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Sample records for high-risk clinically localized

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. Cyberbullying in those at Clinical High Risk for psychosis

    PubMed Central

    Magaud, Emilie; Nyman, Karissa; Addington, Jean

    2012-01-01

    Aim Several studies suggest an association between experiences of childhood trauma including bullying and the development of psychotic symptoms. The use of communications technology has created a new media for bullying called ‘cyberbullying’. Research has demonstrated associations between traditional bullying and cyberbullying. Negative effects of cyberbullying appear similar in nature and severity to the reported effects of traditional bullying. Our aim was to examine the prevalence and correlates of cyberbullying in those at clinical high risk (CHR) for psychosis. Methods Fifty young people at CHR for psychosis were administered the Childhood Trauma Questionnaire with added questions about cyberbullying. Results Cyberbullying was reported in 38% of the sample. Those who experienced cyberbullying also reported experiencing previous trauma. Conclusion It is possible that cyberbullying may be a problem for those at CHR of psychosis and due to the vulnerable nature of these young people, may have longitudinal implications. PMID:23343259

  6. Changing the patterns of failure for high-risk prostate cancer patients by optimizing local control

    SciTech Connect

    Stock, Richard G. . E-mail: richard.stock@msnyuhealth.org; Ho, Alice; Cesaretti, Jamie A.; Stone, Nelson N.

    2006-10-01

    Purpose: Standard therapies for high-risk prostate cancer have resulted in suboptimal outcomes with both local and distant failures. Prostate-specific antigen (PSA) and distant metastases rates as well as biopsy outcomes are reported after a regimen of trimodality therapy with hormonal, radioactive seed, and external beam radiation therapy to demonstrate how patterns of failure are changed when local control is optimized. Methods and Materials: From 1994 to 2003, a total of 360 patients with high-risk prostate cancer were treated with trimodality therapy. Patients were defined as being at high risk if they possessed at least one of the following high-risk features: Gleason score 8 to 10, PSA >20, clinical stage t2c to t3, or two or more intermediate risk features: Gleason score 7, PSA >10 to 20, or stage t2b. Patients were followed for a median of 4.25 years (range, 2 to 10 years). Results: The actuarial 7-year freedom from PSA failure and freedom from distant metastases (FFDM) rates were 83% and 89% respectively. Patients (n = 51) developing PSA failure exhibited aggressive disease behavior with short PSA doubling times (median, 5 months) and a 7-year freedom from distant metastases rate of 48%. Local control was high. The last posttreatment biopsy results were negative in 97% of cases (68 of 70 patients). In multivariate analysis, only PSA >20 predicted biochemical failure (p = 0.04), and only seminal vesicle status predicted developing distant failure (p = 0.01). Conclusions: Trimodality therapy results in excellent local control that alters patterns of failure, resulting in similar actuarial biochemical and distant failure rates. Most failures appear to be distant and exhibit biologically aggressive behavior.

  7. Genetic Profiling to Determine Risk of Relapse Free Survival in High-risk Localized Prostate Cancer

    PubMed Central

    Barnett, Christine M.; Heinrich, Michael C.; Lim, Jeong; Nelson, Dylan; Beadling, Carol; Warrick, Andrea; Neff, Tanaya; Higano, Celestia S.; Garzotto, Mark; Qian, David; Corless, Christopher L.; Thomas, George V.; Beer, Tomasz M.

    2014-01-01

    Purpose The characterization of actionable mutations in human tumors is a prerequisite for the development of individualized, targeted therapy. We examined the prevalence of potentially therapeutically actionable mutations in patients with high risk clinically localized prostate cancer. Experimental Design 48 samples of formalin fixed paraffin embedded prostatectomy tissue from a neoadjuvant chemotherapy trial were analyzed. DNA extracted from microdissected tumor was analyzed for 643 common solid tumor mutations in 53 genes using mass spectroscopy based sequencing. In addition, PTEN loss and ERG translocations were examined using immunohistochemistry in associated tissue microarrays. Association with relapse during 5 years of follow-up was examined in exploratory analyses of the potential clinical relevance of the genetic alterations. Results Of the 40 tumors evaluable for mutations, 10% had point mutations in potentially actionable cancer genes. Of the 47 tumors evaluable for IHC, 36% had PTEN loss and 40% had ERG rearrangement. Individual mutations were not frequent enough to determine associations with relapse. Using Kaplan-Meier analysis with a log-rank test, the 16 patients who had PTEN loss had a significantly shorter median relapse free survival, 19 vs. 106 months (p = .01). Conclusions This study confirms that point mutations in the most common cancer regulatory genes in prostate cancer are rare. However, the PIK3CA/AKT pathway was mutated in 10% of our samples. While point mutations alone did not have a statistically significant association with relapse, PTEN loss was associated with an increased relapse in high risk prostate cancer treated with chemotherapy followed by surgery. PMID:24352642

  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. A Virtual Clinic Improves Pneumococcal Vaccination for Asplenic Veterans at High Risk for Pneumococcal Disease

    PubMed Central

    Jump, Robin L.; Banks, Richard; Wilson, Brigid; Montpetite, Michelle M.; Carter, Rebecca; Phillips, Susan; Perez, Federico

    2015-01-01

    We developed a “virtual clinic” to improve pneumococcal vaccination among asplenic adults. Using an electronic medical record, we identified patients, assessed their vaccination status, entered orders, and notified patients and providers. Within 180 days, 38 of 76 patients (50%) received a pneumococcal vaccination. A virtual clinic may optimize vaccinations among high-risk patients. PMID:26668815

  11. 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

  12. 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.

  13. 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.

  14. Implementation of the High-Risk Alcoholism Relapse Scale in a Liver Transplant Clinic.

    PubMed

    Zhou, Min; Wagner, Laura M; Diflo, Thomas; Naegle, Madeline

    2015-01-01

    Because of the high prevalence of alcohol relapse after liver transplantation, transplant programs are challenged to evaluate alcoholism among liver transplant patients. Relapse after liver transplantation can have detrimental outcomes such as organ rejection, medical and social resource exhaustion, financial burden to the family and society, and negative public perception of organ transplantation. The purpose of this project was to improve post-liver transplant assessment for the risk of relapse to heavy alcohol use by implementing a protocol using the High-Risk Alcoholism Relapse (HRAR) scale (DiMartini et al., 2000; Yates et al., 1993). The project was conducted in an urban organ transplant center's outpatient post liver transplant clinic. Chart reviews assessed the process of patients identified as being at high risk and the transplant providers' completion of the HRAR scale. Eleven percent of patients assessed were identified as being at high risk for relapse of heavy alcohol use and 85% of providers used the HRAR scale in their clinic interviews. This project demonstrates that further refinements in techniques of predicting the risks of relapse are necessary, and nurