, after controlling for age and IQ, the group differences remained significant for measures of theory of mind and social perception, but not for facial emotion recognition. Theory of mind and social perception are impaired in individuals at CHR for psychosis. Age and IQ seem to play an important role in the arising of deficits in facial affect recognition. Future studies should examine the stability of social cognition deficits over time and their role, if any, in the development of psychosis.

  4. Extracranial Carotid Artery Stenting in Surgically High-Risk Patients Using the Carotid Wallstent Endoprosthesis:Midterm Clinical and Ultrasound Follow-Up Results

    SciTech Connect

    Maleux, Geert Bernaerts, Pauwel; Thijs, Vincent; Daenens, Kim; Vaninbroukx, Johan; Fourneau, Inge; Nevelsteen, Andre

    2003-08-15

    The purpose of this study was to evaluate the feasibility, safety and midterm outcome of elective implantation of the Carotid Wallstent (registered) in patients considered to be at high surgical risk. In a prospective study, 54 carotid artery stenoses in 51 patients were stented over a 24-month period. Three patients underwent bilateral carotid artery stenting. Institutional inclusion criteria for invasive treatment of carotid occlusive disease (carotid endarterectomy or carotid artery stenting) are patients presenting with a 70% or more symptomatic stenosis and those with an 80% or more asymptomatic stenosis having a life-expectancy of more than 1 year. All patients treated by carotid artery stenting were considered at high risk for carotid endarterectomy because of a hostile neck (17 patients-31.5%) or because of severe comorbidities (37 patients-68.5%). No cerebral protection device was used. Of the 54 lesions, 33 (61.1%) were symptomatic and 21 (38.8%) were asymptomatic. Follow-up was performed by physical examination and by duplex ultrasonography at 1 month, 6 months, 1 year and 2 years after the procedure. All 54 lesions could be stented successfully without periprocedural stroke. Advert events during follow-up (mean 13.9 {+-} 5.7 months) were non-stroke-related death in 6 patients (11.1%), minor stroke in 4 stented hemispheres(7.4%), transient ipsilateral facial pain in 1 patient (1.8%),infection of the stented surgical patch in 1 patient (1.8%) and asymptomatic in stent restenosis in 4 patients (7.4%). The percutaneous implantation of the Carotid Wallstent (registered) , even without cerebral protection device, appears to be a safe procedure with acceptable clinical and ultrasonographic follow-up results in patients at high surgical risk. But some late adverse events such as ipsilateral recurrence of non-disabling (minor) stroke or in stent restenosis still remain real challenging problems.

  5. The Dark Side of the Moon: Meta-analytical Impact of Recruitment Strategies on Risk Enrichment in the Clinical High Risk State for Psychosis

    PubMed Central

    Fusar-Poli, Paolo; Schultze-Lutter, Frauke; Cappucciati, Marco; Rutigliano, Grazia; Bonoldi, Ilaria; Stahl, Daniel; Borgwardt, Stephan; Riecher-Rössler, Anita; Addington, Jean; Perkins, Diana O.; Woods, Scott W.; McGlashan, Thomas; Lee, Jimmy; Klosterkötter, Joachim; Yung, Alison R.; McGuire, Philip

    2016-01-01

    Background: The individual risk of developing psychosis after being tested for clinical high-risk (CHR) criteria (posttest risk of psychosis) depends on the underlying risk of the disease of the population from which the person is selected (pretest risk of psychosis), and thus on recruitment strategies. Yet, the impact of recruitment strategies on pretest risk of psychosis is unknown. Methods: Meta-analysis of the pretest risk of psychosis in help-seeking patients selected to undergo CHR assessment: total transitions to psychosis over the pool of patients assessed for potential risk and deemed at risk (CHR+) or not at risk (CHR−). Recruitment strategies (number of outreach activities per study, main target of outreach campaign, and proportion of self-referrals) were the moderators examined in meta-regressions. Results: 11 independent studies met the inclusion criteria, for a total of 2519 (CHR+: n = 1359; CHR−: n = 1160) help-seeking patients undergoing CHR assessment (mean follow-up: 38 months). The overall meta-analytical pretest risk for psychosis in help-seeking patients was 15%, with high heterogeneity (95% CI: 9%–24%, I 2 = 96, P < .001). Recruitment strategies were heterogeneous and opportunistic. Heterogeneity was largely explained by intensive (n = 11, β = −.166, Q = 9.441, P = .002) outreach campaigns primarily targeting the general public (n = 11, β = −1.15, Q = 21.35, P < .001) along with higher proportions of self-referrals (n = 10, β = −.029, Q = 4.262, P = .039), which diluted pretest risk for psychosis in patients undergoing CHR assessment. Conclusions: There is meta-analytical evidence for overall risk enrichment (pretest risk for psychosis at 38monhts = 15%) in help-seeking samples selected for CHR assessment as compared to the general population (pretest risk of psychosis at 38monhts=0.1%). Intensive outreach campaigns predominantly targeting the general population and a higher proportion of self-referrals diluted the pretest risk

  6. The adhesion molecule CD44v6 is associated with a high risk for local recurrence in adult soft tissue sarcomas

    PubMed Central

    Maula, S; Huuhtanen, R L; Blomqvist, C P; Wiklund, T A; Laurila, P; Ristamäki, R

    2001-01-01

    In many malignant diseases the expression levels of CD44 and its splice variant v6 (CD44v6) have been associated with the prognosis. The purpose of this study was to investigate the clinical significance of CD44 in adult soft tissue sarcomas (STS). 133 STS patients with a limb or superficial trunk tumour treated at the Helsinki University Central Hospital in 1987–1993 with a median follow-up time of 68 months were included in this study. The expression of CD44 and CD44v6 was determined immunohistochemically on paraffin-embedded tumour samples. 95% of the tumours expressed CD44 and CD44v6 was detected in 57%. Strong CD44 expression was associated with low grade (P = 0.04) and small tumour size (P = 0.02). In diploid tumours the CD44 expression was correlated with low S-phase fraction (P = 0.001). High expression of both, CD44 in general as well as that of CD44v6, predicted a higher risk for local recurrence (CD44: P = 0.01 and CD44v6: P = 0.05). Low CD44v6 content of the primary tumour correlated with poor survival (P = 0.02). Determining the expression of CD44 or CD44v6 in a primary STS could be a valuable tool for selecting the group of patients who might benefit from intensified local tumour treatment. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11161384

  7. Strategies for the treatment of dairy cows at high risk for postpartum metritis and for the treatment of clinical endometritis in Argentina.

    PubMed

    Bartolome, Julian A; Khalloub, Pablo; de la Sota, Rodolfo Luzbel; Drillich, Marc; Melendez, Pedro G

    2014-01-01

    The objectives of this study were to evaluate the efficacy of (1) administering ceftiofur hydrochloride in dairy cows with calving-related disorders to prevent metritis and (2) a combination of GnRH and PGF2α for the treatment of clinical endometritis, under Argentinean dairy farming conditions. Cows at high risk (HRC) for metritis (dystocia, RFM >12 h postpartum, hypocalcaemia, twins, or stillbirth) were randomly assigned to receive either 1.1 mg/Kg of ceftiofur hydrochloride on three consecutive days (HRC treated group HRCT, n = 110) or remained untreated (HRC control group HRCC, n = 126). Cows with low risk (LRC, no calving-related disorders, n = 868) did not receive any treatment (LRC group, n = 868). All cows were examined for metritis between days 4 and 10 and for clinical endometritis between 24 and 30 days postpartum. The body condition score (BCS) was recorded at both examinations. Cows with endometritis at days 24 to 30 postpartum received either 1.5 mg of D-cloprostenol (PGF; n = 129) or 100 μg of GnRH followed by D-cloprostenol after 7 days (GnRH+PGF, n = 119). There was no overall effect of treatment on the incidence of metritis or on time to pregnancy. Treatment, however, reduced the incidence of metritis in cows with high BCS (HRCT = 24.0 %, HRCC = 38.5 %) but had no effect in cows with low BCS (HRCT = 38.7 %, HRCC = 37.5 %). The proportion of pregnant cows by days in milk was greater (P < 0.01) in LRC group compared with that of the HRCT and HRCC groups. No significant differences were found between groups PG and PG+GNRH. GnRH+PGF treatment, however, tended (P = 0.06) to increase pregnancy rate in cows with a moderate loss of BCS (76.5 vs 65.2 %) but tended to reduce pregnancy rate (54.5 vs 76.0 %) in cows with a more pronounced loss in BCS (>0.75 points).

  8. Interval to Biochemical Failure Predicts Clinical Outcomes in Patients With High-Risk Prostate Cancer Treated by Combined-Modality Radiation Therapy

    SciTech Connect

    Shilkrut, Mark; McLaughlin, P. William; Merrick, Gregory S.; Vainshtein, Jeffrey M.; Feng, Felix Y.; Hamstra, Daniel A.

    2013-07-15

    Purpose: To validate the prognostic value of interval to biochemical failure (IBF) in patients with high-risk prostate cancer (HiRPCa) treated with combined-modality radiation therapy (CMRT) with or without androgen deprivation therapy (ADT). Methods and Materials: We conducted a retrospective review of HiRPCa (prostate-specific antigen >20 ng/mL, Gleason score [GS] 8-10, or clinical T stage T3-T4) treated with either dose-escalated external beam radiation therapy (EBRT) or CMRT. Interval to biochemical failure was classified as ≤18 or >18 months from the end of all therapy to the date of biochemical failure (BF). Kaplan-Meier methods and Cox proportional hazards regression were used to evaluate the prognostic value of IBF ≤18 months for distant metastasis (DM) and prostate cancer-specific mortality (PCSM). Results: Of 958 patients with a median follow-up of 63.2 months, 175 patients experienced BF. In those with BF, there were no differences in pretreatment clinical characteristics between the EBRT and CMRT groups, except for a higher proportion of patients with GS 8-10 in the CMRT group (70% vs 52%, P=.02). Median IBF after all therapy was 24.0 months (interquartile range 9.6-46.0) in the EBRT group and 18.9 months (interquartile range 9.2-34.5) in the CMRT group (P=.055). On univariate analysis, IBF ≤18 months was associated with increased risk of DM and PCSM in the entire cohort and the individual EBRT and CMRT groups. On multivariate analysis, only GS 9-10 and IBF ≤18 months, but not the radiation therapy regimen or ADT use, predicted DM (hazard ratio [HR] 3.7, P<.01, 95% confidence interval [CI] 1.4-10.3 for GS 9-10; HR 3.9, P<.0001, 95% CI 2.4-6.5 for IBF ≤18 months) and PCSM (HR 14.8, P<.009, 95% CI 2.0-110 for GS 9-10; HR 4.4, P<.0001, 95% CI 2.4-8.1 for IBF ≤18 months). Conclusions: Short IBF was highly prognostic for higher DM and PCSM in patients with HiRPCa. The prognostic value of IBF for DM and PCSM was not affected by the radiation

  9. Perioperative utility of goal-directed therapy in high-risk cardiac patients undergoing coronary artery bypass grafting: “A clinical outcome and biomarker-based study”

    PubMed Central

    Kapoor, Poonam Malhotra; Magoon, Rohan; Rawat, Rajinder; Mehta, Yatin

    2016-01-01

    Goal-directed therapy (GDT) encompasses guidance of intravenous (IV) fluid and vasopressor/inotropic therapy by cardiac output or similar parameters to help in early recognition and management of high-risk cardiac surgical patients. With the aim of establishing the utility of perioperative GDT using robust clinical and biochemical outcomes, we conducted the present study. This multicenter randomized controlled study included 130 patients of either sex, with European system for cardiac operative risk evaluation ≥3 undergoing coronary artery bypass grafting on cardiopulmonary bypass. The patients were randomly divided into the control and GDT group. All the participants received standardized care; arterial pressure monitored through radial artery, central venous pressure (CVP) through a triple lumen in the right internal jugular vein, electrocardiogram, oxygen saturation, temperature, urine output per hour, and frequent arterial blood gas (ABG) analysis. In addition, cardiac index (CI) monitoring using FloTrac™ and continuous central venous oxygen saturation (ScVO2) using PreSep™ were used in patients in the GDT group. Our aim was to maintain the CI at 2.5–4.2 L/min/m2, stroke volume index 30–65 ml/beat/m2, systemic vascular resistance index 1500–2500 dynes/s/cm5/m2, oxygen delivery index 450–600 ml/min/m2, continuous ScVO2 >70%, and stroke volume variation <10%; in addition to the control group parameters such as CVP 6–8 mmHg, mean arterial pressure 90–105 mmHg, normal ABG values, oxygen saturation, hematocrit value >30%, and urine output >1 ml/kg/h. The aims were achieved by altering the administration of IV fluids and doses of inotropes or vasodilators. The data of sixty patients in each group were analyzed in view of ten exclusions. The average duration of ventilation (19.89 ± 3.96 vs. 18.05 ± 4.53 h, P = 0.025), hospital stay (7.94 ± 1.64 vs. 7.17 ± 1.93 days, P = 0.025), and Intensive Care Unit (ICU) stay (3.74 ± 0.59 vs. 3.41 ± 0

  10. Distant Metastases Following Permanent Interstitial Brachytherapy for Patients With Clinically Localized Prostate Cancer

    SciTech Connect

    Taira, Al V.; Merrick, Gregory S.; Galbreath, Robert W.; Butler, Wayne M.; Lief, Jonathan; Adamovich, Edward; Wallner, Kent E.

    2012-02-01

    Purpose: Recent publications have suggested high-risk patients undergoing radical prostatectomy have a lower risk of distant metastases and improved cause-specific survival (CSS) than patients receiving definitive external beam radiation therapy (XRT). To date, none of these studies has compared distant metastases and CSS in brachytherapy patients. In this study, we evaluate such parameters in a consecutive cohort of brachytherapy patients. Methods and Materials: From April 1995 to June 2007, 1,840 consecutive patients with clinically localized prostate cancer were treated with brachytherapy. Risk groups were stratified according to National Comprehensive Cancer Network ( (www.nccn.org)) guidelines. Subgroups of 658, 893, and 289 patients were assigned to low, intermediate, and high-risk categories. Median follow-up was 7.2 years. Along with brachytherapy implantation, 901 (49.0%) patients received supplemental XRT, and 670 (36.4%) patients received androgen deprivation therapy (median duration, 4 months). The mode of failure (biochemical, local, or distant) was determined for each patient for whom therapy failed. Cause of death was determined for each deceased patient. Multiple parameters were evaluated for impact on outcome. Results: For the entire cohort, metastases-free survival (MFS) and CSS at 12 years were 98.1% and 98.2%, respectively. When rates were stratified by low, intermediate, and high-risk groups, the 12-year MFS was 99.8%, 98.1%, and 93.8% (p < 0.001), respectively. CSS rates were 99.8%, 98.0%, and 95.3% (p < 0.001) for low, intermediate, and high-risk groups, respectively. Biochemical progression-free survival was 98.7%, 95.9% and 90.4% for low, intermediate, and high-risk patients, respectively (p < 0.001). In multivariate Cox-regression analysis, MFS was mostly closely related to Gleason score and year of treatment, whereas CSS was most closely associated with Gleason score. Conclusions: Excellent CSS and MFS rates are achievable with high

  11. High-dose chemotherapy for high-risk retinoblastoma: clinical course and outcome of 14 cases in the National Cancer Center, Japan.

    PubMed

    Yasui, N; Kawamoto, H; Fujiwara, M; Aihara, Y; Ogawa, C; Hosono, A; Suzuki, S

    2015-02-01

    The prognosis of high-risk retinoblastoma (RB) with extraocular disease, relapse, or invasion of the cut end of the optic nerve is extremely poor. Following the discontinuation of thiotepa production in Japan, BU- and melphalan (Mel)-based regimens have been used, followed by the standard treatment for neuroblastoma. This study retrospectively analyzed 14 high-risk RB patients who underwent high-dose chemotherapy (HDC) and hematopoietic SCT; 8 received a BU/Mel conditioning regimen and 6 received other regimens. The disease status at HDC was relapse in 8 patients and extraocular involvement in 5. All patients received peripheral blood stem cell infusion >1.5 × 10(6)/kg. Engraftment occurred within a median of 11 days (BU/Mel: 10-13, others: 9-13). Primary toxicities included mucositis (⩾grade 3) in 9 patients (4 with BU/Mel, 5 with others). Veno-occlusive disease (VOD) occurred in two 1-year-old patients in the BU/Mel group. There were no treatment-related deaths. Of 4 (2 with BU/Mel, 2 with others) patients with central nervous system (CNS) relapse after HDC, 3 died. In conclusion, the BU/Mel regimen may be feasible for high-risk RB under careful monitoring for VOD, particularly in younger patients. CNS relapse associated with a lethal prognosis occurred after all regimens; therefore, further evaluation of HDC efficacy for high-risk RB is required.

  12. Predictions in the face of clinical reality: HistoCheck versus high-risk HLA allele mismatch combinations responsible for severe acute graft-versus-host disease.

    PubMed

    Askar, Medhat; Sobecks, Ronald; Morishima, Yasuo; Kawase, Takakazu; Nowacki, Amy; Makishima, Hideki; Maciejewski, Jaroslaw

    2011-09-01

    HLA polymorphism remains a major hurdle for hematopoietic stem cell transplantation (HSCT). In 2004, Elsner et al. proposed the HistoCheck Web-based tool to estimate the allogeneic potential between HLA-mismatched stem cell donor/recipient pairs expressed as a sequence similarity matching (SSM). SSM is based on the structure of HLA molecules and the functional similarity of amino acids. According to this algorithm, a high SSM score represents high dissimilarity between MHC molecules, resulting in a potentially more deleterious impact on stem cell transplant outcomes. We investigated the potential of SSM to predict high-risk HLA allele mismatch combinations responsible for severe acute graft-versus-host disease (aGVHD grades III and IV) published by Kawase et al., by comparing SSM in low- and high-risk combinations. SSM was calculated for allele mismatch combinations using the HistoCheck tool available on the Web (www.histocheck.org). We compared ranges and means of SSM among high-risk (15 combinations observed in 722 donor/recipient pairs) versus low-risk allele combinations (94 combinations in 3490 pairs). Simulation scenarios were created where the recipient's HLA allele was involved in multiple allele mismatch combinations with at least 1 high-risk and 1 low-risk mismatch combination. SSM values were then compared. The mean SSM for high- versus low-risk combinations were 2.39 and 2.90 at A, 1.06 and 2.53 at B, 16.60 and 14.99 at C, 4.02 and 3.81 at DRB1, and 7.47 and 6.94 at DPB1 loci, respectively. In simulation scenarios, no predictable SSM association with high- or low-risk combinations could be distinguished. No DQB1 combinations met the statistical criteria for our study. In conclusion, our analysis demonstrates that mean SSM scores were not significantly different, and SSM distributions were overlapping among high- and low-risk allele combinations within loci HLA-A, B, C, DRB1, and DPB1. This analysis does not support selecting donors for HSCT recipients

  13. [When research and clinical recommendations are (temporarily) in contradiction: the evaluation of lung cancer screening for high-risk subjects in Europe and in the USA].

    PubMed

    Paci, Eugenio

    2016-01-01

    Lung cancer is the first cancer mortality cause in Italy. In last decades, incidence rates have been falling down, but the annual number of deaths is stable because of population ageing. Survival rates for population-based lung cancer cases were at maximum 17% in the last decades. In 2011, the National Lung Screening Trial (NLST) has published the results of the evaluation of efficacy of low-dose CT scan screening compared with chest X-ray showing a 20%cause-specific mortality reduction, based on the randomization, screening, and follow-up of about 53,000 subjects in USA. In Europe, 7 randomized studies are ongoing: the Nelson study, with about 16,000 people enrolled, is the largest one and its results are expected to be published soon. The US Preventive Service Task Force recommended screening for lung cancer. CT Scan screening will be made available within Medicare to high-risk subjects until 74 years or 80 years of age. In Europe, recommendations continue to discourage screening for lung cancer in all member Countries. The implementation of organised screening in Europe is conditioned by an health technology assessment aimed to the identification of the risk profile, performance of screening (false positive rates), and overdiagnosis harm. All the potential harms of screening must be balanced with expected benefits and evaluated in a formal cost-benefits analysis. Better strategies aimed to selective lung cancer screening of high risk subjects, including asbestos workers, must be evaluated in prospective studies.

  14. Localized scleroderma: clinical spectrum and therapeutic update*

    PubMed Central

    Careta, Mariana Figueiroa; Romiti, Ricardo

    2015-01-01

    Scleroderma is a rare connective tissue disease that is manifested by cutaneous sclerosis and variable systemic involvement. Two categories of scleroderma are known: systemic sclerosis, characterized by cutaneous sclerosis and visceral involvement, and localized scleroderma or morphea which classically presents benign and self-limited evolution and is confined to the skin and/or underlying tissues. Localized scleroderma is a rare disease of unknown etiology. Recent studies show that the localized form may affect internal organs and have variable morbidity. Treatment should be started very early, before complications occur due to the high morbidity of localized scleroderma. In this review, we report the most important aspects and particularities in the treatment of patients diagnosed with localized scleroderma. PMID:25672301

  15. Screening, early detection, education, and trends for melanoma: current status (2007-2013) and future directions: Part I. Epidemiology, high-risk groups, clinical strategies, and diagnostic technology.

    PubMed

    Mayer, Jonathan E; Swetter, Susan M; Fu, Teresa; Geller, Alan C

    2014-10-01

    While most cancers have shown both decreased incidence and mortality over the past several decades, the incidence of melanoma has continued to grow, and mortality has only recently stabilized in the United States and in many other countries. Certain populations, such as men >60 years of age and lower socioeconomic status groups, face a greater burden from disease. For any given stage and across all ages, men have shown worse melanoma survival than women, and low socioeconomic status groups have increased levels of mortality. Novel risk factors can help identify populations at greatest risk for melanoma and can aid in targeted early detection. Risk assessment tools have been created to identify high-risk patients based on various factors, and these tools can reduce the number of patients needed to screen for melanoma detection. Diagnostic techniques, such as dermatoscopy and total body photography, and new technologies, such as multispectral imaging, may increase the accuracy and reliability of early melanoma detection.

  16. The DHEA-sulfate depot following P450c17 inhibition supports the case for AKR1C3 inhibition in high risk localized and advanced castration resistant prostate cancer.

    PubMed

    Tamae, Daniel; Mostaghel, Elahe; Montgomery, Bruce; Nelson, Peter S; Balk, Steven P; Kantoff, Philip W; Taplin, Mary-Ellen; Penning, Trevor M

    2015-06-01

    Prostate cancer is the second leading cause of cancer death in the United States. Treatment of localized high-risk disease and de novo metastatic disease frequently leads to relapse. These metastatic castration resistant prostate cancers (mCRPC) claim a high mortality rate, despite the extended survival afforded by the growing armamentarium of androgen deprivation, radiation and immunotherapies. Here, we review two studies of neoadjuvant treatment of high-risk localized prostate cancer prior to prostatectomy, the total androgen pathway suppression (TAPS) trial and the neoadjuvant abiraterone acetate (AA) trial. These two trials assessed the efficacy of the non-specific P450c17 inhibitor, ketoconazole and the specific P450c17 inhibitor, AA, to inhibit tissue and serum androgen levels. Furthermore, a novel and validated stable isotope dilution liquid chromatography electrospray ionization selected reaction monitoring mass spectrometry assay was used to accurately quantify adrenal and gonadal androgens in circulation during the course of these trials. The adrenal androgens, Δ(4)-androstene-3,17-dione, dehydroepiandrosterone and dehydroepiandrosterone sulfate were significantly reduced in the patients receiving ketoconazole or AA compared to those who did not. However, in both trials, a significant amount of DHEA-S (∼20 μg/dL) persists and thus may serve as a depot for intratumoral conversion to the potent androgen receptor ligands, testosterone (T) and 5α-dihydrotestosterone (DHT). The final step in conversion of Δ(4)-androstene-3,17-dione and 5α-androstanedione to T and DHT, respectively, is catalyzed by AKR1C3. We therefore present the case that in the context of the DHEA-S depot, P450c17 and AKR1C3 inhibition may be an effective combinatorial treatment strategy.

  17. African American Men’s and Women’s Perceptions of Clinical Trials Research: Focusing on Prostate Cancer among a High-Risk Population in the South

    PubMed Central

    Owens, Otis L.; Jackson, Dawnyéa D.; Thomas, Tracey L.; Friedman, Daniela B.; Hébert, James R.

    2013-01-01

    While African Americans are at significantly higher risk for developing certain cancers, they also have low rates of participation in cancer research, particularly clinical trials. This study assessed both African American men’s and African American women’s (1) knowledge of and participation in cancer-related clinical research and (2) barriers to and motivations for participating in clinical research. Data were collected from a total of 81 participants. Phase I of this research consisted of qualitative focus groups (all 81 participants). Phase II included quantitative pre/post survey data from an education program (56 participants). Findings from the study revealed that African American men and women had poor knowledge about clinical trials and the informed consent process, limited experience in participating in clinical trials, and they feared and mistrusted cancer research. Participants identified incentives, assurance of safety, knowledge and awareness, and benefiting others as motivators to participate in clinical trials research. PMID:24185170

  18. Extension of Local Disease in Nasopharyngeal Carcinoma Detected by Magnetic Resonance Imaging: Improvement of Clinical Target Volume Delineation

    SciTech Connect

    Liang Shaobo; Sun Ying; Liu Lizhi; Chen Yong; Chen Lei; Mao Yanping; Tang Linglong; Tian Li; Lin Aihua; Liu Mengzhong; Li Li; Ma Jun

    2009-11-01

    Purpose: To define by MRI the local extension patterns in patients presenting with nasopharyngeal carcinoma (NPC) and to improve clinical target volume delineation. Methods and Materials: Consecutive patients (N = 943) with newly diagnosed and untreated NPC were included in this study. All patients underwent MRI of the nasopharynx and neck, which was reviewed by two radiologists. Results: According to the incidence rates of tumor invasion, the anatomic sites surrounding the nasopharynx were initially classified into three risk grades: high risk (>= 35%), medium risk (>= 5-35%), and low risk (< 5%). Incidence rates of tumor invasion into anatomic sites at medium risk were increased, reaching 55.2%, when adjacent high-risk anatomic sites were involved. However, the rates were substantially lower, mostly < 10%, when adjacent high-risk sites were not involved. The incidence rates of concurrent tumor invasion into bilateral sites were < 10%, except in the case of prevertebral muscle involvement (13.1%). Among the 178 incidences of cavernous sinus invasion, there were often two or more simultaneous infiltration routes (60.6%); when only one route was involved, the foramen ovale was the most common (26.4%). Conclusions: In patients presenting with NPC, local disease spreads stepwise from proximal sites to more distal sites. Tumors extend quickly through privileged pathways such as neural foramina. The anatomic sites surrounding the nasopharynx are at low risk of concurrent bilateral tumor invasion. Selective radiotherapy of the local disease in NPC may be feasible.

  19. AB174. Clinical analysis of transurethral end-fire greenlight PVRP-ST for the treatment of elderly and high-risk patients with

    PubMed Central

    Yang, Guosheng; Qiu, Xiaofo

    2016-01-01

    Objective Analyzing the features of transurethral end-fire greenlight photoselective vaporesection of prostate-shovel technique (PVRP-ST) and evaluating the safety and efficacy of transurethral end-fire greenlight PVRP-ST for high-risk and elderly patients with benign prostatic hyperplasia (BPH) by comparing with TURP. Methods We analyzed a total of 93 high-risk and elderly patients with BPH underwent PVRP-ST (50 cases) and TURP (43 cases) from September 2013 to March 2015 in Guangdong NO. 2 Provincial People’s Hospital prospectively. We collected their generally information (including age, duration of oral drug finasteride time, prostate volume, past medical history, PSA situation and complications etc.), and recorded operative time, blood loss, the number of intraoperative flushing fluid bag, postoperative bladder irrigation time, postoperative catheter indwelling time, the postoperative hospitalization days, intraoperative complications and postoperative complications. The variables such as sodium (Na+) concentration, potassiumions (K+) concentration, hemoglobin (Hb) concentration, and hematocrit (HCT) were compared before and after operation. Detecting the maximum urinary flow rate (Qmax), residual urine volume (RUV), fill in the International Prostate Symptom (IPSS) score sheet, quality of life (QoL) score sheet before the surgery. Following up the IPSS, QoL, Qmax and RUV after 3 months of operation. The IPSS, QoL, Qmax and RUV were compared between preoperation and 3 months after operation. Using relevant statistical methods to compare the data between preoperation and postoperation with SPSS 17.0 software. Results All patients were successfully performed surgery with no serious complications, no deaths, no case turn to open surgery and no capsular perforation. (I) There were not significant differences in values of preoperative general information between two the groups of patients (P>0.05); (II) the average operative time of group PVRP-ST was (68.2±23

  20. The "close-in" or ultra high-risk model: a safe and effective strategy for research and clinical intervention in prepsychotic mental disorder.

    PubMed

    McGorry, Patrick D; Yung, Alison R; Phillips, Lisa J

    2003-01-01

    The development of a new frontier for research and early intervention in psychotic disorders is highly dependent on the construction of synergistic clinical infrastructures. This has catalyzed great progress in the recognition, enhanced treatment, and study of first episode psychosis, and the task is even more challenging when the boundaries are extended to include the earliest clinical phase of illness, the prodromal or prepsychotic phase. This article describes the conceptual and practical building blocks for the construction of service models for intervention in the postonset clinical phase prior to the attainment of current diagnostic thresholds. This is best regarded as indicated prevention, a form of very early secondary prevention, which involves a blend of immediate clinical care combined with research-oriented preventive intervention. The experience of the Personal Assessment and Crisis Evaluation (PACE) Clinic in Melbourne across several stages of growth is described and contrasted with that of several emerging centers in Europe and North America. The progress to date, the lessons learned, and the unresolved challenges and opportunities are detailed. It is concluded that service models can be developed that are acceptable and helpful to young people and their families, and that create a unique environment for the study of the transition to frank psychotic disorder. The ultimate clinical utility and general safety of this approach and the range of effective treatments remain unclear, and will be determined by more extensive research. Such research must be conducted in a logical and rigorous manner with the best designs possible, sensitive to input from consumers and caregivers and to ethical considerations.

  1. The "close-in" or ultra high-risk model: a safe and effective strategy for research and clinical intervention in prepsychotic mental disorder.

    PubMed

    McGorry, Patrick D; Yung, Alison R; Phillips, Lisa J

    2003-01-01

    The development of a new frontier for research and early intervention in psychotic disorders is highly dependent on the construction of synergistic clinical infrastructures. This has catalyzed great progress in the recognition, enhanced treatment, and study of first episode psychosis, and the task is even more challenging when the boundaries are extended to include the earliest clinical phase of illness, the prodromal or prepsychotic phase. This article describes the conceptual and practical building blocks for the construction of service models for intervention in the postonset clinical phase prior to the attainment of current diagnostic thresholds. This is best regarded as indicated prevention, a form of very early secondary prevention, which involves a blend of immediate clinical care combined with research-oriented preventive intervention. The experience of the Personal Assessment and Crisis Evaluation (PACE) Clinic in Melbourne across several stages of growth is described and contrasted with that of several emerging centers in Europe and North America. The progress to date, the lessons learned, and the unresolved challenges and opportunities are detailed. It is concluded that service models can be developed that are acceptable and helpful to young people and their families, and that create a unique environment for the study of the transition to frank psychotic disorder. The ultimate clinical utility and general safety of this approach and the range of effective treatments remain unclear, and will be determined by more extensive research. Such research must be conducted in a logical and rigorous manner with the best designs possible, sensitive to input from consumers and caregivers and to ethical considerations. PMID:14989414

  2. AB174. Clinical analysis of transurethral end-fire greenlight PVRP-ST for the treatment of elderly and high-risk patients with

    PubMed Central

    Yang, Guosheng; Qiu, Xiaofo

    2016-01-01

    Objective Analyzing the features of transurethral end-fire greenlight photoselective vaporesection of prostate-shovel technique (PVRP-ST) and evaluating the safety and efficacy of transurethral end-fire greenlight PVRP-ST for high-risk and elderly patients with benign prostatic hyperplasia (BPH) by comparing with TURP. Methods We analyzed a total of 93 high-risk and elderly patients with BPH underwent PVRP-ST (50 cases) and TURP (43 cases) from September 2013 to March 2015 in Guangdong NO. 2 Provincial People’s Hospital prospectively. We collected their generally information (including age, duration of oral drug finasteride time, prostate volume, past medical history, PSA situation and complications etc.), and recorded operative time, blood loss, the number of intraoperative flushing fluid bag, postoperative bladder irrigation time, postoperative catheter indwelling time, the postoperative hospitalization days, intraoperative complications and postoperative complications. The variables such as sodium (Na+) concentration, potassiumions (K+) concentration, hemoglobin (Hb) concentration, and hematocrit (HCT) were compared before and after operation. Detecting the maximum urinary flow rate (Qmax), residual urine volume (RUV), fill in the International Prostate Symptom (IPSS) score sheet, quality of life (QoL) score sheet before the surgery. Following up the IPSS, QoL, Qmax and RUV after 3 months of operation. The IPSS, QoL, Qmax and RUV were compared between preoperation and 3 months after operation. Using relevant statistical methods to compare the data between preoperation and postoperation with SPSS 17.0 software. Results All patients were successfully performed surgery with no serious complications, no deaths, no case turn to open surgery and no capsular perforation. (I) There were not significant differences in values of preoperative general information between two the groups of patients (P>0.05); (II) the average operative time of group PVRP-ST was (68.2±23

  3. A feasibility study of functional status and follow-up clinic preferences of patients at high risk of post intensive care syndrome.

    PubMed

    Farley, K J; Eastwood, G M; Bellomo, R

    2016-05-01

    After prolonged mechanical ventilation patients may experience the 'post intensive care syndrome' (PICS) and may be candidates for post-discharge follow-up clinics. We aimed to ascertain the incidence and severity of PICS symptoms in patients surviving prolonged mechanical ventilation and to describe their views regarding follow-up clinics. In a teaching hospital, we conducted a cohort study of all adult patients discharged alive after ventilation in ICU for ≥7 days during 2013. We administered the EuroQol-5D (EQ-5D) and Hospital Anxiety and Depression Scale (HADS) via telephone interview and asked patients their views about the possible utility of a follow-up clinic. We studied 48 patients. At follow-up (average 19.5 months), seven (15%) patients had died and 14 (29%) did not participate (eight declined; two were non-English speakers; four were non-contactable). Among the 27 responders, 16 (59%) reported at least moderate problems in ≥1 EQ-5D dimension; 10 (37%) in ≥2 dimensions, and 8 (30%) in ≥3 dimensions. Moreover, 10 (37%) patients reported marked psychological symptoms; six (22%) scored borderline or abnormal on the HADS for both anxiety and depression; and four (15%) scored borderline or abnormal for one component. Finally, 21/26 (81%) patients stated that an ICU follow-up clinic would have been beneficial. At long-term follow-up, the majority of survivors of prolonged mechanical ventilation reported impaired quality of life and significant psychological symptoms. Most believed that a follow-up clinic would have been beneficial. PMID:27246943

  4. A feasibility study of functional status and follow-up clinic preferences of patients at high risk of post intensive care syndrome.

    PubMed

    Farley, K J; Eastwood, G M; Bellomo, R

    2016-05-01

    After prolonged mechanical ventilation patients may experience the 'post intensive care syndrome' (PICS) and may be candidates for post-discharge follow-up clinics. We aimed to ascertain the incidence and severity of PICS symptoms in patients surviving prolonged mechanical ventilation and to describe their views regarding follow-up clinics. In a teaching hospital, we conducted a cohort study of all adult patients discharged alive after ventilation in ICU for ≥7 days during 2013. We administered the EuroQol-5D (EQ-5D) and Hospital Anxiety and Depression Scale (HADS) via telephone interview and asked patients their views about the possible utility of a follow-up clinic. We studied 48 patients. At follow-up (average 19.5 months), seven (15%) patients had died and 14 (29%) did not participate (eight declined; two were non-English speakers; four were non-contactable). Among the 27 responders, 16 (59%) reported at least moderate problems in ≥1 EQ-5D dimension; 10 (37%) in ≥2 dimensions, and 8 (30%) in ≥3 dimensions. Moreover, 10 (37%) patients reported marked psychological symptoms; six (22%) scored borderline or abnormal on the HADS for both anxiety and depression; and four (15%) scored borderline or abnormal for one component. Finally, 21/26 (81%) patients stated that an ICU follow-up clinic would have been beneficial. At long-term follow-up, the majority of survivors of prolonged mechanical ventilation reported impaired quality of life and significant psychological symptoms. Most believed that a follow-up clinic would have been beneficial.

  5. Endorectal MRI assessment of local relapse after surgery for prostate cancer: A model to define treatment field guidelines for adjuvant radiotherapy in patients at high risk for local failure

    SciTech Connect

    Miralbell, Raymond . E-mail: Raymond.Miralbell@hcuge.ch; Vees, Hansjoerg; Lozano, Joan; Khan, Haleem; Molla, Meritxell; Hidalgo, Alberto; Linero, Dolors; Rouzaud, Michel

    2007-02-01

    Purpose: To assess the role of endorectal magnetic resonance imaging (MRI) in defining local relapse after radical prostatectomy for prostate cancer to help to reassess the clinical target volume (CTV) for adjuvant postprostatectomy radiotherapy. Methods and Materials: Sixty patients undergoing an endorectal MRI before salvage radiotherapy were selected. Spatial coordinates of the relapses were assessed using two reference points: the inferior border of the pubic symphysis (point 1) and the urethro-vesical anastomosis (point 2). Every lesion on MRI was delineated on the planning computed tomography and center of mass coordinates were plotted in two separate diagrams (along the x, y, and z axes) with the urethro-vesical anastomosis as the coordinate origin. An 'ideal' CTV was constructed, centered at a point defined by the mathematical means of each of the three coordinates with dimensions defined as twice 2 standard deviations in each of the three axes. The dosimetric impact of the new CTV definition was evaluated in six adjuvantly treated patients. Results: The ideal CTV center of mass was located at coordinates 0 (x), -5 (y), and -3 (z) mm with SDs of 6 (x), 6 (y), and 9 (z) mm, respectively. The CTV size was 24 (x) x 24 (y) x 36 (z) mm. Significant rectal sparing was observed with the new CTV. Conclusions: A CTV with an approximately cylindrical shape ({approx}4 x 3 cm) centered 5 mm posterior and 3 mm inferior to the urethro-vesical anastomosis was defined. Such CTV may reduce the irradiation of normal nontarget tissue in the pelvis potentially improving treatment tolerance.

  6. Clinical validation of the HPV-risk assay, a novel real-time PCR assay for detection of high-risk human papillomavirus DNA by targeting the E7 region.

    PubMed

    Hesselink, A T; Berkhof, J; van der Salm, M L; van Splunter, A P; Geelen, T H; van Kemenade, F J; Bleeker, M G B; Heideman, D A M

    2014-03-01

    The HPV-Risk assay is a novel real-time PCR assay targeting the E7 region of 15 high-risk human papillomavirus (HPV) types (i.e., HPV16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -66, -67, and -68), and provides additional genotype information for HPV16 and HPV18. This study evaluated the clinical performance and reproducibility of the HPV-Risk assay with cervical scraping specimens and its utility with self-collected (cervico)vaginal specimens. The clinical performance of the HPV-Risk assay for cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) with cervical scraping specimens was evaluated by a noninferiority analysis, relative to high-risk HPV GP5+/6+ PCR, following international guidelines for HPV test requirements for cervical cancer screening. The HPV-Risk assay showed clinical sensitivity for CIN2+ of 97.1% (95% confidence interval [CI], 89.1 to 99.3%; 67/69 samples) and a clinical specificity for CIN2+ of 94.3% (95% CI, 92.5 to 95.7%; 777/824 samples). The clinical sensitivity and specificity were noninferior to those of GP5+/6+ PCR (noninferiority score test, P=0.006 and 0.0003, respectively). Intralaboratory reproducibility over time (99.5% [95% CI, 98.6 to 99.8%]; 544/547 samples, kappa=0.99) and interlaboratory agreement (99.2% [95% CI, 98.6 to 99.8%]; 527/531 samples, kappa=0.98) for the HPV-Risk assay with cervical scraping specimens were high. The agreement of the HPV-Risk assay results for self-collected (cervico)vaginal specimens and clinician-obtained cervical scraping specimens was also high, i.e., 95.9% (95% CI, 85.1 to 99.0%; 47/49 samples, kappa=0.90) for self-collected lavage samples and 91.6% (95% CI, 84.6 to 95.6%; 98/107 samples, kappa=0.82) for self-collected brush samples. In conclusion, the HPV-Risk assay meets the cross-sectional clinical and reproducibility criteria of the international guidelines for HPV test requirements and can be considered clinically validated for cervical screening purposes. The

  7. Rapid HIV Testing Is Highly Acceptable and Preferred among High-Risk Gay And Bisexual Men after Implementation in Sydney Sexual Health Clinics

    PubMed Central

    Conway, Damian P.; Guy, Rebecca; Davies, Stephen C; Couldwell, Deborah L.; McNulty, Anna; Smith, Don E.; Keen, Phillip; Cunningham, Philip; Holt, Martin

    2015-01-01

    Background Rapid HIV testing (RHT) is well established in many countries, but it is new in Australia. We assessed the acceptability of RHT and its associations among gay, bisexual and other men who have sex with men (GBM) after implementation of RHT in Sydney sexual health clinics. Methods GBM were invited to complete an acceptability questionnaire before and after provision of the result of finger-prick blood RHT, comparing their experience of RHT with conventional HIV testing (CHT) involving venipuncture. Logistic regression was used to assess associations between patient characteristics and the preference for RHT over CHT next time they tested for HIV. Results Of 1061 GBM who received non-reactive RHT results, 59% found RHT less stressful than CHT and 34% reported no difference, and 61% found RHT more comfortable than CHT and 26% reported no difference. Nearly all men were satisfied with RHT result delivery (99%) and the RHT process overall (99%). Most men (79%) preferred RHT for their next HIV test and this preference was stronger in men who were aged 35-44 years (adjusted odds ratio [AOR] 2.49, p<0.01), reported they would test more often if RHT was available (AOR 1.66, p=0.01), found returning for results annoying (AOR 1.67, p=0.01), and found RHT less stressful (AOR 2.37, p<0.01) and more comfortable (AOR 1.62, p=0.02) than CHT. Men concerned about the reliability of RHT were less than half as likely to prefer RHT for their next HIV test (AOR 0.44, p<0.01). Conclusions Most GBM preferred RHT to CHT next time and this preference was associated with finding RHT more convenient, more comfortable and less stressful than CHT. These findings suggest that in a clinic setting RHT should be considered to improve the patient experience and may potentially increase uptake and frequency of HIV testing. PMID:25898140

  8. Treating Patients with High-Risk Smoldering Myeloma

    Cancer.gov

    In this phase III clinical trial, patients with smoldering myeloma classified as high risk for progression will be randomly assigned to undergo standard observation or six 4-week courses of treatment with the drug lenalidomide.

  9. An Overview. High Risk Series.

    ERIC Educational Resources Information Center

    General Accounting Office, Washington, DC.

    This report provides an overview of efforts undertaken by the U.S. General Accounting Office (GAO) in 1990 to review and report on federal program areas its work identified as high risk because of vulnerabilities to waste, fraud, abuse, and mismanagement. It reviews the current status of efforts to address these concerns. The six categories of…

  10. Perceptions of high risk sports.

    PubMed

    Pedersen, D M

    1997-10-01

    High risk sports were rated as to risk, appeal, and likelihood of participation by 282 men and 162 women. Ascending order of perceived risk was skiing, scuba diving, bungee jumping, rock climbing, motorcycle racing, hang gliding, cliff jumping, and skydiving. Profile analysis showed stated likelihood of participation to be directly related to appeal and inversely related to perceived risk.

  11. Impact of Brachytherapy on Local Recurrence Rates After Sublobar Resection: Results From ACOSOG Z4032 (Alliance), a Phase III Randomized Trial for High-Risk Operable Non–Small-Cell Lung Cancer

    PubMed Central

    Fernando, Hiran C.; Landreneau, Rodney J.; Mandrekar, Sumithra J.; Nichols, Francis C.; Hillman, Shauna L.; Heron, Dwight E.; Meyers, Bryan F.; DiPetrillo, Thomas A.; Jones, David R.; Starnes, Sandra L.; Tan, Angelina D.; Daly, Benedict D.T.; Putnam, Joe B.

    2014-01-01

    Purpose A major concern with sublobar resection (SR) for non–small-cell lung cancer (NSCLC) is high local recurrence (LR). Adjuvant brachytherapy may reduce LR This multicenter randomized trial compares SR to SR with brachytherapy (SRB). Patients and Methods High-risk operable patients with NSCLC ≤ 3 cm were randomly assigned to SR or SRB. The primary end point was time to LR, where LR included recurrence at the staple line (local progression), in the primary tumor lobe away from the staple line, and in ipsilateral hilar nodes. The trial was designed to have a 90% power to detect a hazard ratio (HR) of 0.315 in favor of SRB, using a one-sided type I error rate of 0.05 with a sample size of 100 eligible patients in each arm. Results Two hundred twenty-four patients were randomly assigned; 222 patients were evaluable for intent-to-treat analysis. Median age was 71 years (range, 49 to 87 years). No differences were found in baseline characteristics. Median follow-up time was 4.38 years (range, 0.04 to 5.59 years). There was no difference in time to LR (HR, 1.01; 95% CI, 0.51 to 1.98; log-rank P = .98) or in the types of LR. Local progression occurred in only 17 (7.7%) of 222 patients. In patients with potentially compromised margins (margin < 1 cm, margin-to-tumor ratio < 1, positive staple line cytology, wedge resection, nodule size > 2.0 cm), SRB did not reduce LR, although trends favored the SRB arm. This was most marked in 14 patients with positive staple line cytology (HR, 0.22; P = .24). Three-year overall survival rates were similar for patients in the SR (71%) and SRB (71%) arms (P = .97). Conclusion Brachytherapy did not reduce LR after SR. This finding may have been related to closer attention to parenchymal margins by surgeons participating in this study. PMID:24982457

  12. Incorporation of tissue-based genomic biomarkers into localized prostate cancer clinics.

    PubMed

    Moschini, Marco; Spahn, Martin; Mattei, Agostino; Cheville, John; Karnes, R Jeffrey

    2016-01-01

    Localized prostate cancer (PCa) is a clinically heterogeneous disease, which presents with variability in patient outcomes within the same risk stratification (low, intermediate or high) and even within the same Gleason scores. Genomic tools have been developed with the purpose of stratifying patients affected by this disease to help physicians personalize therapies and follow-up schemes. This review focuses on these tissue-based tools. At present, four genomic tools are commercially available: Decipher™, Oncotype DX®, Prolaris® and ProMark®. Decipher™ is a tool based on 22 genes and evaluates the risk of adverse outcomes (metastasis) after radical prostatectomy (RP). Oncotype DX® is based on 17 genes and focuses on the ability to predict outcomes (adverse pathology) in very low-low and low-intermediate PCa patients, while Prolaris® is built on a panel of 46 genes and is validated to evaluate outcomes for patients at low risk as well as patients who are affected by high risk PCa and post-RP. Finally, ProMark® is based on a multiplexed proteomics assay and predicts PCa aggressiveness in patients found with similar features to Oncotype DX®. These biomarkers can be helpful for post-biopsy decision-making in low risk patients and post-radical prostatectomy in selected risk groups. Further studies are needed to investigate the clinical benefit of these new technologies, the financial ramifications and how they should be utilized in clinics. PMID:27044421

  13. Short- and Long-Term Quality of Life and Bowel Function in Patients With MRI-Defined, High-Risk, Locally Advanced Rectal Cancer Treated With an Intensified Neoadjuvant Strategy in the Randomized Phase 2 EXPERT-C Trial

    SciTech Connect

    Sclafani, Francesco; Peckitt, Clare; Cunningham, David; Tait, Diana; Giralt, Jordi; Glimelius, Bengt; Keränen, Susana Roselló; Bateman, Andrew; Hickish, Tamas; Tabernero, Josep; Thomas, Janet; Brown, Gina; Oates, Jacqueline; Chau, Ian

    2015-10-01

    Objective: Intensified preoperative treatments have been increasingly investigated in locally advanced rectal cancer (LARC), but limited data are available for the impact of these regimens on quality of life (QoL) and bowel function (BF). We assessed these outcome measures in EXPERT-C, a randomized phase 2 trial of neoadjuvant capecitabine combined with oxaliplatin (CAPOX), followed by chemoradiation therapy (CRT), total mesorectal excision, and adjuvant CAPOX with or without cetuximab in magnetic resonance imaging-defined, high-risk LARC. Methods and Materials: QoL was assessed using the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-CR29 questionnaires. Bowel incontinence was assessed using the modified Fecal Incontinence Severity Index questionnaire. Results: Compared to baseline, QoL scores during preoperative treatment were better for symptoms associated with the primary tumor in the rectum (blood and mucus in stool, constipation, diarrhea, stool frequency, buttock pain) but worse for global health status, role functioning, and symptoms related to the specific safety profile of each treatment modality. During follow-up, improved emotional functioning and lessened anxiety and insomnia were observed, but deterioration of body image, increased urinary incontinence, less sexual interest (men), and increased impotence and dyspareunia were observed. Cetuximab was associated with a deterioration of global health status during neoadjuvant chemotherapy but did not have any long-term detrimental effect. An improvement in bowel continence was observed after preoperative treatment and 3 years after sphincter-sparing surgery. Conclusions: Intensifying neoadjuvant treatment by administering induction systemic chemotherapy before chemoradiation therapy improves tumor-related symptoms and does not appear to have a significantly detrimental effect on QoL and BF, in both the short and the long term.

  14. The prognostic value of expression of HIF1α, EGFR and VEGF-A, in localized prostate cancer for intermediate- and high-risk patients treated with radiation therapy with or without androgen deprivation therapy

    PubMed Central

    2012-01-01

    Purpose Androgens stimulate the production of hypoxia-inducible factor (HIF1α) and ultimately vascular endothelial growth factor (VEGF-A). Additionally, epithelial growth factor (EGF) mediates HIF1α production. Carbonic anhydrase IX (CAIX) expression is associated with tumor cell hypoxia in a variety of malignancies. This study assesses the prognostic relation between HIF1α, VEGF-A, EGF Receptor and CAIX expression by immunochemistry in diagnostic samples of patients with intermediate- and high-risk localized prostate cancer treated with radiation therapy, with or without androgen deprivation therapy (ADT). Materials and methods Between 1994 and 2004, 103 prostate cancer patients (mean age, 68.7 ± 6.2), with prostate cancer (mean PSA, 13.3 ± 3.7), were treated with radiation therapy (RT, median dose, 74 Gy). Fifty seven (55.3%) patients received ADT (median duration, 6 months; range, 0 – 24). Median follow-up was 97.6 months (range, 5.9 – 206.8). Results Higher EGFR expression was significantly (p = 0.04) correlated with higher Gleason scores. On univariate analysis, HIF1α nuclear expression was a significant (p = 0.02) prognostic factor for biological progression-free survival (bPFS). A trend towards significance (p = 0.05) was observed with EGFR expression and bPFS. On multivariate analysis, low HIF1α nuclear (p = 0.01) and high EGFR (p = 0.04) expression remained significant adverse prognostic factors. Conclusions Our study suggests that high nuclear expression of HIF1α and low EGFR expression in diagnostic biopsies of prostate cancer patients treated with RT ± ADT is associated with a good prognosis. PMID:22546016

  15. [Clinical efficacy of decitabine plus improved CAG chemotherapy and haplo-identical donor peripheral lymphocyte infusion regimen on elderly patients with high risk myelodysplastic syndrome and acute myeloid leukemia].

    PubMed

    Dou, Li-Ping; Jing, Yu; Wang, Quan-Shun; Mei, Jun-Hui; Yu, Li

    2013-06-01

    This study was aimed to observe the clinical efficacy and adverse effects of decitabine plus improved CAG chemotherapy and haploid-identical donor peripheral lymphocyte infusion regimen on elderly patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Five elderly patients with MDS and AML were treated with decitabine plus improved CAG chemotherapy and donor peripheral lymphocyte infusion regimen. Examinations on liver and renal function, electrocardiogram and bone marrow analysis were performed before and after treatment, and adverse effects were observed. The results indicated that after a course of treatment by decitabine plus improved CAG chemotherapy and haplo-identical donor peripheral lymphocyte infusion regimen, the total effective rate was 100%, and 4 patients (80%) achieved complete remission, 1 patient achieved partial remission. The dominant clinical adverse effect was bone marrow depression, the median time of neutrophil>0.5×10(9)/L and platelet>20×10(9)/L was 15 d and 16 d respectively for patients without previous MDS. It is concluded that decitabine plus improved CAG chemotherapy and haploid-identical donor peripheral lymphocyte infusion regimen may be effective with less adverse effects for elderly primary AML and high risk MDS patients, it is a promising therapeutic methods and worthy to deeply study.

  16. Interaction of social role functioning and coping in people with recent-onset attenuated psychotic symptoms: a case study of three Chinese women at clinical high risk for psychosis

    PubMed Central

    Zhang, TianHong; Li, HuiJun; Woodberry, Kristen A; Seidman, Larry J; Chow, Annabelle; Xiao, ZePing; Wang, JiJun

    2015-01-01

    Clinical high risk of psychosis is defined as the period in which the first signs of psychotic symptoms begin to appear. During this period, there is an increased probability of developing frank psychosis. It is crucial to investigate the interaction between psychotic symptoms and the individual’s personality and life experiences in order to effectively prevent, or delay the development of psychosis. This paper presents case reports of three Chinese female subjects with attenuated positive symptoms, attending their initial outpatient assessment in a mental health service, and their longitudinal clinical outcomes. Information regarding each subject’s symptoms and life stressors was collected at 2-month intervals over a 6-month period. The assessments indicated that these women were suffering from the recent onset of symptoms in different ways. However, all three hid their symptoms from others in their school or workplace, and experienced a decline in performance related to their social roles and in their daily functioning. They were often excluded from the social groups to which they had previously belonged. A decline in social activities may be a risk factor in the development of psychosis and a mediator of functional sequelae in psychosis. Effective treatment strategies may include those that teach individuals to gain insights related to their symptoms and a service that provides a context in which individuals can discuss their psychotic symptoms. PMID:26185448

  17. Timing of High-Dose Rate Brachytherapy With External Beam Radiotherapy in Intermediate and High-Risk Localized Prostate CAncer (THEPCA) Patients and Its Effects on Toxicity and Quality of Life: Protocol of a Randomized Feasibility Trial

    PubMed Central

    Palvai, Sreekanth; Harrison, Michael; Shibu Thomas, Sharon; Hayden, Karen; Green, James; Anderson, Oliver; Romero, Lavinia; Lodge, Richard; Burns, Patricia

    2015-01-01

    Background Prostate cancer is the most common cancer in males in the UK and affects around 105 men for every 100,000. The role of radiotherapy in the management of prostate cancer significantly changed over the last few decades with developments in brachytherapy, external beam radiotherapy (EBRT), intensity-modulated radiotherapy (IMRT), and image-guided radiotherapy (IGRT). One of the challenging factors of radiotherapy treatment of localized prostate cancer is the development of acute and late genitourinary and gastrointestinal toxicities. The recent European guidelines suggest that there is no consensus regarding the timing of high-dose rate (HDR) brachytherapy and EBRT. The schedules vary in different institutions where an HDR boost can be given either before or after EBRT. Few centers deliver HDR in between the fractions of EBRT. Objective Assessment of acute genitourinary and gastrointestinal toxicities at various time points to better understand if the order in which treatment modality is delivered (ie, HDR brachytherapy or EBRT first) has an effect on the toxicity profile. Methods Timing of HDR brachytherapy with EBRT in Prostate CAncer (THEPCA) is a single-center, open, randomized controlled feasibility trial in patients with intermediate and high-risk localized prostate cancer. A group of 50 patients aged 18 years old and over with histological diagnosis of prostate cancer (stages T1b-T3BNOMO), will be randomized to one of two treatment arms (ratio 1:1), following explanation of the study and informed consent. Patients in both arms of the study will be treated with HDR brachytherapy and EBRT, however, the order in which they receive the treatments will vary. In Arm A, patients will receive HDR brachytherapy before EBRT. In Arm B (control arm), patients will receive EBRT before HDR brachytherapy. Study outcomes will look at prospective assessment of genitourinary and gastrointestinal toxicities. The primary endpoint will be grade 3 genitourinary toxicity

  18. A cluster randomised controlled trial to determine the clinical effectiveness and cost-effectiveness of classroom-based cognitive-behavioural therapy (CBT) in reducing symptoms of depression in high-risk adolescents.

    PubMed Central

    Stallard, P; Phillips, R; Montgomery, A A; Spears, M; Anderson, R; Taylor, J; Araya, R; Lewis, G; Ukoumunne, O C; Millings, A; Georgiou, L; Cook, E; Sayal, K

    2013-01-01

    BACKGROUND Depression in adolescents is a significant problem that impairs everyday functioning and increases the risk of severe mental health disorders in adulthood. Although this is a major problem, relatively few adolescents with, or at risk of developing, depression are identified and referred for treatment. This suggests the need to investigate alternative approaches whereby preventative interventions are made widely available in schools. OBJECTIVE To investigate the clinical effectiveness and cost-effectiveness of classroom-based cognitive-behavioural therapy (CBT) in reducing symptoms of depression in high-risk adolescents. DESIGN Cluster randomised controlled trial. Year groups ( n = 28) randomly allocated on a 1 : 1 : 1 basis to one of three trial arms once all schools were recruited and balanced for number of classes, number of students, Personal, Social and Health Education (PSHE) lesson frequency, and scheduling of PSHE. SETTING Year groups 8 to 11 (ages 12-16 years) in mixed-sex secondary schools in the UK. Data were collected between 2009 and 2011. PARTICIPANTS Young people who attended PSHE at participating schools were eligible ( n = 5503). Of the 5030 who agreed to participate, 1064 (21.2%) were classified as 'high risk': 392 in the classroom-based CBT arm, 374 in the attention control PSHE arm and 298 in the usual PSHE arm. Primary outcome data on the high-risk group at 12 months were available for classroom-based CBT ( n = 296), attention control PSHE ( n = 308) and usual PSHE ( n = 242). INTERVENTIONS The Resourceful Adolescent Programme (RAP) is a focused CBT-based intervention adapted for the UK (RAP-UK) and delivered by two facilitators external to the school. Control groups were usual PSHE (usual school curriculum delivered by teachers) and attention control (usual school PSHE with additional support from two facilitators). Interventions were delivered universally to whole classes. PRIMARY OUTCOMES Clinical effectiveness: symptoms of

  19. Local Immunoglobulin E in the Nasal Mucosa: Clinical Implications

    PubMed Central

    De Schryver, Els; Devuyst, Lien; Derycke, Lara; Dullaers, Melissa; Van Zele, Thibaut; Bachert, Claus

    2015-01-01

    Immunoglobulin E (IgE) can be highly elevated in the airway mucosa independently of IgE serum levels and atopic status. Mostly, systemic markers are assessed to investigate inflammation in airway disease for research or clinical practice. A more accurate but more cumbersome approach to determine inflammation at the target organ would be to evaluate markers locally. We review evidence for local production of IgE in allergic rhinitis (AR) and chronic rhinosinusitis with nasal polyps (CRSwNP). Diagnostic and therapeutic consequences in clinical practice are discussed. We describe that the airway mucosa has the intrinsic capability to produce IgE. Moreover, not only do IgE-positive B cells reside within the mucosa, but all tools are present locally for affinity maturation by somatic hypermutation (SHM), clonal expansion, and class switch recombination to IgE. Recognizing local IgE in the absence of systemic IgE has diagnostic and therapeutic consequences. Therefore, we emphasize the importance of local IgE in patients with a history of AR or CRSwNP. PMID:25749769

  20. Improved clinical outcomes of high risk β thalassemia major patients undergoing a HLA matched related allogeneic stem cell transplant with a treosulfan based conditioning regimen and peripheral blood stem cell grafts.

    PubMed

    Mathews, Vikram; George, Biju; Viswabandya, Auro; Abraham, Aby; Ahmed, Rayaz; Ganapule, Abhijeet; Sindhuvi, Eunice; Lakshmi, Kavitha M; Srivastava, Alok

    2013-01-01

    Improving clinical outcomes among high risk Class III β thalassemia major patients (Class IIIHR) receiving an allogeneic SCT remains a challenge. From October, 2009 a treosulfan based regimen (TreoFluT) was used for all consecutive Class III patients (n = 50). The clinical outcomes were compared with the historical conventional busulfan (BuCy) based regimen (n = 139). Use of TreoFluT was associated with a significantly reduced incidence of sinusoidal obstruction syndrome (SOS) among Class IIIHR cases (78% to 30%; P = 0.000) and early TRM (46% to 13%; p = 0.005). There was also a trend towards better engraftment in the Class IIIHR subset (P = 0.055). However, the use of bone marrow (BM) as source of stem cells along with the TreoFluT regimen was associated with 50% early mixed chimerism which reduced to 8.5% with the use of a peripheral blood stem cell graft (PBSC). Use of a PBSC graft was not associated with a significant increase in the incidence of acute or chronic graft versus host disease (GVHD). The overall and event free survival was significantly better among the Class IIIHR subset with the use of TreoFluT Vs. BuCy (86.6 ± 7.3 Vs. 39.4 ± 6.8%; P = 0.002 and 77.8 ± 8.8 Vs. 32.4 ± 6.5%; P = 0.003 respectively). A TreoFluT conditioning regimen with a PBSC graft can significantly improve clinical outcomes of Class IIIHR patients.

  1. Contemporary therapeutic options for children with high risk neuroblastoma.

    PubMed

    Sterba, J

    2002-01-01

    Despite the use of aggressive chemotherapy, stage 4 high risk neuroblastoma still has a very poor prognosis, which is estimated at 25%. Therefore, novel treatment approaches are needed. Increasing number of reports has been concerned with the use of novel treatment modalities. Literature regarding intensive induction, local therapy, myeloablative therapy and immunotherapy and biotherapy was reviewed in order to draw conclusions and recommendations for the management of children with high risk neuroblastic tumors.

  2. The roles of clinical pharmacologists in formulating medicines policy locally.

    PubMed

    Reynolds, D John M; Barker, Charlotte I S

    2012-06-01

    Specialists in Clinical Pharmacology and Therapeutics (CPT) can add value in day-to-day NHS activities in several ways. They provide a breadth of expertise that is not organ-based or disease-specific and that is based on an intimate knowledge and understanding of the effectiveness, safety and cost-effectiveness of pharmacological interventions. More than any other professional group, they can address the growing need for undergraduate and postgraduate teaching to be based on 'thoughtful therapeutics', not just the mechanics of prescribing. CPT specialists can and do take the lead in making local and national policy decisions relating to drug usage and they should be involved in local commissioning decisions. Because of the breadth of experience embraced by CPT, many clinical pharmacologists have taken on local and national senior clinical leadership roles. CPT needs to demonstrate to the NHS, and in particular to trainees, that a CPT post in the NHS is a legitimate and rewarding career path, where they can use their hard earned CPT skills and expertise to the benefit of the NHS as a whole.

  3. Treatment of high-risk neuroblastoma.

    PubMed

    Sung, Ki Woong

    2012-04-01

    Although high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT) have improved the prognosis for patients with high-risk neuroblastoma (NB), event-free survival rates remain in the range of 30 to 40%, which is unsatisfactory. To further improve outcomes, several clinical trials, including tandem HDCT/autoSCT, high-dose (131)I-metaiodobenzylguanidine treatment, and immunotherapy with NB specific antibody, have been undertaken and pilot studies have reported encouraging results. Nonetheless, about half of high-risk NB patients still experience treatment failure and have no realistic chance for cure with conventional treatment options alone after relapse. Therefore, a new modality of treatment is warranted for these patients. In recent years, several groups of investigators have examined the feasibility and effectiveness of reduced-intensity allogeneic stem cell transplantation (RI alloSCT) for the treatment of relapsed/progressed NB. Although a graft-versus-tumor effect has not yet been convincingly demonstrated in the setting of relapsed NB, the strategy of employing RI alloSCT has provided hope that treatment-related mortality will be reduced and a therapeutic benefit will emerge. However, alloSCT for NB is still investigational and there remain many issues to be elucidated in many areas. At present, alloSCT is reserved for specific clinical trials testing the immunomodulatory effect against NB.

  4. Prognostic index score and clinical prediction model of local regional recurrence after mastectomy in breast cancer patients

    SciTech Connect

    Cheng, Skye Hongiun . E-mail: skye@mail.kfcc.org.tw; Horng, C.-F.; Clarke, Jennifer L.; Tsou, M.-H.; Tsai, Stella Y.; Chen, C.-M.; Jian, James J.; Liu, M.-C.; West, Mike; Huang, Andrew T.; Prosnitz, Leonard R.

    2006-04-01

    Purpose: To develop clinical prediction models for local regional recurrence (Lr) of breast carcinoma after mastectomy that will be superior to the conventional measures of tumor size and nodal status. Methods and Materials: Clinical information from 1,010 invasive breast cancer patients who had primary modified radical mastectomy formed the database of the training and testing of clinical prognostic and prediction models of LRR. Cox proportional hazards analysis and Bayesian tree analysis were the core methodologies from which these models were built. To generate a prognostic index model, 15 clinical variables were examined for their impact on LRR. Patients were stratified by lymph node involvement (<4 vs. {>=}4) and local regional status (recurrent vs. control) and then, within strata, randomly split into training and test data sets of equal size. To establish prediction tree models, 255 patients were selected by the criteria of having had LRR (53 patients) or no evidence of LRR without postmastectomy radiotherapy (PMRT) (202 patients). Results: With these models, patients can be divided into low-, intermediate-, and high-risk groups on the basis of axillary nodal status, estrogen receptor status, lymphovascular invasion, and age at diagnosis. In the low-risk group, there is no influence of PMRT on either LRR or survival. For intermediate-risk patients, PMRT improves LR control but not metastases-free or overall survival. For the high-risk patients, however, PMRT improves both LR control and metastasis-free and overall survival. Conclusion: The prognostic score and predictive index are useful methods to estimate the risk of LRR in breast cancer patients after mastectomy and for estimating the potential benefits of PMRT. These models provide additional information criteria for selection of patients for PMRT, compared with the traditional selection criteria of nodal status and tumor size.

  5. [Clinical picture of pure corneal ulcers of different localizations].

    PubMed

    Tarasova, L N; Kudriashova, Iu I

    1999-01-01

    Pure corneal ulcers can be localized at the periphery and in the center. Peripheral ulcers are bilateral in 66% and multifocal in 48% cases. They are combined with local vasculitis of perilimbic vessels of the conjunctiva. In 84% cases the disease occurred in patients with connective tissue and articular diseases. Clinical picture of the peripheral corneal ulcer differs from Mourene's phagodenic ulcer. Central corneal ulcers are bilateral in 40% patients, are associated with primary and secondary "dry eye" syndrome in Sjogren's disease, rheumatoid arthritis, systemic vasculitis, Behçet's disease, and in 18% patients with cicatricial deformation of the conjunctiva after Stevens-Johnson's syndrome, trachoma, and chemical burns of the eyes. Pure corneal ulcers run a chronic relapsing course, complicated in one-fourth of patients by corneal perforation and secondary infections.

  6. Successful commercialisation of locally fabricated bioceramics for clinical applications.

    PubMed

    Fazan, F; Besar, I; Osman, A; Samsudin, A R; Khalid, K A

    2008-07-01

    This paper chronicled the development of a locally produced bone graft substitute based on calcium phosphate bioceramics called "GranuMaS--from concepts to clinics, and finally to its successful commercialization all within 5-year duration. It was a Prioritized Research (PR) collaborative project of 5 institutions namely SIRIM, ANM, USM, UKM and IIUM, funded by MOSTI to the amount of approximately RM2.5 millions under RM8. This paper also highlighted the requirements needed in terms of technical expertise/manpower, facilities and infrastructure, and government/institutional supports, as well as the challenge faced in developing and commercializing such product.

  7. Stabilization of high-risk plaques

    PubMed Central

    Takata, Kohei; Zhang, Bo; Miura, Shin-ichiro; Saku, Keijiro

    2016-01-01

    The prevalence of atherosclerotic cardiovascular diseases (ASCVDs) is increasing globally and they have become the leading cause of death in most countries. Numerous experimental and clinical studies have been conducted to identify major risk factors and effective control strategies for ASCVDs. The development of imaging modalities with the ability to determine the plaque composition enables us to further identify high-risk plaque and evaluate the effectiveness of different treatment strategies. While intensive lipid-lowering by statins can stabilize or even regress plaque by various mechanisms, such as the reduction of lipid accumulation in a necrotic lipid core, the reduction of inflammation, and improvement of endothelial function, there are still considerable residual risks that need to be understood. We reviewed important findings regarding plaque vulnerability and some encouraging emerging approaches for plaque stabilization. PMID:27500090

  8. Photodynamic therapy for locally advanced pancreatic cancer: early clinical results

    NASA Astrophysics Data System (ADS)

    Sandanayake, N. S.; Huggett, M. T.; Bown, S. G.; Pogue, B. W.; Hasan, T.; Pereira, S. P.

    2010-02-01

    Pancreatic adenocarcinoma ranks as the fourth most common cause of cancer death in the USA. Patients usually present late with advanced disease, limiting attempted curative surgery to 10% of cases. Overall prognosis is poor with one-year survival rates of less than 10% with palliative chemotherapy and/or radiotherapy. Given these dismal results, a minimally invasive treatment capable of local destruction of tumor tissue with low morbidity may have a place in the treatment of this disease. In this paper we review the preclinical photodynamic therapy (PDT) studies which have shown that it is possible to achieve a zone of necrosis in normal pancreas and implanted tumour tissue. Side effects of treatment and evidence of a potential survival advantage are discussed. We describe the only published clinical study of pancreatic interstitial PDT, which was carried out by our group (Bown et al Gut 2002), in 16 patients with unresectable locally advanced pancreatic adenocarcinoma. All patients had evidence of tumor necrosis on follow-up imaging, with a median survival from diagnosis of 12.5 months. Finally, we outline a phase I dose-escalation study of verteporfin single fibre PDT followed by standard gemcitabine chemotherapy which our group is currently undertaking in patients with locally advanced pancreatic cancer. Randomized controlled studies are also planned.

  9. Explorations in High-Risk Stimulation: Two Modalities in Mothering.

    ERIC Educational Resources Information Center

    Gochman, Eva R. Grubler; Aisenstein, Clara

    An exploratory study of high-risk mothers' interactions with their infants studied modalities of stimulation; vestibular and auditory. It was hypothesized that stimulation would be lower for non-paranoid than for paranoid types, and than for control mothers. Mothers recruited from inner city gynecological clinics were screened for probable…

  10. The clinical outcomes of triple antiplatelet therapy versus dual antiplatelet therapy for high-risk patients after coronary stent implantation: a meta-analysis of 11 clinical trials and 9,553 patients

    PubMed Central

    Fan, Zhong-Guo; Ding, Guo-Bin; Li, Xiao-Bo; Gao, Xiao-Fei; Gao, Ya-Li; Tian, Nai-Liang

    2016-01-01

    Background The optimal antiplatelet regimen after in-coronary intervention among patients presenting with complex coronary artery lesions or acute coronary syndrome (ACS) has remained unclear. This study sought to evaluate the clinical outcomes of triple antiplatelet treatment (TAPT) (cilostazol added to aspirin plus clopidogrel) in these patients. Methods The PubMed, EMBASE, MEDLINE, and other Internet sources were searched for relevant articles. The primary end point was major adverse cardiac events (MACE), including all-cause mortality, myocardial infarction, and target vessel revascularization. The incidence of definite/probable stent thrombosis and bleeding were analyzed as the safety end points. Results Eleven clinical trials involving 9,553 patients were analyzed. The risk of MACE was significantly decreased following TAPT after stent implantation in the ACS subgroup (odds ratio [OR]: 0.72; 95% confidence interval [CI]: 0.61–0.85; P<0.001), which might mainly result from the lower risk of all-cause mortality in this subset (OR: 0.62; 95% CI: 0.48–0.80; P<0.001). The risk of bleeding was not increased with respect to TAPT. Conclusion TAPT after stent implantation was associated with feasible benefits on reducing the risk of MACE, especially on reducing the incidence of all-cause mortality among patients suffering from ACS, without higher incidence of bleeding. Larger and more powerful randomized trials are still warranted to prove the superiority of TAPT for such patients. PMID:27799743

  11. Analysis of localized erythema using clinical indicators and spectroscopy.

    PubMed

    Sprigle, Stephen; Linden, Maureen; Riordan, Brian

    2003-03-01

    Localized erythema is regularly used as an indicator of post-ischemic events, including reactive hyperemia and Stage I pressure ulcers. The National Pressure Ulcer Advisory Panel definition of a Stage I ulcer includes both visual and nonvisual indicators in part to improve identification in darkly pigmented skin. A prospective, repeated-measures design was used to collect information on pressure-induced erythema that includes reactive hyperemia and Stage I pressure ulcers with an emphasis on distinguishing indicators in light and dark skin The relationships among clinical indicators (skin assessments) and results from tissue reflectance spectroscopy, as well as the clinical utility of spectroscopy for discerning tissue blanching status, were examined in a convenience sample of 76 inpatients and outpatients (95 test/control site pairs). Chi-square analysis and generalized logistic models were used to identify relationships and distinguishing characteristics of erythema. Analysis of variance was used to analyze blanching using spectroscopy. Nonblanching sites were more likely to be persistent erythema (c2=5.3; P = 0.021) but exhibited no relationships to temperature, tissue resilience, or disability. Erythema in subjects with dark skin was more likely to be nonblanching and have poor resilience. Spectrographic analysis of blanching found significant differences across skin pigmentation (P = 0.0001) and blanching status (P = 0.019). These results reinforce the belief that dark skin must be assessed differently than light skin and indicate that clinicians should use persistence of erythema rather than blanching status to judge incipient pressure ulcers. These results validate the use of visual and nonvisual indicators included in the National Pressure Ulcer Advisory Panel Stage I pressure ulcer definition. PMID:12732750

  12. Serum Testosterone Kinetics After Brachytherapy for Clinically Localized Prostate Cancer

    SciTech Connect

    Taira, Al V.; Merrick, Gregory S.; Galbreath, Robert W.; Butler, Wayne M.; Lief, Jonathan H.; Allen, Zachariah A.; Wallner, Kent E.

    2012-01-01

    Purpose: To evaluate temporal changes in testosterone after prostate brachytherapy and investigate the potential impact of these changes on response to treatment. Methods and Materials: Between January 2008 and March 2009, 221 consecutive patients underwent Pd-103 brachytherapy without androgen deprivation for clinically localized prostate cancer. Prebrachytherapy prostate-specific antigen (PSA) and serum testosterone were obtained for each patient. Repeat levels were obtained 3 months after brachytherapy and at least every 6 months thereafter. Multiple clinical, treatment, and dosimetric parameters were evaluated to determine an association with temporal testosterone changes. In addition, analysis was conducted to determine if there was an association between testosterone changes and treatment outcomes or the occurrence of a PSA spike. Results: There was no significant difference in serum testosterone over time after implant (p = 0.57). 29% of men experienced an increase {>=}25%, 23% of men experienced a decrease {>=}25%, and the remaining 48% of men had no notable change in testosterone over time. There was no difference in testosterone trends between men who received external beam radiotherapy and those who did not (p = 0.12). On multivariate analysis, preimplant testosterone was the only variable that consistently predicted for changes in testosterone over time. Men with higher than average testosterone tended to experience drop in testosterone (p < 0.001), whereas men with average or below average baseline testosterone had no significant change. There was no association between men who experienced PSA spike and testosterone temporal trends (p = 0.50) nor between initial PSA response and testosterone trends (p = 0.21). Conclusion: Prostate brachytherapy does not appear to impact serum testosterone over time. Changes in serum testosterone do not appear to be associated with PSA spike phenomena nor with initial PSA response to treatment; therefore, PSA response

  13. The Psychosis High-Risk State

    PubMed Central

    Fusar-Poli, Paolo; Borgwardt, Stefan; Bechdolf, Andreas; Addington, Jean; Riecher-Rössler, Anita; Schultze-Lutter, Frauke; Keshavan, Matcheri; Wood, Stephen; Ruhrmann, Stephan; Seidman, Larry J.; Valmaggia, Lucia; Cannon, Tyrone; Velthorst, Eva; De Haan, Lieuwe; Cornblatt, Barbara; Bonoldi, Ilaria; Birchwood, Max; McGlashan, Thomas; Carpenter, William; McGorry, Patrick; Klosterkötter, Joachim; McGuire, Philip; Yung, Alison

    2014-01-01

    Context During the past 2 decades, a major transition in the clinical characterization of psychotic disorders has occurred. The construct of a clinical high-risk (HR) state for psychosis has evolved to capture the prepsychotic phase, describing people presenting with potentially prodromal symptoms. The importance of this HR state has been increasingly recognized to such an extent that a new syndrome is being considered as a diagnostic category in the DSM-5. Objective To reframe the HR state in a comprehensive state-of-the-art review on the progress that has been made while also recognizing the challenges that remain. Data Sources Available HR research of the past 20 years from PubMed, books, meetings, abstracts, and international conferences. Study Selection and Data Extraction Critical review of HR studies addressing historical development, inclusion criteria, epidemiologic research, transition criteria, outcomes, clinical and functional characteristics, neurocognition, neuroimaging, predictors of psychosis development, treatment trials, socioeconomic aspects, nosography, and future challenges in the field. Data Synthesis Relevant articles retrieved in the literature search were discussed by a large group of leading worldwide experts in the field. The core results are presented after consensus and are summarized in illustrative tables and figures. Conclusions The relatively new field of HR research in psychosis is exciting. It has the potential to shed light on the development of major psychotic disorders and to alter their course. It also provides a rationale for service provision to those in need of help who could not previously access it and the possibility of changing trajectories for those with vulnerability to psychotic illnesses. PMID:23165428

  14. [Non-functional duodenal neuroendocrine neoplasia in the proximal duodenum--case reports and proposal for a "high-risk-/low-risk-concept" in the decision for local endoscopic therapy].

    PubMed

    Scheerer, F; Schmitt, W

    2013-11-01

    Early duodenal neuroendocrine neoplasms (dNENs) are being increasingly diagnosed. Non-functional dNENs in the bulb expressing gastrin are by far the most frequent entity. In the period from 2004 to 2012, 17 cases of 16 patients with NET in the duodenal bulb were evaluated. dNENs of the ampulla of Vater and functional dNEN/gastrinoma were not included due to possibly different malignant potentials. The average age of the patients was 65.7 years, the mean tumour size was 10.2  mm, the maximum proliferation index Ki 67 was 5 % (NET G2). In most cases the maximum depth of invasion was down to the submucosa. In cases of dNEN without risk factors (size up to 10 mm, G1 situation, no invasion of the muscularis propria, no angioinvasion) in 10 out of 11 cases (90.9 %), endoscopic therapy was sufficient. In cases of existing risk factors, sole endoscopic treatment was only possible in 1 out of 5 cases (20 %). In the absence of risk factors in the current follow-up period (mean: 36.7 months) no lymph node metastases were detected. In the presence of risk factors or indications for surgery we found an increase in the rate of lymph node metastases. Our own data indicate that in case of a G2 situation, a tumour size >10  mm or infiltration of the muscularis propria the need for surgical treatment increases significantly for early non-functional dNENs in the duodenal bulb. A high-risk-/low-risk-concept for the endoscopic therapy for early non-functional dNEN has been established.

  15. Telomerase activation by genomic rearrangements in high-risk neuroblastoma

    PubMed Central

    Peifer, Martin; Hertwig, Falk; Roels, Frederik; Dreidax, Daniel; Gartlgruber, Moritz; Menon, Roopika; Krämer, Andrea; Roncaioli, Justin L.; Sand, Frederik; Heuckmann, Johannes M.; Ikram, Fakhera; Schmidt, Rene; Ackermann, Sandra; Engesser, Anne; Kahlert, Yvonne; Vogel, Wenzel; Altmüller, Janine; Nürnberg, Peter; Thierry-Mieg, Jean; Thierry-Mieg, Danielle; Mariappan, Aruljothi; Heynck, Stefanie; Mariotti, Erika; Henrich, Kai-Oliver; Glöckner, Christian; Bosco, Graziella; Leuschner, Ivo; Schweiger, Michal R.; Savelyeva, Larissa; Watkins, Simon C.; Shao, Chunxuan; Bell, Emma; Höfer, Thomas; Achter, Viktor; Lang, Ulrich; Theissen, Jessica; Volland, Ruth; Saadati, Maral; Eggert, Angelika; de Wilde, Bram; Berthold, Frank; Peng, Zhiyu; Zhao, Chen; Shi, Leming; Ortmann, Monika; Büttner, Reinhard; Perner, Sven; Hero, Barbara; Schramm, Alexander; Schulte, Johannes H.; Herrmann, Carl; O’Sullivan, Roderick J.; Westermann, Frank; Thomas, Roman K.; Fischer, Matthias

    2016-01-01

    Neuroblastoma is a malignant paediatric tumour of the sympathetic nervous system1. Roughly half of these tumours regress spontaneously or are cured by limited therapy. By contrast, high-risk neuroblastomas have an unfavourable clinical course despite intensive multimodal treatment, and their molecular basis has remained largely elusive2–4. Here we have performed whole-genome sequencing of 56 neuroblastomas (high-risk, n = 39; low-risk, n = 17) and discovered recurrent genomic rearrangements affecting a chromosomal region at 5p15.33 proximal of the telomerase reverse transcriptase gene (TERT). These rearrangements occurred only in high-risk neuroblastomas (12/39, 31%) in a mutually exclusive fashion with MYCN amplifications and ATRX mutations, which are known genetic events in this tumour type1,2,5. In an extended case series (n = 217), TERT rearrangements defined a subgroup of high-risk tumours with particularly poor outcome. Despite a large structural diversity of these rearrangements, they all induced massive transcriptional upregulation of TERT. In the remaining high-risk tumours, TERT expression was also elevated in MYCN-amplified tumours, whereas alternative lengthening of telomeres was present in neuroblastomas without TERT or MYCN alterations, suggesting that telomere lengthening represents a central mechanism defining this subtype. The 5p15.33 rearrangements juxtapose the TERT coding sequence to strong enhancer elements, resulting in massive chromatin remodelling and DNA methylation of the affected region. Supporting a functional role of TERT, neuroblastoma cell lines bearing rearrangements or amplified MYCN exhibited both upregulated TERT expression and enzymatic telomerase activity. In summary, our findings show that remodelling of the genomic context abrogates transcriptional silencing of TERT in high-risk neuroblastoma and places telomerase activation in the centre of transformation in a large fraction of these tumours. PMID:26466568

  16. High-Risk Childhood Acute Lymphoblastic Leukemia

    PubMed Central

    Bhojwani, Deepa; Howard, Scott C.; Pui, Ching-Hon

    2009-01-01

    Although most children with acute lymphoblastic leukemia (ALL) are cured, certain subsets have a high risk of relapse. Relapse risk can be predicted by early response to therapy, clinical and pharmacogenetic features of the host, and genetic characteristics of leukemic cells. Though early treatment response can be assessed by the peripheral blast cell count after 1 week of single-agent glucocorticoid treatment or percent of bone marrow blasts by morphology after 1 or 2 weeks of multiagent induction treatment, determination of minimal residual disease by polymerase chain reaction (PCR) or flow cytometry after 2 to 6 weeks of induction is the most precise and useful measure. Augmented therapy has improved outcome for the poor responders to initial treatment. Infants with mixed-lineage leukemia (MLL)–rearranged ALL comprise a very poor-risk group wherein further intensification of chemotherapy causes significant toxicity. Hybrid protocols incorporating drugs effective for acute myeloid leukemia could improve survival, a strategy being tested in international trials. Studies on the biology of MLL-induced leukemogenesis have prompted the development of novel targeted agents, currently under evaluation in clinical trials. Short-term outcomes of patients with Philadelphia chromosome (Ph)–positive ALL have improved significantly by adding tyrosine kinase inhibitors to standard chemotherapy regimens. New agents and methods to overcome resistance are under investigation, and allogeneic stem cell transplantation is recommended for certain subsets of patients, for example those with Ph+ and T-cell ALL with poor early response. Genome-wide interrogation of leukemic cell genetic abnormalities and germline genetic variations promise to identify new molecular targets for therapy. PMID:19778845

  17. High-risk acute myelogenous leukemia: treatment today ... and tomorrow.

    PubMed

    Schiller, Gary J

    2013-01-01

    High-risk acute myelogenous leukemia (AML) constitutes a distinct subset of disease based on clinical and biological characteristics and comprises a significant percentage of all cases of adult AML. Biologic features such as distinct clonal cytogenetic and molecular abnormalities identify a subgroup of AML patients characterized by poor response to induction chemotherapy and poor long-term survival after treatment with consolidation chemotherapy. Clinical variables that predict for poor response include AML relapsed after less than 1 year of remission and AML characterized by resistance to conventional agents. We review here our understanding of the defining biologic subtypes of AML and discuss how adequate initial evaluation can be used to inform the choice of treatment. By defining high-risk biologic and clinical variables, a strong case can be made for treating patients with investigational agents, with treatment directed at distinct cytogenetic or molecular abnormalities. Allogeneic transplantation is the only form of therapy available outside of the setting of a clinical trial that may offer a chance for long-term survival for patients with high-risk AML.

  18. The high-risk myocardial infarction database initiative.

    PubMed

    Dickstein, Kenneth; Bebchuk, Judith; Wittes, Janet

    2012-01-01

    Coronary artery disease and myocardial infarction represent a major cause of morbidity and mortality. Four randomized, controlled, double-blind clinical trials--VALIANT, EPHESUS, OPTIMAAL, and CAPRICORN evaluated pharmacologic intervention in a total of 28,771 high-risk patients following acute MI complicated with signs of heart failure or evidence of left ventricular dysfunction. The demographic profiles of the 4 study cohorts were similar. The High-Risk MI Database Initiative constructed a common database by merging the data captured by these 4 large trials. The merged data set did not contain the randomized study treatment, so no comparisons could be made between the agents investigated. A total of more than 17,600 subjects experienced a cardiovascular end point. Approximately 5100 deaths occurred, and more than 15,700 subjects experienced a hospitalization. The primary objectives of this initiative were to use this large database to define more precisely the prognostic profile of this high-risk population, to perform rigorous, adequately-sized, subset analyses, to provide epidemiologic information and event rate estimation based on baseline demographics. The methodological challenges and limitations of such an analyses are discussed. It is proposed that some thoughtful foresight and planning could enable us to use the large number of clinical events that accrue during randomized clinical trials to address questions of scientific and clinical interest. PMID:22226005

  19. Genomic analysis of high-risk smoldering multiple myeloma

    PubMed Central

    López-Corral, Lucía; Mateos, María Victoria; Corchete, Luis A.; Sarasquete, María Eugenia; de la Rubia, Javier; de Arriba, Felipe; Lahuerta, Juan-José; García-Sanz, Ramón; San Miguel, Jesús F.; Gutiérrez, Norma C.

    2012-01-01

    Smoldering myeloma is an asymptomatic plasma cell dyscrasia with a heterogeneous propensity to progress to active myeloma. In order to investigate the biology of smoldering myeloma patients with high risk of progression, we analyzed the genomic characteristics by FISH, SNP-arrays and gene expression profile of a group of patients with high-risk smoldering myeloma included in a multicenter randomized trial. Chromosomal abnormalities detected by FISH and SNP-arrays at diagnosis were not associated to risk of progression to symptomatic myeloma. However, the overexpression of four SNORD genes (SNORD25, SNORD27, SNORD30 and SNORD31) was correlated with shorter time to progression (P<0.03). When plasma cells from high-risk smoldering patients who progressed to symptomatic myeloma were sequentially analyzed, newly acquired lesions together with an increase in the proportion of plasma cells carrying a given abnormality were observed. These findings suggest that gene expression profiling is a valuable technique to identify smoldering myeloma patients with high risk of progression. (Clinical Trials NCT00443235) PMID:22331267

  20. The Matrix Metalloproteinase-7 Polymorphism Rs10895304 Is Associated With Increased Recurrence Risk in Patients With Clinically Localized Prostate Cancer

    SciTech Connect

    Jaboin, Jerry J.; Hwang, Misun; Lopater, Zachary; Chen Heidi; Ray, Geoffrey L.; Perez, Carmen; Cai Qiuyin; Wills, Marcia L.; Lu Bo

    2011-04-01

    Purpose: To evaluate whether selected high-risk matrix metalloproteinase-7 single nucleotide polymorphisms influence clinicopathologic outcomes in patients with early-stage prostate cancer. Methods and Materials: Two hundred twelve prostate cancer patients treated with radical prostatectomy were evaluated with a median follow-up of 9.8 years. Genotyping was performed using hybridization with custom-designed allele-specific probes. Three single nucleotide polymorphisms within the matrix metalloproteinase-7 gene were assessed with respect to age at diagnosis, margin status, extracapsular extension, lymph node involvement, recurrence-free survival, and overall survival in paraffin-embedded prostate tissue specimens from patients with early-stage prostate cancer who underwent radical prostatectomy. Results: Rs10895304 was the sole significant polymorphism. The A/G genotype of rs10895304 had a statistically significant association with recurrence-free survival in postprostatectomy patients (p = 0.0061, log-rank test). The frequency of the risk-reducing genotype (A/A) was 74%, whereas that of the risk-enhancing genotypes (A/G and G/G) were 20% and 6%, respectively. Multivariable Cox regression analyses detected a significant association between rs10895304 and recurrences after adjustment for known prognostic factors. The G allele of this polymorphism was associated with increased risk of prostate cancer recurrence (adjusted hazards ratio, 3.375; 95% confidence interval 1.567-7.269; p < 0.001). The other assayed polymorphisms were not significant, and no correlations were made to other clinical variables. Conclusions: The A/G genotype of rs10895304 is predictive of decreased recurrence-free survival in patients with clinically localized prostate cancer. Our data suggest that for this subset of patients, prostatectomy alone may not be adequate for local control. This is a novel and relevant marker that should be evaluated for improved risk stratification of patients who

  1. Local anesthetics: dentistry's most important drugs, clinical update 2006.

    PubMed

    Malamed, Stanley F

    2006-12-01

    Local anesthetics are the safest most effective drugs in medicine for the control and management of pain. They also represent the most important drugs in dentistry. Today, dentistry has a spectrum of local anesthetics that permit pain control to be tailored to the specific needs of the patient: short-, intermediate-, and long-acting drugs. Bupivacaine has become a standard part of the armamentarium for postsurgical pain control while articaine has become the second-most used local anesthetic in the United States since its introduction in 2000. Despite an increase in anecdotal reports of paresthesia since articaine's introduction there is yet, no supporting scientific evidence.

  2. [Artificial circulation in high-risk percutaneous coronary interventions].

    PubMed

    Bazylev, V V; Evdokimov, M E; Pantiukhina, M A; Morozov, Z A

    2016-01-01

    In their everyday practical clinical work cardiovascular surgeons sometimes have to deal with patients at extremely high risk of both percutaneous coronary interventions (PCIs) and direct myocardial revascularization. A method of choice in such situations may become a PCI supported by artificial circulation (AC), for which foreign and Russian authors propose using systems of prolonged extracorporeal membrane oxygenation (ECMO). The present work was aimed at sharing our experience with using standard systems of AC and their modifications (mini-circuit systems) for performing high-risk PCIs. Between October 2011 and November 2014, PCIs supported by artificial circulation were performed in a total of ten patients. All had extremely high risk of PCI due to coronary artery lesions [subocclusion of the trunk of the left coronary artery (LCA) combined with occlusion or significant stenosis of the right coronary artery (RCA)], concomitant pathology (obesity, diabetes mellitus, age, etc.) or critical state (circulatory arrest, resuscitating measures). Three patients during PCI developed ventricular fibrillation and one patient suffered an episode of asystole. All cardiac arrhythmias after restoration of the coronary blood flow disappeared spontaneously on the background of extracorporeal support. The only lethal outcome was registered during emergency PCI in a female patient admitted to the roentgen-operating room in the state of clinical death, on the background of continuing resuscitation measures. The presented methods of assisted circulation based on the standard AC systems and modification thereof (mini-circuit system) proved efficient. They make it possible to perform high-risk PCIs, including in clinics having neither appropriate equipment nor experience in ECMO. PMID:27626258

  3. A study of the current knowledge base in treating snake bite amongst doctors in the high-risk countries of India and Pakistan: does snake bite treatment training reflect local requirements?

    PubMed

    Simpson, Ian D

    2008-11-01

    The call for greater production of better quality anti-snake venom (ASV) is a major thrust in the effort to reduce snake bite mortality. However, snake bite mortality has many causes and these should also be addressed. A key feature of efficient ASV usage is ensuring that doctors are trained to administer ASV only when it is required and in amounts that are necessary to neutralize venom. The need for better snake bite management training has been referred to, but little attention has been paid to how effectively medical education actually prepares doctors to treat snake bite. The objective of this study is to evaluate the current level of knowledge amongst doctors in India and Pakistan, two countries with the highest snake bite mortality in absolute terms. Results show that the use of current textbooks and medical education do not adequately prepare doctors to treat snake bite, particularly in the areas of use of ASV, dealing with adverse reactions to ASV and specific measures to deal with neurotoxic bites. The central conclusion of the paper is that local protocols and training are required to adequately prepare doctors to improve treatment and reduce mortality.

  4. [Local communalization of clinical records between the municipal community hospital and local medical institutes by using information technology].

    PubMed

    Iijima, Shohei; Shinoki, Keiji; Ibata, Takeshi; Nakashita, Chisako; Doi, Seiko; Hidaka, Kumi; Hata, Akiko; Matsuoka, Mio; Waguchi, Hideko; Mito, Saori; Komuro, Ryutaro

    2012-12-01

    We introduced the electronic health record system in 2002. We produced a community medical network system to consolidate all medical treatment information from the local institute in 2010. Here, we report on the present status of this system that has been in use for the previous 2 years. We obtained a private server, set up a virtual private network(VPN)in our hospital, and installed dedicated terminals to issue an electronic certificate in 50 local institutions. The local institute applies for patient agreement in the community hospital(hospital designation style). They are then entitled to access the information of the designated patient via this local network server for one year. They can access each original medical record, sorted on the basis of the medical attendant and the chief physician; a summary of hospital stay; records of medication prescription; and the results of clinical examinations. Currently, there are approximately 80 new registrations and accesses per month. Information is provided in real time allowing up to date information, helping prescribe the medical treatment at the local institute. However, this information sharing system is read-only, and there is no cooperative clinical pass system. Therefore, this system has a limit to meet the demand for cooperation with the local clinics.

  5. Adverse reactions triggered by dental local anesthetics: a clinical survey.

    PubMed Central

    Kaufman, E.; Goharian, S.; Katz, Y.

    2000-01-01

    One hundred and seventy-nine patients completed a questionnaire focusing on adverse reactions to dental local anesthetics as manifested by 16 signs and symptoms. Twenty-six percent of the participants reported having at least 1 adverse reaction. It was found that most of the adverse reactions occurred within the first 2 hours following the injection of local anesthetics. Pallor, palpitations, diaphoresis, and dizziness were the most common adverse reactions reported in the study. The results pointed to a significant relationship between anxiety, gender, injection technique, and procedure with a higher incidence of adverse reactions. PMID:11432179

  6. Embedded CMs work with high-risk patients.

    PubMed

    2014-01-01

    Care managers embedded in primary care clinics work with patients with high-risk diagnoses and multiple visits to the emergency department or hospital. Patients are identified though risk assessments, suggestions from inpatient case management, and requests from primary care clinicians. Care managers call patients before their clinic visits, look for gaps in care and find out patients' questions and concerns, sharing the information with the treating clinicians. Care managers follow patients for four weeks after their visit, helping them meet their health care goals and follow their treatment plan.

  7. Exemestane Reduces Breast Cancer Risk in High-Risk Postmenopausal Women

    Cancer.gov

    Clinical trial results presented at the 2011 ASCO annual meeting showed that the aromatase inhibitor exemestane—used to treat early and advanced breast cancer—substantially reduced the risk of invasive breast cancer in high-risk postmenopausal women.

  8. Percutaneous implantation of the CoreValve aortic valve prosthesis in patients at high risk or rejected for surgical valve replacement: Clinical evaluation and feasibility of the procedure in the first 30 patients in the AMC-UvA.

    PubMed

    Baan, J; Yong, Z Y; Koch, K T; Henriques, J P S; Bouma, B J; de Hert, S G; van der Meulen, J; Tijssen, J G P; Piek, J J; de Mol, B A J M

    2010-01-01

    Objective. To report the feasibility, safety and efficacy of percutaneous aortic valve implantation (PAVI) with the CoreValve self-expanding aortic valve bioprosthesis in elderly patients with aortic valve stenosis who are rejected for surgery or have a high surgical risk.Methods. PAVI using the CoreValve ReValving System was performed under general anaesthesia in 30 high-risk (surgical) patients with a symptomatic severe aortic valve stenosis.Results. The patients had a mean age of 80.5+/-7.7 years, a mean aortic valve area of 0.71+/-0.19 cm(2), a peak transvalvular aortic gradient of 79+/-25 mmHg, as measured with echo Doppler, a logistic EuroSCORE of 15+/-10% and a Society of Thoracic Surgeons (STS) score of 5.2+/-2.9%. Device success was achieved in all patients and acute procedural success in 27 patients (90%). In the surviving patients, there was in a reduction of the peak aortic pressure gradient from 76+/-24 mmHg to 22+/-7 mmHg (n=24, p<0.00001) 30 days after successful device implantation. At 30 days, major adverse cardiovascular and cerebral events had occurred in seven patients (23%). This included mortality in six patients (20%), of which one death was cardiovascular. The other five non-cardiovascular deaths involved two patients who died of an exacerbation of severe pre-existent pulmonary disease and three of infectious complications.Conclusions. Percutaneous aortic valve implantation was successfully performed in our centre in highrisk patients, with a 30-day mortality of 20%. When successful, marked haemodynamic improvement and relief of symptoms was achieved. (Neth Heart J 2010;18:18-24.).

  9. Stress fractures in rheumatological practice: clinical significance and localizations.

    PubMed

    Peris, Pilar

    2002-06-01

    The objective of this study was to analyze the clinical characteristics, associated disorders, and the most common sites of stress fractures in rheumatological patients. Over a 3-year period, 35 patients with 44 stress fractures were prospectively recruited from an outpatient rheumatological department (32 postmenopausal women and three men aged 47 to 86 years, mean 70+/-10.6 years). Clinical diagnosis was established by compatible clinical and radiological data. In addition, previous skeletal fractures were recorded in all patients. Bone mass assessment was performed in 23 patients and spinal X-ray in 21. The diagnosis of osteoporosis was defined by the presence of atraumatic vertebral fractures and/or densitometric criteria (lumbar or femoral bone mass <-2.5 T score). The most frequent stress fractures were: pelvic ring (13 sacrum and eight pubic) and metatarsal (11 fractures), followed by tibia (seven fractures), calcaneus (three fractures), femur (one), and tarsal (one). Nine patients (26%) presented simultaneous stress fractures. Twenty-four patients (69%) suffered previous osteoporotic fractures, vertebral and Colles' fractures being the most frequent. Most of the evaluated patients (25 out of 30) had osteoporosis (83%). Six patients had associated disorders (glucocorticoids use in three patients, neurologic disorders in two, and rheumatoid arthritis in one). Except for the patient with a femur fracture which required internal fixation, no other clinical complications were observed after conservative treatment. In conclusion, fractures of the pelvic ring, especially sacrum, and metatarsal are the most frequent stress fractures in rheumatological practice. The association with osteoporosis and the history of prior low-trauma fractures are common in these patients.

  10. Determination of high-risk cargo

    NASA Astrophysics Data System (ADS)

    Morris, Leo A.; Smith, Douglas E.; Khan, Siraj M.

    1994-10-01

    The approach and methodology used in the determination of the type of cargo containing concealments of commercial quantities of narcotics such as cocaine and heroin is described. This high-risk cargo enters the United States through border crossings at land, seaports and airports. The volume and variety of cargos make it a complex and challenging task for the U.S. Customs Service.

  11. Guaranteed Student Loans: GAO High Risk Series.

    ERIC Educational Resources Information Center

    Comptroller General of the U.S., Washington, DC.

    As part of a larger program to identify and analyze federal programs at high risk for waste, fraud, abuse and mismanagement, this publication presents an evaluation of the Federal Family Education Loan Program (FFELP), formerly the Guaranteed Student Loan Program. The analysis argues that the program has not been successful in protecting the…

  12. Micronutrient requirements of high-risk infants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Micronutrient requirements are well-established for healthy full-term infants. However, few such recommendations exist for high-risk infants, including full-term infants with a variety of medical disorders or very preterm infants. Key micronutrients considered in this review are calcium, phosphorus,...

  13. Creating Profiles of High Risk Students.

    ERIC Educational Resources Information Center

    Higbee, Jeanne L.; Dwinell, Patricia L.

    Measures used at the Division of Developmental Studies at the University of Georgia in constructing a student profile (specifically, of high-risk college freshmen) are discussed. The areas measured concern: goals; learning styles; career exploration; stress and academic anxiety; developmental tasks; and locus of control. The goals checklist…

  14. Local cause of gingival overgrowth. Clinical and histological study.

    PubMed

    Drăghici, Emma Cristina; CrăiŢoiu, Ştefania; MercuŢ, Veronica; Scrieciu, Monica; Popescu, Sanda Mihaela; Diaconu, Oana Andreea; Oprea, Bogdan; Pascu, Roxana Maria; CrăiŢoiu, Monica Mihaela

    2016-01-01

    The overgrowth, depending on its extension, has multiple effects on the stomatognathic apparatus: functional disorders (impaired speech), difficulty in chewing and aesthetic problems but can cause significant psychological problems. We proposed this study, motivated by the relative increased frequency of the gum outgrowth, its multifactorial etiopathogeny, but especially from the point of view of the specialist practitioner, by the problems that this pathology raises not only for the functionality of the stomatognathic apparatus but also for the facial esthetics, and especially for future therapeutic attitudes needed to solve the existing pathology at this level. We conducted a clinical study and a histological one. For the clinical study, we selected 74 patients who experienced different degrees of gingival outgrowing associated with fillings, dental caries, fixed prostheses, mobile prostheses, orthodontic apparatus. Thirty gingival fragments from patients with gingival outgrowing were processed by paraffin-embedding histological technique and stained with Hematoxylin-Eosin. The morphological results obtained provide the necessary support for understanding the possibility of developing a therapeutic strategy to prevent or minimize the gum outgrowth by administering antibiotic and anti-inflammatory medications associated with medications, which shall cause the apoptosis of the fibroblasts. PMID:27516015

  15. [Combined ultrasound and roentgen localization in ESWL. Initial clinical experiences].

    PubMed

    Gschwend, J; Miller, K; Hautmann, R

    1993-03-01

    Interdisciplinary use of extracorporeal shock-wave lithotripsy with sonographic or fluoroscopic guidance has become a routine procedure in clinical practice, for both urolithiasis and cholecystolithiasis. Therefore, newly developed systems with combined locating devices are gaining in importance. A primary sonographically guided lithotripter was extended by a mobile X-ray system. The results were compared with those obtained with a first-generation lithotripter. The results show that sufficient disintegration of stones throughout the urinary tract is possible with both systems. The retreatment rate with both lithotripters was 30% when stone size was comparable. No essential differences in treatment time, shockwave energy and pain were found. The easy localisation of radiolucent stones, convenient positioning of the patient and successful localisation of ureteral stones near to the spine are advantages of the MPL 9000 X. On the other hand, the technically simpler fluoroscopy system and greater ease of electrode changing are advantages of the HM3 Lithotripter. Altogether, differences in the application of the two systems are slight and insignificant except in special cases.

  16. Perceived vertical and lateropulsion: clinical syndromes, localization, and prognosis.

    PubMed

    Brandt, T; Dieterich, M

    2000-01-01

    We present a clinical classification of central vestibular syndromes according to the three major planes of action of the vestibulo-ocular reflex: yaw, roll, and pitch. The plane-specific syndromes are determined by ocular motor, postural, and perceptual signs. Yaw plane signs are horizontal nystagmus, past pointing, rotational and lateral body falls, deviation of perceived straight-ahead to the left or right. Roll plane signs are torsional nystagmus, skew deviation, ocular torsion, tilts of head, body, and perceived vertical in a clockwise or counterclockwise direction. Pitch plane signs are upbeat/downbeat nystagmus, forward/backward tilts and falls, deviations of the perceived horizon. The thus defined vestibular syndromes allow a precise topographic analysis of brainstem lesions according to their level and side. Special emphasis is placed on the vestibular roll plane syndromes of ocular tilt reaction, lateropulsion in Wallenberg's syndrome, thalamic and cortical astasia and their association with roll plane tilt of perceived vertical. Recovery is based on a functionally significant central compensation of a vestibular tone imbalance, the mechanism of which is largely unknown. Physical therapy may facilitate this central compensation, but this has not yet been proven in prospective studies.

  17. Computed tomography guided localization of clinically occult breast carcinoma-the ''N'' skin guide

    SciTech Connect

    Kopans, D.B.; Meyer, J.E.

    1982-10-01

    Standard computed tomography (CT) can be used for the three-dimensional localization of clinically occult suspicious breast lesions whose exact position cannot be determined by standard mammographic views. A method is described that facilitates accurate preoperative needle localization using CT guidance, once the position of these lesions is defined.

  18. [DEVELOPMENT OF THE LOCAL CLINICAL PATHWAY "PREVENTION OF CARDIOVASCULAR DISEASE" (SCIENTIFIC STATEMENT AND PRACTICAL APPROACH)].

    PubMed

    Dyachuk, D D; Lysenko, I Y; Moroz, G Z; Gidzinska, I M

    2015-01-01

    An overview of scientific data on current approaches to the prevention of cardiovascular diseases has been exposed. The results of proceedings on development of the local clinical pathway "Prevention of cardiovascular disease" in the State Institution of Science "Research and Practical Center of Preventive and Clinical Medicine" State Administrative Department has been generalized. PMID:27491170

  19. Antenatal Care Utilisation and Content between Low-Risk and High-Risk Pregnant Women

    PubMed Central

    Yeoh, Ping Ling; Hornetz, Klaus; Dahlui, Maznah

    2016-01-01

    Background The purpose of antenatal care is to monitor and improve the wellbeing of the mother and foetus. The World Health Organization recommends risk-oriented strategy that includes: (i) routine care to all women, (ii) additional care for women with moderately severe diseases and complications, (iii) specialised obstetrical and neonatal care for women with severe diseases and complications. Antenatal care is concerned with adequate care in order to be effective. Measurement for adequacy of antenatal care often applies indexes that assess initiation of care and number of visits. In addition, adequacy of care content should also be assessed. Results of studies in developed settings demonstrate that women without risk factors use antenatal services more frequently than recommended. Such over-utilisation is problematic for low-resourced settings. Moreover, studies show that a substantial proportion of high-risk women had utilisation or content of care below the recommended standard. Yet studies in developing countries have seldom included a comparison between low-risk and high-risk women. The purpose of the study was therefore to assess adequacy of care and pregnancy outcomes for the different risk groups. Methods A retrospective study using a multistage sampling technique, at public-funded primary health care clinics was conducted. Antenatal utilisation level was assessed using a modified Adequacy of Prenatal Care Utilisation index that measures the timing for initiation of care and observed-to-expected visits ratio. Adequacy of antenatal care content assessed compliance to routine care based on the local guidelines. Results Intensive or “adequate-plus” antenatal care utilisation as defined by the modified index was noted in over half of the low-risk women. On the other hand, there were 26% of the high-risk women without the expected intensive utilisation. Primary- or non-educated high-risk women were less likely to have a higher antenatal care utilisation

  20. Perforated Duodenal Ulcer in High Risk Patients: Is Percutaneous Drainage Justified?

    PubMed Central

    Saber, Aly; Gad, Mohammad A; Ellabban, Gouda M

    2012-01-01

    Background: Conservative treatment was recommended as the treatment of choice in perforated acute peptic ulcer. Here, we adjunct percutaneous peritoneal drainage with nonoperative conservative treatment in high risk elderly patients with perforated duodenal ulcer. Aim: The work was to study the efficacy of percutaneous peritoneal drainage under local anesthesia supported by conservative measures in high risk elderly patients, according to the American Society of Anesthesiologists grading, with perforated duodenal ulcer. Patients and Methods: Twenty four high risk patients with age >65 years having associated medical illness with evidence of perforated duodenal ulcer. Results: The overall morbidity and mortality were comparable with those treated by conservative measures alone. Conclusion: In high risk patients with perforated peptic ulcer and established peritonitis, percutaneous peritoneal drainage under local anesthesia seems to be effective with least operative trauma and mortality rate. PMID:22393546

  1. Clinical Use of the Utrecht Applicator for Combined Intracavitary/Interstitial Brachytherapy Treatment in Locally Advanced Cervical Cancer

    SciTech Connect

    Nomden, Christel N.; Leeuw, Astrid A.C. de; Moerland, Marinus A.; Roesink, Judith M.; Tersteeg, Robbert J.H.A.; Juergenliemk-Schulz, Ina Maria

    2012-03-15

    Purpose: The aims of this study were to investigate the benefit of the Utrecht interstitial CT/MR applicator for combined intracavitary/interstitial (IC/IS) approach, using magnetic resonance imaging-guided brachytherapy, over the intracavitary approach alone in patients with locally advanced cervical cancer and to analyze the clinical use of needles. Methods and Materials: This study includes the first 20 patients treated with the new applicator. Brachytherapy consisted of two pulsed dose rate applications, and the second application was performed with the IC/IS approach. The number of needles, chosen guiding holes through the ovoids, and insertion depths were based on the dose distribution and dosimetric shortcomings of the first application (IC alone). We investigated the dosimetric gain by comparing the clinical interstitial optimized plan (IC/IS{sub clinical}) with an additionally generated optimized plan without needle use (IC{sub study}). Furthermore, we studied the relation of the inserted needles and their source loading patterns with the high-risk clinical target volume (HR-CTV). Results: A total of 54 needles (range, 1-6 per application) were applied with an average depth of 25 mm. The chosen needle positions corresponded with the location of the HR-CTV extensions. The total and individual needle treatment times per application were on average 19% (range, 4-35%) and 7% (range, 2-14%) of the implant treatment time, respectively. The total (external-beam radiotherapy + brachytherapy) D90 HR-CTV for the IC{sub study} and the IC/IS{sub clinical} were on average 79.5 (SD 7.4) Gy{sub {alpha}/{beta}10} and 83.9 (SD 6.7) Gy{sub {alpha}/{beta}10}, respectively, with an average gain of 4.4 (SD 2.3) Gy{sub {alpha}/{beta}10} for the second application. Conclusions: Needle placement was feasible in all patients and resulted in a gain in dose and better coverage of HR-CTV. Defining the location of HR-CTV protrusions and analyzing the associated needles has given us

  2. Refining Neurobehavioral Assessment of the High-Risk Infant Using the NICU Network Neurobehavioral Scale.

    PubMed

    Sullivan, Mary C; Miller, Robin J; Fontaine, Lynne Andreozzi; Lester, Barry

    2012-01-01

    Nurses caring for high-risk infants use advanced assessment skills to identify the nature of infant instability and to assure timely intervention. The NICU Network Neurobehavioral Scale (NNNS) is a comprehensive assessment of neurological integrity and behavioral function of infants at risk. Research evidence supports its validity and reliability for clinical and research use. The NNNS offers nurses a neurobehavioral assessment especially suited to high-risk and premature infants.

  3. Local alignment tool for clinical history: temporal semantic search of clinical databases.

    PubMed

    Lee, Wei-Nchih; Das, Amar K

    2010-11-13

    Data collected through electronic health records is increasingly used for clinical research purposes. Common research tasks like identifying treatment cohorts based on similar treatment histories, assessing adherence to protocol based care, or determining clinical 'best practices' can be difficult given the complex array of treatment choices and the longitudinal nature of patient care. We present a temporal sequence alignment strategy to find patients with similar treatment histories starting from their initial regimen. The algorithm relies on a user defined threshold heuristic to further reduce the search space in large clinical databases. It also uses an ontology based scoring schema to measure the distance between two clinical treatment histories. We validate the algorithm with a search for patients who are placed on a guideline recommended alternative regimen for HIV after failing initial ideal therapy. Our approach can be used to summarize patterns of care as well as predict outcomes of care.

  4. Counseling the high-risk adolescent.

    PubMed

    Busen, N H

    1992-01-01

    Interviewing and counseling high-risk adolescents provides a challenge to nurse practitioners. The problems of poverty, substance abuse, mental illness, and low self-esteem overlay other characteristics of risk, making assessment and management of the adolescent's problems complex and difficult. Survey data, obtained in this study on adolescent risk-taking, suggest that violence, aggression, and thrill-seeking behaviors are increasingly common. The finding is supported by current national statistics on adolescents. A case study is used to show the process of gathering information on home and educational settings that can provide insight into family dysfunction and specific problem behaviors.

  5. Economic value of atopic dermatitis prevention via infant formula use in high-risk Malaysian infants

    PubMed Central

    Bhanegaonkar, Abhijeet J; Horodniceanu, Erica G; Abdul Latiff, Amir Hamzah; Woodhull, Sanjay; Khoo, Phaik Choo; Detzel, Patrick; Ji, Xiang

    2015-01-01

    Background Breastfeeding is best for infants and the World Health Organization recommends exclusive breastfeeding for at least the first 6 months of life. For those who are unable to be breastfed, previous studies demonstrate that feeding high-risk infants with hydrolyzed formulas instead of cow's milk formula (CMF) may decrease the risk of atopic dermatitis (AD). Objective To estimate the economic impact of feeding high-risk, not exclusively breastfed, urban Malaysian infants with partiallyhydrolyzed whey-based formula (PHF-W) instead of CMF for the first 17 weeks of life as an AD risk reduction strategy. Methods A cohort Markov model simulated the AD incidence and burden from birth to age 6 years in the target population fed with PHF-W vs. CMF. The model integrated published clinical and epidemiologic data, local cost data, and expert opinion. Modeled outcomes included AD-risk reduction, time spent post AD diagnosis, days without AD flare, quality-adjusted life years (QALYs), and costs (direct and indirect). Outcomes were discounted at 3% per year. Costs are expressed in Malaysian Ringgit (MYR; MYR 1,000 = United States dollar [US $]316.50). Results Feeding a high-risk infant PHF-W vs. CMF resulted in a 14% point reduction in AD risk (95% confidence interval [CI], 3%-23%), a 0.69-year (95% CI, 0.25-1.10) reduction in time spent post-AD diagnosis, additional 38 (95% CI, 2-94) days without AD flare, and an undiscounted gain of 0.041 (95% CI, 0.007-0.103) QALYs. The discounted AD-related 6-year cost estimates when feeding a high-risk infant with PHF-W were MYR 1,758 (US $556) (95% CI, MYR 917-3,033) and with CMF MYR 2,871 (US $909) (95% CI, MYR 1,697-4,278), resulting in a per-child net saving of MYR 1,113 (US $352) (95% CI, MYR 317-1,884) favoring PHF-W. Conclusion Using PHF-W instead of CMF in this population is expected to result in AD-related costs savings. PMID:25938073

  6. Long-Term Outcome for Clinically Localized Prostate Cancer Treated With Permanent Interstitial Brachytherapy

    SciTech Connect

    Taira, Al V.; Merrick, Gregory S.; Butler, Wayne M.; Galbreath, Robert W.; Lief, Jonathan; Adamovich, Edward; Wallner, Kent E.

    2011-04-01

    Purpose: To present the largest series of prostate cancer brachytherapy patients treated with modern brachytherapy techniques and postimplant day 0 dosimetric evaluation. Methods and Materials: Between April 1995 and July 2006, 1,656 consecutive patients were treated with permanent interstitial brachytherapy. Risk group stratification was carried out according to the Mt. Sinai guidelines. Median follow-up was 7.0 years. The median day 0 minimum dose covering at least 90% of the target volume was 118.8% of the prescription dose. Cause of death was determined for each deceased patient. Multiple clinical, treatment, and dosimetric parameters were evaluated for impact on the evaluated survival parameters. Results: At 12 years, biochemical progression-free survival (bPFS), cause-specific survival (CSS), and overall survival (OS) for the entire cohort was 95.6%, 98.2%, and 72.6%, respectively. For low-, intermediate-, and high-risk patients, bPFS was 98.6%, 96.5%, and 90.5%; CSS was 99.8%, 99.3%, and 95.2%; and OS was 77.5%, 71.1%, and 69.2%, respectively. For biochemically controlled patients, the median posttreatment prostate-specific antigen (PSA) concentration was 0.02 ng/ml. bPFS was most closely related to percent positive biopsy specimens and risk group, while Gleason score was the strongest predictor of CSS. OS was best predicted by patient age, hypertension, diabetes, and tobacco use. At 12 years, biochemical failure and cause-specific mortality were 1.8% and 0.2%, 5.1% and 2.1%, and 10.4% and 7.1% for Gleason scores 5 to 6 and 7 and {>=}8, respectively. Conclusions: Excellent long-term outcomes are achievable with high-quality brachytherapy for low-, intermediate-, and high-risk patients. These results compare favorably to alternative treatment modalities including radical prostatectomy.

  7. Faith-Based Institutions and High-Risk Youth. First Report to the Field. Field Report Series.

    ERIC Educational Resources Information Center

    Trulear, Harold Dean

    Building on a survey of the role of religious institutions in programs for high-risk youth and consultations with experts in the field, a field demonstration project was implemented to test strategies for using religious institutions to anchor local partnerships aimed at high-risk youth. The partnerships were designed to address the developmental…

  8. Effect of Family History on Outcomes in Patients Treated With Definitive Brachytherapy for Clinically Localized Prostate Cancer

    SciTech Connect

    Peters, Christopher A. Stock, Richard G.; Blacksburg, Seth R.; Stone, Nelson N.

    2009-01-01

    Purpose: To determine the impact familial prostate cancer has on prognosis in men treated with brachytherapy for clinically localized prostate cancer. Methods and Materials: A total of 1,738 consecutive patients with prostate cancer (cT1-3, N0/X, M0) received low-dose-rate brachytherapy alone or in combination with external beam radiation therapy or hormone ablation from 1992 to 2005. The primary end-point was freedom from biochemical failure (FFBF) using the Phoenix definition. Minimum follow-up was 2 years and the median follow-up was 60 months (range, 24-197 months). Results: A total of 187 of 1,738 men (11%) had a family history of prostate cancer in a first-degree relative. For the low-risk patients, both groups had similar actuarial 5-year FFBF (97.2% vs. 95.5%, p = 0.516). For intermediate-risk patients, there was a trend toward improved biochemical control in men positive for family history (5-yr FFBF 100% vs. 93.6%, p = 0.076). For the high-risk patients, men with a positive family history had similar 5-year FFBF (92.8% vs. 85.2%, p = 0.124). On multivariate analysis, family history was not significant; use of hormones, high biologic effective dose, initial prostate-specific antigen value, and Gleason score were the significant variables predicting biochemical control. Conclusions: This is the first study to examine the relationship of familial prostate cancer and outcomed in men treated with brachytherapy alone or in combination therapy. Men with a positive family history have clinicopathologic characteristics and biochemical outcomes similar to those with sporadic disease.

  9. Hypofractionated Intensity-Modulated Radiotherapy (70 Gy at 2.5 Gy Per Fraction) for Localized Prostate Cancer: Cleveland Clinic Experience

    SciTech Connect

    Kupelian, Patrick A. . E-mail: patrick.kupelian@orhs.org; Willoughby, Twyla R.; Reddy, Chandana A.; Klein, Eric A.; Mahadevan, Arul

    2007-08-01

    Purpose: To study the outcomes in patients treated for localized prostate cancer with 70 Gy delivered at 2.5-Gy/fraction within 5 weeks. Methods and Materials: The study sample included all 770 consecutive patients with localized prostate cancer treated with hypofractionated intensity-modulated radiotherapy at the Cleveland Clinic between 1998 and 2005. The median follow-up was 45 months (maximum, 86). Both American Society for Therapeutic Radiology and Oncology (ASTRO) biochemical failure definition and the alternate nadir + 2 ng/mL definition were used. Results: The overall 5-year ASTRO biochemical relapse-free survival rate was 82% (95% confidence interval, 79-85%), and the 5-year nadir + 2 ng/mL rate was 83% (95% confidence interval, 79-86%). For patients with low-risk, intermediate-risk, and high-risk disease, the 5-year ASTRO rate was 95%, 85%, and 68%, respectively. The 5-year nadir + 2 ng/mL rate for patients with low-, intermediate-, and high-risk disease was 94%, 83%, and 72%, respectively. The Radiation Therapy Oncology Group acute rectal toxicity scores were 0 in 51%, 1 in 40%, and 2 in 9% of patients. The acute urinary toxicity scores were 0 in 33%, 1 in 48%, 2 in 18%, and 3 in 1% of patients. The late rectal toxicity scores were 0 in 89.6%, 1 in 5.9%, 2 in 3.1%, 3 in 1.3%, and 4 in 0.1% (1 patient). The late urinary toxicity scores were 0 in 90.5%, 1 in 4.3%, 2 in 5.1%, and 3 in 0.1% (1 patient). Conclusion: The outcomes after high-dose hypofractionation were acceptable in the entire cohort of patients treated with the schedule of 70 at 2.5 Gy/fraction.

  10. Alterations in the hippocampus and thalamus in individuals at high risk for psychosis

    PubMed Central

    Harrisberger, Fabienne; Buechler, Roman; Smieskova, Renata; Lenz, Claudia; Walter, Anna; Egloff, Laura; Bendfeldt, Kerstin; Simon, Andor E; Wotruba, Diana; Theodoridou, Anastasia; Rössler, Wulf; Riecher-Rössler, Anita; Lang, Undine E; Heekeren, Karsten; Borgwardt, Stefan

    2016-01-01

    Reduction in hippocampal volume is a hallmark of schizophrenia and already present in the clinical high-risk state. Nevertheless, other subcortical structures, such as the thalamus, amygdala and pallidum can differentiate schizophrenia patients from controls. We studied the role of hippocampal and subcortical structures in clinical high-risk individuals from two cohorts. High-resolution T1-weighted structural MRI brain scans of a total of 91 clinical high-risk individuals and 64 healthy controls were collected in two centers. The bilateral volume of the hippocampus, the thalamus, the caudate, the putamen, the pallidum, the amygdala, and the accumbens were automatically segmented using FSL-FIRST. A linear mixed-effects model and a prospective meta-analysis were applied to assess group-related volumetric differences. We report reduced hippocampal and thalamic volumes in clinical high-risk individuals compared to healthy controls. No volumetric alterations were detected for the caudate, the putamen, the pallidum, the amygdala, or the accumbens. Moreover, we found comparable medium effect sizes for group-related comparison of the thalamus in the two analytical methods. These findings underline the relevance of specific alterations in the hippocampal and subcortical volumes in the high-risk state. Further analyses may allow hippocampal and thalamic volumes to be used as biomarkers to predict psychosis. PMID:27738647

  11. Noninvasive Cerebral Perfusion Imaging in High-Risk Neonates

    PubMed Central

    Goff, Donna A.; Buckley, Erin M.; Durduran, Turgut; Wang, Jiongjong; Licht, Daniel J.

    2010-01-01

    Advances in medical and surgical care of the high-risk neonate have led to increased survival. A significant number of these neonates suffer from neurodevelopmental delays and failure in school. The focus of clinical research has shifted to understanding events contributing to neurological morbidity in these patients. Assessing changes in cerebral oxygenation and regulation of cerebral blood flow (CBF) is important in evaluating the status of the central nervous system. Traditional CBF imaging methods fail for both ethical and logistical reasons. Optical near infrared spectroscopy (NIRS) is increasingly being used for bedside monitoring of cerebral oxygenation and blood volume in both very low birth weight infants and neonates with congenital heart disease. Although trends in CBF may be inferred from changes in cerebral oxygenation and/or blood volume, NIRS does not allow a direct measure of CBF in these populations. Two relatively new modalities, arterial spin-labeled perfusion magnetic resonance imaging and optical diffuse correlation spectroscopy, provide direct, noninvasive measures of cerebral perfusion suitable for the high-risk neonates. Herein we discuss the instrumentation, applications, and limitations of these noninvasive imaging techniques for measuring and/or monitoring CBF. PMID:20109972

  12. Proton Radiotherapy for High-Risk Pediatric Neuroblastoma: Early Outcomes and Dose Comparison

    SciTech Connect

    Hattangadi, Jona A.; Rombi, Barbara; Yock, Torunn I.; Broussard, George; Friedmann, Alison M.; Huang, Mary; Chen, Yen-Lin E.; Lu, Hsiao-Ming; Kooy, Hanne; MacDonald, Shannon M.

    2012-07-01

    Purpose: To report the early outcomes for children with high-risk neuroblastoma treated with proton radiotherapy (RT) and to compare the dose distributions for intensity-modulated photon RT (IMRT), three-dimensional conformal proton RT (3D-CPT), and intensity-modulated proton RT to the postoperative tumor bed. Methods and Materials: All patients with high-risk (International Neuroblastoma Staging System Stage III or IV) neuroblastoma treated between 2005 and 2010 at our institution were included. All patients received induction chemotherapy, surgical resection of residual disease, high-dose chemotherapy with stem cell rescue, and adjuvant 3D-CPT to the primary tumor sites. The patients were followed with clinical examinations, imaging, and laboratory testing every 6 months to monitor disease control and side effects. IMRT, 3D-CPT, and intensity-modulated proton RT plans were generated and compared for a representative case of adjuvant RT to the primary tumor bed followed by a boost. Results: Nine patients were treated with 3D-CPT. The median age at diagnosis was 2 years (range 10 months to 4 years), and all patients had Stage IV disease. All patients had unfavorable histologic characteristics (poorly differentiated histologic features in 8, N-Myc amplification in 6, and 1p/11q chromosomal abnormalities in 4). The median tumor size at diagnosis was 11.4 cm (range 7-16) in maximal dimension. At a median follow-up of 38 months (range 11-70), there were no local failures. Four patients developed distant failure, and, of these, two died of disease. Acute side effects included Grade 1 skin erythema in 5 patients and Grade 2 anorexia in 2 patients. Although comparable target coverage was achieved with all three modalities, proton therapy achieved substantial normal tissue sparing compared with IMRT. Intensity-modulated proton RT allowed additional sparing of the kidneys, lungs, and heart. Conclusions: Preliminary outcomes reveal excellent local control with proton therapy

  13. Clinical Case Registries: Simultaneous Local and National Disease Registries for Population Quality Management

    PubMed Central

    Backus, Lisa I.; Gavrilov, Sergey; Loomis, Timothy P.; Halloran, James P.; Phillips, Barbara R.; Belperio, Pamela S.; Mole, Larry A.

    2009-01-01

    The Department of Veterans Affairs (VA) has a system-wide, patient-centric electronic medical record system (EMR) within which the authors developed the Clinical Case Registries (CCR) to support population-centric delivery and evaluation of VA medical care. To date, the authors have applied the CCR to populations with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). Local components use diagnosis codes and laboratory test results to identify patients who may have HIV or HCV and support queries on local care delivery with customizable reports. For each patient in a local registry, key EMR data are transferred via HL7 messaging to a single national registry. From 128 local registry systems, over 60,000 and 320,000 veterans in VA care have been identified as having HIV and HCV, respectively, and entered in the national database. Local and national reports covering demographics, resource usage, quality of care metrics and medication safety issues have been generated. PMID:19717794

  14. Dermatofibrosarcoma protuberans, a rare but locally aggressive tumor on finger: clinical and aeromedical considerations

    PubMed Central

    Chiang, Kwo-Tsao; Lee, Shih-Yu; Chu, Hsin

    2015-01-01

    Abstract Dermatofibrosarcoma protuberans (DFSP) is a rare, slow growing, locally infiltrative tumor of intermediate malignancy. It is mostly found on the trunk and head, rarely on hands. The course of evaluation and treatment of a young pilot with DFSP on left middle finger is reported. The clinical issues and aeromedical considerations of this rare tumor is discussed. PMID:27252960

  15. The Number of High-Risk Factors and the Risk of Prostate Cancer-Specific Mortality After Brachytherapy: Implications for Treatment Selection

    SciTech Connect

    Wattson, Daniel A.; Chen Minghui; Moul, Judd W.; Moran, Brian J.; Dosoretz, Daniel E.; Robertson, Cary N.; Polascik, Thomas J.; Braccioforte, Michelle H.; Salenius, Sharon A.; D'Amico, Anthony V.

    2012-04-01

    Purpose: To determine whether an increasing number of high-risk factors is associated with higher prostate cancer-specific mortality (PCSM) among men treated with brachytherapy (BT)-based treatment, and whether supplemental therapy has an impact on this risk. Methods and Materials: We analyzed the cases of 2234 men with localized prostate cancer treated between 1991 and 2007 with low-dose rate BT monotherapy (n = 457) or BT with supplemental external-beam radiotherapy (EBRT, n = 229), androgen suppression therapy (AST, n = 424), or both (n = 1124). All men had at least one high-risk factor (prostate-specific antigen >20 ng/mL, biopsy Gleason score 8-10, or clinical stage {>=}T2c). Competing-risks multivariable regressions were performed to determine whether the presence of at least two high-risk factors was associated with an increased risk of PCSM, with adjustment for age, comorbidity, and the type of supplemental treatment. Results: The median follow-up time was 4.3 years. The number of men with at least two high-risk factors was highest in the group treated with BT, EBRT, and AST (21%), followed by BT plus EBRT or AST (13%), and BT alone (8%) (p{sub trend} < 0.001). The adjusted hazard ratio (AHR) for PCSM for those with at least two high-risk factors (as compared with one) was 4.8 (95% confidence interval [CI], 2.8-8.0; p < 0.001). The use of both supplemental EBRT and AST was associated with a decreased risk of PCSM (AHR 0.5; 95% CI, 0.2-0.9; p = 0.03) compared with BT alone. When the high-risk factors were analyzed separately, Gleason score 8-10 was most significantly associated with increased PCSM (AHR 6.2; 95% CI, 3.5-11.2; p < 0.001). Conclusions: Men with high-risk prostate adenocarcinoma treated with BT have decreased PCSM if they receive trimodailty therapy that includes EBRT and AST. This benefit is likely most important in men with multiple determinants of high risk.

  16. Clinical and Radiographic Evaluation of Immediate Loaded Dental Implants With Local Application of Melatonin: A Preliminary Randomized Controlled Clinical Trial.

    PubMed

    El-Gammal, Mona Y; Salem, Ahmed S; Anees, Mohamed M; Tawfik, Mohamed A

    2016-04-01

    Immediate loading of dental implants in situations where low bone density exist, such as the posterior maxillary region, became possible recently after the introduction of biomimetic agents. This 1-year preliminary clinical trial was carried out to clinically and radiographically evaluate immediate-loaded 1-piece implants with local application of melatonin in the osteotomy site as a biomimetic material. 14 patients with missing maxillary premolars were randomized to receive 14 implants of 1-piece type that were subjected to immediate loading after 2 weeks of initial placement. Group I included 7 implants with acid-etched surface while group II included 7 implants with acid-etched surface combined with local application of melatonin gel at the osteotomy site. Patients were recalled for follow up at 1, 3, 6, and 12 months after loading. All implants were considered successful after 12 months of follow-up. Significant difference (P < 0.05) was found between both groups at 1 month of implant loading when considering the implant stability. At 1 and 3 months there were significant differences in the marginal bone level between the 2 groups. These results suggest that the local application of melatonin at the osteotomy site is associated with good stability and minimal bone resorption. However, more studies for longer follow-up periods are required to confirm the effect of melatonin hormone on osseointegration of dental implants.

  17. Easy and fast detection and genotyping of high-risk human papillomavirus by dedicated DNA microarrays.

    PubMed

    Albrecht, Valérie; Chevallier, Anne; Magnone, Virginie; Barbry, Pascal; Vandenbos, Fanny; Bongain, André; Lefebvre, Jean-Claude; Giordanengo, Valérie

    2006-11-01

    Persistent cervical high-risk human papillomavirus (HPV) infection is correlated with an increased risk of developing a high-grade cervical intraepithelial lesion. A two-step method was developed for detection and genotyping of high-risk HPV. DNA was firstly amplified by asymmetrical PCR in the presence of Cy3-labelled primers and dUTP. Labelled DNA was then genotyped using DNA microarray hybridization. The current study evaluated the technical efficacy of laboratory-designed HPV DNA microarrays for high-risk HPV genotyping on 57 malignant and non-malignant cervical smears. The approach was evaluated for a broad range of cytological samples: high-grade squamous intraepithelial lesions (HSIL), low-grade squamous intraepithelial lesions (LSIL) and atypical squamous cells of high-grade (ASC-H). High-risk HPV was also detected in six atypical squamous cells of undetermined significance (ASC-US) samples; among them only one cervical specimen was found uninfected, associated with no histological lesion. The HPV oligonucleotide DNA microarray genotyping detected 36 infections with a single high-risk HPV type and 5 multiple infections with several high-risk types. Taken together, these results demonstrate the sensitivity and specificity of the HPV DNA microarray approach. This approach could improve clinical management of patients with cervical cytological abnormalities. PMID:16879879

  18. High risk factors of pancreatic carcinoma.

    PubMed

    Camara, Soriba Naby; Yin, Tao; Yang, Ming; Li, Xiang; Gong, Qiong; Zhou, Jing; Zhao, Gang; Yang, Zhi-Yong; Aroun, Tajoo; Kuete, Martin; Ramdany, Sonam; Camara, Alpha Kabinet; Diallo, Aissatou Taran; Feng, Zhen; Ning, Xin; Xiong, Jiong-Xin; Tao, Jing; Qin, Qi; Zhou, Wei; Cui, Jing; Huang, Min; Guo, Yao; Gou, Shan-Miao; Wang, Bo; Liu, Tao; Olivier, Ohoya Etsaka Terence; Conde, Tenin; Cisse, Mohamed; Magassouba, Aboubacar Sidiki; Ballah, Sneha; Keita, Naby Laye Moussa; Souare, Ibrahima Sory; Toure, Aboubacar; Traore, Sadamoudou; Balde, Abdoulaye Korse; Keita, Namory; Camara, Naby Daouda; Emmanuel, Dusabe; Wu, He-Shui; Wang, Chun-You

    2016-06-01

    Over the past decades, cancer has become one of the toughest challenges for health professionals. The epidemiologists are increasingly directing their research efforts on various malignant tumor worldwide. Of note, incidence of cancers is on the rise more quickly in developed countries. Indeed, great endeavors have to be made in the control of the life-threatening disease. As we know it, pancreatic cancer (PC) is a malignant disease with the worst prognosis. While little is known about the etiology of the PC and measures to prevent the condition, so far, a number of risk factors have been identified. Genetic factors, pre-malignant lesions, predisposing diseases and exogenous factors have been found to be linked to PC. Genetic susceptibility was observed in 10% of PC cases, including inherited PC syndromes and familial PC. However, in the remaining 90%, their PC might be caused by genetic factors in combination with environmental factors. Nonetheless, the exact mechanism of the two kinds of factors, endogenous and exogenous, working together to cause PC remains poorly understood. The fact that most pancreatic neoplasms are diagnosed at an incurable stage of the disease highlights the need to identify risk factors and to understand their contribution to carcinogenesis. This article reviews the high risk factors contributing to the development of PC, to provide information for clinicians and epidemiologists.

  19. High risk groups in oil shale workforce

    SciTech Connect

    Gratt, L.B.; Perry, B.W.; Marine, W.M.; Savitz, D.A.

    1984-04-01

    The workforce risks of a hypothetical one million barrels-per-day oil shale industry were estimated. The risks for the different workforce segments were compared and high risk groups were identified. Accidents and injuries were statistically described by rates for fatalities, for accidents with days lost from work, and for accidents with no days lost from work. Workforce diseases analyzed were cancers, silicosia, pneumoconiosis, chronic bronchitis, chronic airway obstruction, and high frequency hearing loss. A comparison of the workforce groups under different risk measures (occurrence, fatality, and life-loss expectancy) was performed. The miners represented the group with the largest fatality and the most serious accident rate, although the estimated rates were below the average industry-wide underground mining experience. Lung disease from inhalation exposure of about the nuisance dust threshold limit value presents a significant risk for future concerns. If future environmental dust exposure is at the 100 ..mu..g/m/sup 3/ alpha-quartz level, safety improvements in the mining sector are of prime importance to reduce the oil shale worker's life-loss expectancy. 11 references, 1 figure, 11 tables.

  20. High risk factors of pancreatic carcinoma.

    PubMed

    Camara, Soriba Naby; Yin, Tao; Yang, Ming; Li, Xiang; Gong, Qiong; Zhou, Jing; Zhao, Gang; Yang, Zhi-Yong; Aroun, Tajoo; Kuete, Martin; Ramdany, Sonam; Camara, Alpha Kabinet; Diallo, Aissatou Taran; Feng, Zhen; Ning, Xin; Xiong, Jiong-Xin; Tao, Jing; Qin, Qi; Zhou, Wei; Cui, Jing; Huang, Min; Guo, Yao; Gou, Shan-Miao; Wang, Bo; Liu, Tao; Olivier, Ohoya Etsaka Terence; Conde, Tenin; Cisse, Mohamed; Magassouba, Aboubacar Sidiki; Ballah, Sneha; Keita, Naby Laye Moussa; Souare, Ibrahima Sory; Toure, Aboubacar; Traore, Sadamoudou; Balde, Abdoulaye Korse; Keita, Namory; Camara, Naby Daouda; Emmanuel, Dusabe; Wu, He-Shui; Wang, Chun-You

    2016-06-01

    Over the past decades, cancer has become one of the toughest challenges for health professionals. The epidemiologists are increasingly directing their research efforts on various malignant tumor worldwide. Of note, incidence of cancers is on the rise more quickly in developed countries. Indeed, great endeavors have to be made in the control of the life-threatening disease. As we know it, pancreatic cancer (PC) is a malignant disease with the worst prognosis. While little is known about the etiology of the PC and measures to prevent the condition, so far, a number of risk factors have been identified. Genetic factors, pre-malignant lesions, predisposing diseases and exogenous factors have been found to be linked to PC. Genetic susceptibility was observed in 10% of PC cases, including inherited PC syndromes and familial PC. However, in the remaining 90%, their PC might be caused by genetic factors in combination with environmental factors. Nonetheless, the exact mechanism of the two kinds of factors, endogenous and exogenous, working together to cause PC remains poorly understood. The fact that most pancreatic neoplasms are diagnosed at an incurable stage of the disease highlights the need to identify risk factors and to understand their contribution to carcinogenesis. This article reviews the high risk factors contributing to the development of PC, to provide information for clinicians and epidemiologists. PMID:27376795

  1. Machine-learning model observer for detection and localization tasks in clinical SPECT-MPI

    NASA Astrophysics Data System (ADS)

    Parages, Felipe M.; O'Connor, J. Michael; Pretorius, P. Hendrik; Brankov, Jovan G.

    2016-03-01

    In this work we propose a machine-learning MO based on Naive-Bayes classification (NB-MO) for the diagnostic tasks of detection, localization and assessment of perfusion defects in clinical SPECT Myocardial Perfusion Imaging (MPI), with the goal of evaluating several image reconstruction methods used in clinical practice. NB-MO uses image features extracted from polar-maps in order to predict lesion detection, localization and severity scores given by human readers in a series of 3D SPECT-MPI. The population used to tune (i.e. train) the NB-MO consisted of simulated SPECT-MPI cases - divided into normals or with lesions in variable sizes and locations - reconstructed using filtered backprojection (FBP) method. An ensemble of five human specialists (physicians) read a subset of simulated reconstructed images, and assigned a perfusion score for each region of the left-ventricle (LV). Polar-maps generated from the simulated volumes along with their corresponding human scores were used to train five NB-MOs (one per human reader), which are subsequently applied (i.e. tested) on three sets of clinical SPECT-MPI polar maps, in order to predict human detection and localization scores. The clinical "testing" population comprises healthy individuals and patients suffering from coronary artery disease (CAD) in three possible regions, namely: LAD, LcX and RCA. Each clinical case was reconstructed using three reconstruction strategies, namely: FBP with no SC (i.e. scatter compensation), OSEM with Triple Energy Window (TEW) SC method, and OSEM with Effective Source Scatter Estimation (ESSE) SC. Alternative Free-Response (AFROC) analysis of perfusion scores shows that NB-MO predicts a higher human performance for scatter-compensated reconstructions, in agreement with what has been reported in published literature. These results suggest that NB-MO has good potential to generalize well to reconstruction methods not used during training, even for reasonably dissimilar datasets (i

  2. Are Men at High Risk for Osteoporosis Underscreened? A Quality Improvement Project

    PubMed Central

    Jain, Samta; Bilori, Bilori; Gupta, Amit; Spanos, Pete; Singh, Mamta

    2016-01-01

    Context: Osteoporosis is a major cause of morbidity and mortality in both men and women. The mortality rate in men within 1 year of hip fracture is 37.5%, which is 51% higher than in women. Although clear guidelines exist for osteoporosis screening in women, these are less clear for men. The available guidelines recommend screening high-risk men; however, screening does not appear to be a standard practice. Objective: To increase screening rates of osteoporosis in high-risk men in our primary care clinic by 50%. Design: The screening rate of osteoporosis was determined in high-risk male veterans more than 50 years of age enrolled in the resident physician- and nurse practitioner-staffed primary care clinics at a Veterans Affairs Medical Center in Cleveland, OH. High-risk factors included prolonged use of steroids; hypogonadism; and autoimmune diseases such as rheumatoid arthritis, inflammatory bowel disease, and systemic lupus erythematosus, which are known to be associated with osteoporosis. We surveyed health care professional trainees and nurses to explore their barriers to screening for osteoporosis in high-risk men. Main Outcome Measures: After creating awareness about the importance of this condition among the health care professionals, we analyzed whether this education had any impact on the screening rate. Results: The baseline screening rate in high-risk men was 11%. After phased surveys and awareness building, the screening rate increased to 20%. Conclusion: Osteoporosis in high-risk men is under-screened. Creating more awareness about the impact of this condition among health professional trainees and nurses can lead to improved screening rates. PMID:26824964

  3. Stereotactic Body Radiotherapy for Clinically Localized Prostate Cancer: Toxicity and Biochemical Disease-Free Outcomes from a Multi-Institutional Patient Registry

    PubMed Central

    Sharma, Sanjeev; Shumway, Richard; Perry, David; Bydder, Sean; Simpson, C. Kelley; D'Ambrosio, David

    2015-01-01

    Objectives: To report on initial patient characteristics, treatment practices, toxicity, and early biochemical disease-free survival (bDFS) of localized prostate cancer treated with stereotactic body radiotherapy (SBRT) and enrolled in the RSSearch® Patient Registry. Methods: A retrospective analysis was conducted on patients with clinically localized prostate cancer enrolled in RSSearch® from June 2006 - January 2015. Patients were classified as low-risk (PSA ≤ 10 ng/ml, T1c-T2a, Gleason score ≤ 6), intermediate-risk (PSA 10.1 - 20 ng/ml, T2b-T2c, or Gleason 7), or high-risk (PSA > 20 ng/ml, T3 or Gleason ≥ 8). Toxicity was reported using Common Toxicity Criteria for Adverse Events, version 3. Biochemical failure was assessed using the Phoenix definition (nadir + 2 ng/ml). The Kaplan-Meier analysis was used to calculate bDFS and association of patient and tumor characteristics with the use of SBRT. Results: Four hundred thirty-seven patients (189 low, 215 intermediate, and 33 high-risk) at a median of 69 years (range: 48-88) received SBRT at 17 centers. Seventy-eight percent of patients received 36.25 Gy/5 fractions, 13% received 37 Gy/5 fractions, 6% received 35 Gy/5 fractions, 3% received 38 Gy/4 fractions, and 5% received a boost dose of 19.5-29 Gy following external beam radiation therapy. Median follow-up was 20 months (range: 1–64 months). Genitourinary (GU) and gastrointestinal (GI) toxicities were minimal, with no acute or late Grade 3+ GU or GI toxicity. Late Grade 1 and 2 urinary frequency was 25% and 8%. Late Grade 1 and 2 proctitis was 3% and 2%. Median PSA decreased from 5.8 ng/ml (range: 0.3-43) to 0.88, 0.4, and 0.3 ng/ml at one, two, and three years. Two-year bDFS for all patients was 96.1%. Two-year bDFS was 99.0%, 94.5%, and 89.8% for low, intermediate, and high-risk patients (p < 0.0001). Two-year bDFS was 99.2%, 93.2%, and 90.4% for Gleason ≤ 6, Gleason 7, and Gleason ≥ 8 (p < 0.0001). Two-year bDFS was 96.4%, 97

  4. Effects of Comprehensive, Multiple High-Risk Behaviors Prevention Program on High School Students

    ERIC Educational Resources Information Center

    Collier, Crystal

    2013-01-01

    The purpose of this mixed methods study was to examine the effect of a multiple high-risk behaviors prevention program applied comprehensively throughout an entire school-system involving universal, selective, and indicated levels of students at a local private high school during a 4-year period. The prevention program was created based upon the…

  5. Family Empowerment Intervention: An Innovative Service for High-Risk Youths and Their Families.

    ERIC Educational Resources Information Center

    Dembo, Richard; Schmeidler, James

    This book provides a detailed review of a National Institute on Drug Abuse-funded, long-term clinical trial of the Family Empowerment Intervention (FEI). FEI is a systems-oriented, low-cost intervention delivered in the home by trained nontherapists for high-risk youths who have been arrested and their families. The subjects were a group of over…

  6. Influenza vaccination in children at high risk of respiratory disease.

    PubMed

    Patria, Maria Francesca; Tagliabue, Claudia; Longhi, Benedetta; Esposito, Susanna

    2013-05-01

    Chronic respiratory diseases (CRDs) are a heterogeneous group of diseases that can affect the pediatric population and health authorities throughout the world recommend influenza vaccination because of the significant risk of influenza-related complications. However, despite this recommendation, vaccine coverage is generally unsatisfactory. The aim of this review is to analyze the impact of influenza on children at high risk of respiratory disease, and the immunogenicity, safety and efficacy of influenza vaccination in such children. The results show that there is a significant risk of influenza-related complications in preterm neonates and infants, in whom influenza vaccines are immunogenic and safe (although their efficacy has not been specifically studied). There are conflicting data concerning the effect of influenza infection on asthma morbidity in children, and whether or not influenza vaccination helps to prevent asthma exacerbations. Recent data provide no evidence that influenza is more frequent in patients with cystic fibrosis than in healthy subjects, or that it is responsible for increased lower respiratory tract morbidity. The lack of any clear correlate of protection suggests that future studies should also consider the efficacy of the different influenza vaccines and not only evaluate them in terms of immunogenicity. Furthermore, there is a need for clinical studies to assess the effectiveness of the available vaccines in patients with other rare CRDs and other chronic underlying diseases with possibly severe respiratory involvement. It is also important to determine whether children with recurrent respiratory tract infections should be included in the list of those for whom influenza vaccination is recommended. In the meantime, given the increasing evidence of the burden of influenza on the population as a whole and the benefits associated with vaccination, annual influenza vaccinations should be recommended for all children at high risk of

  7. Local and systemic immune response in pigs during subclinical and clinical swine influenza infection.

    PubMed

    Pomorska-Mól, M; Kwit, K; Markowska-Daniel, I; Kowalski, C; Pejsak, Z

    2014-10-01

    Local and systemic immune responses in pigs intranasally (IN) and intratracheally (IT) inoculated with swine influenza virus (SIV) were studied. No clinical signs were observed in IN-inoculated pigs, while IT-inoculated pigs developed typical signs of influenza. Significantly higher titres of specific antibodies and changes of haematological parameters were found only in IT-inoculated pigs. Because positive correlations between viral titre, local cytokine concentration, and lung pathology have been observed, we hypothesise that both viral load and the local secretion of cytokines play a role in the induction of lung lesions. It could be that a higher replication of SIV stimulates immune cells to secrete higher amounts of cytokines. The results of the present study indicate that pathogenesis of SIV is dependent on both, the damage caused to the lung parenchyma directly by virus, and the effects on the cells of the host's immune system.

  8. Preoperative chemoradiotherapy followed by local excision in clinical T2N0 rectal cancer

    PubMed Central

    Shin, Young Seob; Yoon, Yong sik; Lim, Seok-Byung; Yu, Chang Sik; Kim, Tae Won; Chang, Heung Moon; Park, Jin-hong; Ahn, Seung Do; Lee, Sang-Wook; Choi, Eun Kyung; Kim, Jin Cheon; Kim, Jong Hoon

    2016-01-01

    Purpose To investigate whether preoperative chemoradiotherapy (PCRT) followed by local excision (LE) is feasible approach in clinical T2N0 rectal cancer patients. Materials and Methods Patients who received PCRT and LE because of clinical T2 rectal cancer within 7 cm from anal verge between January 2006 and June 2014 were retrospectively analyzed. LE was performed in case of a good clinical response after PCRT. Patients’ characteristics, treatment record, tumor recurrence, and treatment-related complications were reviewed at a median follow-up of 49 months. Results All patients received transanal excision or transanal minimally invasive surgery. Of 34 patients, 19 patients (55.9%) presented pathologic complete response (pCR). The 3-year local recurrence-free survival and disease free-survival were 100.0% and 97.1%, respectively. There was no recurrence among the patients with pCR. Except for 1 case of grade 4 enterovesical fistula, all other late complications were mild and self-limiting. Conclusion PCRT followed by an LE might be feasible as an alternative to total mesorectal excision in good responders with clinical T2N0 distal rectal cancer. PMID:27730804

  9. Attention-Deficit/Hyperactivity Disorder-Specific Stimulant Misuse, Mood, Anxiety, and Stress in College-Age Women at High Risk for or with Eating Disorders

    ERIC Educational Resources Information Center

    Gibbs, Elise L.; Kass, Andrea E.; Eichen, Dawn M.; Fitzsimmons-Craft, Ellen E.; Trockel, Mickey; Wilfley, Denise E.; Taylor, C. Barr

    2016-01-01

    Objective: To examine the misuse of attention-deficit/hyperactivity disorder (ADHD)-specific stimulants in a college population at high risk for or with clinical or subclinical eating disorders. Participants: Four hundred forty-eight college-age women aged 18-25 at high risk for or with a clinical or subclinical eating disorder. Methods:…

  10. Combined blockade of VEGFR-3 and VLA-1 markedly promotes high-risk corneal transplant survival.

    PubMed

    Zhang, Hui; Grimaldo, Sammy; Yuen, Don; Chen, Lu

    2011-08-01

    PURPOSE. High-risk corneal transplantation refers to grafting performed on inflamed and highly vascularized host beds. It represents a clinical dilemma because the rejection rate can be as high as 90%, irrespective of current treatment modalities. This study was conducted to investigate whether combined blockade of VEGFR-3 (vascular endothelial growth factor receptor-3) and VLA-1 (very late antigen-1) promotes high-risk transplant survival and how it correlates with corneal lymphangiogenesis and hemangiogenesis before and after transplantation. METHODS. High-risk corneal transplantation was performed between normal C57BL/6 (donor) and inflamed BALB/c (recipient) mice. The recipients were randomized to receive intraperitoneal injections of VEGFR-3 and VLA-1-neutralizing antibodies or their controls twice a week for up to 8 weeks after transplantation. Corneal grafts were evaluated by ophthalmic slit-lamp biomicroscopy and analyzed by Kaplan-Meier survival curve. Additionally, whole-mount corneas before and after transplantation were examined by immunofluorescent microscopic assays, and the correlation between lymphatic or blood vessel distribution and transplant outcome was analyzed. RESULTS. The combined blockade markedly promotes 90% survival of high-risk transplants. This strategy specifically modified host beds by selective inhibition of lymphangiogenesis but not hemangiogenesis. A strong correlation was also identified between high-risk transplant rejection and severe lymphatic invasion reaching the donor-graft border. CONCLUSIONS. These novel findings not only provide a new and potentially powerful strategy to promote high-risk transplant survival, they also confirm a critical role of high-degree lymphangiogenesis in mediating high-risk transplant rejection. Results from this study may also shed new light on our understanding and management of other lymphatic- and immune-related diseases in general. PMID:21715348

  11. Prevalence of High-Risk Human Papillomavirus Among Older Women

    PubMed Central

    Lindau, Stacy Tessler; Drum, Melinda L.; Gaumer, Elyzabeth; Surawska, Hanna; Jordan, Jeanne A.

    2009-01-01

    Objective To estimate the prevalence, genotypes, and individual-level correlates of high-risk human papillomavirus (HPV) among women aged 57–85. Methods Community-residing women (n=1550), aged 57–85, were drawn from a nationally-representative probability sample. In-home interviews and biomeasures, including a self-collected vaginal specimen, were obtained between 2005 and 2006. Specimens were analyzed for high-risk HPV DNA using probe hybridization and signal amplification (hc2); of 1,028 specimens provided, 1,010 were adequate for analysis. All samples testing positive were analyzed for HPV DNA by L1 consensus polymerase chain reaction followed by type-specific hybridization. Results The overall population-based weighted estimate of high-risk HPV prevalence by hc2 was 6.0% (95% confidence interval [CI] = 4.5 to 7.9). Current marital and smoking status, frequency of sexual activity, history of cancer, and hysterectomy were associated with high-risk HPV positivity. Among high-risk HPV+ women, 63% had multiple type infections. HPV 16 or 18 was present in 17.4% of all high-risk HPV+ women. The most common high-risk genotypes among high-risk HPV+ women were HPV 61 (19.1%), 31 (13.1%), 52 (12.9%), 58 (12.5%), 83 (12.3%), 66(12.0%), 51 (11.7%), 45 (11.2%), 56 (10.3%), 53 (10.2%), 16 (9.7%), and 62 (9.2%). Being married and having an intact uterus were independently associated with lower prevalence of high-risk HPV. Among unmarried women, current sexual activity and smoking were independently and positively associated with high-risk HPV infection. Conclusions In this nationally representative population, nearly 1 in 16 women aged 57–85 were found to have high-risk HPV and prevalence was stable across older age groups. PMID:18978096

  12. Bioengineered Corneas Grafted as Alternatives to Human Donor Corneas in Three High-Risk Patients

    PubMed Central

    Buznyk, Oleksiy; Pasyechnikova, Nataliya; Islam, M Mirazul; Iakymenko, Stanislav; Fagerholm, Per; Griffith, May

    2015-01-01

    Corneas with severe pathologies have a high risk of rejection when conventionally grafted with human donor tissues. In this early observational study, we grafted bioengineered corneal implants made from recombinant human collagen and synthetic phosphorylcholine polymer into three patients for whom donor cornea transplantation carried a high risk of transplant failure. These patients suffered from corneal ulcers and recurrent erosions preoperatively. The implants provided relief from pain and discomfort, restored corneal integrity by promoting endogenous regeneration of corneal tissues, and improved vision in two of three patients. Such implants could in the future be alternatives to donor corneas for high-risk patients, and therefore, merits further testing in a clinical trial. PMID:25996570

  13. Serosurvey of prevalence of human immunodeficiency virus amongst high risk groups in Port Sudan, Sudan.

    PubMed

    Burans, J P; McCarthy, M; el Tayeb, S M; el Tigani, A; George, J; Abu-Elyazeed, R; Woody, J N

    1990-09-01

    During October, 1987, 593 sera were collected from risk groups in Sudan's only major deepwater port, Port Sudan. The risk groups included prostitutes, lorry drivers and prisoners. A large proportion of the study participants practised high risk behaviour which included sexual promiscuity, medical treatment by injection, scarification and tattooing. Despite high risk behaviour and evidence of a high prevalence of hepatitis B infection, a virus transmitted in a manner similar to HIV, no study participants were positive for HIV infection. This data suggests that the prevalence of HIV infection amongst high risk groups in Port Sudan is very low. These findings confirm a lack of clinical cases of AIDS in hospitalized patients in Port Sudan and the small number of reported cases in other areas of northern Sudan. PMID:2253574

  14. Immunocombination therapy for high-risk neuroblastoma.

    PubMed

    Kroesen, Michiel; Lindau, Dennis; Hoogerbrugge, Peter; Adema, Gosse J

    2012-02-01

    Neuroblastoma (NBL) is an aggressive malignancy of the sympathetic nervous system. Advanced-stage NBLs prove fatal in approximately 50% of patients within 5 years. Therefore, new treatment modalities are urgently needed. Immunotherapy is a treatment modality that can be combined with established forms of treatment. Administration of monoclonal antibodies or dendritic cell-based therapies alone can lead to favorable clinical outcomes in individual cancer patients; for example patients with melanoma, lymphoma and NBL. However, clinical benefit is still limited to a minority of patients, and further improvements are clearly needed. In this article, we review the most commonly used approaches to treat patients with NBL and highlight the prerequisites and opportunities of cell-based immunotherapy, involving both innate and adaptive immune-effector cells. Furthermore, we discuss the potential of the combined application of immunotherapy and novel tumor-targeted therapies for the treatment of both cancer in general and NBL in particular.

  15. [Personality types in patients with atherosclerosis of different localization: prevalence and clinical features].

    PubMed

    Sumin, A N; Raĭkh, O I; Karpovich, A V; Korok, E V; Bezdenezhnykh, A V; Bokhan, I E; Barbarash, O L

    2012-01-01

    The aim of the work was to study the influence of D-type personality on clinical characteristics and extent of the pathological process in patients with atherosclerosis (AS) of different localization. A total of 943 patients (774 men and 169 women, mean age 58.6+-3 yr) were examined prior to arterial surgery. D-type personality was identified using a DS-14 questionnaire. The patients were divided into those with D-type personality (n=182) and without it (n=761). The following parameters were recorded: risk factors of AS, severity of clinical symptoms, history of myocardial infarction, acute cerebrovascular accidents, transitory ischemic attacks, concomitant pathology, and echocardiographic measuremnents. AS of non-coronary basins was diagnosed by color duplex scanning or angiograpgy. The number of affected vascular basins with stenosis of 30% or more arteries was detected. D-type personality was revealed in 19.3% of the patients with AS of different localization. It did not correlate with the social status, risk factors, and clinical symptoms. However D-type was associated with AS of extracranial arteries and combined lesions in several vascular basins as well as with the enhanced level of anxiety and depression and impaired quality of life.

  16. Language Deficits in Children at High Risk for Drug Abuse.

    ERIC Educational Resources Information Center

    Najam, Najma; Tarter, Ralph E.; Kirisci, Levent

    1997-01-01

    Compared the language capacities of children at high risk for substance abuse to low-risk children to uncover focal areas of deficit. Results indicate that high-risk subjects' performance was significantly poorer on several measures of language ability. Findings suggest that poor language mediation increases the risk for substance abuse. (RJM)

  17. Identify and Assist the Development of High Risk Preschool Children.

    ERIC Educational Resources Information Center

    Mann, Marlis

    This speech offers a guide to identifying and teaching high-risk children, those who exhibit a lag in development severe enough to be a handicap in learning. The high-risk children focused on are those whose developmental lag is frequently not recognized until they fail in school. The two major areas of neurodevelopmental learning disorders are in…

  18. 15 CFR 14.14 - High risk special award conditions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false High risk special award conditions. 14.14 Section 14.14 Commerce and Foreign Trade Office of the Secretary of Commerce UNIFORM...-PROFIT, AND COMMERCIAL ORGANIZATIONS Pre-Award Requirements § 14.14 High risk special award...

  19. 40 CFR 35.6790 - High risk recipients.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... described in 40 CFR 31.12. Requirements for Administering a Superfund State Contract (SSC) ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false High risk recipients. 35.6790 Section... Actions Other Administrative Requirements for Cooperative Agreements § 35.6790 High risk recipients....

  20. Improving overall survival and overcoming adverse prognosis in the treatment of cytogenetically high-risk multiple myeloma

    PubMed Central

    Mateos, María-Victoria; Gutierrez, Norma C.; Rajkumar, S. Vincent; San Miguel, Jesús F.

    2013-01-01

    Multiple myeloma (MM) is a heterogeneous disease with certain genetic features [eg, t(4;14), del17p] associated with worse outcome. The introduction of thalidomide, lenalidomide, and bortezomib has dramatically improved the outlook for patients with MM, but their relative benefit (or harm) for different genetic patient subgroups remains unclear. Unfortunately, the small number of patients in each subgroup frequently limits the analysis of high-risk patients enrolled in clinical trials. Strategies that result in survival of high-risk genetic subgroups approximating that of patients lacking high-risk features are said to overcome the poor prognostic impact of these high-risk features. This outcome has been difficult to achieve, and studies in this regard have so far been limited by inadequate sample size. In contrast, strategies that compare the survival of high-risk genetic subgroups randomized to different treatment arms can identify approaches that improve survival. This type of analysis is clinically useful, even if the absolute gains do not improve outcomes to levels seen in patients without high-risk cytogenetics. Reviewing available data in high-risk MM from this perspective, it appears that bortezomib has frequently been associated with improved survival, whereas thalidomide maintenance has sometimes been associated with a shorter survival. PMID:23165477

  1. Local resolved spectroscopy at the human ocular fundus in vivo: technique and clinical examples

    NASA Astrophysics Data System (ADS)

    Hammer, Martin; Schweitzer, Dietrich; Scibor, Mateusz

    1996-01-01

    Ocular fundus reflectometry is known as a method for the determination of the optical density of pigments at the eye ground. This has been described for diagnostic investigations at single locations. The new technique of imaging spectroscopy enables the recording of one dimensional local distribution of spectra from the fundus which is illuminated confocal to the entrance slit of a spectrograph. A fundus reflectometer consisting of a Zeiss fundus camera, an imaging spectrograph, and an intensified CCD-camera are presented. The local resolved spectra gained by this apparatus are approximated by a mathematical model on the basis of the anatomy of the fundus as a structure of layers with different optical properties. Each spectrum is assumed to be described by a function of the absorption spectra of the pigments found in the retinal and choroidal tissue. Assuming the existence of parameters which are independent from the fundus location we have to approximate the measured local distribution of spectra by a system of coupled non-linear equations. By a least square fit the local distribution of the extinction of melanin, xantophyll and hemoglobin may be obtained as well as the extension of pathologic alterations at the fundus. The benefits of the method for clinical diagnostics are discussed at first measurements from physiological and pathological examples.

  2. Localization of needle tip with color doppler during pericardiocentesis: In vitro validation and initial clinical application

    NASA Technical Reports Server (NTRS)

    Armstrong, G.; Cardon, L.; Vilkomerson, D.; Lipson, D.; Wong, J.; Rodriguez, L. L.; Thomas, J. D.; Griffin, B. P.

    2001-01-01

    This study evaluates a new device that uses color Doppler ultrasonography to enable real-time image guidance of the aspirating needle, which has not been possible until now. The ColorMark device (EchoCath Inc, Princeton, NJ) induces high-frequency, low-amplitude vibrations in the needle to enable localization with color Doppler. We studied this technique in 25 consecutive patients undergoing pericardiocentesis, and in vitro, in a urethane phantom with which the accuracy of color Doppler localization of the needle tip was compared with that obtained by direct measurement. Tip localization was excellent in vitro; errors axial to the ultrasound beam (velocity Doppler -0.13 +/- 0.90 mm, power Doppler -0.05 +/- 1.7 mm) were less than lateral errors (velocity -0.36 +/- 1.8 mm, power -0.02 +/- 2.8 mm). In 18 of 25 patients, the needle was identified and guided into the pericardial space with the ColorMark technique, and it allowed successful, uncomplicated drainage of fluid. Initial failures were the result of incorrect settings on the echocardiographic machine and inappropriate combinations of the needle puncture site and imaging window. This study demonstrates a novel color Doppler technique that is highly accurate at localizing a needle tip. The technique is feasible for guiding pericardiocentesis. Further clinical validation of this technique is required.

  3. Massive Localized Lymphedema in the Morbidly Obese Patient: A Clinical Entity Mimicking Lymphosarcoma.

    PubMed

    Kotidis, Efstathios; Cepaityte, Dainora; Petrakis, Georgios; Sapalidis, Konstantinos; Kanellos, Ioannis

    2015-09-01

    Massive localized lymphedema (MLL) is a rare benign soft tissue lesion that develops in morbidly obese patients, most commonly on the medial thigh (though other locations have also been described). The cause of MLL remains unknown, but the common denominator in all reported cases is obesity. The diagnosis of MLL is usually made based on clinical history and presentation but it is believed to be underdiagnosed due to a lack of awareness of this distinct entity. When left untreated, MLL can degenerate into angiosarcoma. This report describes a case of MLL of the right lower abdominal wall in an obese 61-year-old female (BMI = 42 kg/m(2)). PMID:26367787

  4. The topical 5% lidocaine medicated plaster in localized neuropathic pain: a reappraisal of the clinical evidence

    PubMed Central

    de León-Casasola, Oscar A; Mayoral, Victor

    2016-01-01

    Topical 5% lidocaine medicated plasters represent a well-established first-line option for the treatment of peripheral localized neuropathic pain (LNP). This review provides an updated overview of the clinical evidence (randomized, controlled, and open-label clinical studies, real-life daily clinical practice, and case series). The 5% lidocaine medicated plaster effectively provides pain relief in postherpetic neuralgia, and data from a large open-label controlled study indicate that the 5% lidocaine medicated plaster is as effective as systemic pregabalin in postherpetic neuralgia and painful diabetic polyneuropathy but with an improved tolerability profile. Additionally, improved analgesia and fewer side effects were experienced by patients treated synchronously with the 5% lidocaine medicated plaster, further demonstrating the value of multimodal analgesia in LNP. The 5% lidocaine medicated plaster provides continued benefit after long-term (≤7 years) use and is also effective in various other LNP conditions. Minor application-site reactions are the most common adverse events associated with the 5% lidocaine medicated plaster; there is minimal risk of systemic adverse events and drug–drug interactions. Although further well-controlled studies are warranted, the 5% lidocaine medicated plaster is efficacious and safe in LNP and may have particular clinical benefit in elderly and/or medically compromised patients because of the low incidence of adverse events. PMID:26929664

  5. Using local lexicalized rules to identify heart disease risk factors in clinical notes.

    PubMed

    Karystianis, George; Dehghan, Azad; Kovacevic, Aleksandar; Keane, John A; Nenadic, Goran

    2015-12-01

    Heart disease is the leading cause of death globally and a significant part of the human population lives with it. A number of risk factors have been recognized as contributing to the disease, including obesity, coronary artery disease (CAD), hypertension, hyperlipidemia, diabetes, smoking, and family history of premature CAD. This paper describes and evaluates a methodology to extract mentions of such risk factors from diabetic clinical notes, which was a task of the i2b2/UTHealth 2014 Challenge in Natural Language Processing for Clinical Data. The methodology is knowledge-driven and the system implements local lexicalized rules (based on syntactical patterns observed in notes) combined with manually constructed dictionaries that characterize the domain. A part of the task was also to detect the time interval in which the risk factors were present in a patient. The system was applied to an evaluation set of 514 unseen notes and achieved a micro-average F-score of 88% (with 86% precision and 90% recall). While the identification of CAD family history, medication and some of the related disease factors (e.g. hypertension, diabetes, hyperlipidemia) showed quite good results, the identification of CAD-specific indicators proved to be more challenging (F-score of 74%). Overall, the results are encouraging and suggested that automated text mining methods can be used to process clinical notes to identify risk factors and monitor progression of heart disease on a large-scale, providing necessary data for clinical and epidemiological studies.

  6. Pilonidal Sinus Operations Performed Under Local Anesthesia versus the General Anesthesia: Clinical Trial Study

    PubMed Central

    Rahmani, Nasrin; Baradari, Afshin Gholipour; Heydari Yazdi, Seyed Mohammad-Javad; Firouzian, Abolfazl; Hashemi, Seyyed Abbas; Fazli, Mehran; Sadeghian, Iman

    2016-01-01

    Backgrounds: Various methods were defined to prepare patients for the pilonidal sinus surgery including local, spinal, and general anesthesia. But there is no powerful evidence to differ these procedures. Therefore, in the current study, we compared local and general anesthesia in the pilonidal sinus surgery. Methods and Material: In this clinical trial (IRCT201312031786N5) study 60 patients with the pilonidal sinus disease divided to two groups of local anesthesia versus general anesthesia. For local anesthesia we used 6ml of 2% lidocaine with an epinephrine (1:200,000), 6 ml of 0.5% bupivacaine, 1ml fentanyl (50 μg/ml), 1ml clonidine (75 μg/ml) and for general anesthesia fentanyl 1.5 μg.kg-1, thiopental 3-5 mg.kg-1, followed by the trachea intubation facilitated by atracurim 0.5 mg.kg-1 with maintenance of isoflurane 1-3% in nitrous oxygen 70% and oxygen 30%. The student t-test and Chi-square test were applied to evaluate the differences. Results: There were 30 patients with the mean age of 27.43±8.42 years in local anesthesia group and 30 cases with the mean age of 27.5±8.44 years underwent general anesthesia. The recovery time was significantly lower in the local anesthesia group (P=0.000). The oxygen saturation of the general anesthesia group was significantly higher at 1 and 20 minutes after the operation. The average of pain score was significantly higher in general anesthesia group at 3h and 6h after surgery (P<0.001). There were no significant differences in post-operative complications and hospital length of stay. Conclusion: This investigation revealed that local anesthesia has decreased pain during 48 hours after the surgery, shorter recovery time, and the less consumption of painkillers. So, we concluded that we can consider local anesthesia as a good alternative for the general anesthesia in the pilonidal sinus surgery. PMID:27157165

  7. High Risk Infants Follow-Up: A Case Study in Iran.

    PubMed

    Heidarzadeh, Mohammad; Jodeiry, Behzad; Hosseini, Mohammad Baqer; Mirnia, Kayvan; Akrami, Forouzan; Habbibollahi, Abbas; Moazzen, Sara; Dastgiri, Saeed

    2015-01-01

    Background. A follow-up program for high risk infants was initiated in Alzahra Maternity Hospital in Tabriz city, Iran, in 2013. The aim of this paper is to give a brief report of the program. Material and Methods. Two groups of high risk neonates were studied. The first group comprising 509 infants received services in Alzahra Maternity Hospital implemented by the follow-up program. This included a full package for family to look after high risk infant and periodic clinical evaluation at two and four weeks after birth and then two, three, four, five, and six months later again. The second group including 131 infants in Taleqani Maternity Hospital received routine services after birth with no specific follow-up care. Results. Some anthropometric indices showed a significant improvement in the intervention hospital compared to control group. These included the following: head circumference at first and second months; weight in the first, fourth, fifth, and sixth months; and height in sixth month only. Clinical evaluation of infants showed an improvement for some of the medical conditions. Conclusion. Follow-up care program for a minimum of six months after discharge from maternity hospitals may help to avoid adverse and life threatening consequences in high risk infants. PMID:26136787

  8. Clinical efficacy of 2-phase versus 4-phase computed tomography for localization in primary hyperparathyroidism

    PubMed Central

    Ramirez, Adriana G.; Shada, Amber L.; Martin, Allison N.; Raghavan, Prashant; Durst, Christopher R.; Mukherjee, Sugoto; Gaughen, John R.; Ornan, David A.; Hanks, John B.; Smith, Philip W.

    2016-01-01

    Background Four-dimensional computed tomography is being used increasingly for localization of abnormal glands in primary hyperparathyroidism. We hypothesized that compared with traditional 4-phase imaging, 2-phase imaging would halve the radiation dose without compromising parathyroid localization and clinical outcomes. Methods A transition from 4-phase to 2-phase imaging was instituted between 2009 and 2010. A pre-post analysis was performed on patients undergoing operative treatment with a parathyroid protocol computed tomography, and relevant data were correlated with operative findings. Sensitivity, positive predictive value, technical success, and cure rates were calculated. The Fisher exact test or χ2 test assessed the significance of 2-phase and 4-phase imaging and operative findings. Results Twenty-seven patients had traditional four-dimensional computed tomography and 35 had modified 2-phase computed tomography. Effective radiation doses were 6.8 mSy for 2-phase and 14 mSv for 4-phase. Four-phase computed tomography had a sensitivity and positive predictive value of 93% and 96%, respectively. Two-phase computed tomography had a comparable sensitivity and positive predictive value of 97% and 94%, respectively. Eight patients with discordant imaging had an average parathyroid weight of 240 g compared with 1,300 g for all patients. Technical surgical success (90% for 4-phase computed tomography versus 91% 2-phase computed tomography) and normocalcemia rates at 6 months (88% for both) did not differ between computed tomography protocols. Computed tomography correctly predicted multiglandular disease and localization for reoperations in 88% and 90% of cases, respectively, with no difference by computed tomography protocol. Conclusion With regard to surgical outcomes and localization, 2-phase parathyroid computed tomography is equivalent to 4-phase for parathyroid localization, including small adenomas, reoperative cases, and multiglandular disease. Two

  9. Localization Accuracy of the Clinical Target Volume During Image-Guided Radiotherapy of Lung Cancer

    SciTech Connect

    Hugo, Geoffrey D.; Weiss, Elisabeth; Badawi, Ahmed; Orton, Matthew

    2011-10-01

    Purpose: To evaluate the position and shape of the originally defined clinical target volume (CTV) over the treatment course, and to assess the impact of gross tumor volume (GTV)-based online computed tomography (CT) guidance on CTV localization accuracy. Methods and Materials: Weekly breath-hold CT scans were acquired in 17 patients undergoing radiotherapy. Deformable registration was used to propagate the GTV and CTV from the first weekly CT image to all other weekly CT images. The on-treatment CT scans were registered rigidly to the planning CT scan based on the GTV location to simulate online guidance, and residual error in the CTV centroids and borders was calculated. Results: The mean GTV after 5 weeks relative to volume at the beginning of treatment was 77% {+-} 20%, whereas for the prescribed CTV, it was 92% {+-} 10%. The mean absolute residual error magnitude in the CTV centroid position after a GTV-based localization was 2.9 {+-} 3.0 mm, and it varied from 0.3 to 20.0 mm over all patients. Residual error of the CTV centroid was associated with GTV regression and anisotropy of regression during treatment (p = 0.02 and p = 0.03, respectively; Spearman rank correlation). A residual error in CTV border position greater than 2 mm was present in 77% of patients and 50% of fractions. Among these fractions, residual error of the CTV borders was 3.5 {+-} 1.6 mm (left-right), 3.1 {+-} 0.9 mm (anterior-posterior), and 6.4 {+-} 7.5 mm (superior-inferior). Conclusions: Online guidance based on the visible GTV produces substantial error in CTV localization, particularly for highly regressing tumors. The results of this study will be useful in designing margins for CTV localization or for developing new online CTV localization strategies.

  10. Radioguided localization of clinically occult breast lesions (ROLL): a pilot study.

    PubMed

    Medina-Franco, Heriberto; Abarca-Pérez, Leonardo; Ulloa-Gómez, José L; Romero, Cecilia

    2007-01-01

    Management of nonpalpable breast lesions requiring pathologic diagnosis has been with wire localization during the last few decades. Recently, radioguided localization (ROLL) became an alternative for this type of lesions. The objective of the present study was to evaluate the feasibility of this technique in a tertiary referral center in Mexico City. Consecutive patients requiring pathologic diagnosis from a nonpalpable breast lesion were included in the present study. On the same day of operation, all patients were injected with particles of human serum albumin. Localization of the lesion was performed in the operation theater with the aid of a hand-held gamma-probe. All lesions were identified in a control x-ray of the surgical specimen. Demographic, clinical, surgical and pathologic data were recorded. Forty patients with a mean age of 56.8 +/- 7.8 years were included. In 39 of the 40 patients (97.5%) the "hot spot" was identified easily. In all patients, the area of maximum radioactivity corresponded to the site of the lesion. Imaging confirmation of the lesion in the surgical specimen was done during the first excision in 37 patients (92.5%). In the remaining cases (7.5%), a wider excision was performed during the same procedure, finding the suspected lesion in all cases. Diagnosis of cancer was made in seven patients, (17.5%). There were no significant surgical complications. Our data suggest that ROLL offer a simple and reliable method to localize occult breast lesions, allowing complete removal of the lesion in 100% of the patients. Because of the small quantity of radioactivity, the procedure is safe for both patients and the medical staff, producing less discomfort in patients than wire localization.

  11. Preoperative systemic etoposide/ifosfamide/doxorubicin chemotherapy combined with regional hyperthermia in high-risk sarcoma: a pilot study.

    PubMed

    Issels, R D; Bosse, D; Abdel-Rahman, S; Starck, M; Panzer, M; Jauch, K W; Stiegler, H; Berger, H; Sauer, H; Peter, K

    1993-01-01

    From November 1990 to September 1991, 23 adults with high-risk, nonmetastatic sarcomas (20 soft-tissue sarcomas and 3 chondrosarcomas) were entered in a pilot protocol (RHT-91) involving regional hyperthermia combined with systemic chemotherapy followed by surgery. Of these patients, 12 had undergone previous surgery and/or radiation, 5 had received previous multidrug chemotherapy, and 6 were previously untreated. A tumor size of > 8 cm and/or an extracompartmental tumor location (11 patients) or local recurrence (12 patients) were defined as high-risk factors in addition to tumor grading (21 patients had grade 2 or 3 sarcomas). Regional hyperthermia was produced by an electromagnetic deep-regional-heating device. For systemic chemotherapy, all patients received etoposide/ifosfamide/doxorubicin (EIA) and mesna, with regional hyperthermia being given only on days 1 and 4 in repeated EIA/regional hyperthermia cycles every 3 weeks. Tumor temperatures (range, 40 degrees-44 degrees C) were measured by invasive thermometry in all patients during each regional hyperthermia treatment. A total of 181 regional hyperthermia treatments were applied within the pelvic region (11 patients) or extremities (12 patients) bearing relatively large tumors (mean volume, 848 cm3). By the cutoff date for this analysis (October 15, 1991), 13 patients had undergone surgery after receiving 2-6 (mean, 3.8) cycles of EIA chemotherapy combined with regional hyperthermia; all tumors except one were resected without disfiguration. In 22 evaluable patients (minimum, 2 EIA plus regional hyperthermia cycles), the clinical response rate was 27%, with 6 patients showing partial responses (PRs). In addition, a pathologic response to preoperative thermochemotherapy was evaluable in 13 patients, with 4 responders (31%) having > 50% histologic necrosis. In all, 3 of the responders (1 PR and 2 patients with > 50% histologic necrosis) relapsed within 3 months of surgical resection. The other 7 responding

  12. Treatment of Locally Advanced Vaginal Cancer With Radiochemotherapy and Magnetic Resonance Image-Guided Adaptive Brachytherapy: Dose-Volume Parameters and First Clinical Results

    SciTech Connect

    Dimopoulos, Johannes C.A.; Schmid, Maximilian P.; Fidarova, Elena; Berger, Daniel; Kirisits, Christian; Poetter, Richard

    2012-04-01

    Purpose: To investigate the clinical feasibility of magnetic resonance image-guided adaptive brachytherapy (IGABT) for patients with locally advanced vaginal cancer and to report treatment outcomes. Methods and Materials: Thirteen patients with vaginal cancer were treated with external beam radiotherapy (45-50.4 Gy) plus IGABT with or without chemotherapy. Distribution of International Federation of Gynecology and Obstetrics stages among patients were as follows: 4 patients had Stage II cancer, 5 patients had Stage III cancer, and 4 patients had Stage IV cancer. The concept of IGABT as developed for cervix cancer was transferred and adapted for vaginal cancer, with corresponding treatment planning and reporting. Doses were converted to the equivalent dose in 2 Gy, applying the linear quadratic model ({alpha}/{beta} = 10 Gy for tumor; {alpha}/{beta} = 3 for organs at risk). Endpoints studied were gross tumor volume (GTV), dose-volume parameters for high-risk clinical target volume (HRCTV), and organs at risk, local control (LC), adverse side effects, and survival. Results: The mean GTV ({+-} 1 standard deviation) at diagnosis was 45.3 ({+-}30) cm{sup 3}, and the mean GTV at brachytherapy was 10 ({+-}14) cm{sup 3}. The mean D90 for the HRCTV was 86 ({+-}13) Gy. The mean D2cc for bladder, urethra, rectum, and sigmoid colon were 80 ({+-}20) Gy, 76 ({+-}16) Gy, 70 ({+-}9) Gy, and 60 ({+-}9) Gy, respectively. After a median follow-up of 43 months (range, 19-87 months), one local recurrence and two distant metastases cases were observed. Actuarial LC and overall survival rates at 3 years were 92% and 85%. One patient with Stage IVA and 1 patient with Stage III disease experienced fistulas (one vesicovaginal, one rectovaginal), and 1 patient developed periurethral necrosis. Conclusions: The concept of IGABT, originally developed for treating cervix cancer, appears to be applicable to vaginal cancer treatment with only minor adaptations. Dose-volume parameters for HRCTV and

  13. Intraosseous injection as an adjunct to conventional local anesthetic techniques: A clinical study

    PubMed Central

    Idris, Mohamed; Sakkir, Nasil; Naik, Kishore Gopalakrishna; Jayaram, Nandakishore Kunijal

    2014-01-01

    Background: The achievement of successful local anesthesia is a continual challenge in dentistry. Adjunctive local anesthetic techniques and their armamentaria, such as intraosseous injection (the Stabident system and the X-tip system) have been proposed to be advantageous in cases where the conventional local anesthetic techniques have failed. Aim: A clinical study was undertaken using intraosseous injection system by name X-tip to evaluate its effectiveness in cases where inferior alveolar nerve block has failed to provide pulpal anesthesia. Materials and Methods: Sixty adult patients selected were to undergo endodontic treatment for a mandibular molar tooth. Inferior alveolar nerve block was given using 4% articaine with 1:100,000 epinephrine. Twenty-four patients (40%) had pain even after administration of IAN block; intraosseous injection was administered using 4% articaine containing 1:100,000 epinephrine, using the X-tip system. The success of X-tip intraosseous injection was defined as none or mild pain (Heft-Parker visual analog scale ratings ≤ 54 mm) on endodontic access or initial instrumentation. Results: Intraosseous injection technique was successful in 21 out of 24 patients (87.5%), except three patients who had pain even after supplemental X-tip injection. Conclusion: Within the limits of this study, we can conclude that supplemental intraosseous injection using 4% articaine with 1:100,000 epinephrine has a statistically significant influence in achieving pulpal anesthesia in patients with irreversible pulpitis. PMID:25298642

  14. Clinical Evaluation of Stereotactic Target Localization Using 3-Tesla MRI for Radiosurgery Planning

    SciTech Connect

    MacFadden, Derek; Zhang Beibei; Brock, Kristy K.; Hodaie, Mojgan; Laperriere, Normand; Schwartz, Michael; Tsao, May; Stainsby, Jeffrey; Lockwood, Gina; Mikulis, David; Menard, Cynthia

    2010-04-15

    Purpose: Increasing the magnetic resonance imaging (MRI) field strength can improve image resolution and quality, but concerns remain regarding the influence on geometric fidelity. The objectives of the present study were to spatially investigate the effect of 3-Tesla (3T) MRI on clinical target localization for stereotactic radiosurgery. Methods and Materials: A total of 39 patients were enrolled in a research ethics board-approved prospective clinical trial. Imaging (1.5T and 3T MRI and computed tomography) was performed after stereotactic frame placement. Stereotactic target localization at 1.5T vs. 3T was retrospectively analyzed in a representative cohort of patients with tumor (n = 4) and functional (n = 5) radiosurgical targets. The spatial congruency of the tumor gross target volumes was determined by the mean discrepancy between the average gross target volume surfaces at 1.5T and 3T. Reproducibility was assessed by the displacement from an averaged surface and volume congruency. Spatial congruency and the reproducibility of functional radiosurgical targets was determined by comparing the mean and standard deviation of the isocenter coordinates. Results: Overall, the mean absolute discrepancy across all patients was 0.67 mm (95% confidence interval, 0.51-0.83), significantly <1 mm (p < .010). No differences were found in the overall interuser target volume congruence (mean, 84% for 1.5T vs. 84% for 3T, p > .4), and the gross target volume surface mean displacements were similar within and between users. The overall average isocenter coordinate discrepancy for the functional targets at 1.5T and 3T was 0.33 mm (95% confidence interval, 0.20-0.48), with no patient-specific differences between the mean values (p >.2) or standard deviations (p >.1). Conclusion: Our results have provided clinically relevant evidence supporting the spatial validity of 3T MRI for use in stereotactic radiosurgery under the imaging conditions used.

  15. Total Androgen Blockade Versus a Luteinizing Hormone-Releasing Hormone Agonist Alone in Men With High-Risk Prostate Cancer Treated With Radiotherapy

    SciTech Connect

    Nanda, Akash; Moran, Brian J.; Braccioforte, Michelle H.; Dosoretz, Daniel; Salenius, Sharon; Katin, Michael; Ross, Rudi; D'Amico, Anthony V.

    2010-04-15

    Purpose: To assess whether short-course total androgen blockade vs. a luteinizing hormone-releasing hormone (LHRH) agonist alone affects the risk of prostate cancer-specific mortality (PCSM) in men with localized but high-risk disease treated with radiotherapy. Methods and Materials: The study cohort comprised 628 men with T1-T4, N0, M0 prostate cancer with high-risk disease (prostate-specific antigen level >20 ng/mL, Gleason score >=8, or clinical category >=T3) treated with 45 Gy of external beam radiotherapy followed by a brachytherapy boost in addition to receiving a median of 4.3 (interquartile range [IQR], 3.6-6.4) months of hormonal blockade with an LHRH agonist plus an antiandrogen or monotherapy with an LHRH agonist. Fine and Gray's multivariable regression analysis was used to determine whether combination androgen suppression therapy (AST) vs. monotherapy affected the risk of PCSM, adjusting for treatment year, duration of AST, age, and known prognostic factors. Results: After a median follow-up of 4.9 (IQR, 3.5-6.5) years, men receiving combination AST had a lower risk of PCSM than those treated with monotherapy (adjusted hazard ratio [AHR], 0.18; 95% confidence interval [CI], 0.04-0.90; p = 0.04). An increasing prostate-specific antigen level (AHR, 2.70; 95% CI, 1.64-4.45; p < 0.001) and clinical category T3/4 disease (AHR, 29.6; 95% CI, 2.88-303.5; p = 0.004) were also associated with an increased risk of PCSM. Conclusions: In men with localized but high-risk prostate cancer treated with external beam radiotherapy and brachytherapy, short-course AST with an LHRH agonist plus an antiandrogen is associated with a decreased risk of PCSM when compared with monotherapy with an LHRH agonist.

  16. Venous Thromboembolism Risk and Adequacy of Prophylaxis in High Risk Pregnancy in the Arabian Gulf

    PubMed Central

    Alsayegh, Faisal; Al-Jassar, Waleed; Wani, Salima; Tahlak, Muna; Al-Bahar, Awatef; Al-Kharusi, Lamya; Al-Tamimi, Halima; El-Taher, Faten; Mahmood, Naeema; Al-Zakwani, Ibrahim

    2016-01-01

    Objectives: To estimate the prevalence of venous thromboembolism (VTE) risk factors in pregnancy and the proportion of pregnancies at risk of VTE that received the recommended prophylaxis according to the American College of Chest Physicians (ACCP) 2012 published guidelines in antenatal clinics in the Arabian Gulf. Methods: The evaluation of venous thromboembolism (EVE)-Risk project was a non-interventional, cross-sectional, multi-centre, multi-national study of all eligible pregnant women (≥17 years) screened during antenatal clinics from 7 centres in the Arabian Gulf countries (United Arab Emirates, Kuwait, Bahrain, Qatar and Oman). Pregnant women were recruited during a 3-month period between September and December 2012. Results: Of 4,131 screened pregnant women, 32% (n=1,337) had ≥1 risk factors for VTE. Common VTE risk factors included obesity (76%), multiparity (33%), recurrent miscarriages (9.1%), varicose veins (6.9%), thrombophilia (2.6%), immobilization (2.0%), sickle cell disease (2.8%) and previous VTE (1.6%). Only 8.3% (n=111) of the high risk patients were on the recommended VTE prophylaxis. Enoxaparin was used in 80% (n=89) of the cases followed by tinzaparin (4%; n=4). Antiplatelet agents were prescribed in 11% (n=149) of pregnant women. Of those on anticoagulants (n=111), 59% (n=66) were also co-prescribed antiplatelet agents. Side effects (mainly local bruising at the injection site) were reported in 12% (n=13) of the cases. Conclusion: A large proportion of pregnant women in the Arabian Gulf countries have ≥1 VTE risk factor with even a smaller fraction on prophylaxis. VTE risk assessment must be adopted to identify those at risk who would need VTE prophylaxis.

  17. [Anesthesiological management of the high-risk surgical patient].

    PubMed

    Bertoldi, G; Avalle, M

    1980-03-01

    Evaluation of the anaesthesiological risk in surgical patients is described and an account is given of results obtained with an association of ketamin and NLA II in 57 high-risk patients subjected to general surgical management.

  18. Final Report of Multicenter Canadian Phase III Randomized Trial of 3 Versus 8 Months of Neoadjuvant Androgen Deprivation Therapy Before Conventional-Dose Radiotherapy for Clinically Localized Prostate Cancer

    SciTech Connect

    Crook, Juanita Ludgate, Charles; Malone, Shawn; Perry, Gad; Eapen, Libni; Bowen, Julie; Robertson, Susan; Lockwood, Gina M.Math.

    2009-02-01

    Purpose: To evaluate the effect of 3 vs. 8 months of neoadjuvant hormonal therapy before conventional-dose radiotherapy (RT) on disease-free survival for localized prostate cancer. Methods and Materials: Between February 1995 and June 2001, 378 men were randomized to either 3 or 8 months of flutamide and goserelin before 66 Gy RT at four participating centers. The median baseline prostate-specific antigen level was 9.7 ng/mL (range, 1.3-189). Of the 378 men, 26% had low-, 43% intermediate-, and 31% high-risk disease. The two arms were balanced in terms of age, Gleason score, clinical T category, risk group, and presenting prostate-specific antigen level. The median follow-up for living patients was 6.6 years (range, 1.6-10.1). Of the 378 patients, 361 were evaluable, and 290 were still living. Results: The 5-year actuarial freedom from failure rate for the 3- vs. 8-month arms was 72% vs. 75%, respectively (p = 0.18). No difference was found in the failure types between the two arms. The median prostate-specific antigen level at the last follow-up visit for patients without treatment failure was 0.6 ng/mL in the 3-month arm vs. 0.50 ng/mL in the 8-month arm. The disease-free survival rate at 5 years was improved for the high-risk patients in the 8-month arm (71% vs. 42%, p = 0.01). Conclusion: A longer period of NHT before standard-dose RT did not alter the patterns of failure when combined with 66-Gy RT. High-risk patients in the 8-month arm had significant improvement in the 5-year disease-free survival rate.

  19. Development, Implementation, and Use of a Local and Global Clinical Registry for Neurosurgery.

    PubMed

    Kondziolka, Douglas; Cooper, Benjamin T; Lunsford, L Dade; Silverman, Joshua

    2015-06-01

    Physicians are being challenged to obtain data for outcomes research and measures of quality practice in medicine. We developed a prospective data collection system (registry) that provides data points across all elements of a neurosurgical stereotactic radiosurgery practice. The registry architecture is scalable and suitable for any aspect of neurosurgical practice. Our purpose was to outline the challenges in creating systems for high quality data acquisition and describe experiences in initial testing and use. Over a two year period, a multicenter team working with software engineers developed a comprehensive radiosurgery registry based on a MS-Sequel® server platform. Three neurosurgeons at one center were responsible for final editing. Alpha testing began in September 2012 and server-based beta testing began in February 2013. The major elements included demographics, disease-based items (47 categories for different brain tumors, vascular malformations, and functional disorders) with relevant clinical grading systems, treatment-based items (imaging, physics, clinical), and follow-up data (clinical, imaging, subsequent therapeutics). Nine hundred patients were entered into the registry at one test center, with new entries and follow-up data entered daily at the point of contact. With experience, the mean time for one new entry was 6 minutes. Mean time for one follow-up entry was 45 seconds. The system was made secure for individual use and amenable for both data entry and research. Analytics used different filters to create customized outcomes charts as selected by the user (e.g., survival, neurologic function, complications). A local or multicenter prospective data collection registry was created for use across 47 clinical indications for stereotactic cranial radiosurgery. Further refinement of fields and logic is ongoing. The system is reliable, robust, and allows use of rapid analytical tools. Large medical registries will become widely used for collection

  20. Development, Implementation, and Use of a Local and Global Clinical Registry for Neurosurgery.

    PubMed

    Kondziolka, Douglas; Cooper, Benjamin T; Lunsford, L Dade; Silverman, Joshua

    2015-06-01

    Physicians are being challenged to obtain data for outcomes research and measures of quality practice in medicine. We developed a prospective data collection system (registry) that provides data points across all elements of a neurosurgical stereotactic radiosurgery practice. The registry architecture is scalable and suitable for any aspect of neurosurgical practice. Our purpose was to outline the challenges in creating systems for high quality data acquisition and describe experiences in initial testing and use. Over a two year period, a multicenter team working with software engineers developed a comprehensive radiosurgery registry based on a MS-Sequel® server platform. Three neurosurgeons at one center were responsible for final editing. Alpha testing began in September 2012 and server-based beta testing began in February 2013. The major elements included demographics, disease-based items (47 categories for different brain tumors, vascular malformations, and functional disorders) with relevant clinical grading systems, treatment-based items (imaging, physics, clinical), and follow-up data (clinical, imaging, subsequent therapeutics). Nine hundred patients were entered into the registry at one test center, with new entries and follow-up data entered daily at the point of contact. With experience, the mean time for one new entry was 6 minutes. Mean time for one follow-up entry was 45 seconds. The system was made secure for individual use and amenable for both data entry and research. Analytics used different filters to create customized outcomes charts as selected by the user (e.g., survival, neurologic function, complications). A local or multicenter prospective data collection registry was created for use across 47 clinical indications for stereotactic cranial radiosurgery. Further refinement of fields and logic is ongoing. The system is reliable, robust, and allows use of rapid analytical tools. Large medical registries will become widely used for collection

  1. Current clinical practice gaps in the treatment of intermediate- and high-risk non-muscleinvasive bladder cancer (NMIBC) with emphasis on the use of bacillus Calmette- Guérin (BCG): results of an international individual patient data survey (IPDS)

    PubMed Central

    Witjes, J Alfred; Palou, Joan; Soloway, Mark; Lamm, Donald; Kamat, Ashish M; Brausi, Maurizio; Persad, Raj; Buckley, Roger; Colombel, Marc; Böhle, Andreas

    2013-01-01

    Objectives To examine the management of intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC), particularly with regard to the use of bacillus Calmette-Guérin (BCG) therapy, in North America and Europe. To compare NMIBC management practices to European Association of Urology (EAU) and American Urological Association (AUA) guideline recommendations for the management of intermediate- and high-risk NMIBC. Patients and Methods In all, 102 urologists from Europe and North America participated in this retrospective on-line chart review, which was conducted between 1 April 2011 and 30 April 2012. Participants selected the charts of the first 10 intermediate- (defined as multiple or recurrent low-grade tumours) or high-risk (defined as any T1 and/or high-grade/G3 tumours and/or carcinoma in situ) patients who underwent transurethral resection of bladder tumour in 2009. Physicians retrospectively reviewed the charts and completed an on-line survey consisting of questions related to diagnosis, planned treatment, treatment status and follow-up. In all, 971 patients (197 intermediate-risk; 774 high-risk) were included in the analysis; frequency counts and associated percentages were used to analyse treatment variables. Results In all, 47% of intermediate-risk patients received EAU or AUA guideline-recommended intravesical therapy: intravesical chemotherapy, BCG induction therapy or BCG induction plus maintenance. Of the high-risk patients, 50% received maintenance BCG as recommended by the EAU and the AUA; although not recommended for high-risk NMIBC, 12.5% received intravesical chemotherapy. Of patients prescribed maintenance BCG, 93% were scheduled for at least 1 year of therapy. Notably, only 15% discontinued BCG maintenance and, of these discontinuations, 65% were due to reasons unrelated to BCG-associated adverse events. Conclusions There is significant non-adherence to EAU and AUA guideline recommendations for BCG use in intermediate- and high-risk

  2. External Beam Radiotherapy for Clinically Localized Hormone-Refractory Prostate Cancer: Clinical Significance of Nadir Prostate-Specific Antigen Value Within 12 Months

    SciTech Connect

    Ogawa, Kazuhiko Nakamura, Katsumasa; Sasaki, Tomonari; Onishi, Hiroshi; Koizumi, Masahiko; Shioyama, Yoshiyuki; Araya, Masayuki; Mukumoto, Nobutaka M.S.; Mitsumori, Michihide; Teshima, Teruki

    2009-07-01

    Purpose: To analyze retrospectively the results of external beam radiotherapy for clinically localized hormone-refractory prostate cancer and investigate the clinical significance of nadir prostate-specific antigen (PSA) value within 12 months (nPSA12) as an early estimate of clinical outcomes after radiotherapy. Methods and Materials: Eighty-four patients with localized hormone-refractory prostate cancer treated with external beam radiotherapy were retrospectively reviewed. The total radiation doses ranged from 30 to 76 Gy (median, 66 Gy), and the median follow-up period for all 84 patients was 26.9 months (range, 2.7-77.3 months). Results: The 3-year actuarial overall survival, progression-free survival (PFS), and local control rates in all 84 patients after radiotherapy were 67%, 61%, and 93%, respectively. Although distant metastases and/or regional lymph node metastases developed in 34 patients (40%) after radiotherapy, local progression was observed in only 5 patients (6%). Of all 84 patients, the median nPSA12 in patients with clinical failure and in patients without clinical failure was 3.1 ng/mL and 0.5 ng/mL, respectively. When dividing patients according to low (<0.5 ng/mL) and high ({>=}0.5 ng/mL) nPSA12 levels, the 3-year PFS rate in patients with low nPSA12 and in those with high nPSA12 was 96% and 44%, respectively (p < 0.0001). In univariate analysis, nPSA12 and pretreatment PSA value had a significant impact on PFS, and in multivariate analysis nPSA12 alone was an independent prognostic factor for PFS after radiotherapy. Conclusions: External beam radiotherapy had an excellent local control rate for clinically localized hormone-refractory prostate cancer, and nPSA12 was predictive of clinical outcomes after radiotherapy.

  3. Dose-Escalated Radiotherapy for High-Risk Prostate Cancer: Outcomes in Modern Era With Short-Term Androgen Deprivation Therapy

    SciTech Connect

    Liauw, Stanley L.; Stadler, Walter M.; Correa, David B.S.; Weichselbaum, Ralph R.; Jani, Ashesh B.

    2010-05-01

    Purpose: Randomized data have supported the use of long-term androgen deprivation therapy (ADT) combined with radiotherapy (RT) for men with high-risk prostate cancer. The present study reviewed the outcomes of intermediate- and high-risk men treated with RT and short-term ADT. Materials and Methods: A total of 184 men with any single risk factor of prostate-specific antigen >=10 ng/mL, clinical Stage T2b or greater, or Gleason score >=7 were treated with primary external beam RT for nonmetastatic adenocarcinoma of the prostate. The median radiation dose was 74 Gy; 55% were treated with intensity-modulated RT. All patients received ADT for 1 to 6 months (median, 4), consisting of a gonadotropin-releasing hormone analog. Univariate and multivariable analyses were performed for risk factors, including T stage, Gleason score, radiation dose, and prostate-specific antigen level. Results: With a median follow-up of 51 months, the 4-year freedom from biochemical failure (FFBF) using the nadir plus 2 ng/mL definition was 83% for all patients. Clinical Stage T3 disease was the only variable tested associated with FFBF on univariate (4-year FFBF rate, 46% vs. 87% for Stage T1-T2c disease; p = .0303) and multivariable analysis (hazard ratio, 3.9; p = .0016). On a subset analysis of high-risk patients (National Comprehensive Cancer Network criteria), those with clinical Stage T3 disease (4-year FFBF rate, 46% vs. 80%; p = .0303) and a radiation dose <74 Gy (4-year FFBF rate, 64% vs. 80%) had a poorer outcome on univariate analysis. However, clinical Stage T3 disease and radiation dose were not significant on multivariable analysis, although a statistical multivariable trend was seen for both (p = .0650 and p = .0597, respectively). Conclusion: Short-term ADT and RT might be acceptable for men with intermediate- and high-risk prostate cancer, especially for clinically localized disease treated with doses of >=74 Gy.

  4. Disorders associated with systemic or local iron overload: from pathophysiology to clinical practice.

    PubMed

    Sebastiani, Giada; Pantopoulos, Kostas

    2011-10-01

    In healthy subjects, the rate of dietary iron absorption, as well as the amount and distribution of body iron are tightly controlled by hepcidin, the iron regulatory hormone. Disruption of systemic iron homeostasis leads to pathological conditions, ranging from anemias caused by iron deficiency or defective iron traffic, to iron overload (hemochromatosis). Other iron-related disorders are caused by misregulation of cellular iron metabolism, which results in local accumulation of the metal in mitochondria. Brain iron overload is observed in neurodegenerative disorders. Secondary hemochromatosis develops as a complication of another disease. For example, repeated blood transfusions, a standard treatment of various anemias characterized by ineffective erythropoiesis, promote transfusional siderosis, while chronic liver diseases are often associated with mild to moderate secondary iron overload. In this critical review, we discuss pathophysiological and clinical aspects of all types of iron metabolism disorders (265 references).

  5. Social Contexts of Remission from DSM-5 Alcohol Use Disorder in a High-Risk Sample

    PubMed Central

    McCutcheon, Vivia V.; Kramer, John R.; Edenberg, Howard J.; Nurnberger, John I; Kuperman, Samuel; Schuckit, Marc A.; Heath, Andrew C.; Bucholz, Kathleen K.

    2014-01-01

    Background Measures of social context, such as marriage and religious participation, are associated with remission from alcohol use disorders (AUD) in population-based and treatment samples, but whether these associations hold among individuals at high familial risk for AUD is unknown. This study tests associations of measures of social context and treatment with different types of remission from DSM-5 AUD in a high-risk sample. Methods Subjects were 686 relatives of probands (85.7% first-degree) who participated in a high-risk family study of alcohol dependence. All subjects met criteria for AUD at baseline and were re-interviewed 5 years later. Follow-up status was categorized as persistent AUD, high-risk drinking, remitted low-risk drinking, and abstinence. Social context measures were defined as stable or changing from baseline to follow-up, and their bivariate and multivariate associations with follow-up status were tested. Results At follow-up, 62.8% of subjects had persistent AUD, 6.4% were high-risk drinkers, 22.2% were remitted low-risk drinkers, and 8.6% were abstinent. Birth of first child during the interval was the only measure of social context associated with remitted low-risk drinking and was significant for women only. Abstinent remission was characterized by being stably separated or divorced for women, new marriage for both sexes, experiencing low levels of family support and high levels of friend support, and receiving treatment. High-risk drinkers were more likely than individuals with persistent AUD to have a stable number of children and to have been recently unemployed. Conclusions The social contexts accompanying different types of remission in this high-risk sample resemble those found in population-based and clinical samples. Low-risk drinkers resemble natural remitters from population-based samples who change their drinking habits with life transitions. Abstainers resemble clinical samples in marital context, support from friends, and

  6. Nonoperative options for management of residual stones after cholecystostomy in high-risk patients

    NASA Astrophysics Data System (ADS)

    Reed, David M.; Daye, S. S.; Lincer, R. M.

    1993-05-01

    Cholecystostomy is frequently performed to obtain control of sepsis in high risk patients with acute cholecystitis. Retained stones in the gallbladder may cause future clinical problems. We present two patients with cholecystostomy tubes managed non-operatively. A review of other reported methods for stone extraction or destruction is also presented. Knowledge of safe and effective techniques for removal of these stones, using minimally invasive techniques is useful to the general surgeon.

  7. Common variations in BARD1 influence susceptibility to high-risk neuroblastoma

    PubMed Central

    Capasso, Mario; Hou, Cuiping; Asgharzadeh, Shahab; Glessner, Joseph T.; Attiyeh, Edward F.; Mosse, Yael P.; Kim, Cecilia; Diskin, Sharon J.; Cole, Kristina A.; Bosse, Kristopher; Diamond, Maura; Laudenslager, Marci; Winter, Cynthia; Bradfield, Jonathan P.; Scott, Richard H.; Jagannathan, Jayanti; Garris, Maria; McConville, Carmel; London, Wendy B.; Seeger, Robert C.; Grant, Struan F. A.; Li, Hongzhe; Rahman, Nazneen; Rappaport, Eric

    2009-01-01

    We conducted a SNP-based genome-wide association study (GWAS) focused on the high-risk subset of neuroblastoma1. As our previous unbiased GWAS showed strong association of common 6p22 SNP alleles with aggressive neuroblastoma2, we now restricted our analysis to 397 high-risk cases compared to 2,043 controls. We detected new significant association of six SNPs at 2q35 within the BARD1 gene locus (Pallelic = 2.35×10−9 − 2.25×10−8). Each SNP association was confirmed in a second series of 189 high-risk cases and 1,178 controls (Pallelic = 7.90×10−7 − 2.77×10−4). The two most significant SNPs (rs6435862, rs3768716) were also tested in two additional independent high-risk neuroblastoma case series, yielding combined allelic odds-ratios of 1.68 each (P = 8.65×10−18 and 2.74×10−16, respectively). Significant association was also found with known BARD1 nsSNPs. These data show that common variation in BARD1 contributes to the etiology of the aggressive and most clinically relevant subset of human neuroblastoma. PMID:19412175

  8. Movement Recognition Technology as a Method of Assessing Spontaneous General Movements in High Risk Infants

    PubMed Central

    Marcroft, Claire; Khan, Aftab; Embleton, Nicholas D.; Trenell, Michael; Plötz, Thomas

    2015-01-01

    Preterm birth is associated with increased risks of neurological and motor impairments such as cerebral palsy. The risks are highest in those born at the lowest gestations. Early identification of those most at risk is challenging meaning that a critical window of opportunity to improve outcomes through therapy-based interventions may be missed. Clinically, the assessment of spontaneous general movements is an important tool, which can be used for the prediction of movement impairments in high risk infants. Movement recognition aims to capture and analyze relevant limb movements through computerized approaches focusing on continuous, objective, and quantitative assessment. Different methods of recording and analyzing infant movements have recently been explored in high risk infants. These range from camera-based solutions to body-worn miniaturized movement sensors used to record continuous time-series data that represent the dynamics of limb movements. Various machine learning methods have been developed and applied to the analysis of the recorded movement data. This analysis has focused on the detection and classification of atypical spontaneous general movements. This article aims to identify recent translational studies using movement recognition technology as a method of assessing movement in high risk infants. The application of this technology within pediatric practice represents a growing area of inter-disciplinary collaboration, which may lead to a greater understanding of the development of the nervous system in infants at high risk of motor impairment. PMID:25620954

  9. Clinically Apparent Internal Mammary Nodal Metastasis in Patients With Advanced Breast Cancer: Incidence and Local Control

    SciTech Connect

    Zhang Yujing; Oh, Julia L.; Whitman, Gary J.

    2010-07-15

    Purpose: To investigate the incidence and local control of internal mammary lymph node metastases (IMN+) in patients with clinical N2 or N3 locally advanced breast cancer. Methods and Materials: We retrospectively reviewed the records of 809 breast cancer patients diagnosed with advanced nodal disease (clinical N2-3) who received radiation treatment at our institution from January 2000 December 2006. Patients were considered IMN+ on the basis of imaging studies. Results: We identified 112 of 809 patients who presented with IMN+ disease (13.8%) detected on ultrasound, computed tomography (CT), positron emission tomography/CT (PET/CT), and/or magnetic resonance imaging (MRI) studies. All 112 patients with IMN+ disease received anthracycline and taxane-based chemotherapy. Neoadjuvant chemotherapy (NCT) resulted in a complete response (CR) on imaging studies of IMN disease in 72.1% of patients. Excluding 16 patients with progressive disease, 96 patients received adjuvant radiation to the breast or the chest wall and the regional lymphatics including the IMN chain with a median dose of 60 Gy if the internal mammary lymph nodes normalized after chemotherapy and 66 Gy if they did not. The median follow-up of surviving patients was 41 months (8-118 months). For the 96 patients able to complete curative therapy, the actuarial 5-year IMN control rate, locoregional control, overall survival, and disease-free survival were 89%, 80%, 76%, and 56%. Conclusion: Over ten percent of patients with advanced nodal disease will have IMN metastases on imaging studies. Multimodality therapy including IMN irradiation achieves excellent rates of control in the IMN region and a DFS of more than 50% after curative treatment.

  10. Updated Results and Patterns of Failure in a Randomized Hypofractionation Trial for High-risk Prostate Cancer

    SciTech Connect

    Arcangeli, Stefano; Strigari, Lidia; Gomellini, Sara; Saracino, Biancamaria; Petrongari, Maria Grazia; Pinnaro, Paola; Pinzi, Valentina; Arcangeli, Giorgio

    2012-12-01

    Purpose: To report long-term results and patterns of failure after conventional and hypofractionated radiation therapy in high-risk prostate cancer. Methods and Materials: This randomized phase III trial compared conventional fractionation (80 Gy at 2 Gy per fraction in 8 weeks) vs hypofractionation (62 Gy at 3.1 Gy per fraction in 5 weeks) in combination with 9-month androgen deprivation therapy in 168 patients with high-risk prostate cancer. Freedom from biochemical failure (FFBF), freedom from local failure (FFLF), and freedom from distant failure (FFDF) were analyzed. Results: In a median follow-up of 70 months, biochemical failure (BF) occurred in 35 of the 168 patients (21%) in the study. Among these 35 patients, local failure (LF) only was detected in 11 (31%), distant failure (DF) only in 16 (46%), and both LF and DF in 6 (17%). In 2 patients (6%) BF has not yet been clinically detected. The risk reduction by hypofractionation was significant in BF (10.3%) but not in LF and DF. We found that hypofractionation, with respect to conventional fractionation, determined only an insignificant increase in the actuarial FFBF but no difference in FFLF and FFDF, when considering the entire group of patients. However, an increase in the 5-year rates in all 3 endpoints-FFBF, FFLF, and FFDF-was observed in the subgroup of patients with a pretreatment prostate-specific antigen (iPSA) level of 20 ng/mL or less. On multivariate analysis, the type of fractionation, iPSA level, Gleason score of 4+3 or higher, and T stage of 2c or higher have been confirmed as independent prognostic factors for BF. High iPSA levels and Gleason score of 4+3 or higher were also significantly associated with an increased risk of DF, whereas T stage of 2c or higher was the only independent variable for LF. Conclusion: Our results confirm the isoeffectiveness of the 2 fractionation schedules used in this study, although a benefit in favor of hypofractionation cannot be excluded in the subgroup of

  11. Significance of Image Guidance to Clinical Outcomes for Localized Prostate Cancer

    PubMed Central

    Zhong, Qiuzi; Gao, Hong; Li, Gaofeng; Xiu, Xia; Wu, Qinhong; Li, Ming; Xu, Yonggang

    2014-01-01

    Purpose. To compare toxicity profiles and biochemical tumor control outcomes between patients treated with image-guided intensity-modulated radiotherapy (IG-IMRT) and non-IGRT intensity-modulated radiotherapy (IMRT) for clinically localized prostate cancer. Materials and Methods. Between 2009 and 2012, 65 patients with localized prostate cancer were treated with IG-IMRT. This group of patients was retrospectively compared with a similar cohort of 62 patients who were treated between 2004 and 2009 with IMRT to the same dose without image guidance. Results. The median follow-up time was 4.8 years. The rectal volume receiving ≥40 and ≥70 Gy was significantly lower in the IG-IMRT group. Grade 2 and higher acute and late GI and GU toxicity rates were lower in IG-IMRT group, but there was no statistical difference. No significant improvement in biochemical control at 5 years was observed in two groups. In a Cox regression analysis identifying predictors for PSA relapse-free survival, only preradiotherapy PSA was significantly associated with biochemical control; IG-IMRT was not a statistically significant indicator. Conclusions. The use of image guidance in the radiation of prostate cancer at our institute did not show significant reduction in the rates of GI and GU toxicity and did not improve the biochemical control compared with IMRT. PMID:25110701

  12. Quality control of radiation therapy in multi-institutional randomized clinical trial for localized prostate cancer

    SciTech Connect

    Hafermann, M.D.; Gibbons, R.P.; Murphy, G.P.

    1988-02-01

    The National Prostatic Cancer Project (NPCP) from 1978 through 1985 compared definitive radiation therapy for Stages B2, C, D1 lesions in those who received only radiation treatment to those who received two years of additional cyclophosphamide (Cytoxan) or estramustine phosphate (Emcyt) chemotherapy. Two hundred fifty-four patients were entered and 229 evaluated for compliance of the spatial localization of the prostate through review of the simulation and port films. In 78 per cent this was satisfactory, whereas in 12 per cent it was unsatisfactory, and another 10 per cent were not evaluable. The principle cause of an unsatisfactory rating was failure to adequately cover the prostatic target volume, especially the apex which was found to be variable in location. Routine use of retrograde urethrocystography is urged as part of the localization method in patients to receive definitive external beam radiation therapy for prostate cancer. The role and impact of quality assurance programs for radiotherapy in cooperative clinical study groups is reviewed and discussed.

  13. Enhancement of CLAIM (clinical accounting information) for a localized Chinese version.

    PubMed

    Guo, Jinqiu; Takada, Akira; Niu, Tie; He, Miao; Tanaka, Koji; Sato, Junzo; Suzuki, Muneou; Takahashi, Kiwamu; Daimon, Hiroyuki; Suzuki, Toshiaki; Nakashima, Yusei; Araki, Kenji; Yoshihara, Hiroyuki

    2005-10-01

    CLinical Accounting InforMation (CLAIM) is a standard for the exchange of data between patient accounting systems and electronic medical record (EMR) systems. It uses eXtensible Markup Language (XML) as a meta-language and was developed in Japan. CLAIM is subordinate to the Medical Markup Language (MML) standard, which allows the exchange of medical data between different medical institutions. It has inherited the basic structure of MML 2.x and the current version, version 2.1, contains two modules and nine data definition tables. In China, no data exchange standard yet exists that links EMR systems to accounting systems. Taking advantage of CLAIM's flexibility, we created a localized Chinese version based on CLAIM 2.1. Since Chinese receipt systems differ from those of Japan, some information such as prescription formats, etc. are also different from those in Japan. Two CLAIM modules were re-engineered and six data definition tables were either added or redefined. The Chinese version of CLAIM takes local needs into account, and consequently it is now possible to transfer data between the patient accounting systems and EMR systems of Chinese medical institutions effectively.

  14. Plaque-Associated Local Toxicity Increases over the Clinical Course of Alzheimer Disease.

    PubMed

    Serrano-Pozo, Alberto; Betensky, Rebecca A; Frosch, Matthew P; Hyman, Bradley T

    2016-02-01

    Amyloid (senile) plaques, one of the two pathologic hallmarks of Alzheimer disease (AD), are associated with dystrophic neurites and glial responses, both astrocytic and microglial. Although plaque burden remains relatively stable through the clinical course of AD, whether these features of local plaque toxicity continue to worsen over the course of the disease is unclear. We performed an unbiased plaque-centered quantification of SMI312(+) dystrophic neurites, GFAP(+) reactive astrocytes, and IBA1(+) and CD68(+) activated microglia in randomly selected dense-core (Thioflavin-S(+)) plaques from the temporal neocortex of 40 AD subjects with a symptom duration ranging from 4 to 20 years, and nine nondemented control subjects with dense-core plaques. Dystrophic neurites (Kendall τ = 0.34, P = 0.001), reactive astrocytes (Kendall τ = 0.30, P = 0.003), and CD68(+) (Kendall τ = 0.48, P < 0.0001), but not IBA1 microglia (Kendall τ = 0.045, P = 0.655), exhibited a significant positive correlation with symptom duration. When excluding control subjects, only the positive association between CD68(+) microglia and symptom duration remained significant (Kendall τ = 0.39, P = 0.0003). The presence of the APOEε4 allele did not affect these results. We conclude that plaques exert an increasing toxicity in the surrounding neuropil over the clinical course of AD, thereby potentially contributing to cognitive decline.

  15. Photodynamic therapy of locally advanced pancreatic cancer (VERTPAC study): final clinical results

    NASA Astrophysics Data System (ADS)

    Huggett, M. T.; Jermyn, M.; Gillams, A.; Mosse, S.; Kent, E.; Bown, S. G.; Hasan, T.; Pogue, B. W.; Pereira, S. P.

    2013-03-01

    We undertook a phase I dose-escalation study of verteporfin photodynamic therapy (PDT) in 15 patients with locally advanced pancreatic cancer. Needle placement and laser delivery were technically successful in all patients. Thirteen patients were treated with a single laser fibre. Three treatments were carried out each at 5, 10 and 20 J/cm2; and 5 treatments (4 patients) at 40 J/cm2. A further 2 patients were treated with 2 or 3 laser fibres at 40 J/cm2. Tumour necrosis was measured on CT (computed tomography) by two radiologists 5 days after treatment. There was a clear dosedependent increase in necrosis with a median area of 20 x 16 mm (range 18 x 16 to 35 x 30 mm) at 40 J/cm2. In the 2 patients treated with multiple fibres, necrosis was 40 x 36 mm and 30 x 28 mm, respectively. There were no early complications in patients treated with a single fibre. Both patients treated with multiple fibres had evidence on CT of inflammatory change occurring anterior to the pancreas but without clinical deterioration. These results suggest that single fibre verteporfin PDT is safe in a clinical setting up to 40J/cm2 and produces a dose-dependent area of pancreatic necrosis.

  16. Interobserver consistency of digital rectal examination in clinical staging of localized prostatic carcinoma.

    PubMed

    Angulo, J C; Montie, J E; Bukowsky, T; Chakrabarty, A; Grignon, D J; Sakr, W; Shamsa, F H; Edson Pontes, J

    1995-01-01

    A prospective study was undertaken to determine the reproducibility of clinical staging based on digital rectal examination (DRE) in prostate carcinoma. We evaluated 48 consecutive patients diagnosed with localized prostatic cancer. Four urologists performed DRE and sorted the patients according to the 1992 American Joint Committee on Cancer Classification for prostate cancer. Both the percentage observed total agreement among each couple of two different observers and the interobserver variability (Kappa index) were analyzed. The percentage observed total agreement among observers in distinguishing five clinical subcategories (T1c, T2a, T2b, T2c, and T3a) ranged between 38-60% (mean 49%) and the Kappa index showed interobserver agreement was poor (overall Kappa = 0.3 1). All four examiners agreed in assigning the same subcategory in only 21 % of cases, and 90% of them were T I. If only categories are distinguished (T I, T2, or T3), the percentage observed total agreement rises to 60-71% (mean 66%) and the interexaminer agreement improves to good (overall Kappa = 0.4 1). Accurate pathologic staging was obtained in every patient and the percentage observed agreement between every examiner and the pathologist was calculated, excluding cases interpreted as T I c. Regarding subcategories, clinicopathologic agreement ranges between 17-46%. If only categories T2 and9T3 are distinguished, agreement rises to 57-69%. In summary, the ability to reproduce clinical staging based on DRE among multiple examiners is disappointingly low and understandably correlates poorly with pathologic stage.

  17. Hormone levels are associated with clinical markers and cytokine levels in human localized cutaneous leishmaniasis.

    PubMed

    Baccan, Gyselle Chrystina; Oliveira, Fabiano; Sousa, Adenilma Duranes; Cerqueira, Natali Alexandrino; Costa, Jackson Mauricio Lopes; Barral-Netto, Manoel; Barral, Aldina

    2011-03-01

    Leishmaniasis is a serious health problem in several parts of the world, and localized cutaneous leishmaniasis (LCL) is the most frequent presentation of the tegumentary form of this disease cluster. Clinical presentations of leishmaniasis are influenced by both parasite and host factors, with emphasis on the host immune response. Alterations in plasma hormone levels have been described in many infections, and changes in hormone levels could be related to an imbalanced cytokine profile. In the present work, we evaluated a group of patients with LCL to determine changes in plasma hormone levels (cortisol, DHEA-S, estradiol, prolactin and testosterone) and their association with clinical markers of disease (lesion size, dose used to reach cure and time to cure) and with cytokines produced by PBMC stimulated by SLA (IFN-γ, IL-10 and TNF-α). Individuals with LCL exhibited lower plasma levels of DHEA-S, prolactin and testosterone compared with sex-matched controls, whereas levels of cortisol and estradiol were similar between patients and controls. Plasma levels of cortisol, estradiol or prolactin positively correlated with at least one clinical parameter. Cortisol and prolactin levels exhibited a negative correlation with levels of IFN-γ, whereas no correlation was observed with IL-10 or TNF-α levels. A decrease in DHEA-S levels was observed in male LCL patients when compared to male healthy controls. No other differences between the sexes were observed. Our results indicate a role for neuroendocrine regulation that restricts Th1 responses in human LCL. It is possible that, although impairing parasite killing, such neuroimmunomodulation may contribute to limiting tissue damage.

  18. Establishing a Program for Individuals at High Risk for Breast Cancer

    PubMed Central

    Cadiz, Fernando; Kuerer, Henry M.; Puga, Julio; Camacho, Jamile; Cunill, Eduardo; Arun, Banu

    2013-01-01

    Our need to create a program for individuals at high risk for breast cancer development led us to research the available data on such programs. In this paper, we summarize our findings and our thinking process as we developed our own program. Breast cancer incidence is increasing worldwide. Even though there are known risk factors for breast cancer development, approximately 60% of patients with breast cancer have no known risk factor, although this situation will probably change with further research, especially in genetics. For patients with risk factors based on personal or family history, different models are available for assessing and quantifying risk. Assignment of risk levels permits tailored screening and risk reduction strategies. Potential benefits of specialized programs for women with high breast cancer risk include more cost -effective interventions as a result of patient stratification on the basis of risk; generation of valuable data to advance science; and differentiation of breast programs from other breast cancer units, which can result in increased revenue that can be directed to further improvements in patient care. Guidelines for care of patients at high risk for breast cancer are available from various groups. However, running a high-risk breast program involves much more than applying a guideline. Each high-risk program needs to be designed by its institution with consideration of local resources and country legislation, especially related to genetic issues. Development of a successful high-risk program includes identifying strengths, weaknesses, opportunities, and threats; developing a promotion plan; choosing a risk assessment tool; defining “high risk”; and planning screening and risk reduction strategies for the specific population served by the program. The information in this article may be useful for other institutions considering creation of programs for patients with high breast cancer risk. PMID:23833688

  19. Thromboembolism Prophylaxis in Hip Arthroplasty: Routine and High Risk Patients.

    PubMed

    Nam, Denis; Nunley, Ryan M; Johnson, Staci R; Keeney, James A; Clohisy, John C; Barrack, Robert L

    2015-12-01

    This study's purpose was to present the use of a risk stratification protocol in which "routine" risk patients receive a mobile compression device with aspirin and "high" risk patients receive warfarin for thromboprophylaxis after hip arthroplasty. 1859 hip arthroplasty patients were prospectively enrolled (1402 routine risk--75.4%, 457 high risk--24.6%). The cumulative rate of venous thromboembolism events was 0.5% in the routine versus 0.5% in the high-risk cohort within 6weeks postoperatively (P=1.00). Patients in the routine risk cohort had a lower rate of major bleeding (0.5% versus 2.0%, P=0.006) and wound complications (0.2% versus 1.2%, P=0.01). Use of our risk stratification protocol allowed the avoidance of more aggressive anticoagulation in 75% of patients while achieving a low overall incidence of symptomatic VTE. PMID:26182980

  20. Implementation of a follow-up telephone call process for patients at high risk for readmission.

    PubMed

    Miller, Danielle A; Schaper, Ana M

    2015-01-01

    This project included the development and implementation of a follow-up telephone call within 72 hours of discharge, targeting patients at high risk for readmission. The goal was to improve understanding of aftercare instructions and decrease readmissions. Clinical nurse leaders provided an intervention in 66% of patient contacts. Readmission rate within 7 days of discharge was significantly lower (P < .05), and the rate within 30 days of discharge trended lower (P = .053), in the clinical nurse leader contact group than in patients who were not contacted. PMID:24844916

  1. Local Recurrence After Complete Clinical Response and Watch and Wait in Rectal Cancer After Neoadjuvant Chemoradiation: Impact of Salvage Therapy on Local Disease Control

    SciTech Connect

    Habr-Gama, Angelita; Gama-Rodrigues, Joaquim; São Julião, Guilherme P.; Proscurshim, Igor; Sabbagh, Charles; Lynn, Patricio B.; Perez, Rodrigo O.

    2014-03-15

    Purpose: To review the risk of local recurrence and impact of salvage therapy after Watch and Wait for rectal cancer with complete clinical response (cCR) after chemoradiation therapy (CRT). Methods and Materials: Patients with cT2-4N0-2M0 distal rectal cancer treated with CRT (50.4-54 Gy + 5-fluorouracil-based chemotherapy) and cCR at 8 weeks were included. Patients with cCR were enrolled in a strict follow-up program with no immediate surgery (Watch and Wait). Local recurrence-free survival was compared while taking into account Watch and Wait strategy alone and Watch and Wait plus salvage. Results: 90 of 183 patients experienced cCR at initial assessment after CRT (49%). When early tumor regrowths (up to and including the initial 12 months of follow-up) and late recurrences were considered together, 28 patients (31%) experienced local recurrence (median follow-up time, 60 months). Of those, 26 patients underwent salvage therapy, and 2 patients were not amenable to salvage. In 4 patients, local re-recurrence developed after Watch and Wait plus salvage. The overall salvage rate for local recurrence was 93%. Local recurrence-free survival at 5 years was 69% (all local recurrences) and 94% (after salvage procedures). Thirteen patients (14%) experienced systemic recurrence. The 5-year cancer-specific overall survival and disease-free survival for all patients (including all recurrences) were 91% and 68%, respectively. Conclusions: Local recurrence may develop in 31% of patients with initial cCR when early regrowths (≤12 months) and late recurrences are grouped together. More than half of these recurrences develop within 12 months of follow-up. Salvage therapy is possible in ≥90% of recurrences, leading to 94% local disease control, with 78% organ preservation.

  2. Psychological characteristics in high-risk MSM in China

    PubMed Central

    2012-01-01

    Background Men who have sex with men (MSM) have become a high-risk group of HIV infection in China. To date, little is known regarding the behavioral, social and psychological characteristics in Chinese MSM, which makes the implementation of preventive and therapeutic strategies for this high-risk subpopulation of people extremely difficult. Methods A total of 714 questionnaires were retrieved from the database of a Chinese government-sponsored National Key Research Project titled "Risk Analysis and Strategic Prevention of HIV Transmission from MSM to the General Population in China". The respondents were categorized into a high-risk group and a control group. Their behavioral, social and psychological characteristics were comparatively analyzed. Results Of the 714 MSM analyzed, 59 (8.26%) had high-risk homosexual behaviors. This sub-group of MSM had a higher in-marriage rate, a higher monthly income, heavier alcohol consumption and more serious problems with sexual abuse in childhood, intentional suicide attempts and mistaken assumption on condom's role in protecting HIV infection, as compared with the control group (P < 0.05). In contrast, the two groups did not differ significantly the sexual orientation, level of education, types of profession, drug use, condom use and experience of social stigma and discrimination (P > 0.05). A vast majority of the individuals in both behavior categories expressed support of legally protected gay clubs as well as gay marriage legislation in China. There was a strong correlation between high-risk behaviors and sexual abuse in childhood, alcohol drinking, income level and a mistaken belief in perfect HIV protection through the use of condoms. Conclusions MSM with and without high-risk homosexual behaviors have different social and psychological characteristics, which should be taken into account when implementing behavioral and therapeutic interventions aimed at preventing HIV/AIDS transmission among MSM as well as from MSM to

  3. Effectiveness of Palivizumab in Preventing RSV Hospitalization in High Risk Children: A Real-World Perspective

    PubMed Central

    Rawlinson, William; Snelling, Thomas L.; Jaffe, Adam

    2014-01-01

    Infection with respiratory syncytial virus (RSV) is one of the major causes globally of childhood respiratory morbidity and hospitalization. Palivizumab, a humanized monoclonal antibody, has been recommended for high risk infants to prevent severe RSV-associated respiratory illness. This recommendation is based on evidence of efficacy when used under clinical trial conditions. However the real-world effectiveness of palivizumab outside of clinical trials among different patient populations is not well established. We performed a systematic review focusing on postlicensure observational studies of the protective effect of palivizumab prophylaxis for reducing RSV-associated hospitalizations in infants and children at high risk of severe infection. We searched studies published in English between 1 January 1999 and August 2013 and identified 420 articles, of which 20 met the inclusion criteria. This review supports the recommended use of palivizumab for reducing RSV-associated hospitalization rates in premature infants born at gestational age < 33 weeks and in children with chronic lung and heart diseases. Data are limited to allow commenting on the protective effect of palivizumab among other high risk children, including those with Down syndrome, cystic fibrosis, and haematological malignancy, indicating further research is warranted in these groups. PMID:25548575

  4. Quantitative clinical nonpulsatile and localized visible light oximeter: design of the T-Stat tissue oximeter

    NASA Astrophysics Data System (ADS)

    Benaron, David A.; Parachikov, Ilian H.; Cheong, Wai-Fung; Friedland, Shai; Duckworth, Joshua L.; Otten, David M.; Rubinsky, Boris E.; Horchner, Uwe B.; Kermit, Eben L.; Liu, Frank W.; Levinson, Carl J.; Murphy, Aileen L.; Price, John W.; Talmi, Yair; Weersing, James P.

    2003-07-01

    We report the development of a general, quantitative, and localized visible light clinical tissue oximeter, sensitive to both hypoxemia and ischemia. Monitor design and operation were optimized over four instrument generations. A range of clinical probes were developed, including non-contact wands, invasive catheters, and penetrating needles with injection ports. Real-time data were collected (a) from probes, standards, and reference solutions to optimize each component, (b) from ex vivo hemoglobin solutions co-analyzed for StO2% and pO2 during deoxygenation, and (c) from normoxic human subject skin and mucosal tissue surfaces. Results show that (a) differential spectroscopy allows extraction of features with minimization of the effects of scattering, (b) in vitro oximetry produces a hemoglobin saturation binding curve of expected sigmoid shape and values, and (c) that monitoring human tissues allows real-time tissue spectroscopic features to be monitored. Unlike with near-infrared (NIRS) or pulse oximetry (SpO2%) methods, we found non-pulsatile, diffusion-based tissue oximetry (StO2%) to work most reliably for non-contact reflectance monitoring and for invasive catheter- or needle-based monitoring, using blue to orange light (475-600 nm). Measured values were insensitive to motion artifact. Down time was non-existent. We conclude that the T-Stat oximeter design is suitable for the collection of spectroscopic data from human subjects, and that the oximeter may have application in the monitoring of regional hemoglobin oxygen saturation in the capillary tissue spaces of human subjects.

  5. Long-Term Outcome and Toxicities of Intraoperative Radiotherapy for High-Risk Neuroblastoma

    SciTech Connect

    Gillis, Amy M.; Sutton, Elizabeth; DeWitt, Kelly D.; Matthay, Katherine K.; Weinberg, Vivian; Fisch, Benjamin M.; Chan, Albert; Gooding, Charles; Daldrup-Link, Heike; Wara, William M.; Farmer, Diana L.; Harrison, Michael R.; Haas-Kogan, Daphne

    2007-11-01

    Purpose: To review a historical cohort of consecutively accrued patients with high-risk neuroblastoma treated with intraoperative radiotherapy (IORT) to determine the therapeutic effect and late complications of this treatment. Methods and Materials: Between 1986 and 2002, 31 patients with newly diagnosed high-risk neuroblastoma were treated with IORT as part of multimodality therapy. Their medical records were reviewed to determine the outcome and complications. Kaplan-Meier probability estimates of local control, progression-free survival, and overall survival at 36 months after diagnosis were recorded. Results: Intraoperative radiotherapy to the primary site and associated lymph nodes achieved excellent local control at a median follow-up of 44 months. The 3-year estimate of the local recurrence rate was 15%, less than that of most previously published series. Only 1 of 22 patients who had undergone gross total resection developed recurrence at the primary tumor site. The 3-year estimate of local control, progression-free survival, and overall survival was 85%, 47%, and 60%, respectively. Side effects attributable to either the disease process or multimodality treatment were observed in 7 patients who developed either hypertension or vascular stenosis. These late complications resulted in the death of 2 patients. Conclusions: Intraoperative radiotherapy at the time of primary resection offers effective local control in patients with high-risk neuroblastoma. Compared with historical controls, IORT achieved comparable control and survival rates while avoiding many side effects associated with external beam radiotherapy in young children. Although complications were observed, additional analysis is needed to determine the relative contributions of the disease process and specific components of the multimodality treatment to these adverse events.

  6. High-risk neuroblastoma: a therapy in evolution.

    PubMed

    Fong, Abraham; Park, Julie R

    2009-11-01

    High-risk neuroblastoma remains a therapeutic challenge for pediatric oncologists. It is becoming increasingly evident that conventional chemotherapeutics are approaching or perhaps have already attained their maximum therapeutic potential. The focus of this review is to summarize current therapies and bring to light some of the novel strategies for treating high-risk neuroblastoma. These rationally designed therapies include molecular- and immune-targeted agents in an attempt to exploit the biology of the neuroblastoma cell. These novel therapies are likely to pose a whole new set of challenges and questions and emphasize the need for continued enrollment of patients in therapeutic studies.

  7. Social cognition in children at familial high-risk of developing an eating disorder

    PubMed Central

    Kothari, Radha; Barona, Manuela; Treasure, Janet; Micali, Nadia

    2015-01-01

    Objective: Diagnosis of an eating disorder (ED) has been associated with differences in social cognition. To date research investigating social cognition and ED has mainly employed patient and recovered samples. It is therefore unclear whether differences in social cognition are present prior to onset of ED, potentially contributing to development, or whether differences observed are a consequence of the disorder. We aimed to further explore whether individuals at high-risk for ED present social cognition characteristics previously found in ED groups. Methods: Our sample was drawn from a population-based cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC). Data on maternal ED behaviors over the lifetime were collected through in-depth clinical interviews (n = 1128) conducted using the Structured Clinical Interview for DSM disorders (SCID), and were used to categorize mothers according to ED behaviors over the lifetime: Restricting and Excessive Exercising (n = 58), Purging (n = 70), Binge-eating (n = 72), Binging and Purging (n = 66), no ED (n = 862). High-risk status of children was determined using these maternal lifetime behavioral phenotypes. Children at high-risk (maternal ED exposure) were compared to children at low-risk (born to mothers with no ED) on three measures of social cognition: the Social Communication Disorders Checklist (SCDC) (n = 922), the faces subtest of the Diagnostic Analysis of Non-Verbal Accuracy (DANVA) (n = 722), and the Emotional Triangles Task (n = 750). Results: Children at high-risk for ED showed poorer performance on measures of social cognition compared to children at low-risk. Maternal lifetime binge-eating, and maternal lifetime binging and purging were associated with poorer social communication in children (OR: 2.4, 95% CI: 1.0, 5.7, p = 0.05; and OR: 2.7, 95% CI: 1.1, 6.5, p = 0.03 respectively). Maternal binging and purging was also found to be associated with differential facial emotion processing and

  8. Adolescent gambling and coping within a generalized high-risk behavior framework.

    PubMed

    van Hamel, Anton; Derevensky, Jeffrey; Takane, Yoshio; Dickson, Laurie; Gupta, Rina

    2007-12-01

    Data were collected for 1998 middle/high-school students in Ontario to assess involvement in gambling, substance use, and generalized risky behavior. To predict these outcomes, measures for anxiety, family cohesion, and coping style were also administered. Three a-priori models were posited to account for the impact of risk factors, protective factors, and combined risk/protective factors on the development of risky behaviors. A high-risk cohort composed of subjects endorsing at least one risky behavior (gambling, substance use, or generalized risky behavior) within the clinical range was created to test an unobserved outcome variable created from all three measures of risky behavior, which was successfully predicted by two of the three a-priori models. Implications for the inclusion of gambling within a constellation of high-risk behaviors and recommendations for future prevention efforts are discussed. PMID:17577646

  9. Is screening for pharyngeal Chlamydia trachomatis warranted in high-risk groups?

    PubMed

    Tipple, C; Hill, S C; Smith, A

    2010-11-01

    A recent survey reported that 36% of UK genitourinary medicine clinics offer testing for pharyngeal Chlamydia trachomatis (CT). Screening at this site is targeted at high-risk groups attending our centre, including female sex workers (FSWs) and male sex workers (MSWs). A total of 2406 patients were screened between November 2006 and October 2007. A retrospective case-note review was performed for positive cases. The prevalence of pharyngeal CT was 1.9% in both men and women. The mean number of sexual partners reported in the preceding three months was 168 and 56 for FSWs and MSWs, respectively. Lack of consistent condom use and high numbers of sexual partners identify this population as potential core transmitters of infection. While the British Association of Sexual Health and HIV (BASHH) guidelines do not recommend routine screening for pharyngeal CT, there may be a role in selected high-risk populations.

  10. Is screening for pharyngeal Chlamydia trachomatis warranted in high-risk groups?

    PubMed

    Tipple, C; Hill, S C; Smith, A

    2010-11-01

    A recent survey reported that 36% of UK genitourinary medicine clinics offer testing for pharyngeal Chlamydia trachomatis (CT). Screening at this site is targeted at high-risk groups attending our centre, including female sex workers (FSWs) and male sex workers (MSWs). A total of 2406 patients were screened between November 2006 and October 2007. A retrospective case-note review was performed for positive cases. The prevalence of pharyngeal CT was 1.9% in both men and women. The mean number of sexual partners reported in the preceding three months was 168 and 56 for FSWs and MSWs, respectively. Lack of consistent condom use and high numbers of sexual partners identify this population as potential core transmitters of infection. While the British Association of Sexual Health and HIV (BASHH) guidelines do not recommend routine screening for pharyngeal CT, there may be a role in selected high-risk populations. PMID:21187360

  11. Genetic/Familial High-Risk Assessment: Breast and Ovarian, Version 2.2015.

    PubMed

    Daly, Mary B; Pilarski, Robert; Axilbund, Jennifer E; Berry, Michael; Buys, Saundra S; Crawford, Beth; Farmer, Meagan; Friedman, Susan; Garber, Judy E; Khan, Seema; Klein, Catherine; Kohlmann, Wendy; Kurian, Allison; Litton, Jennifer K; Madlensky, Lisa; Marcom, P Kelly; Merajver, Sofia D; Offit, Kenneth; Pal, Tuya; Rana, Huma; Reiser, Gwen; Robson, Mark E; Shannon, Kristen Mahoney; Swisher, Elizabeth; Voian, Nicoleta C; Weitzel, Jeffrey N; Whelan, Alison; Wick, Myra J; Wiesner, Georgia L; Dwyer, Mary; Kumar, Rashmi; Darlow, Susan

    2016-02-01

    The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast and Ovarian provide recommendations for genetic testing and counseling and risk assessment and management for hereditary cancer syndromes. Guidelines focus on syndromes associated with an increased risk of breast and/or ovarian cancer and are intended to assist with clinical and shared decision-making. These NCCN Guidelines Insights summarize major discussion points of the 2015 NCCN Genetic/Familial High-Risk Assessment: Breast and Ovarian panel meeting. Major discussion topics this year included multigene testing, risk management recommendations for less common genetic mutations, and salpingectomy for ovarian cancer risk reduction. The panel also discussed revisions to genetic testing criteria that take into account ovarian cancer histology and personal history of pancreatic cancer. PMID:26850485

  12. Combination Therapy with Zoledronic Acid and Parathyroid Hormone Improves Bone Architecture and Strength following a Clinically-Relevant Dose of Stereotactic Radiation Therapy for the Local Treatment of Canine Osteosarcoma in Athymic Rats

    PubMed Central

    Curtis, Ryan C.; Custis, James T.; Ehrhart, Nicole P.; Ehrhart, E. J.; Condon, Keith W.; Gookin, Sara E.; Donahue, Seth W.

    2016-01-01

    Clinical studies using definitive-intent stereotactic radiation therapy (SRT) for the local treatment of canine osteosarcoma (OSA) have shown canine patients achieving similar median survival times as the current standard of care (amputation and adjuvant chemotherapy). Despite this, there remains an unacceptable high risk of pathologic fracture following radiation treatment. Zoledronic acid (ZA) and parathyroid hormone (PTH) are therapeutic candidates for decreasing this fracture risk post-irradiation. Due to differing mechanisms, we hypothesized that the combined treatment with ZA and PTH would significantly improve bone healing more than ZA or PTH treatment alone. Using an orthotopic model of canine osteosarcoma in athymic rats, we evaluated bone healing following clinically-relevant doses of radiation therapy (12 Gy x 3 fractions, 36 Gy total). Groups included 36 Gy SRT only, 36 Gy SRT plus ZA, 36 Gy SRT plus ZA and PTH, 36 Gy SRT plus PTH, and 36 Gy SRT plus localized PTH treatment. Our study showed significant increases in bone volume and increased polar moments of inertia (in the distal femoral metaphysis) 8 weeks after radiation in the combined (ZA/PTH) treatment group as compared to radiation treatment alone. Histomorphometric analysis revealed evidence of active mineralization at the study endpoint as well as successful tumor-cell kill across all treatment groups. This work provides further evidence for the expanding potential indications for ZA and PTH therapy, including post-irradiated bone disease due to osteosarcoma. PMID:27332712

  13. Combination Therapy with Zoledronic Acid and Parathyroid Hormone Improves Bone Architecture and Strength following a Clinically-Relevant Dose of Stereotactic Radiation Therapy for the Local Treatment of Canine Osteosarcoma in Athymic Rats.

    PubMed

    Curtis, Ryan C; Custis, James T; Ehrhart, Nicole P; Ehrhart, E J; Condon, Keith W; Gookin, Sara E; Donahue, Seth W

    2016-01-01

    Clinical studies using definitive-intent stereotactic radiation therapy (SRT) for the local treatment of canine osteosarcoma (OSA) have shown canine patients achieving similar median survival times as the current standard of care (amputation and adjuvant chemotherapy). Despite this, there remains an unacceptable high risk of pathologic fracture following radiation treatment. Zoledronic acid (ZA) and parathyroid hormone (PTH) are therapeutic candidates for decreasing this fracture risk post-irradiation. Due to differing mechanisms, we hypothesized that the combined treatment with ZA and PTH would significantly improve bone healing more than ZA or PTH treatment alone. Using an orthotopic model of canine osteosarcoma in athymic rats, we evaluated bone healing following clinically-relevant doses of radiation therapy (12 Gy x 3 fractions, 36 Gy total). Groups included 36 Gy SRT only, 36 Gy SRT plus ZA, 36 Gy SRT plus ZA and PTH, 36 Gy SRT plus PTH, and 36 Gy SRT plus localized PTH treatment. Our study showed significant increases in bone volume and increased polar moments of inertia (in the distal femoral metaphysis) 8 weeks after radiation in the combined (ZA/PTH) treatment group as compared to radiation treatment alone. Histomorphometric analysis revealed evidence of active mineralization at the study endpoint as well as successful tumor-cell kill across all treatment groups. This work provides further evidence for the expanding potential indications for ZA and PTH therapy, including post-irradiated bone disease due to osteosarcoma. PMID:27332712

  14. An optimal adaptive design to address local regulations in global clinical trials.

    PubMed

    Luo, Xiaolong; Shih, Weichung Joe; Ouyang, S Peter; Delap, Robert J

    2010-01-01

    After multi-regional clinical trials (MRCTs) have demonstrated overall significant effects, evaluation for a region-specific effect is often important. Recent guidance from regulatory authorities regarding evaluation for possible country-specific effects has led to research on statistical designs that incorporate such evaluations in MRCTs. These statistical designs are intended to use the MRCTs to address the requirements for global registration of a medicinal product. Adding a regional requirement could change the probability for declaring positive effect for the region when there is indeed no treatment difference as well as when there is in fact a true difference within the region. In this paper, we first quantify those probability structures based on the guidance issued by the Ministry of Health, Labour and Welfare (MHLW) of Japan. An adaptive design is proposed to consider those probabilities and to optimize the efficiency for regional objectives. This two-stage approach incorporates comprehensive global objectives into an integrated study design and may mitigate the need for a separate local bridging study. A procedure is used to optimize region-specific enrollment based on an objective function. The overall sample size requirement is assessed. We will use simulation analyses to illustrate the performance of the proposed study design. PMID:20872620

  15. From the Cover: Alterations in Optineurin Expression and Localization in Pre-clinical Parkinson's Disease Models.

    PubMed

    Wise, John Pierce; Cannon, Jason

    2016-10-01

    Parkinson's disease (PD) is a progressive neurodegenerative disease that affects ∼5 million people around the world. PD etiopathogenesis is poorly understood and curative or disease modifying treatments are not available. Mechanistic studies have identified numerous pathogenic pathways that overlap with many other neurodegenerative diseases. Mutations in the protein optineurin (OPTN) have recently been identified as causative factors for glaucoma and amyotrophic lateral sclerosis. OPTN has multiple recognized roles in neurons, notably in mediating autophagic flux, which has been found to be disrupted in most neurodegenerative diseases. OPTN(+ )aggregates have preliminarily been identified in cytoplasmic inclusions in numerous neurodegenerative diseases, however, whether OPTN has a role in PD pathogenesis has yet to be tested. Thus, we chose to test the hypothesis that OPTN expression and localization would be modulated in pre-clinical PD models. To test our hypothesis, we characterized midbrain OPTN expression in normal rats and in a rat rotenone PD model. For the first time, we show that OPTN is enriched in dopamine neurons in the midbrain, and its expression is modulated by rotenone treatment in vivo Here, animals were sampled at time-points both prior to overt neurodegeneration and after severe behavioral deficits, where a lesion to the nigrostriatal dopamine system is present. The effect and magnitude of OPTN expression changes are dependent on duration of treatment. Furthermore, OPTN colocalizes with LC3 (autophagic vesicle marker) and alpha-synuclein positive puncta in rotenone-treated animals, potentially indicating an important role in autophagy and PD pathogenesis. PMID:27473339

  16. Breast cancer risk in women who fulfill high-risk criteria: at what age should surveillance start?

    PubMed

    Brandt, Andreas; Lorenzo Bermejo, Justo; Sundquist, Jan; Hemminki, Kari

    2010-05-01

    Family history is a strong predictor of hereditary breast cancer, particularly when it includes cases of early onset or bilateral breast cancers and multiple cases of breast or ovarian cancers. This article provides relative risks and cumulative risks of breast cancer in women whose family history indicates high risk. Specifically, the aim was to determine how many years earlier the high-risk women reach the cumulative risk of women without family history at the age at which screening in average-risk women is initiated. The women of the nation-wide Swedish Family-Cancer Database were classified according to clinical criteria based on family history suggesting high risk for hereditary breast ovarian cancer syndrome. The relative risks of breast cancer were calculated as hazard ratio using Cox regression. Cumulative risks of breast cancer were estimated with a stratified Cox model based on Tsiatis' method. The hazard ratios of breast cancer for the considered criteria ranged from 1.50 to 5.99. The cumulative risks ranged from 1 to 10% by age 50 years. The age to reach the same cumulative risk as women lacking a family history at the age of 50 years ranged between 32.0 and 40.8 years. Relative and cumulative risks of women at high risk of breast cancer associated with different clinical criteria were diverse, which may be helpful in considering when current clinical criteria are revised. According to the present results, current recommendations of starting clinical interventions 10 years earlier in high-risk women, based on expert opinions, appear justified at least for the largest high-risk groups. PMID:19641988

  17. The Effect of Radiation Timing on Patients With High-Risk Features of Parameningeal Rhabdomyosarcoma: An Analysis of IRS-IV and D9803

    SciTech Connect

    Spalding, Aaron C.; Hawkins, Douglas S.; Anderson, James R.; Lyden, Elizabeth; Laurie, Fran; Wolden, Suzanne L.; Arndt, Carola A.S.; Michalski, Jeff M.

    2013-11-01

    Purpose: Radiation therapy remains an essential treatment for patients with parameningeal rhabdomyosarcoma (PMRMS), and early radiation therapy may improve local control for patients with intracranial extension (ICE). Methods and Materials: To address the role of radiation therapy timing in PMRMS in the current era, we reviewed the outcome from 2 recent clinical trials for intermediate-risk RMS: Intergroup Rhabdomyosarcoma Study (IRS)-IV and Children's Oncology Group (COG) D9803. The PMRMS patients on IRS-IV with any high-risk features (cranial nerve palsy [CNP], cranial base bony erosion [CBBE], or ICE) were treated immediately at day 0, and PMRMS patients without any of these 3 features received week 6-9 radiation therapy. The D9803 PMRMS patients with ICE received day 0 X-Ray Therapy (XRT) as well; however, those with either CNP or CBBE had XRT at week 12. Results: Compared with the 198 PMRMS patients from IRS-IV, the 192 PMRMS patients from D9803 had no difference (P<.05) in 5-year local failure (19% vs 19%), failure-free-survival (70% vs 67%), or overall survival (75% vs 73%) in aggregate. The 5-year local failure rates by subset did not differ when patients were classified as having no risk features (None, 15% vs 19%, P=.25), cranial nerve palsy/cranial base of skull erosion (CNP/CBBE, 15% vs 28%, P=.22), or intracranial extension (ICE, 21% vs 15%, P=.27). The D9083 patients were more likely to have received initial staging by magnetic resonance imaging (71% vs 53%). Conclusions: These data support that a delay in radiation therapy for high-risk PMRMS features of CNP/CBBE does not compromise clinical outcomes.

  18. The High-Risk (Disturbed and Disturbing) College Student

    ERIC Educational Resources Information Center

    Hollingsworth, Kathy R.; Dunkle, John H.; Douce, Louise

    2009-01-01

    The disturbed and disturbing college student causes the most vexing concerns for student affairs administrators. The Assessment-Intervention of Student Problems (AISP) model offers a useful and easily understood framework for dealing with the various challenges of this high-risk student population. This chapter focuses on changes that have…

  19. Prediction of Violence Perpetration Among High-Risk Youth

    ERIC Educational Resources Information Center

    Sussman, Steve; Skara, Silvana; Weiner, Michelle D.; Dent, Clyde W.

    2004-01-01

    Objectives: To prospectively examine demographic background, personality, perceived environment, and behavior as violence perpetration predictors in emerging adulthood among high-risk adolescents using problem-behavior theory as a conceptual perspective. Methods: Self-report questionnaires were administered 5 years apart to 676 participants.…

  20. Early Identification of Educationally High Potential and High Risk Children.

    ERIC Educational Resources Information Center

    Keogh, Barbara K.; Smith, Carol E.

    Early identification of educationally high potential and high risk children was investigated by following the same 49 children from kindergarten entrance through grade five of a regular school program. Kindergarten predictive measures were the Bender Gestalt Test and teachers' evaluations; follow-up measures were yearly standard achievement test…

  1. Distribution of influenza vaccine to high-risk groups.

    PubMed

    Ompad, Danielle C; Galea, Sandro; Vlahov, David

    2006-01-01

    Vaccine distribution programs have historically targeted individuals at high risk of complications due to influenza. Despite recommendations from the Advisory Committee on Immunization Practices, vaccination coverage among high-risk populations has been generally low. This review systematically summarizes the recent literature evaluating programs in different settings, from within medical settings to venue-based and community-based approaches, in an effort to identify successful program components. The published literature was identified by using the MEDLINE database from 1990 to 2006 covering studies that reported on interventions or programs aimed at vaccinating high-risk populations. The authors reviewed 56 studies. In the United States, the Healthy People 2010 goals included 90% vaccination coverage for adults aged > or = 65 years and 60% for high-risk adults aged 18-64 years. Only a handful of the studies reviewed managed to meet those goals. Interventions that increased vaccination coverage to Healthy People 2010 goals included advertising, provider and patient mailings, registry-based telephone calls, patient and staff education, standing orders coupled with standardized forms, targeting of syringe exchange customers, and visiting nurses. Few studies evaluated the impact of vaccination programs by race/ethnicity and socioeconomic status. Few studies targeted individuals outside of the health-care and social services sectors. Given the growing disparities in health and health-care access, understanding the way in which interventions can remedy disparities is crucial.

  2. High Risk Drinking among Non-Affiliated College Students

    ERIC Educational Resources Information Center

    Smith, Margaret; Finneran, John; Droppa, Marj

    2014-01-01

    This study investigated the high risk drinking practices of unaffiliated college students who are not involved in formal athletics, fraternities, or sororities. Using a qualitative research design, the investigators interviewed students at a northeast public college in fall 2010 to learn about unaffiliated students' drinking experiences and…

  3. Intervening with High-Risk Families via Infant Daycare.

    ERIC Educational Resources Information Center

    Ramey, Craig T.; Farran, Dale C.

    A longitudinal study was conducted at the Frank Porter Graham Center NC to explore the use of educational day care and related services as a mechanism for preparing socially disadvantaged children for success in later public schooling. Infant children of mothers who met a criterion score on a high risk index were randomly assigned to either an…

  4. Identification of High Risk Students from Matriculation Information.

    ERIC Educational Resources Information Center

    Sandusky, Sam T.

    A study was conducted at Sacramento City College (California) to determine the possibility of identifying high-risk students from information available from applications, assessment results, transcripts, and college enrollment data. Fall 1985 grade point averages (GPA) and progress percentages were used for high or low risk determination. Study…

  5. Troubled Relationships: High-Risk Latina Adolescents and Nonresident Fathers

    ERIC Educational Resources Information Center

    Lopez, Vera; Corona, Rosalie

    2012-01-01

    This qualitative study explored 18 high-risk adolescent Latinas' perceptions of their relationships with nonresident fathers. A number of interrelated factors--early childhood memories, mothers' interpretations, and fathers' behaviors--shaped girls' perceptions, which in turn, influenced how they interacted with fathers. Some girls struggled to…

  6. ORGANOPHOSPHATE PESTICIDE EXPOSURES - WHERE ARE THE HIGH RISK CHILDREN?

    EPA Science Inventory

    Methods to identify children at high-risk for organophosphate (OP) pesticide exposure are difficult to develop because biological markers reflect only recent "snapshots" of exposure due to the short half-life of OP compounds (generally about 24 hours). We conducted a series of p...

  7. Staying Alive! Training High-Risk Teams for Self Correction

    NASA Technical Reports Server (NTRS)

    Slack, Kelley; Noe, Raymond; Weaver, Sallie

    2011-01-01

    Research examining teams working in high-risk operations has been lacking. The present symposium showcases research on team training that helps to optimize team performance in environments characterized by life or death situations arising spontaneously after long periods of mundane activity by pulling experts from diverse areas of industry: space flight, health care, and medical simulation.

  8. Cumulative Experiences of Violence among High-Risk Urban Youth

    ERIC Educational Resources Information Center

    Taylor, Catherine A.; Boris, Neil W.; Heller, Sherryl Scott; Clum, Gretchen A.; Rice, Janet C.; Zeanah, Charles H.

    2008-01-01

    This study examines type-specific and cumulative experiences of violence among a vulnerable population of youth. Sixty high-risk, shelter-dwelling, urban youth were interviewed regarding their history of childhood maltreatment, exposure to community violence (ECV), and experience with intimate partner violence (IPV). Results show a high prevalence…

  9. Diagnosis and Management of High Risk Group for Gastric Cancer

    PubMed Central

    Yoon, Hyuk; Kim, Nayoung

    2015-01-01

    Gastric cancer is associated with high morbidity and mortality worldwide. To reduce the socioeconomic burden related to gastric cancer, it is very important to identify and manage high risk group for gastric cancer. In this review, we describe the general risk factors for gastric cancer and define high risk group for gastric cancer. We discuss strategies for the effective management of patients for the prevention and early detection of gastric cancer. Atrophic gastritis (AG) and intestinal metaplasia (IM) are the most significant risk factors for gastric cancer. Therefore, the accurate selection of individuals with AG and IM may be a key strategy for the prevention and/or early detection of gastric cancer. Although endoscopic evaluation using enhanced technologies such as narrow band imaging-magnification, the serum pepsinogen test, Helicobacter pylori serology, and trefoil factor 3 have been evaluated, a gold standard method to accurately select individuals with AG and IM has not emerged. In terms of managing patients at high risk of gastric cancer, it remains uncertain whether H. pylori eradication reverses and/or prevents the progression of AG and IM. Although endoscopic surveillance in high risk patients is expected to be beneficial, further prospective studies in large populations are needed to determine the optimal surveillance interval. PMID:25547086

  10. Prospective screening for deep vein thrombosis in high risk patients.

    PubMed

    Barnes, R W

    1977-08-01

    In 257 patients undergoing total hip replacement, gastric bypass for morbid obesity, major abdominal surgery, and major leg amputation, Doppler ultrasonic screening revealed only five instances of deep vein thrombosis. The present study suggests that Doppler screening of high risk patients is a useful alternative to routine anticoagulant prophylaxis of venous thromboembolic disease.

  11. [USA approval of high-risk medical device].

    PubMed

    Chang, Yongheng

    2013-03-01

    During the practice of supervision and management of medical device in different countries, the strict regulatory and needs of the program by the regulations is to be determined by the risk level of the medical equipment. This paper briefly describes the regulatory requirements of the United States to enter the market for high-risk medical device. PMID:23777072

  12. Diagnosis and management of high risk group for gastric cancer.

    PubMed

    Yoon, Hyuk; Kim, Nayoung

    2015-01-01

    Gastric cancer is associated with high morbidity and mortality worldwide. To reduce the socioeconomic burden related to gastric cancer, it is very important to identify and manage high risk group for gastric cancer. In this review, we describe the general risk factors for gastric cancer and define high risk group for gastric cancer. We discuss strategies for the effective management of patients for the prevention and early detection of gastric cancer. Atrophic gastritis (AG) and intestinal metaplasia (IM) are the most significant risk factors for gastric cancer. Therefore, the accurate selection of individuals with AG and IM may be a key strategy for the prevention and/or early detection of gastric cancer. Although endoscopic evaluation using enhanced technologies such as narrow band imaging-magnification, the serum pepsinogen test, Helicobacter pylori serology, and trefoil factor 3 have been evaluated, a gold standard method to accurately select individuals with AG and IM has not emerged. In terms of managing patients at high risk of gastric cancer, it remains uncertain whether H. pylori eradication reverses and/or prevents the progression of AG and IM. Although endoscopic surveillance in high risk patients is expected to be beneficial, further prospective studies in large populations are needed to determine the optimal surveillance interval.

  13. Biochemical profile and outcome in normal and high risk subjects.

    PubMed

    Vijayalaxmi, K G; Urooj, Asna

    2009-07-01

    The present study was carried out to assess the biochemical profile and outcome of pregnancy and study the adverse consequences if any, among normal and high risk pregnant women. The study group included 182 normal and 168 high risk cases attending to private and Government Hospitals in Bangalore. The high risk groups were: Pregnancy induced hypertension (PIH), gestational diabetes mellitus (GDM), Adolescents and anemic cases. Lipid peroxidation was enhanced in PIH and GDM groups (5.56 nmol/ml and 3.98 nmol/ml) MDA values as compared to other groups. Vitamin E levels were significantly (p< 0.05) lower in PIH group (0.38 mg/dl) as compared to other groups. Caesarean as a mode of delivery indicating more number of complications were higher among GDM (61.9%) followed by PIH group. Incidences of low birth weight were observed more in PIH group. The study revealed occurrence of oxidative stress and adverse outcome among high risk pregnancy groups. PMID:23105848

  14. Impact of a Parenting Program in a High-Risk, Multi-Ethnic Community: The PALS Trial

    ERIC Educational Resources Information Center

    Scott, Stephen; O'Connor, Thomas G.; Futh, Annabel; Matias, Carla; Price, Jenny; Doolan, Moira

    2010-01-01

    Background: Parenting programs have been shown to work when delivered to motivated ethnic majority parents in demonstration projects, but comparatively little is known about their impact when delivered to high-risk, multi-ethnic populations by routine local services. Methods: The Primary Age Learning Skills (PALS) trial was a randomized controlled…

  15. Female seafarers adopt the high risk lifestyle of male seafarers

    PubMed Central

    Hansen, H. L.; Jensen, J.

    1998-01-01

    OBJECTIVE: To study the mortality of women in an occupation known to have a high mortality among men. METHODS: A total of 6788 female seafarers of all job categories who had been employed on Danish merchant ships, passenger ships, and privately owned ferries between 1986 and 1993, were followed up until the end of 1993. RESULTS: Standardised mortality ratio (SMR) was 1.20 (95% confidence interval (95% CI) 0.89 to 1.58) for all causes of death and job categories together. For women in traditionally male jobs, SMR was 2.82 (1.41- 5.05), whereas galley and catering staff had SMRs close to the general female population. The high mortality among women in traditional male jobs could be explained by a high risk of fatal accidents including occupational accidents. In the whole cohort, there were fewer deaths from natural causes than expected but an excess risk of death due to lung cancer, heart diseases, and non-natural deaths. CONCLUSION: The increased mortality could primarily be explained by an excess risk of fatal accidents and suicide. Especially, female seafarers entering traditional male jobs had a high risk of fatal accidents, not only at sea but also ashore. An excess risk of dying of lung cancer and heart diseases probably reflects a high tobacco consumption. Female seafarers are probably influenced by their occupation towards hazardous behaviour and a high risk lifestyle but people with a high risk lifestyle may also be attracted by or forced into high risk jobs such as traditional male jobs at sea.   PMID:9536163

  16. An Automated System for Generating Situation-Specific Decision Support in Clinical Order Entry from Local Empirical Data

    ERIC Educational Resources Information Center

    Klann, Jeffrey G.

    2011-01-01

    Clinical Decision Support is one of the only aspects of health information technology that has demonstrated decreased costs and increased quality in healthcare delivery, yet it is extremely expensive and time-consuming to create, maintain, and localize. Consequently, a majority of health care systems do not utilize it, and even when it is…

  17. Psychiatric Symptoms and Community Violence among High-Risk Patients: A Test of the Relationship at the Weekly Level

    ERIC Educational Resources Information Center

    Skeem, Jennifer L.; Schubert, Carol; Odgers, Candice; Mulvey, Edward P.; Gardner, William; Lidz, Charles

    2006-01-01

    Given the availability of violence risk assessment tools, clinicians are now better able to identify high-risk patients. Once these patients have been identified, clinicians must monitor risk state and intervene when necessary to prevent harm. Clinical practice is dominated by the assumption that increases in psychiatric symptoms elevate risk of…

  18. Spine radiosurgery for the local treatment of spine metastases: Intensity-modulated radiotherapy, image guidance, clinical aspects and future directions

    PubMed Central

    de Moraes, Fabio Ynoe; Taunk, Neil Kanth; Laufer, Ilya; Neves-Junior, Wellington Furtado Pimenta; Hanna, Samir Abdallah; de Andrade Carvalho, Heloisa; Yamada, Yoshiya

    2016-01-01

    Many cancer patients will develop spinal metastases. Local control is important for preventing neurologic compromise and to relieve pain. Stereotactic body radiotherapy or spinal radiosurgery is a new radiation therapy technique for spinal metastasis that can deliver a high dose of radiation to a tumor while minimizing the radiation delivered to healthy, neighboring tissues. This treatment is based on intensity-modulated radiotherapy, image guidance and rigid immobilization. Spinal radiosurgery is an increasingly utilized treatment method that improves local control and pain relief after delivering ablative doses of radiation. Here, we present a review highlighting the use of spinal radiosurgery for the treatment of metastatic tumors of the spine. The data used in the review were collected from both published studies and ongoing trials. We found that spinal radiosurgery is safe and provides excellent tumor control (up to 94% local control) and pain relief (up to 96%), independent of histology. Extensive data regarding clinical outcomes are available; however, this information has primarily been generated from retrospective and nonrandomized prospective series. Currently, two randomized trials are enrolling patients to study clinical applications of fractionation schedules spinal Radiosurgery. Additionally, a phase I clinical trial is being conducted to assess the safety of concurrent stereotactic body radiotherapy and ipilimumab for spinal metastases. Clinical trials to refine clinical indications and dose fractionation are ongoing. The concomitant use of targeted agents may produce better outcomes in the future. PMID:26934240

  19. Stereotactic Body Radiotherapy for Localized Prostate Cancer: Interim Results of a Prospective Phase II Clinical Trial

    SciTech Connect

    King, Christopher R. Brooks, James D.; Gill, Harcharan; Pawlicki, Todd; Cotrutz, Cristian; Presti, Joseph C.

    2009-03-15

    Purpose: The radiobiology of prostate cancer favors a hypofractionated dose regimen. We report results of a prospective Phase II clinical trial of stereotactic body radiotherapy (SBRT) for localized prostate cancer. Methods and Materials: Forty-one low-risk prostate cancer patients with 6 months' minimum follow-up received 36.25 Gy in five fractions of 7.25 Gy with image-guided SBRT alone using the CyberKnife. The early (<3 months) and late (>6 months) urinary and rectal toxicities were assessed using validated quality of life questionnaires (International Prostate Symptom Score, Expanded Prostate Cancer Index Composite) and the Radiation Therapy Oncology Group (RTOG) toxicity criteria. Patterns of prostate-specific antigen (PSA) response are analyzed. Results: The median follow-up was 33 months. There were no RTOG Grade 4 acute or late rectal/urinary complications. There were 2 patients with RTOG Grade 3 late urinary toxicity and none with RTOG Grade 3 rectal complications. A reduced rate of severe rectal toxicities was observed with every-other-day vs. 5 consecutive days treatment regimen (0% vs. 38%, p = 0.0035). A benign PSA bounce (median, 0.4 ng/mL) was observed in 12 patients (29%) occurring at 18 months (median) after treatment. At last follow-up, no patient has had a PSA failure regardless of biochemical failure definition. Of 32 patients with 12 months minimum follow-up, 25 patients (78%) achieved a PSA nadir {<=}0.4 ng/mL. A PSA decline to progressively lower nadirs up to 3 years after treatment was observed. Conclusions: The early and late toxicity profile and PSA response for prostate SBRT are highly encouraging. Continued accrual and follow-up will be necessary to confirm durable biochemical control rates and low toxicity profiles.

  20. Validation of the High-Risk Pregnancy Stress Scale in a sample of hospitalized Greek high-risk pregnant women.

    PubMed

    Gourounti, Kleanthi; Karpathiotaki, Natassa; Karapanou, Vassiliki; Antzaklis, Panos; Daskalakis, Georgios

    2016-01-01

    The aim of the authors in this study was to determine the psychometric properties of the Greek adaptation of the High-Risk Pregnancy Stress Scale (HRPSS) in a sample of high-risk hospitalized pregnant women. The sample consisted of 133 high-risk pregnant women with gestational age from 9 to 37 weeks. Data were collected between February and June of 2014. HRPSS was "forward-backward" translated from English to Greek. Principal axis factoring with promax rotation was used to test the factor structure of the HRPSS. Measures of state anxiety (STAI) and depressive symptoms (EPDS) were used to assess the convergent validity of the HRPSS. Exploratory factor analysis suggested three factors: concerns of pregnancy, movement restriction, and isolation and restriction of external activities. Construct validity was confirmed by computing correlations between the HRPSS and constructions of anxiety and depressive symptoms. Internal consistency reliability was satisfactory (α = 0.813). The original factor structure of the HRPSS was only partly replicated. The results of the exploratory factor analysis suggested that a three-factor solution instead of a two-factor solution would be the most adequate. The HRPSS is an appropriate measure for assessing the levels of concerns regarding pregnancy outcome, movement restriction, isolation, and external activity restrictions in Greek high-risk pregnant women.

  1. Lenalidomide Maintenance for High Risk Multiple Myeloma after Allogeneic Hematopoietic Cell Transplantation

    PubMed Central

    Alsina, Melissa; Becker, Pamela S.; Zhong, Xiaobo; Adams, Alexia; Hari, Parameswaran; Rowley, Scott; Stadtmauer, Edward A.; Vesole, David H.; Logan, Brent; Weisdorf, Daniel; Qazilbash, Muzaffar; Popplewell, Leslie L.; McClune, Brian; Bensinger, William; Riches, Marcie; Giralt, Sergio A.; Pasquini, Marcelo C.

    2016-01-01

    Allogeneic hematopoietic cell transplantation (alloHCT) with reduced intensity conditioning is an appealing option for patients with high risk multiple myeloma (MM). However, progression after alloHCT remains a challenge. Maintenance therapy after alloHCT may offer additional disease control and allow time for a graft-versus-myeloma effect. The primary objective of this clinical trial was to determine the tolerability and safety profile of maintenance lenalidomide (LEN) given on days 1–21 of 28 days cycles, with intra-patient dose escalation during 12 months/cycles after alloHCT. Thirty alloHCT recipients (median age 54 years) with high risk MM were enrolled at 8 centers between 2009–2012. The median time from alloHCT to LEN initiation was 96 days (66–171 days). Eleven patients (37%) completed maintenance and 10 mg daily was the most commonly delivered dose (44%).Most common reasons for discontinuation were aGVHD (37%) and disease progression (37%). Cumulative incidence of grades III–IV acute GVHD from time of initiation of Len was 17%. Outcomes at 18 months after initiation of maintenance were MM progression, 28%; transplant related mortality, 11%; and progression-free and overall survival, 63% and 78%, respectively. The use of LEN post alloHCT is feasible at lower doses, although associated with a 38% incidence of aGVHD. Survival outcomes observed in this high risk MM population warrant further study of this approach. PMID:24769014

  2. Quantitative breast MRI radiomics for cancer risk assessment and the monitoring of high-risk populations

    NASA Astrophysics Data System (ADS)

    Mendel, Kayla R.; Li, Hui; Giger, Maryellen L.

    2016-03-01

    Breast density is routinely assessed qualitatively in screening mammography. However, it is challenging to quantitatively determine a 3D density from a 2D image such as a mammogram. Furthermore, dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) is used more frequently in the screening of high-risk populations. The purpose of our study is to segment parenchyma and to quantitatively determine volumetric breast density on pre-contrast axial DCE-MRI images (i.e., non-contrast) using a semi-automated quantitative approach. In this study, we retroactively examined 3D DCE-MRI images taken for breast cancer screening of a high-risk population. We analyzed 66 cases with ages between 28 and 76 (mean 48.8, standard deviation 10.8). DCE-MRIs were obtained on a Philips 3.0 T scanner. Our semi-automated DCE-MRI algorithm includes: (a) segmentation of breast tissue from non-breast tissue using fuzzy cmeans clustering (b) separation of dense and fatty tissues using Otsu's method, and (c) calculation of volumetric density as the ratio of dense voxels to total breast voxels. We examined the relationship between pre-contrast DCE-MRI density and clinical BI-RADS density obtained from radiology reports, and obtained a statistically significant correlation [Spearman ρ-value of 0.66 (p < 0.0001)]. Our method within precision medicine may be useful for monitoring high-risk populations.

  3. Progression-free survival of two cases of high-risk neuroblastoma with refractory/relapsed disease following surgery alone.

    PubMed

    Sokol, Elizabeth; Haut, Paul R; Gosiengfiao, Yasmin; Feinstein, Kate; Pytel, Peter; Cohn, Susan L

    2013-03-01

    Outcome for the vast majority of high-risk neuroblastoma patients with refractory or relapsed disease is dismal. We report two high-risk patients who remain progression-free for more than 113 and 18 months following the diagnosis of refractory/relapsed disease who were treated with surgery alone. Complete resolution of a refractory thoracic mass and relapsed liver nodules was observed in one patient. The refractory/relapsed disease in the second patient has remained stable. In both cases, the tumor showed histologic evidence of neuroblastoma maturation. These cases demonstrate that refractory/relapsed neuroblastoma is clinically heterogeneous and highlight the need for better biomarkers to optimize patient care.

  4. A comparative study-efficacy and safety of combined spinal epidural anesthesia versus spinal anesthesia in high-risk geriatric patients for surgeries around the hip joint

    PubMed Central

    Tummala, Vengamamba; Rao, Lella Nageswara; Vallury, Manoj Kumar; Sanapala, Anitha

    2015-01-01

    Context: Combined spinal epidural anesthesia (CSEA) has a significant advantage by enabling the use of low dose intrathecal local anesthetic, with knowledge that the epidural catheter may be used to extend the block as necessary. CSEA is useful in high-risk geriatric patients by providing greater hemodynamic stability. Aim: This study is designed to compare the clinical effects of CSEA versus spinal anesthesia in high-risk geriatric patients undergoing surgeries around the hip joint. Materials and Methods: Sixty patients aged >65 years, American Society of Anaesthesiology III and IV were randomly allocated into two equal groups. Group A (n = 30) received CSEA with 1 ml (5 mg) of 0.5% hyperbaric bupivacaine with 25 μg fentanyl through spinal route, and the expected incompleteness of spinal block was managed with small incremental dose of 0.5% isobaric bupivacaine through epidural catheter, 1–1.5 ml for every unblocked segment to achieve T10 sensory level. Group B (n = 30) received spinal anesthesia with 2.5 ml (12.5 mg) of 0.5% hyperbaric bupivacaine and 25 μg fentanyl. Result: Both the groups showed rapid onset, excellent analgesia and good quality motor block. Group A showed a significantly less incidence of hypotension (P < 0.01) along with the provision of prolonging analgesia as compared to Group B. Conclusion: CSEA is a safe, effective, reliable technique with better hemodynamic stability along with the provision of prolonging analgesia compared to spinal anesthesia for high-risk geriatric patients undergoing surgeries around the hip joint. PMID:26417125

  5. Gender disparities in latent tuberculosis infection in high-risk individuals: a cross-sectional study.

    PubMed

    Ting, Wen-Ying; Huang, Shiang-Fen; Lee, Ming-Che; Lin, Yung-Yang; Lee, Yu-Chin; Feng, Jia-Yih; Su, Wei-Juin

    2014-01-01

    Male predominance in active tuberculosis (TB) is widely-reported globally. Gender inequalities in socio-cultural status are frequently regarded as contributing factors for disparities in sex in active TB. The disparities of sex in the prevalence of latent TB infection (LTBI) are less frequently investigated and deserve clarification. In this cross-sectional study conducted in a TB endemic area, we enrolled patients at high-risk for LTBI and progression from LTBI to active TB from 2011 to 2012. Diagnosis of LTBI was made by QuantiFERON-TB Gold In-Tube (QFT-GIT). Differences in sex in terms of prevalence of LTBI and clinical predictors for LTBI were investigated. Associations among age, smoking status, and sex disparities in LTBI were also analyzed. A total of 1018 high-risk individuals with definite QFT-GIT results were included for analysis, including 534 males and 484 females. The proportion of LTBI was significantly higher in males than in females (32.6% vs. 25.2%, p = 0.010). Differences in the proportion of LTBI between sexes were most prominent in older patients (age ≥ 55 years). In multivariate analysis, independent clinical factors associated with LTBI were age (p = 0.014), smoking (p = 0.048), and fibro-calcified lesions on chest radiogram (p = 0.009). Male sex was not an independent factor for LTBI (p = 0.88). When stratifying patients according to the smoking status, the proportion of LTBI remained comparable between sexes among smokers and non-smokers. In conclusion, although the proportion of LTBI is higher in men, there is no significant disparity in terms of sex in LTBI among high-risk individuals after adjusting for age, smoking status, and other clinical factors. PMID:25369472

  6. Gender Disparities in Latent Tuberculosis Infection in High-Risk Individuals: A Cross-Sectional Study

    PubMed Central

    Ting, Wen-Ying; Huang, Shiang-Fen; Lee, Ming-Che; Lin, Yung-Yang; Lee, Yu-Chin

    2014-01-01

    Male predominance in active tuberculosis (TB) is widely-reported globally. Gender inequalities in socio-cultural status are frequently regarded as contributing factors for disparities in sex in active TB. The disparities of sex in the prevalence of latent TB infection (LTBI) are less frequently investigated and deserve clarification. In this cross-sectional study conducted in a TB endemic area, we enrolled patients at high-risk for LTBI and progression from LTBI to active TB from 2011 to 2012. Diagnosis of LTBI was made by QuantiFERON-TB Gold In-Tube (QFT-GIT). Differences in sex in terms of prevalence of LTBI and clinical predictors for LTBI were investigated. Associations among age, smoking status, and sex disparities in LTBI were also analyzed. A total of 1018 high-risk individuals with definite QFT-GIT results were included for analysis, including 534 males and 484 females. The proportion of LTBI was significantly higher in males than in females (32.6% vs. 25.2%, p = 0.010). Differences in the proportion of LTBI between sexes were most prominent in older patients (age ≥55 years). In multivariate analysis, independent clinical factors associated with LTBI were age (p = 0.014), smoking (p = 0.048), and fibro-calcified lesions on chest radiogram (p = 0.009). Male sex was not an independent factor for LTBI (p = 0.88). When stratifying patients according to the smoking status, the proportion of LTBI remained comparable between sexes among smokers and non-smokers. In conclusion, although the proportion of LTBI is higher in men, there is no significant disparity in terms of sex in LTBI among high-risk individuals after adjusting for age, smoking status, and other clinical factors. PMID:25369472

  7. Applying the lessons of high risk industries to health care.

    PubMed

    Hudson, P

    2003-12-01

    High risk industries such as commercial aviation and the oil and gas industry have achieved exemplary safety performance. This paper reviews how they have managed to do that. The primary reasons are the positive attitudes towards safety and the operation of effective formal safety management systems. The safety culture provides an important explanation of why such organisations perform well. An evolutionary model of safety culture is provided in which there is a range of cultures from the pathological through the reactive to the calculative. Later, the proactive culture can evolve towards the generative organisation, an alternative description of the high reliability organisation. The current status of health care is reviewed, arguing that it has a much higher level of accidents and has a reactive culture, lagging behind both high risk industries studied in both attitude and systematic management of patient risks. PMID:14645741

  8. Applying the lessons of high risk industries to health care

    PubMed Central

    Hudson, P

    2003-01-01

    High risk industries such as commercial aviation and the oil and gas industry have achieved exemplary safety performance. This paper reviews how they have managed to do that. The primary reasons are the positive attitudes towards safety and the operation of effective formal safety management systems. The safety culture provides an important explanation of why such organisations perform well. An evolutionary model of safety culture is provided in which there is a range of cultures from the pathological through the reactive to the calculative. Later, the proactive culture can evolve towards the generative organisation, an alternative description of the high reliability organisation. The current status of health care is reviewed, arguing that it has a much higher level of accidents and has a reactive culture, lagging behind both high risk industries studied in both attitude and systematic management of patient risks. PMID:14645741

  9. High-risk energy plans yield low rewards

    NASA Astrophysics Data System (ADS)

    Gwynne, Peter

    2009-10-01

    Scientists have complained that a new research body run by the US Department of Energy (DOE) is suffering from management problems and is rejecting funding proposals without stating why. The DOE's Advanced Research Projects Agency-Energy (ARPA-E) - created in 2007 - is designed to fund high-risk, high-payoff research and development projects in energy. However, the agency, which received its first budget in April, has so far turned down almost 95% of proposals after the first round.

  10. Adaptation of a Published Risk Model to Point-of-care Clinical Decision Support Tailored to Local Workflow.

    PubMed

    Sobel, Jeffrey L; Baker, Craig C; Levy, David; Cain, Carol H

    2015-01-01

    Electronic clinical decision support can bring newly published knowledge to the point of care. However, local organizational buy-in, support for team workflows, IT system ease of use and other sociotechnical factors are needed to promote adoption. We successfully implemented a multi-variate cardiac risk stratification model from another institution into ours. We recreated the model and integrated it into our workflow, accessing it from our EHR with patient-specific data and facilitating clinical documentation if the user accepts the model results. Our clinical leaders championed the change and led educational dissemination efforts. We describe the ad-hoc social and technical collaboration needed to build and deploy the tool. The tool complements a clinical initiative within a community of practice, and is correlated with appropriate use of nuclear imaging. PMID:26958255

  11. Delivering asthma education to special high risk groups.

    PubMed

    FitzGerald, J M; Turner, M O

    1997-12-01

    Patients at high risk from their asthma and therefore worthy of more focused asthma education are those at risk of fatal and near fatal asthma(NFA). In recent years the characteristics of these patients have been better defined. The most important risk factor appears to be a prior history of NFA. Other important features include prior emergency room visits or hospitalization for asthma. Excess use of beta-agonists, especially in the absence of inhaled corticosteroids, also confers increased risk. High risk groups also share similar psychosocial barriers as well as economic deprivation. The benefits of asthma education in these groups have been assessed in a number of studies. In general, asthma education has been shown to have an impact on these patients. Greater effects have been achieved where there has been consistent follow-up by the same physician. Patients require frequent reinforcement of their asthma management, especially regarding their response to acute exacerbations. A sub-group of patients with more severe asthma appear to have a problem perceiving dyspnoea and may therefore benefit from peak flow monitoring but the problem of compliance with this intervention is significant. Behaviour modification plays an important role as does ensuring the patient has adequate resources to purchase medications especially the more expensive anti-inflammatory therapy. Future studies should focus on optimizing the potential benefits of educating high risk patients as they are not only those at greatest risk of death but also consume a disproportionate amount of health care resources.

  12. Screening for pancreatic neoplasia in high-risk individuals: who, what, when, how?

    PubMed

    Canto, Marcia Irene

    2005-07-01

    Pancreatic cancer (PC) is a highly lethal disease. Most symptomatic, clinically detected PCs are advanced and not curable. Indeed, the estimated 5-year survival rate is 4%, which is attributable to late diagnosis and low resection rate. Screening of high-risk individuals and early detection of small PCs and precursor lesions might improve the outcome if curative therapy could be offered in the presymptomatic stage. This article summarizes the available published data and preliminary results and discusses the different approaches to screening for pancreatic neoplasia at 2 university-based programs in the United States.

  13. The Prostate Cancer Intervention Versus Observation Trial: VA/NCI/AHRQ Cooperative Studies Program #407 (PIVOT): design and baseline results of a randomized controlled trial comparing radical prostatectomy with watchful waiting for men with clinically localized prostate cancer.

    PubMed

    Wilt, Timothy J

    2012-12-01

    categorizations incorporating PSA levels, Gleason histologic grade, and tumor stage, it was found that approximately 40% had low-risk, 34% had medium-risk, and 21% had high-risk prostate cancer based on local histopathology. Comparison to our national sample of eligible men declining PIVOT participation as well as to men enrolled in the Scandinavian trial indicated that PIVOT enrollees are representative of men being diagnosed and treated in the United States and quite different from men in the Scandinavian trial. PIVOT enrolled an ethnically diverse population representative of men diagnosed with prostate cancer in the United States. Results will yield important information regarding the relative effectiveness and harms of surgery compared with WW for men with predominately PSA-detected clinically localized prostate cancer.

  14. The Prostate Cancer Intervention Versus Observation Trial: VA/NCI/AHRQ Cooperative Studies Program #407 (PIVOT): design and baseline results of a randomized controlled trial comparing radical prostatectomy with watchful waiting for men with clinically localized prostate cancer.

    PubMed

    Wilt, Timothy J

    2012-12-01

    categorizations incorporating PSA levels, Gleason histologic grade, and tumor stage, it was found that approximately 40% had low-risk, 34% had medium-risk, and 21% had high-risk prostate cancer based on local histopathology. Comparison to our national sample of eligible men declining PIVOT participation as well as to men enrolled in the Scandinavian trial indicated that PIVOT enrollees are representative of men being diagnosed and treated in the United States and quite different from men in the Scandinavian trial. PIVOT enrolled an ethnically diverse population representative of men diagnosed with prostate cancer in the United States. Results will yield important information regarding the relative effectiveness and harms of surgery compared with WW for men with predominately PSA-detected clinically localized prostate cancer. PMID:23271771

  15. Glocal Clinical Registries: Pacemaker Registry Design and Implementation for Global and Local Integration – Methodology and Case Study

    PubMed Central

    da Silva, Kátia Regina; Costa, Roberto; Crevelari, Elizabeth Sartori; Lacerda, Marianna Sobral; de Moraes Albertini, Caio Marcos; Filho, Martino Martinelli; Santana, José Eduardo; Vissoci, João Ricardo Nickenig; Pietrobon, Ricardo; Barros, Jacson V.

    2013-01-01

    Background The ability to apply standard and interoperable solutions for implementing and managing medical registries as well as aggregate, reproduce, and access data sets from legacy formats and platforms to advanced standard formats and operating systems are crucial for both clinical healthcare and biomedical research settings. Purpose Our study describes a reproducible, highly scalable, standard framework for a device registry implementation addressing both local data quality components and global linking problems. Methods and Results We developed a device registry framework involving the following steps: (1) Data standards definition and representation of the research workflow, (2) Development of electronic case report forms using REDCap (Research Electronic Data Capture), (3) Data collection according to the clinical research workflow and, (4) Data augmentation by enriching the registry database with local electronic health records, governmental database and linked open data collections, (5) Data quality control and (6) Data dissemination through the registry Web site. Our registry adopted all applicable standardized data elements proposed by American College Cardiology / American Heart Association Clinical Data Standards, as well as variables derived from cardiac devices randomized trials and Clinical Data Interchange Standards Consortium. Local interoperability was performed between REDCap and data derived from Electronic Health Record system. The original data set was also augmented by incorporating the reimbursed values paid by the Brazilian government during a hospitalization for pacemaker implantation. By linking our registry to the open data collection repository Linked Clinical Trials (LinkedCT) we found 130 clinical trials which are potentially correlated with our pacemaker registry. Conclusion This study demonstrates how standard and reproducible solutions can be applied in the implementation of medical registries to constitute a re-usable framework

  16. [Local information systems at the Pediatric Clinic at the University Clinical Center in Sarajevo--experience and perspectives].

    PubMed

    Buljina, A; Zubcević, S; Hadziselimović, E; Zecević, E; Dzumhur, Z

    1999-01-01

    Computer were first introduced at Pediatric hospital in Sarajevo in 1989 and since 1990 first programs for managing data have been started. They were used for administration of patients and history taking, as well as for collecting clinical data of them. In the beginning, introduction was slow because lot of doctors and nurses were reluctant in using new techniques. But, in a year most of them realized all the advantages PC offers. At that time all the PCs were separated, that has limited their full facilitated data gathering especially in the periods when we lacked all other office materials (paper, typing machines ... even pencils). Thanks to them we have preserved all medical data about patients in 4 years war period. After the end of the War we started project of making clinical network and program that should run most of the work that is performed at Pediatric Hospital in Sarajevo. Everything that is done at hospital and could be helped by the use of the computers was recorded and algorithms were made. The network consists of 15 PC units. Program was developed through several phases from the admittance of the patients and administration regarding it to the discharge letter. Outpatient work was incorporated, as well as gathering all the medical findings of the patients at one place. First experiences are extremely positive. We have speeded up "paper work" and freed much time that medical stuff can spend with patients. The main problems that we encounter are need for permanent education in working with system, lack of more powerful server that can handle more data and introducing of the pictures in the medical records. We conclude that clinical network with the use of good program for managing all the data gathered in the hospital is essential for today's work. PMID:10870623

  17. Fifteen-Year Biochemical Relapse-Free Survival, Cause-Specific Survival, and Overall Survival Following I{sup 125} Prostate Brachytherapy in Clinically Localized Prostate Cancer: Seattle Experience

    SciTech Connect

    Sylvester, John E.; Grimm, Peter D.; Wong, Jason; Galbreath, Robert W.; Merrick, Gregory; Blasko, John C.

    2011-10-01

    Purpose: To report 15-year biochemical relapse-free survival (BRFS), cause-specific survival (CSS), and overall survival (OS) outcomes of patients treated with I{sup 125} brachytherapy monotherapy for clinically localized prostate cancer early in the Seattle experience. Methods and Materials: Two hundred fifteen patients with clinically localized prostate cancer were consecutively treated from 1988 to 1992 with I{sup 125} monotherapy. They were prospectively followed as a tight cohort. They were evaluated for BRFS, CSS, and OS. Multivariate analysis was used to evaluate outcomes by pretreatment clinical prognostic factors. BRFS was analyzed by the Phoenix (nadir + 2 ng/mL) definition. CSS and OS were evaluated by chart review, death certificates, and referring physician follow-up notes. Gleason scoring was performed by general pathologists at a community hospital in Seattle. Time to biochemical failure (BF) was calculated and compared by Kaplan-Meier plots. Results: Fifteen-year BRFS for the entire cohort was 80.4%. BRFS by D'Amico risk group classification cohort analysis was 85.9%, 79.9%, and 62.2% for low, intermediate, and high-risk patients, respectively. Follow-up ranged from 3.6 to 18.4 years; median follow-up was 15.4 years for biochemically free of disease patients. Overall median follow-up was 11.7 years. The median time to BF in those who failed was 5.1 years. CSS was 84%. OS was 37.1%. Average age at time of treatment was 70 years. There was no significant difference in BRFS between low and intermediate risk groups. Conclusion: I{sup 125} monotherapy results in excellent 15-year BRFS and CSS, especially when taking into account the era of treatment effect.

  18. Short-, Intermediate-, and Long-term Quality of Life Outcomes Following Radical Prostatectomy for Clinically Localized Prostate Cancer

    PubMed Central

    Prabhu, Vinay; Lee, Ted; McClintock, Tyler R; Lepor, Herbert

    2013-01-01

    Many clinically localized prostate cancers that are diagnosed today are low risk, and prevention of disease-specific mortality may only be realized decades after treatment. Radical prostatectomy (RP) may adversely impact health-related quality of life (HRQOL) by causing both transient or permanent urinary incontinence and erectile dysfunction. In contrast, RP may also improve HRQOL via relief of lower urinary tract symptoms in men suffering from these symptoms prior to surgery. Because the average man treated for prostate cancer has a life expectancy of approximately 14 years, it is imperative to consider the long-term impact of RP on both survival and HRQOL in treatment decision making. This comprehensive literature review examines short-, intermediate-, and long-term HRQOL following RP. In addition, the long-term results of RP are compared with other treatment modalities for treating clinically localized prostate cancer. PMID:24659913

  19. Multiparametric magnetic resonance imaging for pre-treatment local staging of prostate cancer: A Cancer Care Ontario clinical practice guideline

    PubMed Central

    Salerno, Jennifer; Finelli, Antonio; Morash, Chris; Morgan, Scott C.; Power, Nicholas; Schieda, Nichola; Haider, Masoom A.

    2016-01-01

    Introduction: The utility of T2-weighted magnetic resonance imaging (MRI) in the local staging of prostate cancer is controversial. Due to the success of multiparametric MRI in cancer localization, there is renewed interested in MRI (± functional sequences) for local staging. Guidance on pre-treatment local staging of prostate cancer by MRI was developed using systematic review methodology and expert consultation. Methods: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and other databases were searched to identify studies comparing: (1) MRI staging vs. radical prostatectomy staging on diagnostic accuracy outcomes; and (2) MRI staging vs. routine clinical staging on clinical and patient outcomes. Studies meeting inclusion criteria were synthesized by outcome and sensitivity/specificity analysis by tumour location was performed. Evidence quality of included studies was assessed and considered in recommendation formulation. Results: The literature search identified 2510 citations; 62 studies were included. Analysis of MRI ≥1.5 T plus endorectal coil (ER) (± functional sequences) in the detection of extraprostatic extension or seminal vesicle invasion showed modest sensitivities (≥50%) and excellent specificities (>85%) among patients scheduled for radical prostatectomy. MRI upstaging was shown in 20/21 studies, with large variation in correctness (11–85%). Scarcity of clinical and patient outcomes among studies limited synthesis and evaluation. Quality assessment found non-trivial biases. Conclusions: Modest imaging performance was shown for MRI (1.5 T + ER and 3 T ± ER) ± functional sequences in regards to sensitivity. Limitations in study design, reporting of clinical and patient outcomes, and the heterogeneous use of MRI tempered the strength of the recommendations. PMID:27800062

  20. Candidate Risks Indicators for Bipolar Disorder: Early Intervention Opportunities in High-Risk Youth

    PubMed Central

    Jones, Steven; Goodday, Sarah; Bentall, Richard

    2016-01-01

    Background: Psychiatric illnesses like bipolar disorder are increasingly understood to be neurodevelopmental disorders with clinical, psychological, and biological indicators recognizable long before the emergence of the full-blown syndromes. Methods: This paper is a selective review of findings from studies of high-risk children of affected parents that inform the knowledge of illness risk and development markers of bipolar disorder. We specifically focus on candidate clinical, biological, and psychological risk indicators that could serve as targets for future early intervention and prevention studies. Results: There is convergent evidence from prospective studies that bipolar disorder typically debuts as depressive episodes after puberty. In some high-risk children, sleep and anxiety disorders precede mood disorders by several years and reflect an increased vulnerability. An association between early exposure to adversity (eg, exposure to parental illness, neglect from mother) and increased risk of psychopathology may be mediated through increased stress reactivity evident at both behavioral and biological levels. Inter-related psychological processes including reward sensitivity, unstable self-esteem, rumination, and positive self-appraisal are risk factors for mood disorders. Disturbances in circadian rhythm and immune dysfunction are associated with mood disorders and may be vulnerability markers influenced by these other risk factors. Conclusions: There is accruing evidence of a number of measurable and potentially modifiable markers of vulnerability and developing illness in youth at familial risk for bipolar disorder. Longitudinal studies of multiple biological and psychological risk processes in high-risk offspring, both individually and together, will improve our understanding of illness onset and lead to the development of specific early interventions. PMID:26116493

  1. The meaning of anti-Müllerian hormone levels in patients at a high risk of poor ovarian response.

    PubMed

    Park, Hyun Jong; Lee, Geun Ho; Gong, Du Sik; Yoon, Tae Ki; Lee, Woo Sik

    2016-09-01

    Measurements of ovarian reserve play an important role in predicting the clinical results of assisted reproductive technology (ART). The ideal markers of ovarian reserve for clinical applications should have high specificity in order to determine genuine poor responders. Basal follicle-stimulating hormone levels, antral follicle count, and serum anti-Müllerian hormone (AMH) levels have been suggested as ovarian reserve tests that may fulfill this requirement, with serum AMH levels being the most promising parameter. Serum AMH levels have been suggested to be a predictor of clinical pregnancy in ART for older women, who are at a high risk for decreased ovarian response. We reviewed the prognostic significance of ovarian reserve tests for patients undergoing ART treatment, with a particular focus on the significance of serum AMH levels in patients at a high risk of poor ovarian response. PMID:27689035

  2. The meaning of anti-Müllerian hormone levels in patients at a high risk of poor ovarian response

    PubMed Central

    Park, Hyun Jong; Lee, Geun Ho; Gong, Du Sik; Yoon, Tae Ki

    2016-01-01

    Measurements of ovarian reserve play an important role in predicting the clinical results of assisted reproductive technology (ART). The ideal markers of ovarian reserve for clinical applications should have high specificity in order to determine genuine poor responders. Basal follicle-stimulating hormone levels, antral follicle count, and serum anti-Müllerian hormone (AMH) levels have been suggested as ovarian reserve tests that may fulfill this requirement, with serum AMH levels being the most promising parameter. Serum AMH levels have been suggested to be a predictor of clinical pregnancy in ART for older women, who are at a high risk for decreased ovarian response. We reviewed the prognostic significance of ovarian reserve tests for patients undergoing ART treatment, with a particular focus on the significance of serum AMH levels in patients at a high risk of poor ovarian response. PMID:27689035

  3. The meaning of anti-Müllerian hormone levels in patients at a high risk of poor ovarian response

    PubMed Central

    Park, Hyun Jong; Lee, Geun Ho; Gong, Du Sik; Yoon, Tae Ki

    2016-01-01

    Measurements of ovarian reserve play an important role in predicting the clinical results of assisted reproductive technology (ART). The ideal markers of ovarian reserve for clinical applications should have high specificity in order to determine genuine poor responders. Basal follicle-stimulating hormone levels, antral follicle count, and serum anti-Müllerian hormone (AMH) levels have been suggested as ovarian reserve tests that may fulfill this requirement, with serum AMH levels being the most promising parameter. Serum AMH levels have been suggested to be a predictor of clinical pregnancy in ART for older women, who are at a high risk for decreased ovarian response. We reviewed the prognostic significance of ovarian reserve tests for patients undergoing ART treatment, with a particular focus on the significance of serum AMH levels in patients at a high risk of poor ovarian response.

  4. Selective use of post-mastectomy flap irradiation in high-risk breast cancer patients.

    PubMed

    Asgeirsson, Kristjan S; Holroyd, Ben; Morgan, David A L; Robertson, John F R; Blamey, Roger W; Pinder, Sarah E; Macmillan, R Douglas

    2005-08-01

    The incidence of local recurrence after mastectomy can be reduced by chest wall radiotherapy. However, only a minority of patients are at substantial risk. No UK national guidelines exist for the use of mastectomy flap radiotherapy. This study evaluated a protocol, whereby only high-risk patients were treated with post-mastectomy flap radiotherapy; identified histologically by grade, vascular invasion and nodal status. All women treated by simple mastectomy for invasive breast cancer at the Nottingham Breast Unit from January 1993 to December 1995 were studied (n=292). Postoperative flap radiotherapy was given to 147 high-risk women (50.3%). Median follow-up was 76 months. Overall, 12 women (4.1%) developed a chest wall recurrence; six were single spot recurrences and the remaining six were either multiple spot (n=3) or field change (field change dermal invasion, n=3). The chest wall recurrence rate was 2.7% in those treated with radiotherapy. A low rate of local recurrence has been achieved with selective use of mastectomy flap radiotherapy.

  5. [The PreFord Study. A prospective cohort study to evaluate the risk of a cardiovascular event (overall-collective) as well as a prospective, randomized, controlled, multicentre clinical intervention study (high-risk-collective) on primary prevention of cardiovascular diseases in the Ford Motor Company employees in Germany].

    PubMed

    Gysan, D B; Latsch, J; Bjarnason-Wehrens, B; Albus, C; Falkowski, G; Herold, G; Mey, E; Heinzler, R; Montiel, G; Schneider, C A; Stützer, H; Türk, S; Weisbrod, M; Predel, H G

    2004-02-01

    The PreFord Study is a multicenter prospective cohort study to evaluate guideline based risk management on primary prevention of cardiovascular diseases. Furthermore a randomised controlled trial (RCT) will be designed to analyse the effect of a special intervention program. 40,000 employees of the Ford Motor Company, Visteon Company and Deutz Company in Germany will be included, monitored for ten years and the following primary endpoints will be investigated: 1. evaluation and comparison of established and newly developed risk-scores, 2. the relative impact of single and combined cardiovascular risk factors on cardiovascular diseases, 3. the influence of a novel occupationally integrated ambulant rehabilitation program in combination with a guideline oriented optimal drug therapy within a high risk group on the primary endpoint: risk reduction by, 4. the influence of this intervention on secondary endpoints: death, myocardial infarction and stroke, combined appearance of angina pectoris and hospitalisation, occurrence of cerebral circulatory disorder and hospitalisation, occurrence of peripheral occlusive arterial disease and hospitalisation and single cardiovascular risk factors and cost-benefit-analysis. Beginning with an cross sectional study there will be a systemic screening of cardiovascular risk profiles, of anthropometric data and different lifestyle-factors. Based on these data participants will be differentiated into three risk-groups according to the risk score of the European Society of Cardiology (risk of a lethal primary acute cardiovascular event: I < or = 1%; II > 1-< 5% and III > or = 5%). In the following longitudinal study different strategies will be applied: Group I: low risk (< 0.5% per year): repetition of the investigation after five and ten years. Group II: middle risk, (0.6% to 1.4% per year), repetition of the investigation every two years, instruction of the patients general practitioner (GP) with respect to a risk factor oriented and

  6. Autonomic dysfunction in subjects at high risk for Parkinson's disease.

    PubMed

    Liepelt-Scarfone, Inga; Pilotto, Andrea; Müller, Katharina; Bormann, Christian; Gauss, Katharina; Wurster, Isabel; Streffer, Johannes; Berg, Daniela

    2015-12-01

    Aim of this project was to evaluate autonomic dysfunction in subjects proposed to be at high risk to develop Parkinson's disease (PD) compared to control subjects and PD patients at different disease stages. Combinations of substantia nigra hyperechogenicity (SN+) assessed by transcranial ultrasound (TCS), hyposmia, lifetime prevalence of depression and mild PD-specific motor signs were used to identify subjects at high risk for motor Parkinson's disease (HR-PD). Supine and standing blood pressure (BP), hearth rate (HR), orthostatic, urinary, sexual and bowel symptoms were evaluated in HR-PD, healthy control subjects and PD patients, divided into mild and advanced stages. The study group consisted of 113 PD patients (mild PD n = 71, advanced PD, n = 42), 40 HR-PD individuals and 50 controls. Compared to controls, HR-PD subjects complained more often about urinary (p = 0.002) and bowel dysfunction (p = 0.001) and had a higher diastolic BP drop after standing (p = 0.01). The cumulative number of autonomic symptoms differentiated PD as well as HR-PD significantly from controls (p < 0.001). Advanced PD patients presented often and severe orthostatic symptoms, not significantly different from mild PD after concomitant medication correction. Our results support the presence of urinary and bowel dysfunction in subjects at high risk for motor PD. Presence and severity of orthostatic symptoms was higher during stages and increase in advanced stages, at least partly due to increase in dopaminergic and conflicting medication. Understanding the progression of non-motor aspects in PD might offer the possibility to use them as targets for disease-modifying therapies.

  7. New dimensions in the care of high risk pregnancy.

    PubMed

    Sanchez, P

    1989-01-01

    In June 1989, the past president of the Philippine Nurses Association spoke at the annual convention of the Maternal Child Nurses Association at the Children's Medical Center in Quezon City. She addressed maternal health and high risk pregnancies in the Philippines. The maternal mortality rate was 90/100,000 live births each year. It was 4-5 times higher among remote tribes such as the Muslims of Sulu than the national rate. 54% of maternal deaths were attributed to pregnancy complications especially eclampsia (28%). About 2 million women experienced pregnancy annually and almost 1 million had anemia or were malnourished. 20% of these 1 million women gave birth to low birth weight infants who were at high risk of death from infections. About 574,000 out of 1.4 million infants born annually were unwanted. 63% of pregnant women each year did not want any children. Nurses can play an important role to reduce suffering and death among mothers and infants if they practice good health teaching. For example, they can inform mothers about child spacing and birth limiting. They can also identify high risk pregnancies and refer them to other health professionals to manage them. In September 1987, the Philippines Department of Health sponsored a conference on maternal health. Participants made 6 resolutions. The 1st resolution was to consider maternal mortality an indicator of Health for All by year 2000. They also resolved to declare 1988-97 the Decade of Safe Motherhood which included the creation of a multisectoral task force under the Department of Health. The speaker concluded by encouraging Philippine nurses to resist the temptation to work abroad to make more money and instead stay in the Philippines to care for their own people.

  8. Cardiovascular intervention for high-risk families: the Heart Smart Program.

    PubMed

    Johnson, C C; Nicklas, T A; Arbeit, M L; Harsha, D W; Mott, D S; Hunter, S M; Wattigney, W; Berenson, G S

    1991-11-01

    The Heart Smart Family Health Promotion Program is a multidisciplinary, school-based program for cardiovascular risk reduction among high-risk children and their families. As a program that includes young adults at high risk, it is adaptable to a clinical practice. Nineteen fourth and fifth graders were selected as probands for elevated risk factors after a general screening to identify families for an intervention program. Twenty-three parents participated in a 12-week program focused on eating, exercise, and smoking behavior changes enhanced by behavicral support strategies. Weekly sessions were held in the auditorium/cafeteria of the elementary school and consisted of orientation and presentations, cardiovascular (CV) screening with medical feedback, activities, self-monitoring, counseling, and contingency contracting. Information gathered before and after the program included medical history, CV health knowledge and relevant behavior, blood pressure, serum lipid and lipoprotein values, anthropometric measurements, and urine electrolyte excretion. Both children and parents showed positive changes in eating habits and physical activity and significant changes in knowledge and blood pressure levels, while the children halted their weight gain. We believe this multidisciplinary, behavior-oriented, school-based program can be an effective cardiovascular risk intervention adaptable for a clinical office practice.

  9. Treatment of a High-Risk Diabetic Patient with Peripheral Vascular Disease and Osteomyelitis.

    PubMed

    Allen, Latricia L; Kalmar, Garrett; Driver, Vickie R

    2016-06-01

    We report a case of calcaneal osteomyelitis that was surgically resected from a patient with diabetes and peripheral vascular disease. A 91-year-old male with history of type 2 diabetes, peripheral vascular disease, balloon angioplasty, and recent (2 months ago) stent of the superficial femoral artery presented to the emergency department with a left heel wound infection probed to bone. The patient reported having been on intravenous Zosyn for several months via an outside infectious disease provider for clinical suspicion of osteomyelitis, but noted no improvement. This report includes information regarding the clinical examination and imaging findings, which were used to assess this high-risk patient. Our patient underwent a partial calcanectomy and completed a 6-week course of intravenous antibiotics. The purpose of this case report is to illustrate limb preservation in a high-risk patient with compromised vascular supply who underwent a partial calcanectomy for treatment of calcaneal osteomyelitis. The patient underwent surgical resection of the calcaneus without complications and healed unremarkably with the ability to ambulate while wearing an ankle foot orthosis with a custom shoe. This report was authorized for publication as an educational report to contribute to generalizable knowledge and does not include any patient health information. PMID:27423990

  10. Pragmatic fluid optimization in high-risk surgery patients: when pragmatism dilutes the benefits.

    PubMed

    Reuter, Daniel A

    2012-01-31

    There is increasing evidence that hemodynamic optimization by fluid loading, particularly when performed in the early phase of surgery, is beneficial in high-risk surgery patients: it leads to a reduction in postoperative complications and even to improved long-term outcome. However, it is also true that goal- directed strategies of fluid optimization focusing on cardiac output optimization have not been applied in the clinical routine of many institutions. Reasons are manifold: disbelief in the level of evidence and on the accuracy and practicability of the required monitoring systems, and economics. The FOCCUS trial examined perioperative fluid optimization with a very basic approach: a standardized volume load with 25 ml/kg crystalloids over 6 hours immediately prior to scheduled surgery in high-risk patients. The hypothesis was that this intervention would lead to a compensation of preoperative fluid deficit caused by overnight fasting, and would result in improved perioperative fluid homeostasis with less postoperative complications and earlier hospital discharge. However, the primary study endpoints did not improve significantly. This observation points towards the facts that: firstly, the differentiation between interstitial fluid deficit caused by fasting and intravascular volume loss due to acute blood loss must be recognized in treatment strategies; secondly, the type of fluid replacement may play an important role; and thirdly, protocolized treatment strategies should also always be tailored to suit the patients' individual needs in every individual clinical situation.

  11. Four genes predict high risk of progression from smoldering to symptomatic multiple myeloma (SWOG S0120)

    PubMed Central

    Khan, Rashid; Dhodapkar, Madhav; Rosenthal, Adam; Heuck, Christoph; Papanikolaou, Xenofon; Qu, Pingping; van Rhee, Frits; Zangari, Maurizio; Jethava, Yogesh; Epstein, Joshua; Yaccoby, Shmuel; Hoering, Antje; Crowley, John; Petty, Nathan; Bailey, Clyde; Morgan, Gareth; Barlogie, Bart

    2015-01-01

    Multiple myeloma is preceded by an asymptomatic phase, comprising monoclonal gammopathy of uncertain significance and smoldering myeloma. Compared to the former, smoldering myeloma has a higher and non-uniform rate of progression to clinical myeloma, reflecting a subset of patients with higher risk. We evaluated the gene expression profile of smoldering myeloma plasma cells among 105 patients enrolled in a prospective observational trial at our institution, with a view to identifying a high-risk signature. Baseline clinical, bone marrow, cytogenetic and radiologic data were evaluated for their potential to predict time to therapy for symptomatic myeloma. A gene signature derived from four genes, at an optimal binary cut-point of 9.28, identified 14 patients (13%) with a 2-year therapy risk of 85.7%. Conversely, a low four-gene score (<9.28) combined with baseline monoclonal protein <3 g/dL and albumin ≥3.5 g/dL identified 61 patients with low-risk smoldering myeloma with a 5.0% chance of progression at 2 years. The top 40 probe sets showed concordance with indices of chromosome instability. These data demonstrate high discriminatory power of a gene-based assay and suggest a role for dysregulation of mitotic checkpoints in the context of genomic instability as a hallmark of high-risk smoldering myeloma. PMID:26022710

  12. Air pollution exposure: Who is at high risk?

    NASA Astrophysics Data System (ADS)

    Peled, Ronit

    2011-04-01

    This article reviews the sub-population groups who are at high risk and first to be harmed by air pollution coming from anthropogenic combustions. Epidemiological studies from the last few decades contributed to the understanding of the different levels of susceptibility to air pollution. Older people and young infants, people who suffer from allergies, pulmonary and heart diseases, pregnant women and newborn babies, and deprived populations that suffer from low socio-economic status have all been described as populations at risk. A better understanding of the role of air pollution on large as well as specific populations' health, will promote a better protection policy.

  13. Teamwork in high-risk environments analogous to space

    NASA Technical Reports Server (NTRS)

    Kanki, Barbara G.

    1990-01-01

    Mountaineering expeditions combine a number of factors which make them potentially good analogs to the planetary exploration facet of long-duration space missions. A study of mountain climbing teams was conducted in order to evaluate the usefulness of the environment as a space analog and to specifically identify the factors and issues surrounding teamwork and 'successful' team performance in two mountaineering environments. This paper focuses on social/organizational factors, including team size and structure, leadership styles and authority structure which were found in the sample of 22 climb teams (122 individuals). The second major issue discussed is the construction of a valid performance measure in this high-risk environment.

  14. High-risk human papillomavirus (HPV) DNA sequences in metaplastic breast carcinomas of Mexican women

    PubMed Central

    2013-01-01

    Background Metaplastic carcinoma, an uncommon subtype of breast cancer, is part of the spectrum of basal-like, triple receptor-negative breast carcinomas. The present study examined 20 surgical specimens of metaplastic breast carcinomas, for the presence of high-risk Human papillomavirus (HPV), which is suspected to be a potential carcinogenic agent for breast carcinoma. Methods Mastectomy specimens from patients harboring metaplastic breast carcinoma, as defined by the World Health Organization (WHO), and who attended the Instituto Nacional de Cancerologia in Mexico City, were retrieved from the files of the Department of Pathology accumulated during a 16-year period (1995–2008). Demographic and clinical information was obtained from patients’ medical records. DNA was extracted from formalin-fixed, paraffin-embedded tumors and HPV type-specific amplification was performed by means of Polymerase chain reaction (PCR). Quantitative Real-time (RT) PCR was conducted in HPV positive cases. Statistically, the association of continuous or categorical variables with HPV status was tested by the Student t, the Chi square, or Fisher’s exact tests, as appropriate. Results High-risk HPV DNA was detected in eight (40%) of 20 metaplastic breast carcinomas: seven (87.5%) HPV-16 and one (12.5%) HPV-18. Mean age of patients with HPV-positive cases was 49 years (range 24–72 years), the same as for HPV-negative cases (range, 30–73 years). There were not striking differences between HPV + and HPV– metaplastic carcinomas regarding clinical findings. Nearly all cases were negative for estrogen, progesterone and Human epidermal growth factor receptor 2 (HER2), but positive for Epidermal growth factor receptor (EGFR). Conclusions High-risk HPV has been strongly associated with conventional breast carcinomas, although the subtle mechanism of neoplastic transformation is poorly understood. In Mexican patients, the prevalence of HPV infection among metaplastic breast

  15. Analysis of clinical records of dental patients attending Jordan University Hospital: Documentation of drug prescriptions and local anesthetic injections

    PubMed Central

    Dar-Odeh, Najla; Ryalat, Soukaina; Shayyab, Mohammad; Abu-Hammad, Osama

    2008-01-01

    Objectives: The aim of this study was to analyze clinical records of dental patients attending the Dental Department at the University of Jordan Hospital: a teaching hospital in Jordan. Analysis aimed at determining whether dental specialists properly documented the drug prescriptions and local anesthetic injections given to their patients. Methods: Dental records of the Dental Department at the Jordan University Hospital were reviewed during the period from April 3rd until April 26th 2007 along with the issued prescriptions during that period. Results: A total of 1000 records were reviewed with a total of 53 prescriptions issued during that period. Thirty records documented the prescription by stating the category of the prescribed drug. Only 13 records stated the generic or the trade names of the prescribed drugs. Of these, 5 records contained the full elements of a prescription. As for local anesthetic injections, the term “LA used” was found in 22 records while the names and quantities of the local anesthetics used were documented in only 13 records. Only 5 records documented the full elements of a local anesthetic injection. Conclusion: The essential data of drug prescriptions and local anesthetic injections were poorly documented by the investigated group of dental specialists. It is recommended that the administration of the hospital and the dental department implement clear and firm guidelines for dental practitioners in particular to do the required documentation procedure. PMID:19209291

  16. High-Dose-Rate Interstitial Brachytherapy as Monotherapy for Clinically Localized Prostate Cancer: Treatment Evolution and Mature Results

    SciTech Connect

    Zamboglou, Nikolaos; Tselis, Nikolaos; Baltas, Dimos; Buhleier, Thomas; Martin, Thomas; Milickovic, Natasa; Papaioannou, Sokratis; Ackermann, Hanns; Tunn, Ulf W.

    2013-03-01

    Purpose: To report the clinical outcome of high-dose-rate (HDR) interstitial (IRT) brachytherapy (BRT) as sole treatment (monotherapy) for clinically localized prostate cancer. Methods and Materials: Between January 2002 and December 2009, 718 consecutive patients with clinically localized prostate cancer were treated with transrectal ultrasound (TRUS)-guided HDR monotherapy. Three treatment protocols were applied; 141 patients received 38.0 Gy using one implant in 4 fractions of 9.5 Gy with computed tomography-based treatment planning; 351 patients received 38.0 Gy in 4 fractions of 9.5 Gy, using 2 implants (2 weeks apart) and intraoperative TRUS real-time treatment planning; and 226 patients received 34.5 Gy, using 3 single-fraction implants of 11.5 Gy (3 weeks apart) and intraoperative TRUS real-time treatment planning. Biochemical failure was defined according to the Phoenix consensus, and toxicity was evaluated using Common Toxicity Criteria for Adverse Events version 3. Results: The median follow-up time was 52.8 months. The 36-, 60-, and 96-month biochemical control and metastasis-free survival rates for the entire cohort were 97%, 94%, and 90% and 99%, 98%, and 97%, respectively. Toxicity was scored per event, with 5.4% acute grade 3 genitourinary and 0.2% acute grade 3 gastrointestinal toxicity. Late grade 3 genitourinary and gastrointestinal toxicities were 3.5% and 1.6%, respectively. Two patients developed grade 4 incontinence. No other instance of grade 4 or greater acute or late toxicity was reported. Conclusion: Our results confirm IRT-HDR-BRT is safe and effective as monotherapy for clinically localized prostate cancer.

  17. Management of high-risk gestational trophoblastic disease.

    PubMed

    Lurain, J R

    1998-01-01

    Multimodality therapy with combination chemotherapy employing etoposide, high-dose methotrexate, actinomycin D, cyclophosphamide and vincristine (EMA-CO), and adjuvant radiotherapy and surgery, when indicated, has resulted in cure rates of 80-90% in patients with high-risk metastatic gestational trophoblastic tumors. However, approximately 25-30% of high-risk patients will have an incomplete response to first-time chemotherapy or will relapse from remission. Most of these patients will have a clinicopathologic diagnosis of choriocarcinoma, metastases to sites other than the lung and vagina, more than eight metastases and/or failed inappropriate previous chemotherapy, resulting in very high World Health Organization scores. Salvage chemotherapy with cisplatin/etoposide, usually in conjunction with bleomycin or ifosfamide, as well as surgical resection of sites of resistant disease in selected patients, will result in a cure in most patients. New technology, such as the use of colony-stimulating factors to prevent treatment delays and dose reductions or high-dose chemotherapy with or without autologous bone marrow transplantation or peripheral blood stem cell support, may play an important role in the future management of patients who develop drug resistance. PMID:9475149

  18. Great expectations: different high-risk activities satisfy different motives.

    PubMed

    Barlow, Matthew; Woodman, Tim; Hardy, Lew

    2013-09-01

    Research on people's motives for engaging in high-risk activities has typically been viewed through the single-focused lens of sensation seeking. We provide evidence that comprehensively challenges that view. First, we develop and confirm the structure of a 3-factor measure of motives: the Sensation Seeking, Emotion Regulation, and Agency Scale (SEAS; Study 1). We then use the SEAS to provide evidence of differential motives for 2 high-risk activities: skydiving and mountaineering. The motive for skydiving is strongly associated with sensation seeking; the motive for mountaineering is strongly associated with emotion regulation and agency but not with sensation seeking (Study 2). We also show that these conclusions cannot be drawn from existing measures of personality and sensation seeking (Study 3). Finally, individuals who are motivated by emotion regulation and agency needs also have greater expectations regarding their emotion regulation and agency. It is these greater expectations that most successfully discriminate mountaineers from skydivers and control participants (Study 4). It is concluded that researchers should no longer consider risk takers as a homogenous sensation-seeking group and that they should consider risk taking as a potential model of human endeavor. The SEAS can be used as a measure of motives for behavior whenever sensation seeking, agency, or emotion regulation is thought to be at the core of such motives, and the results are discussed in the context of encouraging personality researchers to consider the specific spontaneous behaviors that motivate different people.

  19. Personality differences in high risk sports amateurs and instructors.

    PubMed

    Watson, Alison E; Pulford, Briony D

    2004-08-01

    This study investigated the personality differences of 21 amateurs and 20 instructors who participated in the high risk sports of skydiving, hang-gliding, paragliding, scuba diving, microlighting, and rock climbing, versus those who did not. 38 men and 28 women (M age=32.6 yr., SD= 10.0) were assessed using the Eysenck Personality Questionnaire-Revised, the General Health Questionnaire, the Generalised Self-efficacy Scale, and a Type A/B personality measure. Instructors and Amateurs scored significantly higher on Extroversion and lower on Neuroticism than Nonparticipants; however, they differed from each other on the General Health Questionnaire and Type A/B personality scores. Amateurs scored significantly higher on Psychoticism and Self-efficacy than Instructors and Nonparticipants. In conclusion, these test scores suggest that people who are attracted to high risk sports tend to be at the extroverted and emotionally stable end of the scale, with a tendency to exhibit Type A characteristics; however, Instructors' scores on Psychoticism and Self-efficacy are more akin to those of Nonparticipants.

  20. Multicentre clinical study with tolciclate in the local treatment of skin mycoses in 1083 patients.

    PubMed

    Intini, C; Battaglia, A; Mangiarotti, A M; Picco, A M; Viaro, D; Sacchetti, G

    1980-01-01

    A multicentre clinical trial with tolciclate was carried out in Italy on 1083 patients suffering from skin mycoses (tinea corporis, tinea cruris, tinea pedis, tinea manuum and pityriasis versicolor). Both preparations (1% cream and lotion) showed a good activity evaluated weekly by clinical examinations and mycological assessments, i.e. culture for tineas and microscopy for pityriasis versicolor. Favourable clinical results ranged from 83% to 97% according to diagnoses. Cultural or microscopic conversions obtained in a mean time of about 2 weeks varied from 70% to 91%. Mycological relapses a month after the end of treatment were seen in 6.5% of cases examined. Adverse reactions were observed in 5.6% of patients but the treatment was discontinued only in 2.6%.

  1. [Progress of clinical application of functional MRI in the localization of brain language area].

    PubMed

    Zhang, Nan; Lu, Junfeng; Wu, Jinsong

    2016-02-01

    For surgical operation in the functional area in the brain, it's commonly demanded to resect the lesion to the maximal extent on the basis of preserve the normal neural function, thus the precise localization of functional area is extremely important. As for the advantages of being widely available, easy to grasp and non-invasive, the functional MRI (fMRI) has come into wide use, while the application of language fMRI is still in the initial stage. It's important to choose appropriate fMRI task according to the individual condition of the subject, the commonly-adopted tasks include verb generation, picture naming, word recognition, word generation, etc. However, the effectiveness of using fMRI to localize language area is not totally satisfactory, adopting multiple task is an effective approach to improve the sensitivity of this technique. The application of resting state fMRI in the localization of language area and the further research of the role of fMRI in localizing the Chinese language area are the important future directions.

  2. Clarification of the circulatory patho-physiology of anaesthesia - implications for high-risk surgical patients.

    PubMed

    Wolff, Christopher B; Green, David W

    2014-12-01

    The paper examines the effects of anaesthesia on circulatory physiology and their implications regarding improvement in perioperative anaesthetic management. Changes to current anaesthetic practice, recommended recently, such as the use of flow monitoring in high risk patients, are already beginning to have an impact in reducing complications but not mortality [1]. Better understanding of the patho-physiology should help improve management even further. Analysis of selected individual clinical trials has been used to illustrate particular areas of patho-physiology and how changes in practice have improved outcome. There is physiological support for the importance of achieving an appropriate rate of oxygen delivery (DO2), particularly following induction of anaesthesia. It is suggested that ensuring adequate DO2 during anaesthesia will avoid development of oxygen debt and hence obviate the need to induce a high, compensatory, DO2 in the post-operative period. In contrast to the usual assumptions underlying strategies requiring a global increase in blood flow [1] by a stroke volume near maximization strategy, blood flow control actually resides entirely at the tissues not at the heart. This is important as the starting point for understanding failed circulatory control as indicated by 'volume dependency'. Local adjustments in blood flow at each individual organ - auto-regulation - normally ensure the appropriate local rate of oxygen supply, i.e. local DO2. Inadequate blood volume leads to impairment of the regulation of blood flow, particularly in the individual tissues with least capable auto-regulatory capability. As demonstrated by many studies, inadequate blood flow first occurs in the gut, brain and kidney. The inadequate blood volume which occurs with induction of anaesthesia is not due to blood volume loss, but probably results from redistribution due to veno-dilation. The increase in venous capacity renders the existing blood volume inadequate to maintain

  3. Adjunctive Systemic and Local Antimicrobial Therapy in the Surgical Treatment of Peri-implantitis: A Randomized Controlled Clinical Trial.

    PubMed

    Carcuac, O; Derks, J; Charalampakis, G; Abrahamsson, I; Wennström, J; Berglundh, T

    2016-01-01

    The aim of the present randomized controlled clinical trial was to investigate the adjunctive effect of systemic antibiotics and the local use of chlorhexidine for implant surface decontamination in the surgical treatment of peri-implantitis. One hundred patients with severe peri-implantitis were recruited. Surgical therapy was performed with or without adjunctive systemic antibiotics or the local use of chlorhexidine for implant surface decontamination. Treatment outcomes were evaluated at 1 y. A binary logistic regression analysis was used to identify factors influencing the probability of treatment success, that is, probing pocket depth ≤5 mm, absence of bleeding/suppuration on probing, and no additional bone loss. Treatment success was obtained in 45% of all implants but was higher in implants with a nonmodified surface (79%) than those with a modified surface (34%). The local use of chlorhexidine had no overall effect on treatment outcomes. While adjunctive systemic antibiotics had no impact on treatment success at implants with a nonmodified surface, a positive effect on treatment success was observed at implants with a modified surface. The likelihood for treatment success using adjunctive systemic antibiotics in patients with implants with a modified surface, however, was low. As the effect of adjunctive systemic antibiotics depended on implant surface characteristics, recommendations for their use in the surgical treatment of peri-implantitis should be based on careful assessments of the targeted implant (ClinicalTrials.gov NCT01857804).

  4. Concurrent Androgen Deprivation Therapy During Salvage Prostate Radiotherapy Improves Treatment Outcomes in High-Risk Patients

    SciTech Connect

    Soto, Daniel E.; Passarelli, Michael N.; Daignault, Stephanie; Sandler, Howard M.

    2012-03-01

    Purpose: To determine whether concurrent androgen deprivation therapy (ADT) during salvage radiotherapy (RT) improves prostate cancer treatment outcomes. Methods and Materials: A total of 630 postprostatectomy patients were retrospectively identified who were treated with three-dimensional conformal RT. Of these, 441 were found to be treated for salvage indications. Biochemical failure was defined as prostate-specific antigen (PSA) of 0.2 ng/mL or greater above nadir with another PSA increase or the initiation of salvage ADT. Progression-free survival (PFS) was defined as the absence of biochemical failure, continued PSA rise despite salvage therapy, initiation of systemic therapy, clinical progression, or distant failure. Multivariate-adjusted Cox proportional hazards modeling was performed to determine which factors predict PFS. Results: Low-, intermediate-, and high-risk patients made up 10%, 24%, and 66% of patients, respectively. The mean RT dose was 68 Gy. Twenty-four percent of patients received concurrent ADT (cADT). Regional pelvic nodes were treated in 16% of patients. With a median follow-up of 3 years, the 3-year PFS was 4.0 years for cADT vs. 3.4 years for cADT patients (p = 0.22). Multivariate analysis showed that concurrent ADT (p = 0.05), Gleason score (p < 0.001), and pre-RT PSA (p = 0.03) were independent predictors of PFS. When patients were stratified by risk group, the benefits of cADT (hazard ratio, 0.65; p = 0.046) were significant only for high-risk patients. Conclusions: This retrospective study showed a PFS benefit of concurrent ADT during salvage prostate RT. This benefit was observed only in high-risk patients.

  5. Myeloablative therapy against high risk Ewing's sarcoma: A single institution experience and literature review

    PubMed Central

    Lopez, Jose Luis; Pérez, Concepcion; Marquez, Catalina; Cabrera, Patricia; Perez, Jose Maria; Ramirez, Gema Lucia; Ordoñez, Rafael; Praena-Fernandez, Juan Manuel; Ortiz, Maria Jose

    2011-01-01

    Background Attempts to improve survival outcomes of patients with high risk Ewing's sarcoma (ES) have focused on chemotherapy dose intensification strategies. Aim The objective of this study is to retrospectively evaluate clinical characteristics and outcome of pediatric patients with high risk ES treated at a single institution. Materials and methods From 1995 to 2008, seventeen patients (male:female, 14:3) were treated with dose-intensive therapy in our institution. Median age at diagnosis was 10 years (range: 2–15). Seven patients had metastases at diagnosis (lung in 6 cases and bone in one case). Eleven patients presented with unresectable disease. Fifteen (88.2%) received the Spanish Society of Pediatric Oncology protocol which includes six cycles of vincristine, doxorubicin, ifosfamide and etoposide. Two out of the six cases that were resectable received postoperative radiation. In addition, eleven patients received definitive radiation therapy. Finally, twelve (70.5%) out of 17 patients received myeloablative therapy with melphalan/etoposide. The rest of patients (N = 5) received busulfan/melphalan. Results Median follow-up was 78 months (range: 15–155 months). Initial responses were complete in all patients, but 9 of them developed progression disease. Seven patients became long-term event-free survivors. No patient died of toxicity after transplantation. The 2- and 5-year overall survival rates for all patients were 93% and 73%, respectively. Event-free survival rates were 74% and 54% at 2 and 5 years, respectively. Conclusion This single-institution experience suggests that myeloablative therapy against high risk ES is effective and safe. PMID:24376974

  6. Lenalidomide maintenance for high-risk multiple myeloma after allogeneic hematopoietic cell transplantation.

    PubMed

    Alsina, Melissa; Becker, Pamela S; Zhong, Xiaobo; Adams, Alexia; Hari, Parameswaran; Rowley, Scott; Stadtmauer, Edward A; Vesole, David H; Logan, Brent; Weisdorf, Daniel; Qazilbash, Muzaffar; Popplewell, Leslie L; McClune, Brian; Bensinger, William; Riches, Marcie; Giralt, Sergio A; Pasquini, Marcelo C

    2014-08-01

    Allogeneic hematopoietic cell transplantation (alloHCT) with reduced-intensity conditioning is an appealing option for patients with high-risk multiple myeloma (MM). However, progression after alloHCT remains a challenge. Maintenance therapy after alloHCT may offer additional disease control and allow time for a graft-versus-myeloma effect. The primary objective of this clinical trial was to determine the tolerability and safety profile of maintenance lenalidomide (LEN) given on days 1 to 21 of 28 days cycles, with intrapatient dose escalation during 12 months/cycles after alloHCT. Thirty alloHCT recipients (median age, 54 years) with high-risk MM were enrolled at 8 centers between 2009 and 2012. The median time from alloHCT to LEN initiation was 96 days (range, 66 to 171 days). Eleven patients (37%) completed maintenance and 10 mg daily was the most commonly delivered dose (44%). Most common reasons for discontinuation were acute graft-versus-host disease (GVHD) (37%) and disease progression (37%). Cumulative incidence of grades III to IV acute GVHD from time of initiation of LEN was 17%. Outcomes at 18 months after initiation of maintenance were MM progression, 28%; transplantation-related mortality, 11%; and progression-free and overall survival, 63% and 78%, respectively. The use of LEN after alloHCT is feasible at lower doses, although it is associated with a 38% incidence of acute GVHD. Survival outcomes observed in this high-risk MM population warrant further study of this approach. PMID:24769014

  7. Evaluation of the Modified Asthma Predictive Index in High-Risk Preschool Children

    PubMed Central

    Chang, Timothy S.; Lemanske, Robert F.; Guilbert, Theresa W.; Gern, James E.; Coen, Michael H.; Evans, Michael D.; Gangnon, Ronald E.; Page, C. David; Jackson, Daniel J.

    2013-01-01

    BACKGROUND Prediction of subsequent school-age asthma during the preschool years has proven challenging. OBJECTIVE To confirm in a post hoc analysis the predictive ability of the modified Asthma Predictive Index (mAPI) in a high-risk cohort and a theoretical unselected population. We also tested a potential mAPI modification with a 2-wheezing episode requirement (m2API) in the same populations. METHODS Subjects (n = 289) with a family history of allergy and/or asthma were used to predict asthma at age 6, 8, and 11 years with the use of characteristics collected during the first 3 years of life. The mAPI and the m2API were tested for predictive value. RESULTS For the mAPI and m2API, school-age asthma prediction improved from 1 to 3 years of age. The mAPI had high predictive value after a positive test (positive likelihood ratio ranging from 4.9 to 55) for asthma development at years 6, 8, and 11. Lowering the number of wheezing episodes to 2 (m2API) lowered the predictive value after a positive test (positive likelihood ratio ranging from 1.91 to 13.1) without meaningfully improving the predictive value of a negative test. Posttest probabilities for a positive mAPI reached 72% and 90% in unselected and high-risk populations, respectively. CONCLUSIONS In a high-risk cohort, a positive mAPI greatly increased future asthma probability (eg, 30% pretest probability to 90% posttest probability) and is a preferred predictive test to the m2API. With its more favorable positive posttest probability, the mAPI can aid clinical decision making in assessing future asthma risk for preschool-age children. PMID:24187656

  8. Cryosurgery would be An Effective Option for Clinically Localized Prostate Cancer: A Meta-analysis and Systematic Review

    PubMed Central

    Gao, Liang; Yang, Lu; Qian, Shengqiang; Tang, Zhuang; Qin, Feng; Wei, Qiang; Han, Ping; Yuan, Jiuhong

    2016-01-01

    Cryosurgery (CS) has been used on patients with clinically localized PCa for more than 10 years. However, clinical studies evaluating its effectiveness and safety have reported conflicting results. This systematic assessment was performed to obtain comprehensive evidence regarding the potential benefits and safety of CS compared with those of radiotherapy (RT) and radical prostatectomy (RP), respectively. All controlled trials comparing CS with RT or RP and single-arm studies reporting results of CS therapy were identified through comprehensive searches of PubMed, the Cochrane Library and Embase. Ten publications from seven trials, with totally 1252 patients, were included in the meta-analysis, which revealed no significant differences in comparisons of CS vs RT and CS vs RP for overall survival and disease specific survival. However, a significantly lower disease-free survival could be observed for CS than RP. Moreover, a systematic review of literature focusing on comparative data of databases and materials of single-arm trials revealed satisfactory survival results in both primary and salvage CS. Our results showed that cryosurgery would be a relatively effective method for clinically localized prostate cancer with survival results comparable to radiotherapy and radical prostatectomy. However, the large percentage of complications caused by cryosurgery should be carefully monitored. PMID:27271239

  9. When the risks are high: psychological adjustment among melanoma survivors at high risk of developing new primary disease.

    PubMed

    McLoone, Jordana; Watts, Kaaren; Menzies, Scott; Meiser, Bettina; Butow, Phyllis; Kasparian, Nadine

    2012-08-01

    In this study we explored the psychosocial experiences of melanoma survivors at high risk of developing new primary disease. A total of 20 survivors (9 men, 11 women, mean age 57.6 years) completed a semistructured telephone interview, exploring melanoma-related beliefs and experiences, psychological adjustment to melanoma risk, and supportive care needs. Participants perceived melanoma as potentially terminal and reported persistent worries about the possibility of developing new or metastatic disease. Fear of developing a new melanoma endured for years after treatment completion and, for some, created a pervasive sense of uncertainty. Still, not a single participant sought formal emotional support to address his or her melanoma-related concerns. Belief in the benefits of early intervention, including self- and clinical skin examination, provided a sense of control and a recommended course of action in an otherwise uncontrollable situation. The expertise of the High Risk Clinic physicians was perceived as instrumental in creating a sense of reassurance.

  10. Characterizing and Reaching High-Risk Drinkers Using Audience Segmentation

    PubMed Central

    Moss, Howard B.; Kirby, Susan D.; Donodeo, Fred

    2010-01-01

    Background Market or audience segmentation is widely used in social marketing efforts to help planners identify segments of a population to target for tailored program interventions. Market-based segments are typically defined by behaviors, attitudes, knowledge, opinions, or lifestyles. They are more helpful to health communication and marketing planning than epidemiologically-defined groups because market-based segments are similar in respect to how they behave or might react to marketing and communication efforts. However, market segmentation has rarely been used in alcohol research. As an illustration of its utility, we employed commercial data that describes the sociodemographic characteristics of high-risk drinkers as an audience segment; where they tend to live, lifestyles, interests, consumer behaviors, alcohol consumption behaviors, other health-related behaviors, and cultural values. Such information can be extremely valuable in targeting and planning public health campaigns, targeted mailings, prevention interventions and research efforts. Methods We describe the results of a segmentation analysis of those individuals who self-report consuming five or more drinks per drinking episode at least twice in the last 30-days. The study used the proprietary PRIZM™ audience segmentation database merged with Center for Disease Control and Prevention's (CDC) Behavioral Risk Factor Surveillance System (BRFSS) database. The top ten of the 66 PRIZM™ audience segments for this risky drinking pattern are described. For five of these segments we provide additional in-depth details about consumer behavior and the estimates of the market areas where these risky drinkers reside. Results The top ten audience segments (PRIZM clusters) most likely to engage in high-risk drinking are described. The cluster with the highest concentration of binge drinking behavior is referred to as the “Cyber Millenials.” This cluster is characterized as “the nation's tech-savvy singles

  11. Comparison and improvements of LCMV and MUSIC source localization techniques for use in real clinical environments.

    PubMed

    Hoyos, A de; Portillo, J; Portillo, I; Marín, P; Maestú, F; Poch-Broto, J; Ortiz, T; Hernando, Antonio

    2012-04-15

    The present work shows some improvements realized on practical aspects of the implementation of Singular Value Decomposition (SVD) methods to localize the sources of neural activity by means of magnetoencephalograph (MEG). Two methods have been improved and compared i.e. a spatial filter, the Linearly Constrained Minimum Variance Beamformer (LCMV) method, and a signal subspace method that is an implementation of the MUSIC (Multiple Signal Classification) method due to Mosher et al. (1992). It also shows the performance of both methods comparing three different averaging procedures. The influence of the correct selection of the noise subspace dimension has been analyzed. Using acoustic stimulus for real patient measurements, we discuss the relevant differences of both methods and propose an adequate strategy for future diagnosis based on correct source localization.

  12. Prognostic Factors Affecting Locally Recurrent Rectal Cancer and Clinical Significance of Hemoglobin

    SciTech Connect

    Rades, Dirk Kuhn, Hildegard; Schultze, Juergen; Homann, Nils; Brandenburg, Bernd; Schulte, Rainer; Krull, Andreas; Schild, Steven E.; Dunst, Juergen

    2008-03-15

    Purpose: To investigate potential prognostic factors, including hemoglobin levels before and during radiotherapy, for associations with survival and local control in patients with unirradiated locally recurrent rectal cancer. Patients and Methods: Ten potential prognostic factors were investigated in 94 patients receiving radiotherapy for recurrent rectal cancer: age ({<=}68 vs. {>=}69 years), gender, Eastern Cooperative Oncology Group performance status (0-1 vs. 2-3), American Joint Committee on Cancer (AJCC) stage ({<=}II vs. III vs. IV), grading (G1-2 vs. G3), surgery, administration of chemotherapy, radiation dose (equivalent dose in 2-Gy fractions: {<=}50 vs. >50 Gy), and hemoglobin levels before (<12 vs. {>=}12 g/dL) and during (majority of levels: <12 vs. {>=}12 g/dL) radiotherapy. Multivariate analyses were performed, including hemoglobin levels, either before or during radiotherapy (not both) because these are confounding variables. Results: Improved survival was associated with better performance status (p < 0.001), lower AJCC stage (p = 0.023), surgery (p = 0.011), chemotherapy (p = 0.003), and hemoglobin levels {>=}12 g/dL both before (p = 0.031) and during (p < 0.001) radiotherapy. On multivariate analyses, performance status, AJCC stage, and hemoglobin levels during radiotherapy maintained significance. Improved local control was associated with better performance status (p = 0.040), lower AJCC stage (p = 0.010), lower grading (p = 0.012), surgery (p < 0.001), chemotherapy (p < 0.001), and hemoglobin levels {>=}12 g/dL before (p < 0.001) and during (p < 0.001) radiotherapy. On multivariate analyses, chemotherapy, grading, and hemoglobin levels before and during radiotherapy remained significant. Subgroup analyses of the patients having surgery demonstrated the extent of resection to be significantly associated with local control (p = 0.011) but not with survival (p = 0.45). Conclusion: Predictors for outcome in patients who received radiotherapy for

  13. [Activity and Future Perspective of Local Independent Clinical Trial Group (OGSG)].

    PubMed

    Tsujinaka, Toshimasa

    2016-04-01

    Osaka Gastrointestinal Cancer Chemotherapy Study Group (OGSG) was established in 2000 and has been conducting investigator initiated multi-institutional collaboration trials regarding the treatment of gastrointestinal cancer, especially using chemotherapeutic agents. Although organization of OGSG has been renovated to perform post-marketing clinical trials with high quality, OGSG is now facing severe financial crisis because of shortage of donation from pharmaceutical companies. Here, present problems and future perspectives are discussed. PMID:27220796

  14. Localized Low-Dose Radiotherapy for Follicular Lymphoma: History, Clinical Results, Mechanisms of Action, and Future Outlooks

    SciTech Connect

    Ganem, Gerard; Cartron, Guillaume; Girinsky, Theodore; Haas, Rick L.M.; Cosset, Jean Marc; Solal-Celigny, Philippe

    2010-11-15

    The extreme radiosensitivity of indolent lymphomas was reported in the early years of radiotherapy (RT). The efficacy of low-dose total body irradiation (1.5-2 Gy) was particularly demonstrative. Higher doses were considered appropriate for localized disease. The optimal (or conventional) dose of curative RT derived from the early studies was determined to be 30-35 Gy. Nevertheless, in older series addressing the tumoricidal radiation dose in non-Hodgkin's lymphomas, investigators noted that a significant number of 'nodular' lymphomas were controlled with a dose of <22 Gy for >3 years. The idea of reintroducing localized low-dose radiotherapy (LDRT) for indolent non-Hodgkin's lymphomas came from a clinical observation. The first study showing the high efficacy of LDRT (4 Gy in two fractions of 2 Gy within 3 days) in selected patients with chemoresistant, indolent, non-Hodgkin's lymphomas was published in 1994. Since this first report, at least eight series of patients treated with localized LDRT have been published, showing a 55% complete response rate in irradiated sites, with a median duration of 15-42 months. How LDRT induces lymphoma cell death remains partly unknown. However, some important advances have recently been reported. Localized LDRT induces an apoptosis of follicular lymphoma cells. This apoptotic cell death elicits an immune response mediated by macrophages and dendritic cells. Follicular lymphoma is probably an ideal model to explore these mechanisms. This review also discusses the future of LDRT for follicular lymphoma.

  15. Auricular malignant neoplasms. Identification of high-risk lesions and selection of method of reconstruction.

    PubMed

    Bumsted, R M; Ceilley, R I

    1982-04-01

    A prospective study of 17 auricular malignant neoplasms was conducted comparing recommended margins for conventional surgical excision to the actual margins obtained after microscopically controlled excision (Mohs' chemosurgery technique) to identify lesions at high risk for inadequate excision with conventional excision. High-risk lesions included all tumors larger than 1 cm, morpheaform basal cell carcinoma, and multiply recurrent lesions of any size. Successful excision by conventional surgery would have resulted in a defect notably larger than the actual Mohs' defect in all cases. The excess tissue excised by conventional surgery averaged 180% larger than the actual defect in primary lesions and 347% larger in recurrent lesions. Methods of reconstruction used include the following: secondary intention (granulation), primary closure, skin grafts, local flaps, and meatoplasty. The incidence, indications, and usual results obtained are discussed in detail. Mohs' chemosurgery technique provides substantial benefit and should be considered in all recurrent lesions and primary lesions larger than 1 cm to reduce recurrence and minimize the resultant deformity.

  16. Identifying high-risk areas of bacillary dysentery and associated meteorological factors in Wuhan, China.

    PubMed

    Li, Zhenjun; Wang, Ligui; Sun, Weige; Hou, Xuexin; Yang, Haiyan; Sun, Lina; Xu, Shuai; Sun, Qiangzheng; Zhang, Jingshan; Song, Hongbin; Lin, Hualiang

    2013-11-21

    Spatial distribution of bacillary dysentery incidence was mapped at the district level in Wuhan, China. And a generalized additive time series model was used to examine the effect of daily weather factors on bacillary dysentery in the high-risk areas, after controlling for potential confounding factors. Central districts were found to be the high-risk areas. The time series analysis found an acute effect of meteorological factors on bacillary dysentery occurrence. A positive association was found for mean temperature (excess risk (ER) for 1°C increase being 0.94% (95% confidence interval (CI): 0.46% to 1.43% on the lag day 2), while a negative effect was observed for relative humidity and rainfall, the ER for 1% increase in relative humidity was -0.21% (95% CI: -0.34% to -0.08%), and the ER for 1 mm increase in rainfall was -0.23% (95% CI: -0.37% to -0.09%). This study suggests that bacillary dysentery prevention and control strategy should consider local weather variations.

  17. Reentry Programming for High-Risk Offenders: Insights From Participants.

    PubMed

    Bender, Kimberly A; Cobbina, Jennifer E; McGarrell, Edmund F

    2016-10-01

    The mass increase in imprisonment of the last two decades has led to an increasing number of adults released from prison. Scholarly accounts of prisoner reentry have demonstrated that incarcerated individuals face barriers on release from prison and that intervention programs are necessary to assist their transition to the community. Here, we build from the insights of previous research by examining how high-risk offenders perceive a reentry program. Using a qualitative approach, our findings suggest that procedural and substantive justice affect their satisfaction and involvement with the program. This study highlights the importance of providing employment opportunities, social support, and fair and respectful delivery of services to assist incarcerated individuals transitioning to the community.

  18. Prevalence of Hearing Impairment in High Risk Infants.

    PubMed

    Vashistha, Ishika; Aseri, Yogesh; Singh, B K; Verma, P C

    2016-06-01

    Hearing impairment is prevalent in the general population, early intervention facilitates proper development. The aim of this study was to establish the prevalence of hearing impairment in high-risk infants born between 2013 and 2014. 100 newborns were evaluated using evoked otoacoustic emissions and distortion produce and auditory behavior. Tests were reported if the results were altered. If altered results persisted, the child was referred for impedance testing and when necessary for medical evaluation. Infants referred for BOA and OAE undergone Brainstem auditory evoked potential testing. Of 100 children, 85 children have hearing within normal limits. Hearing impairment was found in 15 out of which 7 had unilateral hearing loss and 8 had bilateral hearing loss. The high prevalence of hearing impairment in this population underlines the importance of early audiological testing.

  19. Antibody-based immunotherapy in high-risk neuroblastoma.

    PubMed

    Johnson, Erik; Dean, Shannon M; Sondel, Paul M

    2007-01-01

    Although great advances have been made in the treatment of low- and intermediate-risk neuroblastoma in recent years, the prognosis for advanced disease remains poor. Therapies based on monoclonal antibodies that specifically target tumour cells have shown promise for treatment of high-risk neuroblastoma. This article reviews the use of monoclonal antibodies either as monotherapy or as part of a multifaceted treatment approach for advanced neuroblastoma, and explains how toxins, cytokines, radioactive isotopes or chemotherapeutic drugs can be conjugated to antibodies to enhance their effects. Tumour resistance, the development of blocking antibodies, and other problems hindering the effectiveness of monoclonal antibodies are also discussed. Future therapies under investigation in the area of immunotherapy for neuroblastoma are considered.

  20. High risk groups in an oil shale workforce

    SciTech Connect

    Gratt, L.B.; Marine, W.M.; Perry, B.W.; Savitz, D.A.

    1984-04-01

    The workforce risks of a hypothetical one million barrels-per-day oil shale industry were estimated. The risks for the different workforce segments were compared and high risk groups were identified. Accidents and injuries were statistically described by rates for fatalities, for accidents with days lost from work, and for accidents with no days lost from work. Workforce diseases analyzed were cancers, silicosis, pneumoconiosis, chronic bronchitis, chronic airway obstruction, and high frequency hearing loss. A comparison of the workforce groups under different risk measures (occurrence, fatality, and life-loss expectancy) was performed. The miners represented the group with the largest fatality and the most serious accident rate, although the estimated rates were below the average industry-wide underground mining experience. Lung disease from inhalation exposure of about the nuisance dust threshold limit value presents a significant risk for future concerns.

  1. Prevalence of Hearing Impairment in High Risk Infants.

    PubMed

    Vashistha, Ishika; Aseri, Yogesh; Singh, B K; Verma, P C

    2016-06-01

    Hearing impairment is prevalent in the general population, early intervention facilitates proper development. The aim of this study was to establish the prevalence of hearing impairment in high-risk infants born between 2013 and 2014. 100 newborns were evaluated using evoked otoacoustic emissions and distortion produce and auditory behavior. Tests were reported if the results were altered. If altered results persisted, the child was referred for impedance testing and when necessary for medical evaluation. Infants referred for BOA and OAE undergone Brainstem auditory evoked potential testing. Of 100 children, 85 children have hearing within normal limits. Hearing impairment was found in 15 out of which 7 had unilateral hearing loss and 8 had bilateral hearing loss. The high prevalence of hearing impairment in this population underlines the importance of early audiological testing. PMID:27340640

  2. Prenatal diagnosis of osteochondrodysplasias in high risk pregnancy.

    PubMed

    Gordienko IYu; Grechanina EYa; Sopko, N I; Tarapurova, E N; Mikchailets, L P

    1996-05-01

    We collected data on 39 prenatally diagnosed osteochondrodysplasias. We detected 30 (76.9%) cases in the first and second trimesters, including 18 (46.2%) with two twins before the 24th week of gestation. Of 39 cases 11 (28.2%) had osteogenesis imperfecta (OI) type II. Verification of the prenatal diagnosis was attempted in 26 cases on the basis of the data obtained from ultrasonographs, radiographs, external examination, and autopsy protocols. The prenatal diagnosis was confirmed in 19 (73%) fetuses. In 13 cases verification was not possible because one or several investigations could not be performed. Counselling followed all identified cases with osteochondrodysplasia. We present the pedigree of two families indicating the possibility of early prenatal diagnosis of achondrogenesis type I and metatropic dysplasia. We propose indications for ultrasonographic anatomical screening with subsequent phenotype analysis in high risk pregnancy to provide for the prenatal detection of malformations and hereditary diseases. PMID:8723093

  3. Practical opportunities to improve early detection and prevention of colorectal cancer (CRC) in members of high-risk families.

    PubMed

    Patel, S G; Lowery, J T; Gatof, D; Ahnen, D J

    2015-03-01

    Colorectal cancer (CRC) incidence and mortality are steadily declining and CRC screening rates are increasing in the United States. Although this a very good news, several definable groups still have very low screening rates including younger (under age 50) members of high-risk CRC families. This opinion piece describes five strategies that could be incorporated into routine practice to improve identification and guideline-based screening in members of high-risk families. Routine incorporation of a simple family history screening tool and outreach to high-risk family members could substantially improve guideline-based screening in this population. Identification of CRCs and advanced adenomas in the endoscopy suite defines another group of high-risk families for similar outreach. Lynch syndrome families can be identified by testing CRCs and selected adenomas for microsatellite instability or loss of DNA repair protein expression. Finally, selective addition of aspirin to surveillance endoscopy can decrease the risk of new adenomas and CRCs. The rationale for these strategies as well as mechanisms for their implementation and evaluation in clinical practice is described. PMID:25698379

  4. Intravascular near-infrared fluorescence molecular imaging of atherosclerosis: toward coronary arterial visualization of biologically high-risk plaques

    NASA Astrophysics Data System (ADS)

    Calfon, Marcella A.; Vinegoni, Claudio; Ntziachristos, Vasilis; Jaffer, Farouc A.

    2010-01-01

    New imaging methods are urgently needed to identify high-risk atherosclerotic lesions prior to the onset of myocardial infarction, stroke, and ischemic limbs. Molecular imaging offers a new approach to visualize key biological features that characterize high-risk plaques associated with cardiovascular events. While substantial progress has been realized in clinical molecular imaging of plaques in larger arterial vessels (carotid, aorta, iliac), there remains a compelling, unmet need to develop molecular imaging strategies targeted to high-risk plaques in human coronary arteries. We present recent developments in intravascular near-IR fluorescence catheter-based strategies for in vivo detection of plaque inflammation in coronary-sized arteries. In particular, the biological, light transmission, imaging agent, and engineering principles that underlie a new intravascular near-IR fluorescence sensing method are discussed. Intravascular near-IR fluorescence catheters appear highly translatable to the cardiac catheterization laboratory, and thus may offer a new in vivo method to detect high-risk coronary plaques and to assess novel atherosclerosis biologics.

  5. Hard and Soft Tissue Management of a Localized Alveolar Ridge Atrophy with Autogenous Sources and Biomaterials: A Challenging Clinical Case

    PubMed Central

    Andreoni, D.

    2016-01-01

    Particularly in the premaxillary area, the stability of hard and soft tissues plays a pivotal role in the success of the rehabilitation from both a functional and aesthetic aspect. The present case report describes the clinical management of a localized alveolar ridge atrophy in the area of the upper right canine associated with a thin gingival biotype with a lack of keratinized tissue. An autogenous bone block harvested from the chin associated with heterologous bone particles was used to replace the missing bone, allowing for a prosthetic driven implant placement. Soft tissues deficiency was corrected by means of a combined epithelialized and subepithelial connective tissue graft. The 3-year clinical and radiological follow-up demonstrated symmetric gingival levels of the upper canines, with physiological peri-implant probing depths and bone loss. Thus, the use of autogenous tissues combined with biomaterials might be considered a reliable technique in case of highly aesthetic demanding cases. PMID:27738534

  6. Clinical Data Systems to Support Public Health Practice: A National Survey of Software and Storage Systems Among Local Health Departments

    PubMed Central

    Goodin, Kate

    2016-01-01

    Context: Numerous software and data storage systems are employed by local health departments (LHDs) to manage clinical and nonclinical data needs. Leveraging electronic systems may yield improvements in public health practice. However, information is lacking regarding current usage patterns among LHDs. Objective: To analyze clinical and nonclinical data storage and software types by LHDs. Design: Data came from the 2015 Informatics Capacity and Needs Assessment Survey, conducted by Georgia Southern University in collaboration with the National Association of County and City Health Officials. Participants: A total of 324 LHDs from all 50 states completed the survey (response rate: 50%). Main Outcome Measures: Outcome measures included LHD's primary clinical service data system, nonclinical data system(s) used, and plans to adopt electronic clinical data system (if not already in use). Predictors of interest included jurisdiction size and governance type, and other informatics capacities within the LHD. Bivariate analyses were performed using χ2 and t tests. Results: Up to 38.4% of LHDs reported using an electronic health record (EHR). Usage was common especially among LHDs that provide primary care and/or dental services. LHDs serving smaller populations and those with state-level governance were both less likely to use an EHR. Paper records were a common data storage approach for both clinical data (28.9%) and nonclinical data (59.4%). Among LHDs without an EHR, 84.7% reported implementation plans. Conclusions: Our findings suggest that LHDs are increasingly using EHRs as a clinical data storage solution and that more LHDs are likely to adopt EHRs in the foreseeable future. Yet use of paper records remains common. Correlates of electronic system usage emerged across a range of factors. Program- or system-specific needs may be barriers or facilitators to EHR adoption. Policy makers can tailor resources to address barriers specific to LHD size, governance, service

  7. Using risk to target HPV vaccines in high-risk, low-resource organizations.

    PubMed

    Small, Stephanie L; Sampselle, Carolyn M; Martyn, Kristy K; Dempsey, Amanda F

    2013-05-01

    Organizations in developed countries with limited financial resources may find it difficult to determine whether it is preferable to use these resources for HPV vaccination, management of HPV-related diseases, or a "hybrid" strategy, such as vaccinating only the highest risk individuals. We determined the organizational costs and clinical impacts of three different organizational approaches to female HPV vaccination in a low-resource setting, including vaccinating everyone, vaccinating no one, or vaccinating only those considered high-risk. To determine patients at highest risk, HPV risk factors were identified using information routinely gathered at the annual preventive maintenance visit. The three vaccination strategies were then compared using a decision tree analysis. The three strategies demonstrated very little difference in cost. However, the least expensive strategy was to vaccinate no one. In contrast, the strategy with the best clinical outcomes was for the organization to vaccinate everyone. Organizations with limited resources must decide how to best allocate these funds to provide the greatest clinical benefits. This study showed little difference in costs but improved clinical outcomes when using the universal HPV vaccination strategy. Thus, the improvement in clinical outcomes when vaccinating everyone may be worth the relatively small increase in cost of vaccinating everyone.

  8. Development of early treatment strategies for high-risk myeloma precursor disease in the future.

    PubMed

    Landgren, Ola; Rajkumar, S Vincent

    2011-01-01

    Smoldering myeloma (SMM) is a precursor state of multiple myeloma. It is defined by an M-protein concentration ≥3 g/dL and/or ≥10% clonal bone marrow plasma cells, in the absence of end-organ damage. Based on clinical observations, the natural history of SMM varies greatly, from stable, monoclonal gammopathy of undetermined significance (MGUS)-like disease to highly progressive disease. Using conventional clinical markers, SMM patients can be stratified into clinical risk groups. However, due to considerable molecular heterogeneity, we currently lack reliable markers to predict prognosis for individual SMM patients. Based on the International Myeloma Working Group 2010 guidelines, patients diagnosed with MGUS and SMM should not be treated outside of clinical trials. Overall, treatment trials for MGUS patients are complicated, as these individuals are relatively healthy and the majority has a low life-time risk of progression, especially when other causes of death are taken into account. In contrast to MGUS, early treatment strategies for SMM are particularly attractive, as the rate of progression to multiple myeloma is substantially higher. Until recently, potent drugs with reasonable toxicity profiles have not been available for the development of early multiple myeloma treatment strategies. This review discusses how the integration of novel biological markers and clinical monitoring of SMM could facilitate the development of early treatment strategies for high-risk SMM patients in the future. PMID:21232660

  9. Automated analysis of free speech predicts psychosis onset in high-risk youths

    PubMed Central

    Bedi, Gillinder; Carrillo, Facundo; Cecchi, Guillermo A; Slezak, Diego Fernández; Sigman, Mariano; Mota, Natália B; Ribeiro, Sidarta; Javitt, Daniel C; Copelli, Mauro; Corcoran, Cheryl M

    2015-01-01

    Background/Objectives: Psychiatry lacks the objective clinical tests routinely used in other specializations. Novel computerized methods to characterize complex behaviors such as speech could be used to identify and predict psychiatric illness in individuals. AIMS: In this proof-of-principle study, our aim was to test automated speech analyses combined with Machine Learning to predict later psychosis onset in youths at clinical high-risk (CHR) for psychosis. Methods: Thirty-four CHR youths (11 females) had baseline interviews and were assessed quarterly for up to 2.5 years; five transitioned to psychosis. Using automated analysis, transcripts of interviews were evaluated for semantic and syntactic features predicting later psychosis onset. Speech features were fed into a convex hull classification algorithm with leave-one-subject-out cross-validation to assess their predictive value for psychosis outcome. The canonical correlation between the speech features and prodromal symptom ratings was computed. Results: Derived speech features included a Latent Semantic Analysis measure of semantic coherence and two syntactic markers of speech complexity: maximum phrase length and use of determiners (e.g., which). These speech features predicted later psychosis development with 100% accuracy, outperforming classification from clinical interviews. Speech features were significantly correlated with prodromal symptoms. Conclusions: Findings support the utility of automated speech analysis to measure subtle, clinically relevant mental state changes in emergent psychosis. Recent developments in computer science, including natural language processing, could provide the foundation for future development of objective clinical tests for psychiatry. PMID:27336038

  10. Treatment of high-risk neuroblastoma with anti-GD2 antibodies.

    PubMed

    Castel, Victoria; Segura, Vanessa; Cañete, Adela

    2010-12-01

    Anticancer monoclonal antibodies (mAbs) targeting specific antigens on the tumour surface are increasingly being applied in cancer treatment. Potential advantages include long half-life, low toxicity, high affinity and specificity. In order to develop novel immune therapies for high-risk cancers, finding tumour targets that are not widely shared by normal cells is a goal. GD2-disialoganglioside is one of them. It is expressed on the surface of a variety of tumours with no curative therapies for patients with advanced disease. In childhood, neuroblastoma is the most common GD2-expressing tumour. Because of this tumour-selective expression, it is an attractive target for tumour-specific therapies such as antibody therapy. Over the last two decades, several anti-GD2 antibodies have been developed. To reduce both toxicity and development of human anti-mouse antibodies (HAMA), research efforts have primarily focused on exploring anti-GD2 antibodies that substitute mouse components by human ones. This review will examine antibodies currently undergoing clinical testing as well as the most recent advances to improve antibody therapy for patients with high-risk neuroblastoma.

  11. Electrochemical chip-based genomagnetic assay for detection of high-risk human papillomavirus DNA.

    PubMed

    Bartosik, Martin; Durikova, Helena; Vojtesek, Borivoj; Anton, Milan; Jandakova, Eva; Hrstka, Roman

    2016-09-15

    Cervical cancer, being the fourth leading cause of cancer death in women worldwide, predominantly originates from a persistent infection with a high-risk human papillomavirus (HPV). Detection of DNA sequences from these high-risk strains, mostly HPV-16 and HPV-18, represents promising strategy for early screening, which would help to identify women with higher risk of cervical cancer. In developing countries, inadequate screening options lead to disproportionately high mortality rates, making a fast and inexpensive detection schemes highly important. Electrochemical sensors and assays offer an alternative to current methods of detection. We developed an electrochemical-chip based assay, in which target HPV DNA is captured via magnetic bead-modified DNA probes, followed by an antidigoxigenin-peroxidase detection system at screen-printed carbon electrode chips, enabling parallel measurements of eight samples simultaneously. We show sensitive detection in attomoles of HPV DNA, selective discrimination between HPV-16 and HPV-18 and good reproducibility. Most importantly, we show application of the assay into both cancer cell lines and cervical smears from patients. The electrochemical results correlated well with standard methods, making this assay potentially applicable in clinical practice.

  12. Reaching and retaining high-risk HIV/AIDS clients through the Internet.

    PubMed

    Feldacker, Caryl; Torrone, Elizabeth; Triplette, Matthew; Smith, Justin C; Leone, Peter A

    2011-07-01

    The Internet is a popular way for people to meet casual sex partners. However, online outreach remains largely unexplored to promote voluntary counseling and testing for HIV. The Student Health Action Coalition's HIV testing program (SHAC-HIV) targets high-risk clients through tailored Internet outreach via chat rooms, social networking sites, and online forums. The SHAC-HIV model also demonstrates that nontraditional testing sites can provide low-cost, client-centered, high-quality services to support increased demand for HIV-testing services. Within the clinic, SHAC-HIV's testing model includes four major components: (a) reliance on a team of well-trained health sciences student volunteers; (b) rapid oral-fluid HIV tests; (c) universal, consent-based testing with client-centered health education and counseling; and (d) coordinated referrals for follow-up testing, treatment, and care. This approach reaches high-risk clients as well as undiagnosed infections. In 2007, there were nine confirmed positive results out of 389 tests, yielding a 2.3% positivity rate. This positivity percentage is higher than any other nontraditional testing site in North Carolina. This article describes the SHAC-HIV outreach and voluntary counseling and testing program with the aim of encouraging adoption of the model by other nontraditional testing sites. PMID:20160022

  13. Sleep apnoea, anxiety, depression and somatoform pain: a community-based high-risk sample.

    PubMed

    Hrubos-Strøm, Harald; Einvik, Gunnar; Nordhus, Inger Hilde; Randby, Anna; Pallesen, Ståle; Moum, Torbjørn; Omland, Torbjørn; Dammen, Toril

    2012-08-01

    Community-based studies that measure both psychiatric diagnoses and obstructive sleep apnoea (OSA) are lacking. This study reports current psychiatric disorders in community-dwelling adults at high risk for OSA identified by the Berlin Questionnaire. Furthermore, associations between OSA and current psychiatric disorders, unadjusted and adjusted for putative confounders, are reported. A subsample of the Akershus Sleep Apnoea Project consisting of 290 adults, aged 30-65 yrs, with positive Berlin Questionnaire screening underwent the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, version IV and polysomnography. Auxiliary analyses of depression are provided. The median apnoea/hypopnoea index score in the sample was 7.7 (interquartile range 2.4-22.2). Major depressive disorder, current anxiety and somatoform pain disorder were diagnosed in 12.4%, 14.8% and 19.3% of participants, respectively. At least one psychiatric disorder was diagnosed in 110 participants. The odds ratio of participants with OSA having a psychiatric disorder compared with participants without OSA was 0.54 (95% CI 0.33-0.88). A negative association did not exist among Berlin Questionnaire low-risk participants. In conclusion, more than one-third of participants in a community-based, Berlin Questionnaire high-risk sample were diagnosed with a psychiatric disorder. A negative association between OSA and psychiatric morbidity was found.

  14. Cyclical pattern of non-nutritive sucking in normal and high-risk neonates.

    PubMed

    Simbrón, Alicia V; Sorbera-Ferrer, Lucas; Gómez de Ferraris, María E; Carranza, Miriam L

    2013-01-01

    This study determined patterns of suction cycles by recording sucking pressure in full-term infants, normal pre-term infants and newborns with pathology (hypoxia at birth). Associations between these patterns and some clinical parameters were established in order to evaluate feeding capacity for the purpose of guiding specific stimulation and aiding hospital discharge in better health conditions. Seventy-five infants of both sexes were assessed after informed consent, grouped by their status at birth. Body weight and Apgar score were determined. Sucking pressure was evaluated with an ad-hoc device. Maximum and minimum pressure scores and the number of suction cycles were measured. Data were analyzed statistically at a significance level of p < 0.05. Maximum sucking pressure values varied between study groups. Full-term infants showed the highest pressure values and number of suction cycles. In pre-term infants, lower pressure values and fewer suction cycles were observed. Those with hypoxia showed great variability in both parameters. This study found a cyclical pattern of non-nutritive sucking in normal and high-risk newborns. Normal and preterm infants showed a significant direct correlation between suction cycles and Apgar scores at 5 minutes, but the infants with pathology due to hypoxia group did not show the same association. These findings are an important tool that will contribute to improving newborn maternal nutrition and optimizing the quality of life for high-risk newborns in our environment.

  15. Adjuvant radiotherapy for pathological high-risk muscle invasive bladder cancer: time to reconsider?

    PubMed Central

    Baumann, Brian C.; Eapen, Libni J.; Bahl, Amit; Murthy, Vedang; Roubaud, Guilhem; Orré, Mathieu; Efstathiou, Jason A.; Shariat, Shahrokh; Larré, Stephane; Richaud, Pierre; Christodouleas, John P.

    2016-01-01

    Radical cystectomy with extended pelvic lymph-node dissection, associated with neo-adjuvant chemotherapy, remains the standard of care for advanced, non-metastatic muscle-invasive bladder cancer (MIBC). Loco-regional control is a key factor in the outcome of patients since it is related to overall survival (OS), disease-free survival (DFS) and cause-specific survival. The risk of loco-regional recurrence (LRR) is correlated to pathological factors as well as the extent of the lymphadenectomy. In addition, neither pre- nor post-operative chemotherapy have shown a clear impact on LRR-free survival. Several recent publications have led to the development of a nomogram predicting the risk of LRR, in order to identify patients most likely to benefit from adjuvant radiotherapy. Given the high risk of LRR for selected patients and improvements in radiation techniques that can reduce toxicity, there is a growing interest in adjuvant radiotherapy; international cooperative groups have come together to provide the rationale in favor of adjuvant radiotherapy. Clinical trials in order to reduce the risk of pelvic relapse are opened based on this optimizing patient selection. The aim of this critical literature review is to provide an overview of the rationale supporting the studies of adjuvant radiation for patients with pathologic high-risk MIBC. PMID:27785427

  16. High-risk diagnosis, social stress, and parent-child relationships: A moderation model.

    PubMed

    Bentley, Eryn; Millman, Zachary B; Thompson, Elizabeth; Demro, Caroline; Kline, Emily; Pitts, Steven C; DeVylder, Jordan E; Smith, Melissa Edmondson; Reeves, Gloria; Schiffman, Jason

    2016-07-01

    Stress is related to symptom severity among youth at clinical high-risk (CHR) for psychosis, although this relation may be influenced by protective factors. We explored whether the association of CHR diagnosis with social stress is moderated by the quality of parent-child relationships in a sample of 96 (36 CHR; 60 help-seeking controls) adolescents and young adults receiving mental health services. We examined self-reported social stress and parent-child relationships as measured by the Behavior Assessment System for Children, Second Edition (BASC-2), and determined CHR status from the clinician-administered Structured Interview for Psychosis-Risk Syndrome (SIPS). The social stress subscale, part of the clinical domain of the BASC-2, assesses feelings of stress and tension in personal relationships and the relations with parents subscale, part of the adaptive domain of the BASC-2, assesses perceptions of importance in family and quality of parent-child relationship. There was a modest direct relation between risk diagnosis and social stress. Among those at CHR, however, there was a significant relation between parent-child relationships and social stress (b=-0.73, t[92]=-3.77, p<0.001, f(2)=0.15) that was not observed among non-CHR individuals, suggesting that a positive parent-child relationship may be a protective factor against social stress for those at risk for psychosis. Findings provide additional evidence to suggest that interventions that simultaneously target both social stress and parent-child relationships might be relevant for adolescents and young adults at clinical high-risk for psychosis.

  17. Genomic and epigenomic analysis of high-risk prostate cancer reveals changes in hydroxymethylation and TET1

    PubMed Central

    Spans, Lien; Van den Broeck, Thomas; Smeets, Elien; Prekovic, Stefan; Thienpont, Bernard; Lambrechts, Diether; Karnes, R. Jeffrey; Erho, Nicholas; Alshalalfa, Mohammed; Davicioni, Elai; Helsen, Christine; Gevaert, Thomas; Tosco, Lorenzo; Haustermans, Karin; Lerut, Evelyne; Joniau, Steven; Claessens, Frank

    2016-01-01

    The clinical heterogeneity of prostate cancer (PCa) makes it difficult to identify those patients that could benefit from more aggressive treatments. As a contribution to a better understanding of the genomic changes in the primary tumor that are associated with the development of high-risk disease, we performed exome sequencing and copy number determination of a clinically homogeneous cohort of 47 high-risk PCas. We confirmed recurrent mutations in SPOP, PTEN and TP53 among the 850 point mutations we detected. In seven cases, we discovered genomic aberrations in the TET1 (Ten-Eleven Translocation 1) gene which encodes a DNA hydroxymethylase than can modify methylated cytosines in genomic DNA and thus is linked with gene expression changes. TET1 protein levels were reduced in tumor versus non-tumor prostate tissue in 39 of 40 cases. The clinical relevance of changes in TET1 levels was demonstrated in an independent PCa cohort, in which low TET1 mRNA levels were significantly associated with worse metastases-free survival. We also demonstrate a strong reduction in hydroxymethylated DNA in tumor tissue in 27 of 41 cases. Furthermore, we report the first exploratory (h)MeDIP-Seq analyses of eight high-risk PCa samples. This reveals a large heterogeneity in hydroxymethylation changes in tumor versus non-tumor genomes which can be linked with cell polarity. PMID:27014907

  18. Localization and upregulation of survivin in cancer health disparities: a clinical perspective.

    PubMed

    Khan, Salma; Ferguson Bennit, Heather; Asuncion Valenzuela, Malyn May; Turay, David; Diaz Osterman, Carlos J; Moyron, Ron B; Esebanmen, Grace E; Ashok, Arjun; Wall, Nathan R

    2015-01-01

    Survivin is one of the most important members of the inhibitors of apoptosis protein family, as it is expressed in most human cancers but is absent in normal, differentiated tissues. Lending to its importance, survivin has proven associations with apoptosis and cell cycle control, and has more recently been shown to modulate the tumor microenvironment and immune evasion as a result of its extracellular localization. Upregulation of survivin has been found in many cancers including breast, prostate, pancreatic, and hematological malignancies, and it may prove to be associated with the advanced presentation, poorer prognosis, and lower survival rates observed in ethnically diverse populations. PMID:26185415

  19. Rationale and design of a multicenter prospective cohort study for the eVALuation and monitoring of HPV infections and relATEd cervical diseases in high-risk women (VALHIDATE study)

    PubMed Central

    2012-01-01

    Background Pap screening, an effective method for cervical cancer prevention, is now supported by molecular human papillomavirus (HPV) testing. Recently commercialised preventive vaccines also provide new tools for the primary prevention of cervical cancer. To determine appropriate prevention strategies, the Health General Direction, Lombardy Region, funded a project that aims to characterize and monitor HPV infections and related cervical diseases in high-risk women. Methods/design VALHIDATE is a 5-year multicentre open prospective cohort study. It will recruit 7000 consenting women aged 13–65 years to provide information about the local biomolecular epidemiology of HPV infection and cervical diseases in high-risk women recruited from nine clinical centres and one faith-based organisation. The study will estimate the overall and type-specific prevalence of HPV infection and cervical abnormalities. It also aims to compare standard Pap screening with biomolecular screening, and to assist in the design of targeted regional prevention programs directed specifically at high-risk groups. Three groups of high-risk women: 1000 HIV-infected women (aged 26–65 years), 1000 recent migrant women (aged 26–65 years) and 3000 young women (aged 13–26 years) and 1 control group: 2000 women (aged 26–45 years) attending a spontaneous screening program, will be recruited. Sample sizes will be revised after the first year. Adult participants will undergo conventional cervical cytology, HPV DNA screening and genotyping. Paediatric participants will undergo HPV DNA testing and genotyping of urine samples. HPV DNA, cytological abnormalities and HPV types will be analysed according to demographic, epidemiological, behavioural, and clinical data collected in an electronic case report form. Overall and stratified prevalences will be estimated to analyse the associations between HPV infection and selected characteristics. Logistic regression models will be used to estimate

  20. 45 CFR 153.250 - Coordination with high-risk pools.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 45 Public Welfare 1 2014-10-01 2014-10-01 false Coordination with high-risk pools. 153.250 Section... ACT State Standards Related to the Reinsurance Program § 153.250 Coordination with high-risk pools. (a) General requirement. The State must eliminate or modify any State high-risk pool to the extent...

  1. Adjuvant chemo- and hormonal therapy in locally advanced breast cancer: a randomized clinical study

    SciTech Connect

    Schaake-Koning, C.; van der Linden, E.H.; Hart, G.; Engelsman, E.

    1985-10-01

    Between 1977 and 1980, 118 breast cancer patients with locally advanced disease, T3B-4, any N, M0 or T1-3, tumor positive axillary apex biopsy, were randomized to one of three arms: I: radiotherapy (RT) to the breast and adjacent lymph node areas; II: RT followed by 12 cycles of cyclophosphamide, methotrexate, 5 fluorouracil (CMF) and tamoxifen during the chemotherapy period; III: 2 cycles of adriamycin and vincristine (AV), alternated with 2 cycles of CMF, then RT, followed by another 4 cycles of AV, alternated with 4 CMF; tamoxifen during the entire treatment period. The median follow-up period was 5 1/2 years. The adjuvant chemo- and hormonal therapy did not improve the overall survival; the 5-year survival was 37% for all three treatment arms. There was no statistically significant difference in RFS between the three modalities, nor when arm I was compared to arm II and III together. LR was not statistically different over the three treatment arms. In 18 of the 24 patients with LR, distant metastases appeared within a few months from the local recurrence. The menopausal status did not influence the treatment results. Dose reduction in more than 4 cycles of chemotherapy was accompanied by better results. In conclusion: adjuvant chemo- and hormonal therapy did not improve RFS and overall survival. These findings do not support the routine use of adjuvant chemo- and endocrine therapy for inoperable breast cancer.

  2. Clinical diversity and chromosomal localization of X-linked cone dystrophy (COD1).

    PubMed Central

    Hong, H. K.; Ferrell, R. E.; Gorin, M. B.

    1994-01-01

    X-linked progressive cone dystrophy (COD1) causes progressive deterioration of visual acuity, deepening of central scotomas, macular changes, and bull's-eye lesions. The cone electroretinography (ERG) is variably abnormal in affected males, and the rod ERG may also be abnormal. The clinical picture of heterozygous females ranges from asymptomatic to a widespread spectrum of cone-mediated dysfunction. A prior linkage study demonstrated linkage between the COD1 locus and the marker locus DXS84, assigned to Xp21.1, with no recombination. In the present study, we have clinically characterized a large four-generation family with COD1 and have performed a linkage analysis using seven polymorphic markers on the short arm of the X chromosome. No recombination was observed between the disease and the marker loci DXS7 and MAOA, suggesting that the location of COD1 is in the region Xp11.3, distal to DXS84 and proximal to ARAF1. Images Figure 2 PMID:7977377

  3. Intermittent androgen deprivation (IAD) in patients with biochemical failure after radical retropubic prostatectomy (RRP) for clinically localized prostate cancer.

    PubMed

    Sciarra, A; Di Chiro, C; Di Silverio, F

    2000-12-01

    We report a study in which our objective was to analyze the clinical response during IAD in patients with biochemical failure after RRP for clinically localized prostate cancer. Between February 1994 and May 1996, 34 patients who exhibited a primary postoperative decrease in PSA to below the detection limit after RRP and then showed PSA progression during follow-up were included as group 1 and 17 patients in whom PSA did not decrease after RRP were included as group 2. Patients were offered IAD when PSA progressed over 0.4 ng/ml in group 1 and over 4.0 ng/ml in group 2. Median follow-up is 184 weeks in group 1 and 206 weeks in group 2. The median time "off" therapy increased from 25% (1st cycle) to 68.7% (5th cycle) of the entire cycle in group 1 and from 33.3% to 58.3% in group 2. Nine out of 12 cases with Gleason score > or =8 failed to respond to IAD and all developed metastatic and/or local failure. No case with Gleason score <7 failed to respond to IAD. Our conclusions suggest that IAD may be effective in patients with biochemical progression after RRP. In our experience, Gleason score seems to be an important variable.

  4. [Extracorporeal shockwave lithotripsy of the ureteral calculus--clinical results with local shockwave lithotripsy].

    PubMed

    Wilbert, D M; Voges, G E; Müller, S C; Alken, P

    1987-11-01

    Second generation local shockwave lithotripsy appliances (Lithostar) were used for the treatment of upper and lower ureteral stones in 199 patients, 145 of whom had upper ureteral stones. In 78 patients the calculi were pushed back and all but one disintegrated. In 33 patients a catheter was inserted past the stone, which resulted of primary disintegration in 66%. In 19 of 34 patients (56%) in whom the stones could not be moved, primary disintegration was achieved. Distal ureteral stones were present in 54 patients and these were treated successfully by ESWL alone in 83.3%. Auxiliary measures (total 10%) included ureteroscopy, percutaneous extraction and ureterolithotomy. The results are discussed under the aspects of 'in situ' versus 'push-and-smash' procedures.

  5. Measurement of localized tissue water - clinical application of bioimpedance spectroscopy in wound management

    NASA Astrophysics Data System (ADS)

    Ward, L. C.; Sharpe, K.; Edgar, D.; Finlay, V.; Wood, F.

    2013-04-01

    Wound healing is a complex process which can be impeded by the presence of accumulated cell fluid or oedema. A simple and convenient method for the assessment of wound oedema would aid improvement in patient care. In this proof of concept study we investigated whether bioelectrical impedance spectroscopy has the potential to provide such a tool. A number of important observations were made. Firstly, the method was highly reproducible and data can be obtained from electrodes located at different positions around the region of interest; important given the highly variable topography of surface wounds, e.g. burns. Secondly, the method was highly sensitive with the potential to detect changes of as little as 20 μl in extracellular fluid. Thirdly the relative changes in R0, R∞ and Ri following sub-cutaneous injections of saline were consistent with redistribution of water from the extracellular to intracellular space and /or removal from the local area as may occur during wound healing.

  6. Clinical Outcome of Palliative Radiotherapy for Locally Advanced Symptomatic Gastric Cancer in the Modern Era

    PubMed Central

    Tey, Jeremy; Choo, Bok Ai; Leong, Cheng Nang; Loy, En Yun; Wong, Lea Choung; Lim, Keith; Lu, Jiade Jay; Koh, Wee Yao

    2014-01-01

    Abstract The purpose of this study was to report the outcomes of patients with symptomatic locally advanced/recurrent gastric cancer treated with radiotherapy (RT) using modern 3-dimensional conformal techniques. We retrospectively reviewed patients who had palliative RT for index symptoms of gastric bleeding, pain, and obstruction. Study endpoints included symptom response, median survival, and treatment toxicity. Of 115 patients with median age of 77 years, 78 (67.8%) patients had metastatic disease at the time of treatment. Index symptoms were gastric bleeding, pain, and obstruction in 89.6%, 9.2%, and 14.3% of patients, respectively. Dose fractionation regimen ranged from 8-Gy single fraction to 40 Gy in 16 fractions. One hundred eleven patients (93.3%) were computed tomography (CT) planned. Median follow-up was 85 days. Response rates for bleeding, pain, and obstruction were 80.6% (83/103), 45.5% (5/11), and 52.9% (9/17), respectively, and median duration of response was 99 days, 233 days, and 97 days, respectively. Median survival was 85 days. Actuarial 12-month survival was 15.3%. There was no difference in response rates between low (≤39 Gy) and high (>39 Gy) biologically effective dose (BED) regimens (α/β ratio = 10). Median survival was significantly longer in patients who responded to RT compared with patients who did not (113.5 vs 47 days, P < 0.001). Three patients (2.6%) had grade 3 Common Toxicity Criteria equivalent toxicity (nausea/vomiting/anorexia). External beam RT delivered using 3-dimensional conformal techniques is highly effective and well tolerated in the local palliation of gastric cancer, with palliation lasting the majority of patient’s lives. Short (≤39 Gy BED) RT schedules are adequate for effective symptom palliation. A phase II study of palliative gastric RT is ongoing. PMID:25396330

  7. Preclinical Rationale and Clinical Considerations for Radiotherapy Plus Immunotherapy: Going Beyond Local Control.

    PubMed

    Schoenhals, Jonathan E; Seyedin, Steven N; Tang, Chad; Cortez, Maria A; Niknam, Sharareh; Tsouko, Efrosini; Chang, Joe Y; Hahn, Stephen M; Welsh, James W

    2016-01-01

    The use of radiation for cancer therapy has expanded and sparked interest in possible synergistic effects by combining it with current immunotherapies. In this review, we present a case of a patient who responded to programmed cell death 1 (PD1) blockade and radiation therapy and discuss possible mechanisms. We provide background on the blockade of the cytotoxic T-lymphocyte antigen 4 (CTLA-4) and PD1 checkpoints and highlight future immune-based therapies that may synergize with radiation, including cytosine-phosphate-guanine vaccines, OX40 agonists, CD40 agonists, regulatory T-cell depletion, and metabolic "rewiring" of cancer cells. Clinical considerations are noted for combining radiation with immunotherapies to extend the benefit of immunotherapy to more patients. New trials are needed to appropriately investigate the best sequencing and radiation dose to prime an immune response and to identify predictive biomarkers of such responses. PMID:27111909

  8. Patterns and predictors of high-risk sexual behavior in female partners of HIV-infected men with hemophilia.

    PubMed

    Dublin, S; Rosenberg, P S; Goedert, J J

    1992-05-01

    This study sought to characterize and quantify the high-risk heterosexual activity in HIV-discordant couples. An analysis of cross-sectional and longitudinal questionnaire data from 217 HIV-negative female sexual partners of HIV-infected hemophiliac men were included in this study. There was a comparison of prevalence rates of anal sex, oral sex, vaginal intercourse with or without condoms, and use of other contraceptives between 1985-91. Logistic regression analysis of demographic, sexual, and clinical variables was used to predict unprotected vaginal sex. Actuarial estimates of semiannual relapse rates to unsafe sex were used. The proportion of women at low risk increases from 7 to 69% between 1985-91, mainly because more women were using condoms during all acts of vaginal intercourse. Other contraceptive practices did not change during this time. The proportion who engaged in oral or anal sex decreased from 26 to 13% and from 13% to 4%, respectively. Unprotected vaginal sex was more common among women who enrolled earlier, had less education, engaged in oral or anal sex, and among those whose partners had not had AIDS. Unprotected vaginal sex before enrollment was the strongest predictor of this high-risk activity during followup. 2-year rates of relapse to high-risk behavior were significantly higher among women who enrolled at high risk compared with those who enrolled at low risk (39 vs 8%, p=0.005). Although high risk sexual behavior become much less prevalent in this population between 1985-91, many continued to have unprotected vaginal sex occasionally. Counseling efforts should target couples who have been the most sexually active or have less education, and should emphasize not only initial risk reduction but also maintenance of low-risk behavior. PMID:1616653

  9. Evaluation of a Pharmacist-Specific Intervention on 30-Day Readmission Rates for High-Risk Patients with Pneumonia

    PubMed Central

    Carroll, Douglas N.; Pinner, Nathan A.

    2015-01-01

    Background: Pharmacist interventions have been shown to have an impact on reducing readmission rates, however further research is necessary to target resources to high-risk populations and determine the most effective bundle of interventions. Objective: To evaluate the effect of a pharmacist-bundled intervention on 30-day readmission rates for high-risk patients with pneumonia. Methods: A pilot study with a historical control conducted at a community, teaching-affiliated medical center. Up to 65 selected subjects were included if they had pneumonia and any of the following high-risk criteria: admission within 6 months, at least 5 scheduled home medications, chronic obstructive pulmonary disease (COPD), or heart failure. A retrospective chart review was conducted to compile the historical control group that received usual care between June and November 2013. Patients admitted from December 2013 through March 2014 were reviewed to receive a bundled intervention. The primary outcome was 30-day readmission rates. Risk factors and reasons for readmission, pharmacist clinical interventions, and the time interval between discharge and readmission were also evaluated. Results: A trend toward a reduced 30-day readmission rate was observed in the intervention group (n = 43) compared to those who received usual care (n = 65) (27.9% vs 40.0%; relative risk [RR], 0.6977; 95% CI, 0.3965–1.2278; P = .2119). The most commonly identified high-risk inclusion criteria were having at least 5 scheduled home medications and COPD. The time interval between discharge and readmission did not considerably differ between groups (10.8 vs 10.6 days). Conclusions: The pharmacist-bundled intervention was associated with a reduced 30-day readmission rate for high-risk patients with pneumonia. PMID:26823619

  10. Dissemination of high-risk clones of extensively drug-resistant Pseudomonas aeruginosa in colombia.

    PubMed

    Correa, Adriana; Del Campo, Rosa; Perenguez, Marcela; Blanco, Victor M; Rodríguez-Baños, Mercedes; Perez, Federico; Maya, Juan J; Rojas, Laura; Cantón, Rafael; Arias, Cesar A; Villegas, Maria V

    2015-04-01

    The ability of Pseudomonas aeruginosa to develop resistance to most antimicrobials represents an important clinical threat worldwide. We report the dissemination in several Colombian hospitals of two predominant lineages of extensively drug-resistant (XDR) carbapenemase-producing P. aeruginosa strains. These lineages belong to the high-risk clones sequence type 111 (ST111) and ST235 and harbor blaVIM-2 on a class 1 integron and blaKPC-2 on a Tn4401 transposon, respectively. Additionally, P. aeruginosa ST1492, a novel single-locus variant of ST111, was identified. Clonal dissemination and the presence of mobile genetic elements likely explain the successful spread of XDR P. aeruginosa strains in Colombia. PMID:25605362

  11. Psychological and Neurobiological Precursors of Alcohol Use Disorders in High Risk Youth

    PubMed Central

    Hill, Shirley Y.; O'Brien, Jessica

    2015-01-01

    It has long been known that Alcohol Use Disorders (AUDs) run in families with substantial heritability. Determining the specific genetic underpinnings of these disorders has been challenging because of the clinical heterogeneity and variable expression across the lifespan. The search for endophenotypic biological variation associated with the AUD and related substance use disorder (SUD) phenotypes is based on the belief that an endophenotype is more proximal to the causative gene. Identification of genes conferring increased susceptibility has important implications for treatment through the potential development of medications that target specific genetic pathways. High risk family designs that contrast offspring with and without a familial/genetic background have provided valuable insights into the psychological characteristics (executive control, affective regulation, decision making and social cognition) that differentiate such individuals. The current chapter will review these with a focus on brain morphology of specific regions, the coordinated activity of neural networks, and developmental trajectories of electrophysiological activity. PMID:26301172

  12. Pediatric Bipolar Disorder: Combination Pharmacotherapy, Adverse Effects, and Treatment of High-Risk Youth.

    PubMed

    Chang, Kiki D

    2016-01-01

    Treating bipolar disorder in pediatric patients is challenging because data from rigorous trials of pharmacotherapy in this population are still not plentiful enough. Furthermore, the treatment of children and adolescents is complicated by the frequent need to combine pharmacotherapies to address all bipolar symptoms as well as this population's elevated risk for experiencing side effects. Additionally, young patients with depressive episodes who are at high risk for developing bipolar disorder need careful treatment to prevent or delay the emergence of mania. Despite these challenges, clinicians should evaluate the existing pediatric literature, extrapolate evidence obtained from adult patients, and draw from clinical experience to guide treatment decisions for children and adolescents with bipolar disorder. PMID:27570929

  13. Dissemination of High-Risk Clones of Extensively Drug-Resistant Pseudomonas aeruginosa in Colombia

    PubMed Central

    del Campo, Rosa; Perenguez, Marcela; Blanco, Victor M.; Rodríguez-Baños, Mercedes; Perez, Federico; Maya, Juan J.; Rojas, Laura; Cantón, Rafael; Arias, Cesar A.; Villegas, Maria V.

    2015-01-01

    The ability of Pseudomonas aeruginosa to develop resistance to most antimicrobials represents an important clinical threat worldwide. We report the dissemination in several Colombian hospitals of two predominant lineages of extensively drug-resistant (XDR) carbapenemase-producing P. aeruginosa strains. These lineages belong to the high-risk clones sequence type 111 (ST111) and ST235 and harbor blaVIM-2 on a class 1 integron and blaKPC-2 on a Tn4401 transposon, respectively. Additionally, P. aeruginosa ST1492, a novel single-locus variant of ST111, was identified. Clonal dissemination and the presence of mobile genetic elements likely explain the successful spread of XDR P. aeruginosa strains in Colombia. PMID:25605362

  14. Web Services-Based Access to Local Clinical Trial Databases: A Standards Initiative of the Association of American Cancer Institutes

    PubMed Central

    Stahl, Douglas C.; Evans, Richard M.; Afrin, Lawrence B.; DeTeresa, Richard M.; Ko, Dave; Mitchell, Kevin

    2003-01-01

    Electronic discovery of the clinical trials being performed at a specific research center is a challenging task, which presently requires manual review of the center’s locally maintained databases or web pages of protocol listings. Near real-time automated discovery of available trials would increase the efficiency and effectiveness of clinical trial searching, and would facilitate the development of new services for information providers and consumers. Automated discovery efforts to date have been hindered by issues such as disparate database schemas, vocabularies, and standards for intersystem exchange of high-level data, but adequate infrastructure now exists that makes possible the development of applications for near real-time automated discovery of trials. This paper describes the current state (design and implementation) of the Web Services Specification for Publication and Discovery of Clinical Trials as developed by the Technology Task Force of the Association of American Cancer Institutes. The paper then briefly discusses a prototype web service-based application that implements the specification. Directions for evolution of this specification are also discussed. PMID:14728248

  15. Identification of local clinical Candida isolates using CHROMagar Candida™ as a primary identification method for various Candida species.

    PubMed

    Madhavan, P; Jamal, F; Chong, P P; Ng, K P

    2011-08-01

    The objective of our study was to study the effectiveness of CHROMagar Candida™ as the primary identification method for various clinical Candida isolates, other than the three suggested species by the manufacturer. We studied 34 clinical isolates which were isolated from patients in a local teaching hospital and 7 ATCC strains. These strains were first cultured in Sabouraud dextrose broth (SDB) for 36 hours at 35ºC, then on CHROMagar plates at 30ºC, 35ºC and 37ºC. The sensitivity of this agar to identify Candida albicans, Candida dubliniensis, Candida tropicalis, Candida glabrata, Candida rugosa, Candida krusei and Candida parapsilosis ranged between 25 and 100% at 30ºC, 14% and 100% at 35ºC, 56% and 100% at 37ºC. The specificity of this agar was 100% at 30ºC, between 97% and 100% at 35ºC, 92% and 100% at 37ºC. The efficiency of this agar ranged between 88 and 100% at 30ºC, 83% and 100% at 35ºC, 88% and 100% at 37ºC. Each species also gave rise to a variety of colony colours ranging from pink to green to blue of different colony characteristics. Therefore, the chromogenic agar was found to be useful in our study for identifying clinical Candida isolates. PMID:22041745

  16. Web services-based access to local clinical trial databases: a standards initiative of the Association of American Cancer Institutes.

    PubMed

    Stahl, Douglas C; Evans, Richard M; Afrin, Lawrence B; DeTeresa, Richard M; Ko, Dave; Mitchell, Kevin

    2003-01-01

    Electronic discovery of the clinical trials being performed at a specific research center is a challenging task, which presently requires manual review of the center's locally maintained databases or web pages of protocol listings. Near real-time automated discovery of available trials would increase the efficiency and effectiveness of clinical trial searching, and would facilitate the development of new services for information providers and consumers. Automated discovery efforts to date have been hindered by issues such as disparate database schemas, vocabularies, and insufficient standards for easy intersystem exchange of high-level data, but adequate infrastructure now exists that make possible the development of applications for near real-time automated discovery of trials. This paper describes the current state (design and implementation) of the Web Services Specification for Publication and Discovery of Clinical Trials as developed by the Technology Task Force of the Association of American Cancer Institutes. The paper then briefly discusses a prototype web service-based application that implements the specification. Directions for evolution of this specification are also discussed.

  17. Active surveillance for acute flaccid paralysis in poliomyelitis high-risk areas in southern China.

    PubMed Central

    Chiba, Y.; Hikita, K.; Matuba, T.; Chosa, T.; Kyogoku, S.; Yu, J.; Wang, Z.

    2001-01-01

    OBJECTIVE: On 29 October 2000 poliomyelitis was officially declared to have been eradicated from the Western Pacific Region. This article describes the results of surveillance for cases of acute flaccid paralysis (AFP) in China during the final phase of the eradication effort. METHODS: We conducted hospital-based active surveillance in high-risk areas for poliomyelitis in 5 provinces of southern-China (Sichuan, Yunnan, Guizhou, Guangxi and Jiangxi) between 1995 and 1997 to determine the adequacy of reporting and laboratory diagnosis of cases of AFP. FINDINGS: A total of 1069 AFP cases occurring since 1993 were identified in 311 hospital visits. Less than 50% of AFP cases occurring in 1993 and 1994 had been reported by AFP surveillance, and laboratory diagnosis had been carried out on only a small proportion of these. However, improved cooperation between hospital sectors increased the rate of case reporting and laboratory diagnosis to 85% and 78%, respectively, in 1997. Despite this overall improvement, these two indicators were approximately 10-20% lower in Yunnan Province. Epidemiological analysis revealed that cases of clinical poliomyelitis accounted for as much as one-third of all AFP in 1993 and that some of these cases were clustered. Clusters were rarely observed after 1994. Active surveillance in the China-Myanmar border areas of Yunnan over 1995-96 detected 9 cross-border cases of clinical poliomyelitis, including 2 of wild poliomyelitis. Import of poliomyelitis was thus considered to have occurred frequently until 1996 in this border area of Yunnan. These data were important for the outbreak response immunization carried out in 1996 in the border prefectures of Yunnan. CONCLUSION: Our investigation confirmed a high level of AFP surveillance in poliomyelitis high-risk areas of the five provinces and provided valuable information on the interruption of wild poliovirus circulation in southern China that will be of use to countries in other regions that have

  18. Stereotactic Body Radiation Therapy in Treating Patients With High Risk Locally Advanced Head and Neck Cancer

    ClinicalTrials.gov

    2016-09-29

    Recurrent Hypopharyngeal Squamous Cell Carcinoma; Recurrent Laryngeal Squamous Cell Carcinoma; Recurrent Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Recurrent Nasopharyngeal Keratinizing Squamous Cell Carcinoma; Recurrent Oral Cavity Squamous Cell Carcinoma; Recurrent Oropharyngeal Squamous Cell Carcinoma; Stage II Nasopharyngeal Keratinizing Squamous Cell Carcinoma; Stage III Hypopharyngeal Squamous Cell Carcinoma; Stage III Laryngeal Squamous Cell Carcinoma; Stage III Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage III Nasopharyngeal Keratinizing Squamous Cell Carcinoma; Stage III Oral Cavity Squamous Cell Carcinoma; Stage III Oropharyngeal Squamous Cell Carcinoma; Stage IVA Hypopharyngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Squamous Cell Carcinoma; Stage IVA Nasopharyngeal Keratinizing Squamous Cell Carcinoma; Stage IVA Oral Cavity Squamous Cell Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma; Stage IVB Hypopharyngeal Squamous Cell Carcinoma; Stage IVB Laryngeal Squamous Cell Carcinoma; Stage IVB Nasopharyngeal Keratinizing Squamous Cell Carcinoma; Stage IVB Oral Cavity Squamous Cell Carcinoma; Stage IVB Oropharyngeal Squamous Cell Carcinoma; Stage IVC Hypopharyngeal Squamous Cell Carcinoma; Stage IVC Laryngeal Squamous Cell Carcinoma; Stage IVC Nasopharyngeal Keratinizing Squamous Cell Carcinoma; Stage IVC Oral Cavity Squamous Cell Carcinoma; Stage IVC Oropharyngeal Squamous Cell Carcinoma

  19. Factors contributing to the duration of untreated prodromal positive symptoms in individuals at ultra-high risk for psychosis.

    PubMed

    Chon, Myong-Wuk; Lee, Tae Young; Kim, Sung Nyun; Huh, Min Jung; Park, Hye Youn; Lee, Cho Rong; Shin, Na Young; Kwon, Jun Soo

    2015-03-01

    Individuals at ultra-high risk (UHR) for psychosis experience a considerable delay before appropriate clinical attention is provided. Therefore, we investigated the correlates of this delay by examining clinical, socio-demographic and neuropsychological contributors to the duration of untreated prodromal positive symptoms (DUPP) in them (n=73). The slowly progressive mode of functional decline, defined as a small percentage drop in the Global Assessment of Functioning (GAF) score within the past year, and male gender, explained a considerable portion of the DUPP in the multivariate regression model (F=9.269, p<0.001). Slower functional decline may be correlated with delayed care during the UHR period.

  20. Clinical and radiographic evaluation of intra-bony defects in localized aggressive periodontitis patients with platelet rich plasma/hydroxyapatite graft: A comparative controlled clinical trial

    PubMed Central

    Gupta, Geeti

    2014-01-01

    Background: Aggressive periodontitis is a characterized by rapid attachment loss, bone destruction and familial aggregation. Platelet-rich plasma (PRP) has been proposed to promote regeneration of the lost periodontal tissues. The aim of this study was to evaluate and compare the efficacy of PRP combined with hydroxyapatite (HA) graft in the treatment of intra-bony defects in localized aggressive periodontitis (L-AgP) patients. Materials and Methods: Ten L-AgP patients having bilateral intra-bony defect ≥2 mm and probing depth (PD) ≥6 mm were randomly treated either with the PRP/HA graft or HA graft alone. The clinical (plaque control record, bleeding on probing index, PD, and relative attachment level [RAL]), and radiographic parameters (size of the bone defect) were recorded pre- and post-operatively at 3, 6, and 12 months. Results: After 12 months, for both maxillary and mandibular arches, the mean PD decrease was significantly more (P < 0.05) for the test group than the control group (3.2 mm vs. 1.9 mm and 3.6 mm vs. 1.9 mm, respectively). Furthermore, the mean RAL decrease in both maxillary and mandibular arches was significantly more (P < 0.05) for the test group than the control group (3.0 mm vs. 1.2 mm and 3.1 mm vs. 1.4 mm, respectively). Radiographically, the test group showed significantly more defect fill as compared with the control group. Conclusion: Both treatments provided significant improvements in clinical and radiographic parameters in a 12-month postoperative period. PRP/HA group presented superior results regarding PD reduction, clinical attachment gain and radiographic bone fill than HA group. PMID:25395757

  1. Protecting military personnel from high risk dietary supplements.

    PubMed

    Deuster, Patricia A; Lieberman, Harris R

    2016-01-01

    It is legal tomarketmost naturally occurring substances as dietary supplements in the USA without manufacturers demonstrating they are safe or effective, and an endless variety of ingredients, from esoteric botanicals to unapproved pharmaceuticals, can be found in dietary supplements. Use of certain supplements can pose a risk, but since a robust reporting systemdoes not exist in the USA it is difficult to know which are problematic and the number of adverse events (AE) resulting from their use. Certain populations, includingmilitary personnel, aremore likely to use dietary supplements than the general population. Approximately 70% of military personnel take dietary supplements while about 50% of civilians do. Service members prefer supplements purported to enhance physical performance such as supposedly natural stimulants, protein and amino acids, and combination products. Since some of thesemay be problematic, Servicemembers are probably at higher risk of injury than the general population. Ten percent of military populations appear to be taking potentially risky supplements, and the US Department of Defense (DoD) has taken variousmeasures to protect uniformed personnel including education, policy changes, and restricting sales. Actions taken include launching Operation Supplement Safety (OPSS), introducing a High Risk Supplement list, educating health care professionals on reporting AE thatmight be associated with dietary supplements, recommending policy for reporting AE, and developing an online AE reporting system. OPSS is a DoD-wide effort to educate service members, leaders, health care providers, military families, and retirees on how to safely select supplements PMID:26472157

  2. Protecting military personnel from high risk dietary supplements.

    PubMed

    Deuster, Patricia A; Lieberman, Harris R

    2016-01-01

    It is legal tomarketmost naturally occurring substances as dietary supplements in the USA without manufacturers demonstrating they are safe or effective, and an endless variety of ingredients, from esoteric botanicals to unapproved pharmaceuticals, can be found in dietary supplements. Use of certain supplements can pose a risk, but since a robust reporting systemdoes not exist in the USA it is difficult to know which are problematic and the number of adverse events (AE) resulting from their use. Certain populations, includingmilitary personnel, aremore likely to use dietary supplements than the general population. Approximately 70% of military personnel take dietary supplements while about 50% of civilians do. Service members prefer supplements purported to enhance physical performance such as supposedly natural stimulants, protein and amino acids, and combination products. Since some of thesemay be problematic, Servicemembers are probably at higher risk of injury than the general population. Ten percent of military populations appear to be taking potentially risky supplements, and the US Department of Defense (DoD) has taken variousmeasures to protect uniformed personnel including education, policy changes, and restricting sales. Actions taken include launching Operation Supplement Safety (OPSS), introducing a High Risk Supplement list, educating health care professionals on reporting AE thatmight be associated with dietary supplements, recommending policy for reporting AE, and developing an online AE reporting system. OPSS is a DoD-wide effort to educate service members, leaders, health care providers, military families, and retirees on how to safely select supplements

  3. Influenza and pneumococcal pneumonia immunization. Protecting our high risk population.

    PubMed

    Siegel, B R; Mahan, C S; Witte, J J; Janowski, H T

    1990-06-01

    Pneumonia and influenza (P & I) constitute Florida's sixth leading cause of death. The P & I death rate in 1987, 10.5 per 100,000, was the highest since 1978. Major target groups for one or both vaccines used in prevention, as recommended by the Immunization Practices Advisory Committee (ACIP), include persons with chronic diseases of the heart or lungs, residents of nursing homes and other chronic care facilities, and persons aged 65 and older. Despite well-defined recommendations, vaccine coverage rates in Florida are as low as 30% in persons greater than or equal to 65 years of age. Knowledge and attitude surveys demonstrate that low coverage among various population groups may be due largely to insufficient awareness and/or negative attitudes regarding pneumococcal and influenza vaccines. Conversely, recommendations by physicians and other health care providers are strongly associated with receiving either vaccine. If the incidence of P & I is to decrease substantively in Florida, much wider use of the vaccines must occur. Because so many high-risk patients depend on private physicians for health care, their role is critical to the success of Florida public health strategies to reverse P & I trends.

  4. Upper tract urothelial carcinoma: epidemiology, high risk populations and detection.

    PubMed

    Redrow, Grant P; Matin, Surena F

    2016-08-01

    Upper tract urothelial carcinoma (UTUC) is a rare but highly morbid genitourinary malignancy. In 2014 approximately 15,000 new cases were diagnosed in the United States. It accounts for approximately 5-10% of all urothelial cell carcinomas, and 10% of renal tumors. Recent research has increased understanding of the epidemiology of this disease, including several high-risk populations. Environmental exposure to tobacco as well as aristolochic acid, and other carcinogens significantly increase the development of UTUC. Additionally, the genetic condition of hereditary nonpolyposis colorectal carcinoma (HNPCC), also known as Lynch Syndrome (LS) is linked to development of UTUC. Advances in imaging, ureteroscopy, cytological techniques and pathological recognition have allowed for improved detection of primary tumors and recurrent disease. Non-invasive imaging with computed tomography (CT) and magnetic resonance imaging (MRI) now represent the gold standard in imaging detection and surveillance, while technological advances in ureteroscopy allow for minimally invasive approaches to obtain pathologic diagnosis anywhere within the upper tracts. This review will highlight these recent improvements to allow better understanding of who is affected by this rare and morbid disease, as well as the latest developments in detection and surveillance. PMID:27008468

  5. Neurophysiology for Detection of High Risk for Psychosis

    PubMed Central

    2016-01-01

    Schizophrenia is a complex and often disabling disorder that is characterized by a wide range of social, emotional, and cognitive deficits. Increasing research suggests that the greatest social and cognitive therapeutic impact comes from early identification. The present study applied a well-established neurophysiological paradigm in the schizophrenia literature, mismatch negativity (MMN), to college students identified as high risk (HR) for psychosis to investigate MMN as a potential biomarker for the onset of psychosis. The hypothesis was that HR would exhibit attenuated MMN amplitudes compared to controls, as has been established in individuals with chronic schizophrenia. Participants (N = 121) were separated into Group 1 (controls) (n1 = 72) and Group 2 (HR) (n2 = 49) based on the established cutoff score of the 16-item Prodromal Questionnaire. Participants then completed a time based MMN paradigm during which brain activity was recorded with EEG. For all electrode locations, controls demonstrated significantly more negative amplitudes than HR (Cz: F(1,119) = 8.09, p = .005; Fz: F(1, 119) = 5.74, p = .018; Pz: F(1,119) = 5.88, p = .017). Results suggested that MMN may assist in identifying those who appear high-functioning but may be at risk for later development of psychosis or cognitive and psychological difficulties associated with psychosis. PMID:27579180

  6. Decontamination of High-risk Animal and Zoonotic Pathogens

    PubMed Central

    Menrath, Andrea; Tomuzia, Katharina; Braeunig, Juliane; Appel, Bernd

    2013-01-01

    Preparedness for the decontamination of affected environments, premises, facilities, and products is one prerequisite for an immediate response to an animal disease outbreak. Various information sources provide recommendations on how to proceed in an outbreak situation to eliminate biological contaminants and to stop the spread of the disease. In order to facilitate the identification of the right decontamination strategy, we present an overview of relevant references for a collection of pathogenic agents. The choice of pathogens is based on a survey of lists containing highly pathogenic agents and/or biological agents considered to be potential vehicles for deliberate contamination of food, feed, or farm animals. European legislation and guidelines from national and international institutions were screened to find decontamination protocols for each of the agents. Identified recommendations were evaluated with regard to their area of application, which could be facilities and equipment, wastes, food, and other animal products. The requirements of a disinfectant for large-scale incidents were gathered, and important characteristics (eg, inactivating spectrum, temperature range, toxicity to environment) of the main recommended disinfectants were summarized to assist in the choice of a suitable and efficient approach in a crisis situation induced by a specific high-risk animal or zoonotic pathogen. The literature search revealed numerous relevant recommendations but also legal gaps for certain diseases, such as Q fever or brucellosis, and legal difficulties for the use of recommended disinfectants. A lack of information about effective disinfectants was identified for some agents. PMID:23971795

  7. Neurophysiology for Detection of High Risk for Psychosis.

    PubMed

    Pantlin, Lara N; Davalos, Deana

    2016-01-01

    Schizophrenia is a complex and often disabling disorder that is characterized by a wide range of social, emotional, and cognitive deficits. Increasing research suggests that the greatest social and cognitive therapeutic impact comes from early identification. The present study applied a well-established neurophysiological paradigm in the schizophrenia literature, mismatch negativity (MMN), to college students identified as high risk (HR) for psychosis to investigate MMN as a potential biomarker for the onset of psychosis. The hypothesis was that HR would exhibit attenuated MMN amplitudes compared to controls, as has been established in individuals with chronic schizophrenia. Participants (N = 121) were separated into Group 1 (controls) (n 1 = 72) and Group 2 (HR) (n 2 = 49) based on the established cutoff score of the 16-item Prodromal Questionnaire. Participants then completed a time based MMN paradigm during which brain activity was recorded with EEG. For all electrode locations, controls demonstrated significantly more negative amplitudes than HR (Cz: F(1,119) = 8.09, p = .005; Fz: F(1, 119) = 5.74, p = .018; Pz: F(1,119) = 5.88, p = .017). Results suggested that MMN may assist in identifying those who appear high-functioning but may be at risk for later development of psychosis or cognitive and psychological difficulties associated with psychosis. PMID:27579180

  8. Professional drivers: protection needed for a high-risk occupation.

    PubMed Central

    Baker, S P; Wong, J; Baron, R D

    1976-01-01

    "On the job" motor vehicle deaths number more than 4,000 annually in the U.S. and comprise nearly one-third of all work-related deaths. Yet the Department of Labor has set no standards relating to on-the-road safety of the millions of workers whose jobs entail large amounts of driving, and Department of Transportation standards affecting occupational safety cover only drivers in interstate commerce. Drivers of some commercial vehicles, such as heavy trucks, are at special risk of injury because trucks have usually been exempted for many years from federal motor vehicle safety standards--such as standards for brakes and seatbelts--designed to prevent crashes or protect occupants in crashes. Observations based on a series of 150 fatal crashes involving tractor trailers illustrate the need for better protection of this large population of high-risk workers. Clarification of responsibility within the various federal agencies and application of available knowledge and technology are essential. PMID:937611

  9. Early detection of tumor relapse/regrowth by consecutive minimal residual disease monitoring in high-risk neuroblastoma patients

    PubMed Central

    Hirase, Satoshi; Saitoh, Atsuro; Hartomo, Tri Budi; Kozaki, Aiko; Yanai, Tomoko; Hasegawa, Daiichiro; Kawasaki, Keiichiro; Kosaka, Yoshiyuki; Matsuo, Masafumi; Yamamoto, Nobuyuki; Mori, Takeshi; Hayakawa, Akira; Iijima, Kazumoto; Nishio, Hisahide; Nishimura, Noriyuki

    2016-01-01

    Neuroblastoma is an aggressive pediatric tumor accounting for ~15% of cancer-associated mortalities in children. Despite the current intensive therapy, >50% of high-risk patients experience tumor relapse or regrowth caused by the activation of minimal residual disease (MRD). Although several MRD detection protocols using various reverse transcription-quantitative polymerase chain reaction (RT-qPCR) markers have been reported to evaluate the therapeutic response and disease status of neuroblastoma patients, their clinical significance remains elusive. The present study reports two high-risk neuroblastoma patients, whose MRD was consecutively monitored using 11 RT-qPCR markers (CHRNA3, CRMP1, DBH, DCX, DDC, GABRB3, GAP43, ISL1, KIF1A, PHOX2B and TH) during their course of treatment. The two patients initially responded to the induction therapy and reached MRD-negative status. The patients' MRD subsequently became positive with no elevation of their urinary homovanillic acid, urinary vanillylmandelic acid and serum neuron-specific enolase levels at 13 or 19 weeks prior to the clinical diagnosis of tumor relapse or regrowth. The present cases highlight the possibility of consecutive MRD monitoring using 11 markers to enable an early detection of tumor relapse or regrowth in high-risk neuroblastoma patients. PMID:27446404

  10. Epidermal Th22 and Tc17 cells form a localized disease memory in clinically healed psoriasis.

    PubMed

    Cheuk, Stanley; Wikén, Maria; Blomqvist, Lennart; Nylén, Susanne; Talme, Toomas; Ståhle, Mona; Eidsmo, Liv

    2014-04-01

    Psoriasis is a common and chronic inflammatory skin disease in which T cells play a key role. Effective treatment heals the skin without scarring, but typically psoriasis recurs in previously affected areas. A pathogenic memory within the skin has been proposed, but the nature of such site-specific disease memory is unknown. Tissue-resident memory T (TRM) cells have been ascribed a role in immunity after resolved viral skin infections. Because of their localization in the epidermal compartment of the skin, TRM may contribute to tissue pathology during psoriasis. In this study, we investigated whether resolved psoriasis lesions contain TRM cells with the ability to maintain and potentially drive recurrent disease. Three common and effective therapies, narrowband-UVB treatment and long-term biologic treatment systemically inhibiting TNF-α or IL-12/23 signaling were studied. Epidermal T cells were highly activated in psoriasis and a high proportion of CD8 T cells expressed TRM markers. In resolved psoriasis, a population of cutaneous lymphocyte-associated Ag, CCR6, CD103, and IL-23R expressing epidermal CD8 T cells was highly enriched. Epidermal CD8 T cells expressing the TRM marker CD103 responded to ex vivo stimulation with IL-17A production and epidermal CD4 T cells responded with IL-22 production after as long as 6 y of TNF-α inhibition. Our data suggest that epidermal TRM cells are retained in resolved psoriasis and that these cells are capable of producing cytokines with a critical role in psoriasis pathogenesis. We provide a potential mechanism for a site-specific T cell-driven disease memory in psoriasis.

  11. Local bupivacaine for postoperative pain management in thyroidectomized patients: A prospective and controlled clinical study

    PubMed Central

    Dumlu, Ersin Gürkan; Tokaç, Mehmet; Öcal, Haydar; Durak, Doğukan; Kara, Halil; Kılıç, Mehmet; Yalçın, Abdussamed

    2016-01-01

    Objective We aimed to evaluate the effect of bupivacaine and to compare the routes of administration of bupivacaine in the management of postoperative incision site pain after thyroidectomy. Material and Methods Consecutive patients who were planned for thyroidectomy surgery were randomized into three groups of 30 patients each: Group 1 (control group): standard thyroidectomy surgery without additional intervention; Group 2 (paratracheal infiltration with bupivacaine): following thyroidectomy, 0.25% bupivacaine was applied on the surgical area; Group 3 (subcutaneous infiltration with bupivacaine): following thyroidectomy, 0.25% bupivacaine was injected into the cutaneous, subcutaneous region and fascia of the surgical area. Postoperative pain was evaluated by a visual analog scale (VAS) at 1st, 4th, and 12th hours after thyroidectomy. Total daily requirement for additional analgesia was recorded. Results The mean age of 90 patients was 44.37±13.42 years, and the female:male ratio was 62:28. There was no difference between study groups in terms of age, thyroid volume, TSH and T4 levels. VAS score of patients in paratracheal infiltration with bupivacaine group was significantly lower than control group patients at 1st, 4th and 12th hours following thyroidectomy (p=0.030, p=0.033, p=0.039, respectively). The need for analgesics was significantly lower in both paratracheal infiltration and subcutaneous infiltration groups than the control group (86.7%, 83.0%, and 73.3%, respectively, p=0.049). Conclusions Intraoperative local bupivacaine application is effective in decreasing postoperative pain in patients with thyroidectomy. PMID:27528810

  12. Minocycline Ointment as a Local Drug Delivery in the Treatment of Generalized Chronic Periodontitis - A Clinical Study

    PubMed Central

    Abbas, Sara; Ari, Geetha

    2016-01-01

    Introduction The primary goal in periodontal therapy includes removal of the etiological factors by mechanical periodontal treatment, which sometimes fail to eliminate the anaerobic infection at the base of the pocket and requires adjuvant chemical therapy. Aim The aim of the study was to evaluate the effectiveness of 2% minocycline ointment when used as an adjunct to periodontal flap surgery and post-operative maintenance period for the treatment of generalized chronic periodontitis. Materials and Methods The study included 30 subjects comprising of 60 posterior sextants in a split mouth design in which 30 sextants were treated as experimental and 30 sextants as control with a probing pocket depth≥6mm. In Group A (experimental group) 30 sextants were treated with open flap debridement followed by the application of minocycline ointment as a local drug delivery. In Group B (control group) 30 sextants were treated with open flap debridement alone. Minocycline hydrochloride ointment was applied on the 0 day and 3rd month. The clinical parameters such as plaque index, probing pocket depth, clinical attachment level and gingival bleeding index were recorded at 0 day, 3rd month and 6th month in both the groups. Paired and unpaired t-test were used to compare the means of the two groups. Results When Group A and Group B were compared, Group A showed significantly greater reduction in gingival bleeding index, probing pocket depth and gain in clinical attachment level than Group B, from 0 day to 3 months and from 0 day to 6 months. Group A showed significant reduction in plaque index than Group B when they were compared at 6 months. Conclusion The results demonstrate that there was significant reduction in the clinical parameters with improvement in the periodontal status on application of minocycline ointment as an adjunct to periodontal flap surgery in generalized chronic periodontitis. PMID:27504402

  13. Social cognition in children at familial high-risk of developing an eating disorder

    PubMed Central

    Kothari, Radha; Barona, Manuela; Treasure, Janet; Micali, Nadia

    2015-01-01

    Objective: Diagnosis of an eating disorder (ED) has been associated with differences in social cognition. To date research investigating social cognition and ED has mainly employed patient and recovered samples. It is therefore unclear whether differences in social cognition are present prior to onset of ED, potentially contributing to development, or whether differences observed are a consequence of the disorder. We aimed to further explore whether individuals at high-risk for ED present social cognition characteristics previously found in ED groups. Methods: Our sample was drawn from a population-based cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC). Data on maternal ED behaviors over the lifetime were collected through in-depth clinical interviews (n = 1128) conducted using the Structured Clinical Interview for DSM disorders (SCID), and were used to categorize mothers according to ED behaviors over the lifetime: Restricting and Excessive Exercising (n = 58), Purging (n = 70), Binge-eating (n = 72), Binging and Purging (n = 66), no ED (n = 862). High-risk status of children was determined using these maternal lifetime behavioral phenotypes. Children at high-risk (maternal ED exposure) were compared to children at low-risk (born to mothers with no ED) on three measures of social cognition: the Social Communication Disorders Checklist (SCDC) (n = 922), the faces subtest of the Diagnostic Analysis of Non-Verbal Accuracy (DANVA) (n = 722), and the Emotional Triangles Task (n = 750). Results: Children at high-risk for ED showed poorer performance on measures of social cognition compared to children at low-risk. Maternal lifetime binge-eating, and maternal lifetime binging and purging were associated with poorer social communication in children (OR: 2.4, 95% CI: 1.0, 5.7, p = 0.05; and OR: 2.7, 95% CI: 1.1, 6.5, p = 0.03 respectively). Maternal binging and purging was also found to be associated with differential facial emotion processing and

  14. TAIMA (Stop) TB: The Impact of a Multifaceted TB Awareness and Door-to-Door Campaign in Residential Areas of High Risk for TB in Iqaluit, Nunavut

    PubMed Central

    Alvarez, Gonzalo G.; VanDyk, Deborah D.; Aaron, Shawn D.; Cameron, D. William; Davies, Naomi; Stephen, Natasha; Mallick, Ranjeeta; Momoli, Franco; Moreau, Katherine; Obed, Natan; Baikie, Maureen; Osborne, Geraldine

    2014-01-01

    Background The incidence rate of active tuberculosis (TB) disease in the Canadian Territory of Nunavut has shown a rising trend over the past 10 years. In 2010 it was 60 times greater than the national incidence rate. The objective of the Taima (translates to “stop” in Inuktitut) TB study was to implement and evaluate a public health campaign to enhance existing TB prevention efforts in Nunavut. Methods A TB awareness campaign followed by a door-to-door screening campaign was carried out in Iqaluit, Nunavut. The aim of the campaign was to raise awareness about TB, and to provide in-home screening and treatment for people living in residential areas at high risk for TB. Screening was based on geographic location rather than on individual risk factors. Results During the general awareness campaign an increase in the number of people who requested TB testing at the local public health clinic was observed. However, this increase was not sustained following cessation of the awareness campaign. Targeted TB screening in high risk residential areas in Iqaluit resulted in 224 individuals having TSTs read, and detection of 42 previously unidentified cases of latent TB, (overall yield of 18.8% or number needed to screen = 5.3). These cases of latent TB infection (LTBI) were extra cases that had not been picked up by traditional screening practices (34% relative increase within the community). This resulted in a 33% relative increase in the completion of LTBI treatment within the community. The program directly and indirectly identified 5/17 new cases of active TB disease in Iqaluit during the study period (29.5% of all incident cases). Conclusions While contact tracing investigations remain a cornerstone of TB prevention, additional awareness, screening, and treatment programs like Taima TB may contribute to the successful control of TB in Aboriginal communities. PMID:25033320

  15. Verrucous carcinomas of the head and neck, including those with associated squamous cell carcinoma, lack transcriptionally active high-risk human papillomavirus.

    PubMed

    Patel, Kalyani R; Chernock, Rebecca D; Zhang, Tian R; Wang, Xiaowei; El-Mofty, Samir K; Lewis, James S

    2013-11-01

    Most oropharyngeal squamous cell carcinomas (SCC) and histologic variants harbor transcriptionally active human papillomavirus (HPV). While HPV DNA can be found in many non-oropharyngeal head and neck carcinomas, transcriptionally active HPV is rare. Verrucous carcinoma is a variant with bland cytology, warty appearance, locally destructive growth, and lack of metastasis when lacking a frankly invasive carcinoma component. Studies have shown variable rates of HPV DNA and p16 protein expression in such tumors but still have not clearly addressed if the virus has biological activity or clinical relevance in the positive cases. Department files were searched for verrucous neoplasms, including pure verrucous carcinoma, verrucous carcinoma with dysplasia or minimal invasion, and SCC arising in verrucous carcinoma (ie, having a major component of frankly invasive carcinoma). p16 immunohistochemistry, HPV DNA polymerase chain reaction (PCR) and E6/E7 mRNA reverse transcription PCR for high-risk HPV types were performed. Of the 49 cases, 6 (12.2%) showed strong (>50%) staining for p16. HPV DNA was detected in 7/49 (14.3%) cases, but only one case was positive for both p16, and HPV DNA. A total of 36 cases yielded sufficient RNA for RT-PCR (18 verrucous carcinomas, 13 atypical verrucous carcinomas, and 5 SCC arising in verrucous carcinoma). All 36 were negative, including the four p16-positive and three HPV DNA-positive tumors tested. Although a minority of verrucous carcinoma lesions are p16 and HPV DNA positive, transcriptionally active high-risk HPV is uniformly absent. These findings argue that verrucous carcinoma and its related squamous cell carcinomas are not HPV-driven tumors.

  16. Misuse of prescription and illicit drugs among high-risk young adults in Los Angeles and New York.

    PubMed

    Lankenau, Stephen E; Schrager, Sheree M; Silva, Karol; Kecojevic, Alex; Bloom, Jennifer Jackson; Wong, Carolyn; Iverson, Ellen

    2012-02-14

    BACKGROUND: Prescription drug misuse among young adults is increasingly viewed as a public health concern, yet most research has focused on student populations and excluded high-risk groups. Furthermore, research on populations who report recent prescription drug misuse is limited. This study examined patterns of prescription drug misuse among high-risk young adults in Los Angeles (LA) and New York (NY), which represent different local markets for illicit and prescription drugs. DESIGN AND METHODS: Between 2009 and 2011, 596 young adults (16 to 25 years old) who had misused prescription drugs within the past 90 days were interviewed in Los Angeles and New York. Sampling was stratified to enroll three groups of high-risk young adults: injection drug users (IDUs); homeless persons; and polydrug users. RESULTS: In both sites, lifetime history of receiving a prescription for an opioid, tranquilizer, or stimulant was high and commonly preceded misuse. Moreover, initiation of opioids occurred before heroin and initiation of prescription stimulants happened prior to illicit stimulants. NY participants more frequently misused oxycodone, heroin, and cocaine, and LA participants more frequently misused codeine, marijuana, and methamphetamine. Combining prescription and illicit drugs during drug using events was commonly reported in both sites. Opioids and tranquilizers were used as substitutes for other drugs, e.g., heroin, when these drugs were not available. CONCLUSION: Patterns of drug use among high-risk young adults in Los Angeles and New York appear to be linked to differences in local markets in each city for illicit drugs and diverted prescription drugs. PMID:22798990

  17. Misuse of Prescription and Illicit Drugs Among High-risk Young Adults in Los Angeles and New York

    PubMed Central

    Lankenau, Stephen E.; Schrager, Sheree M.; Silva, Karol; Kecojevic, Alex; Bloom, Jennifer Jackson; Wong, Carolyn; Iverson, Ellen

    2012-01-01

    Background Prescription drug misuse among young adults is increasingly viewed as a public health concern, yet most research has focused on student populations and excluded high-risk groups. Furthermore, research on populations who report recent prescription drug misuse is limited. This study examined patterns of prescription drug misuse among high-risk young adults in Los Angeles (LA) and New York (NY), which represent different local markets for illicit and prescription drugs. Design and Methods Between 2009 and 2011, 596 young adults (16 to 25 years old) who had misused prescription drugs within the past 90 days were interviewed in Los Angeles and New York. Sampling was stratified to enroll three groups of high-risk young adults: injection drug users (IDUs); homeless persons; and polydrug users. Results In both sites, lifetime history of receiving a prescription for an opioid, tranquilizer, or stimulant was high and commonly preceded misuse. Moreover, initiation of opioids occurred before heroin and initiation of prescription stimulants happened prior to illicit stimulants. NY participants more frequently misused oxycodone, heroin, and cocaine, and LA participants more frequently misused codeine, marijuana, and methamphetamine. Combining prescription and illicit drugs during drug using events was commonly reported in both sites. Opioids and tranquilizers were used as substitutes for other drugs, e.g., heroin, when these drugs were not available. Conclusion Patterns of drug use among high-risk young adults in Los Angeles and New York appear to be linked to differences in local markets in each city for illicit drugs and diverted prescription drugs. PMID:22798990

  18. Family-Focused Treatment for Adolescents and Young Adults at High Risk for Psychosis: Results of a Randomized Trial

    PubMed Central

    Miklowitz, David J.; O’Brien, Mary P.; Schlosser, Danielle A.; Addington, Jean; Candan, Kristin A.; Marshall, Catherine; Domingues, Isabel; Walsh, Barbara C.; Zinberg, Jamie L.; De Silva, Sandra D.; Friedman-Yakoobian, Michelle; Cannon, Tyrone D.

    2014-01-01

    Objective Longitudinal studies have begun to clarify the phenotypic characteristics of adolescents and young adults at clinical high risk for psychosis. This 8-site randomized trial examined whether a 6-month program of family psychoeducation was effective in reducing the severity of attenuated positive and negative psychotic symptoms and enhancing functioning among individuals at high risk. Method Adolescents and young adults (mean 17.4±4.1 years) with attenuated positive psychotic symptoms, brief and intermittent psychosis, or genetic risk with functional deterioration were randomly assigned to 18 sessions of family-focused therapy for individuals at clinical high risk (FFT-CHR) in 6 months or 3 sessions of family psychoeducation (enhanced care, or EC). FFT-CHR included psychoeducation about early signs of psychosis, stress management, communication training, and problem-solving skills training, whereas EC focused on symptom prevention. Independent evaluators assessed participants at baseline and 6 months on positive and negative symptoms and social-role functioning. Results Of 129 participants, 102 (79.1%) were followed at 6 months. Participants in FFT-CHR showed greater improvements in attenuated positive symptoms over 6 months than participants in EC (F[1,97]=5.49, P=.02). Negative symptoms improved independently of psychosocial treatments. Changes in psychosocial functioning depended on age: participants over 19 years showed more role improvement in FFT-CHR, whereas participants between 16 and 19 years showed more role improvement in EC. The results were independent of concurrent pharmacotherapy. Conclusion Interventions that focus on improving family relationships may have prophylactic efficacy in individuals at high risk for psychosis. Future studies should examine the specificity of effects of family intervention compared to individual therapy of the same duration and frequency. PMID:25062592

  19. Comorbidity and Inflammatory Markers May Contribute to Predict Mortality of High-Risk Patients With Chronic Obstructive Pulmonary Disease Exacerbation

    PubMed Central

    Kim, Yu Jin; Lim, Byeongwoo; Kyung, Sun Young; Park, Jeong-woong; Jeong, Sung Hwan

    2016-01-01

    Background Acute exacerbation of chronic obstructive pulmonary disease (COPD) causes not only an accelerated disease progression, but also an increased mortality rate. The purpose of this study was to analyze the factors associated with clinical features, comorbidities and mortality in patients at high risk for acute COPD exacerbation who had been hospitalized at least once in a year. Methods The study enrolled 606 patients who had been diagnosed with and were being treated for COPD at university affiliated hospital. Among them, there were 61 patients at high risk for acute exacerbation of COPD who had been hospitalized at least once in a year. A retrospective analysis was conducted to examine the factors affecting mortality. The analysis divided the patients into non-survivor and survivor groups, and reviewed their medical records for clinical aspects, comorbidities, pulmonary function tests and blood tests. Results In the high-risk group, the number of comorbidities at diagnosis (P = 0.020) and the Charlson comorbidity index value (P = 0.018) were higher in the non-survivor group than in the survivor group. During hospitalization, the non-survivor group had a significantly higher neutrophil (%) and a significantly lower lymphocyte (%) in complete blood count. Under stable conditions, the high-sensitivity C-reactive protein (hsCRP) concentration in blood plasma and neutrophil (%) were significantly higher (P = 0.025 and P = 0.036), while the lymphocyte (%) was significantly lower (P = 0.005) in the non-survivor group. A pulmonary function test revealed no statistically significant differences between the two groups. Conclusion The number of comorbidities, neutrophil (%), lymphocyte (%) in complete blood cell (CBC) and hsCRP in blood plasma concentration among the groups at high risk for COPD exacerbation are associated with increased mortality. PMID:27298662

  20. Linkages between insomnia and suicidality: prospective associations, high-risk subgroups and possible psychological mechanisms.

    PubMed

    Winsper, Catherine; Tang, Nicole K Y

    2014-04-01

    Insomnia can be lethal, increasing the risk of suicide and accidental death by overdose. In this review we present a synthesis of the literature investigating the insomnia-suicide link and the psychological mechanisms underpinning the association. Specifically, we review the findings of prospective epidemiological studies demonstrating the insomnia-suicide link in adult and adolescent community populations. Robust associations between insomnia and suicide are observed in clinically depressed and anxious populations, and there are indications across a number of cross-sectional and longitudinal studies that these linkages are attributable to a disrupted sleep pattern, dysfunctional beliefs about sleep and nightmares, independent of depression and anxiety symptoms. Borderline personality disorder (BPD) and chronic pain (CP) are highlighted as high-risk subgroups given the elevated rates of insomnia and suicidality in both conditions. Aside from the influence of comorbid depression and anxiety symptoms, emerging evidence has identified impulsivity and emotional dysregulation as possible mechanisms driving the insomnia-suicide link in BPD, and catastrophizing and the sense of defeat/entrapment as potential cognitive pathways through which insomnia aggravates suicidality in CP. Screening for, and interventions that tackle, insomnia and these associated psychological mechanisms, offer a novel avenue for reducing suicidality across a range of clinical and non-clinical populations. PMID:24892894

  1. Dinutuximab for the treatment of pediatric patients with high-risk neuroblastoma.

    PubMed

    Mora, Jaume

    2016-01-01

    Neuroblastoma (NB) is the most common extra cranial solid tumor of childhood, with 60% of patients presenting with high risk (HR) NB by means of clinical, pathological and biological features. The 5-year survival rate for HR-NB remains below 40%, with the majority of patients suffering relapse from chemorefractory tumor. Immunotherapy is the main strategy against minimal residual disease and clinical experience has mostly focused on monoclonal antibodies (MoAb) against the glycolipid disialoganglioside GD2. Three anti-GD2 antibodies have been tested in the clinic including murine 14G2a, human-mouse chimeric ch14.18 and 3F8. Anti-GD2 MoAb induces cellular cytoxicity against NB and is most effective when effector cells like natural killer cells, granulocytes and macrophages are amplified by cytokines. The combination of cytokines IL-2 and GM-CSF with the anti-GD2 MoAb ch14.18 (Dinutuximab) has shown a significant improvement in outcome for HR-NB. The FDA and EMA approved dinutuximab (Unituxin(R)) in 2015 for the treatment of patients with HR-NB who achieved at least a partial response after multimodality therapy.

  2. Sentinel-base DNA genotyping using multiple sequencing primers for high-risk human papillomaviruses

    PubMed Central

    Gharizadeh, Baback; Zheng, Biying; Akhras, Michael; Ghaderi, Mehran; Jejelowo, Olufisayo; Strander, Björn; Nyrén, Pål; Wallin, Keng-Ling; Pourmand, Nader

    2009-01-01

    Despite the various technologies in place for genotyping human papillomaviruses (HPV), clinical use and clinical research demand a method that is fast, more reliable and cost-effective. The technology described here represents a breakthrough development in that direction. By combining the method of multiple sequencing primers with DNA sequencing, we have developed a rapid assay for genotyping HPV that relies on the identification of a single, type-specific ‘sentinel’ base. As described here, the prototype assay has been developed to recognize the 12 most high-risk HPV types (HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59) and is capable of recognizing and simultaneously genotyping multiple HPV co-infections. By providing sequence information on multiple HPV infections, this method eliminates the need for labor- and cost-intensive PCR cloning. These proof-of-concept studies establish the assay to be accurate, reliable, rapid, flexible, and cost-effective, providing evidence of the feasibility this technique for use in clinical settings. PMID:16516439

  3. Dinutuximab for the treatment of pediatric patients with high-risk neuroblastoma.

    PubMed

    Mora, Jaume

    2016-01-01

    Neuroblastoma (NB) is the most common extra cranial solid tumor of childhood, with 60% of patients presenting with high risk (HR) NB by means of clinical, pathological and biological features. The 5-year survival rate for HR-NB remains below 40%, with the majority of patients suffering relapse from chemorefractory tumor. Immunotherapy is the main strategy against minimal residual disease and clinical experience has mostly focused on monoclonal antibodies (MoAb) against the glycolipid disialoganglioside GD2. Three anti-GD2 antibodies have been tested in the clinic including murine 14G2a, human-mouse chimeric ch14.18 and 3F8. Anti-GD2 MoAb induces cellular cytoxicity against NB and is most effective when effector cells like natural killer cells, granulocytes and macrophages are amplified by cytokines. The combination of cytokines IL-2 and GM-CSF with the anti-GD2 MoAb ch14.18 (Dinutuximab) has shown a significant improvement in outcome for HR-NB. The FDA and EMA approved dinutuximab (Unituxin(R)) in 2015 for the treatment of patients with HR-NB who achieved at least a partial response after multimodality therapy. PMID:26934530

  4. Comparison of methods trial for high-risk HPV.

    PubMed

    Kurtycz, Daniel F I; Smith, Michele; He, Rong; Miyazaki, Kayo; Shalkham, John

    2010-02-01

    In efforts to improve service, we compared the performance of four methods of HPV detection: Invader HPV (Hologic), Hybrid Capture 2 (Qiagen), Inform HPV detection (Ventana), and standard PCR.Using blinded/de-identified cervical samples in Preservcyt (Hologic), we compared Ventana's Inform HPV Test, against Hologic's HPV Invader and PCR. In a separate evaluation, we compared Inform versus Invader versus hc2. Ventana employs in situ hybridization; Hologic's technology uses three specifically designed oligonucleotides and a fluorescent signal for detection. Qiagen's hc2 method incorporates enzyme-linked antibody detection of RNA-DNA hybrids. PCR testing was provided by Access Genetics (Minneapolis, MN). The United States Food and Drug Administration recently approved the Third Wave/Hologic Invader HPV high-risk test (rebranded as Cervista HPV HR Test).In this small study, involving a few hundred tests, Third Wave, Qiagen, and PCR tests were comparable. Kappa statistics comparing Third Wave to PCR and Third Wave to Qiagen were 0.88 and 0.74, respectively. Ventana's method did not correlate well with any of the other methods with Kappa's ranging from a low of 0.25 versus Qiagen to 0.31 versus PCR. Kappa statistics measure correlation and not accuracy of measurement.Although we felt that the specificity of our original HPV method, Ventana Inform was satisfactory and lowered our subsequent colposcopy rate, worries about its lower sensitivity caused us to look at other techniques. Other methods, PCR, hc2, and Invader, appeared comparable with one another in our series. We chose to implement the Third Wave test in our laboratory.

  5. Locally Advanced Rectal Cancer Patients Receiving Radio-Chemotherapy: A Novel Clinical-Pathologic Score Correlates With Global Outcome

    SciTech Connect

    Berardi, Rossana; Mantello, Giovanna; Scartozzi, Mario; Del Prete, Stefano; Luppi, Gabriele; Martinelli, Roberto; Fumagalli, Marco; Grillo-Ruggieri, Filippo; Bearzi, Italo; Mandolesi, Alessandra; Marmorale, Cristina; Cascinu, Stefano

    2009-12-01

    Purpose: To determine the importance of downstaging of locally advanced rectal cancer after neoadjuvant treatment. Methods and Materials: The study included all consecutive patients with locally advanced rectal cancer who underwent neoadjuvant treatment (chemotherapy and/or radiotherapy) in different Italian centers from June 1996 to December 2003. A novel score was used, calculated as the sum of numbers obtained by giving a negative or positive point, respectively, to each degree of increase or decrease in clinical to pathologic T and N status. Results: A total of 317 patients were eligible for analysis. Neoadjuvant treatments performed were as follows: radiotherapy alone in 75 of 317 patients (23.7%), radiotherapy plus chemotherapy in 242 of 317 patients (76.3%). Worse disease-free survival was observed in patients with a lower score (Score 1 = -3 to +3 vs. Score 2 = +4 to +7; p = 0.04). Conclusions: Our results suggest that a novel score, calculated from preoperative and pathologic tumor and lymph node status, could represent an important parameter to predict outcome in patients receiving neoadjuvant treatment for rectal cancer. The score could be useful to select patients for adjuvant chemotherapy after neoadjuvant treatment and surgery.

  6. Improvement of periodontal status by green tea catechin using a local delivery system: a clinical pilot study.

    PubMed

    Hirasawa, Masatomo; Takada, Kazuko; Makimura, Masaharu; Otake, Shigeo

    2002-12-01

    The purpose of this study was to determine the usefulness of green tea catechin for the improvement of periodontal disease. The minimum inhibitory concentration (MIC) and bactericidal activity of green tea catechin against black-pigmented, Gram-negative anaerobic rods (BPR) were measured. Hydroxypropylcellulose strips containing green tea catechin as a slow release local delivery system were applied in pockets in patients once a week for 8 weeks. The clinical, enzymatic and microbiological effects of the catechin were determined. Green tea catechin showed a bactericidal effect against Porphyromonas gingivalis and Prevotella spp. in vitro with an MIC of 1.0 mg/ml. In the in vivo experiment, the pocket depth (PD) and the proportion of BPR were markedly decreased in the catechin group with mechanical treatment at week 8 compared with the baseline with significant difference. In contrast, PD and BPR were similar to the baseline and the value at the end of the experimental period in the placebo sites of scaled groups. The peptidase activities in the gingival fluid were maintained at lower levels during the experimental period in the test sites, while it reached 70% of that at baseline in the placebo sites. No morbidity was observed in the placebo and catechin groups without mechanical treatment. Green tea catechin showed a bactericidal effect against BPR and the combined use of mechanical treatment and the application of green tea catechin using a slow release local delivery system was effective in improving periodontal status.

  7. Clinical application of a novel sliver nanoparticles biosensor based on localized surface plasmon resonance for detecting the microalbuminuria.

    PubMed

    Lai, Ting; Hou, Qiannan; Yang, Huan; Luo, Xiangang; Xi, Mingrong

    2010-11-01

    In order to explore the clinical application of the nanobiosensor based on localized surface plasmon resonance (LSPR), we used our LSPR biosensor to detect the microalbuminuria in this work. The sliver nanoparticles were fabricated by using nanosphere lithography. The anti-human albumin antibody was immobilized on the sensor surface by amine coupling method. The different concentrations of commercial albumin and albumin in urine samples from three mild preeclampsia patients were determined according to the peak of LSPR extinction spectra. Under optimum conditions, our results showed that the biosensor displayed a detection limit of 1 ng/ml and wide dynamic range of 1 ng/ml to 1 μg/ml. Furthermore, the microalbuminuria of three patients was determined by our biosensor within a short assay time, without sample purification. This biosensor proposed herein is easy to prepare and could be used for low-cost, rapid, label-free, and sensitive screening of the microalbuminuria. This approach provides a promising platform for developing clinical diagnostic applications.

  8. Effect of hydralazine on duration of soft tissue local anesthesia following dental treatment: a randomized clinical trial.

    PubMed

    Fakheran Esfahani, Omid; Pouraboutaleb, Mohammad Fazel; Khorami, Behnam

    2015-01-01

    Prolonged numbness following routine dental treatments can cause difficulties in speaking and swallowing and may result in inadvertent biting of soft tissues. Local injection of vasodilator agents may represent a solution to this problem. The aim of this study was to evaluate the effect of submucosal injection of hydralazine hydrochloride (HCl) on the duration of oral soft tissue anesthesia after routine dental treatment. This randomized, single-blinded, controlled clinical trial included 50 patients who received inferior alveolar nerve block (2% lidocaine with 1:100,000 epinephrine) for simple restorative treatment. Upon completion of the dental treatment, patients randomly received a hydralazine HCl or sham injection in the same site as the local anesthetic injection. The reversal time to normal sensation of soft tissues (lips, tongue, and perioral skin) was evaluated and reported every 5 minutes by the patients, who followed an assessment protocol that they were taught in advance of treatment. Median recovery times in the hydralazine group and the sham group were 81.4 (SD, 3.6) and 221.8 (SD, 6.3) minutes, respectively. Based on Kaplan-Meier survival analysis, the duration of soft tissue anesthesia in the 2 groups was significantly different (P < 0.0001). By 1 hour after the reversal injection, 76% of subjects receiving hydralazine HCl had returned to normal intraoral and perioral sensation, but none of the subjects in the sham group reported normal sensation. Based on these results, submucosal injection of hydralazine HCl can be considered a safe and effective method to reduce the duration of local anesthetic-induced soft tissue numbness and the related functional problems.

  9. Phase 1 Trial of Neoadjuvant Radiation Therapy Before Prostatectomy for High-Risk Prostate Cancer

    SciTech Connect

    Koontz, Bridget F.; Quaranta, Brian P.; Pura, John A.; Lee, W.R.; Vujaskovic, Zeljko; Gerber, Leah; Haake, Michael; Anscher, Mitchell S.; Robertson, Cary N.; Polascik, Thomas J.; Moul, Judd W.

    2013-09-01

    Purpose: To evaluate, in a phase 1 study, the safety of neoadjuvant whole-pelvis radiation therapy (RT) administered immediately before radical prostatectomy in men with high-risk prostate cancer. Methods and Materials: Twelve men enrolled and completed a phase 1 single-institution trial between 2006 and 2010. Eligibility required a previously untreated diagnosis of localized but high-risk prostate cancer. Median follow-up was 46 months (range, 14-74 months). Radiation therapy was dose-escalated in a 3 × 3 design with dose levels of 39.6, 45, 50.4, and 54 Gy. The pelvic lymph nodes were treated up to 45 Gy with any additional dose given to the prostate and seminal vesicles. Radical prostatectomy was performed 4-8 weeks after RT completion. Primary outcome measure was intraoperative and postoperative day-30 morbidity. Secondary measures included late morbidity and oncologic outcomes. Results: No intraoperative morbidity was seen. Chronic urinary grade 2+ toxicity occurred in 42%; 2 patients (17%) developed a symptomatic urethral stricture requiring dilation. Two-year actuarial biochemical recurrence-free survival was 67% (95% confidence interval 34%-86%). Patients with pT3 or positive surgical margin treated with neoadjuvant RT had a trend for improved biochemical recurrence-free survival compared with a historical cohort with similar adverse factors. Conclusions: Neoadjuvant RT is feasible with moderate urinary morbidity. However, oncologic outcomes do not seem to be substantially different from those with selective postoperative RT. If this multimodal approach is further evaluated in a phase 2 setting, 54 Gy should be used in combination with neoadjuvant androgen deprivation therapy to improve biochemical outcomes.

  10. Evaluation of a cloud-based local-read paradigm for imaging evaluations in oncology clinical trials for lung cancer

    PubMed Central

    Kobayashi, Naomi; Bonnard, Eric; Charbonnier, Colette; Yamamichi, Junta; Mizobe, Hideaki; Kimura, Shinya

    2015-01-01

    Background Although tumor response evaluated with radiological imaging is frequently used as a primary endpoint in clinical trials, it is difficult to obtain precise results because of inter- and intra-observer differences. Purpose To evaluate usefulness of a cloud-based local-read paradigm implementing software solutions that standardize imaging evaluations among international investigator sites for clinical trials of lung cancer. Material and Methods Two studies were performed: KUMO I and KUMO I Extension. KUMO I was a pilot study aiming at demonstrating the feasibility of cloud implementation and identifying issues regarding variability of evaluations among sites. Chest CT scans at three time-points from baseline to progression, from 10 patients with lung cancer who were treated with EGFR tyrosine kinase inhibitors, were evaluated independently by two oncologists (Japan) and one radiologist (France), through a cloud-based software solution. The KUMO I Extension was performed based on the results of KUMO I. Results KUMO I showed discordance rates of 40% for target lesion selection, 70% for overall response at the first time-point, and 60% for overall response at the second time-point. Since the main reason for the discordance was differences in the selection of target lesions, KUMO I Extension added a cloud-based quality control service to achieve a consensus on the selection of target lesions, resulting in an improved rate of agreement of response evaluations. Conclusion The study shows the feasibility of imaging evaluations at investigator sites, based on cloud services for clinical studies involving multiple international sites. This system offers a step forward in standardizing evaluations of images among widely dispersed sites. PMID:26668754

  11. Presence of high-risk clones of OXA-23-producing Acinetobacter baumannii (ST79) and SPM-1-producing Pseudomonas aeruginosa (ST277) in environmental water samples in Brazil.

    PubMed

    Turano, Helena; Gomes, Fernando; Medeiros, Micheli; Oliveira, Silvane; Fontes, Lívia C; Sato, Maria I Z; Lincopan, Nilton

    2016-09-01

    This study reports the presence of hospital-associated high-risk lineages of OXA-23-producing ST79 Acinetobacter baumannii and SPM-1-producing ST277 Pseudomonas aeruginosa in urban rivers in Brazil. These findings indicate that urban rivers can act as reservoirs of clinically important multidrug-resistant bacteria, which constitute a potential risk to human and animal health. PMID:27342783

  12. Therapeutic benefit of decitabine, a hypomethylating agent, in patients with high-risk primary myelofibrosis and myeloproliferative neoplasm in accelerated or blastic/acute myeloid leukemia phase.

    PubMed

    Badar, Talha; Kantarjian, Hagop M; Ravandi, Farhad; Jabbour, Elias; Borthakur, Gautam; Cortes, Jorge E; Pemmaraju, Naveen; Pierce, Sherry R; Newberry, Kate J; Daver, Naval; Verstovsek, Srdan

    2015-09-01

    Myeloproliferative neoplasm (MPN) transformed to acute myeloid leukemia (MPN-AML), MPN in accelerated phase (MPN-AP), and high-risk primary myelofibrosis (PMF) are associated with a poor response to therapy and very short survival. Several reports have suggested clinical activity of hypomethylating agents in these patients. We conducted a retrospective study of 21 patients with MPN-AML, 13 with MPN-AP and 11 with DIPSS-plus high-risk PMF treated with decitabine at our institution over the last 7 years and evaluated their clinical outcomes. Six patients (29%) with MPN-AML responded to decitabine (3 CR, 2 CRi, and 1 PR); median response duration was 7 months. The median overall survival (OS) was significantly higher in those who responded (10.5 vs 4 months). Among patients with MPN-AP, 8 patients (62%) benefited; the median response duration was 6.5 months. The median OS was 11.8 months in responders vs 4.7 months in non-responders. Among patients with DIPSS-plus high-risk PMF, 9 (82%) benefited; the median response duration was 9 months. The median OS was 32 months in responders vs 16.3 months in non-responders. Decitabine is a viable therapeutic option for patients with MPN-AML, MP-AP and high-risk PMF. Prospective clinical studies combining decitabine with other clinically active agents are needed to improve overall outcome.

  13. Therapeutic benefit of decitabine, a hypomethylating agent, in patients with high-risk primary myelofibrosis and myeloproliferative neoplasm in accelerated or blastic/acute myeloid leukemia phase

    PubMed Central

    Badar, Talha; Kantarjian, Hagop M.; Ravandi, Farhad; Jabbour, Elias; Borthakur, Gautam; Cortes, Jorge E.; Pemmaraju, Naveen; Pierce, Sherry R.; Newberry, Kate J.; Daver, Naval; Verstovsek, Srdan

    2015-01-01

    Myeloproliferative neoplasm (MPN) transformed to acute myeloid leukemia (MPN-AML), MPN in accelerated phase (MPN-AP), and high-risk primary myelofibrosis (PMF) are associated with a poor response to therapy and very short survival. Several reports have suggested clinical activity of hypomethylating agents in these patients. We conducted a retrospective study of 21 patients with MPN-AML, 13 with MPN-AP and 11 with DIPSS-plus high-risk PMF treated with decitabine at our institution over the last 7 years and evaluated their clinical outcomes. Six patients (29%) with MPN-AML responded to decitabine (3 CR, 2 CRi, and 1 PR); median response duration was 7 months. The median overall survival (OS) was significantly higher in those who responded (10.5 vs 4 months). Among patients with MPN-AP, 8 patients (62%) benefited; median response duration was 6.5 months. The median OS was 11.8 months in responders vs 4.7 months in non-responders. Among patients with DIPSS-plus high-risk PMF, 9 (82%) benefited; median response duration was 9 months. The median OS was 32 months in responders vs 16.3 months in non-responders. Decitabine is a viable therapeutic option for patients with MPN-AML, MP-AP and high-risk PMF. Prospective clinical studies combining decitabine with other clinically active agents are needed to improve overall outcome. PMID:26183878

  14. The Effect of Brief Interventions on the Drinking Behaviour of Pregnant Women in a High-Risk Rural South African Community: A Cluster Randomised Trial

    ERIC Educational Resources Information Center

    Marais, Sandra; Jordaan, Esme; Viljoen, Dennis; Olivier, Leana; de Waal, Johanna; Poole, Caroline

    2011-01-01

    The purpose of this paper is to assess the impact of a series of brief interventions (BIs) on anti-natal alcohol consumption of women from a disadvantaged and high-risk background attending state health clinics in a rural district, Western Cape Province, South Africa. A pragmatic cluster randomised trial design was followed. All pregnant women,…

  15. Behavioral Parent Training in Infancy: A Window of Opportunity for High-Risk Families.

    PubMed

    Bagner, Daniel M; Coxe, Stefany; Hungerford, Gabriela M; Garcia, Dainelys; Barroso, Nicole E; Hernandez, Jennifer; Rosa-Olivares, Jose

    2016-07-01

    To meet the mental health needs of infants from high-risk families, we examined the effect of a brief home-based adaptation of Parent-child Interaction Therapy (PCIT) on improvements in infant and parent behaviors and reductions in parenting stress. Participants included 60 infants (55 % male; average age of 13.5 ± 1.31 months) who were recruited at a large urban primary care clinic and were included if their scores exceeded the 75th percentile on a brief screener of early behavior problems. Most infants were from an ethnic or racial minority background (98 %) and lived below the poverty line (60 %). Families were randomly assigned to receive the home-based parenting intervention or standard pediatric primary care. Observational and parent-report measures of infant and parenting behaviors were examined at pre- and post-intervention and at 3- and 6-month follow-ups. Infants receiving the intervention were more compliant with maternal commands at the 6-month follow-up and displayed lower levels of externalizing and internalizing behavior problems across post and follow-up assessments compared to infants in standard care. Mothers receiving the intervention displayed a significantly higher proportion of positive and lower proportion of negative behaviors with their infant during play compared to mothers in the standard care group. There were no significant group differences for parenting stress. Results provide initial evidence for the efficacy of this brief and home-based adaptation of PCIT for infants. These findings highlight the benefit of identification and intervention as early as possible to promote mental health for infants from high-risk families.

  16. Exposure to High Risk Medications is Associated with Worse Outcomes in Older Veterans with Chronic Pain

    PubMed Central

    Makris, Una E; Pugh, Mary Jo; Alvarez, Carlos A; Berlowitz, Dan R; Turner, Barbara J; Aung, KoKo; Mortensen, Eric M

    2016-01-01

    Background Chronic pain is common, costly, and leads to significant morbidity in older adults, yet we have limited data on medication safety. We sought to evaluate the association of incident High Risk Medication in the Elderly (HRME) with mortality, emergency department (ED) or hospital care among older adults with chronic pain. Methods A retrospective Veterans Health Administration cohort study was conducted examining older Veterans with chronic pain diagnoses and use of incident HRME (opioids, skeletal muscle relaxants, antihistamines, and psychotropics). Outcomes evaluated included all-cause mortality, ED visits, or inpatient hospital care. Descriptive statistics summarized variables for the overall cohort, the chronic pain cohort, and those with and without HRME. Separate generalized linear mixed-effect regression models were used to examine the association of incident HRME on each outcome, controlling for potential confounders. Results Among 1,807,404 Veterans who received VA care in 2005–2006, 584,066 (32.3%) had chronic pain; 45,945 Veterans with chronic pain (7.9%) had incident HRME exposure. The strongest significant associations of incident HRME were for: high-risk opioids with all-cause hospitalizations (OR 2.08, 95%CI 1.95–2.23); skeletal muscle relaxants with all-cause ED visits (OR 2.62, 95%CI 2.52–2.73) and mortality (OR 0.80, 95%CI 0.74–0.86); antihistamines with all-cause ED visits (OR 2.82 95%CI 2.72–2.95); and psychotropics with all-cause hospitalizations (OR 2.15, 95%CI 1.96–2.35). Conclusions Our data indicate that incident HRME is associated with clinically important adverse outcomes in older Veterans with chronic pain and highlight the importance of being judicious with prescribing certain classes of drugs in this vulnerable population. PMID:26418380

  17. Synthetic ACTH in High Risk Patients with Idiopathic Membranous Nephropathy: A Prospective, Open Label Cohort Study

    PubMed Central

    van de Logt, Anne-Els; Beerenhout, Charles H.; Brink, Hans S.; van de Kerkhof, Jos J.; Wetzels, Jack F.; Hofstra, Julia M.

    2015-01-01

    New therapeutic agents are warranted in idiopathic membranous nephropathy. Synthetic ACTH may be advantageous with reported remission rates up to 85% and few side effects. We conducted a prospective open label cohort study from 2008 till 2010 (NCT00694863). We prospectively selected patients with idiopathic membranous nephropathy and high risk for progression (defined as βeta-2-microglobulin (β2m) excretion of >500 ng/min). For comparison, we selected matched historical controls treated with cyclophosphamide. The prospectively selected patients received intramuscular injections of synthetic ACTH during 9 months (maximal dose 1 mg twice a week). The primary endpoints concerned the feasibility and incidence of remissions as a primary event. Secondary endpoints included side effects of treatment and the incidence of remissions and relapses at long-term follow-up. Twenty patients (15 men) were included (age 54±14 years, serum creatinine 104 μmol/l [IQR 90–113], urine protein:creatinine ratio 8.7 g/10 mmol creatinine [IQR 4.3–11.1]). Seventeen patients (85%) completed treatment. 97% of injections were administered correctly. Cumulative remission rate was 55% (complete remission in 4 patients, partial remission 7 patients). In a group of historical controls treated with cyclophosphamide and steroids, 19 of 20 patients (95%) developed a remission (complete remission in 13 patients, partial remission in 6 patients) (p<0.01). The main limitation of our study is its small size and the use of a historical control group. We show that treatment with intramuscular injections of synthetic ACTH is feasible. Our data suggest that synthetic ACTH is less effective than cyclophosphamide in inducing a remission in high risk patients with idiopathic membranous nephropathy. The use of synthetic ACTH was also associated with many adverse events. Therefore, we advise against synthetic ACTH as standard treatment in membranous nephropathy. Trial Registration ClinicalTrials.gov NCT

  18. Identification of high risk DISC1 protein structural variants in patients with bipolar spectrum disorder.

    PubMed

    Song, Wenjia; Li, Wenyan; Noltner, Katie; Yan, Jin; Green, Elaine; Grozeva, Detelina; Jones, Ian R; Craddock, Nick; Longmate, Jeff; Feng, Jinong; Sommer, Steve S

    2010-12-17

    In a large Scottish pedigree, a balanced translocation t (1;11)(q42.1;q14.3) disrupting the DISC1 and DISC2 genes segregates with major mental illness, including schizophrenia and depression. A frame-shift carboxyl-terminal deletion was reported in DISC1 in an American family with schizophrenia, but subsequently found in two controls. Herein, we test one hypothesis utilizing a large scale case-control mutation analysis: uncommon DISC1 variants are associated with high risk for bipolar spectrum disorder. We have analyzed the regions of likely functional significance in the DISC1 gene in 504 patients with bipolar spectrum disorder and 576 ethnically similar controls. Five patients were heterozygous for ultra-rare protein structural variants not found in the 576 controls (p=0.02, one-sided Fisher's exact test) and shown to be ultra-rare by their absence in a pool of 10,000 control alleles. In our sample, ultra-rare (private) protein structural variants in DISC1 are associated with an estimated attributable risk of about 0.5% in bipolar spectrum disorder. These data are consist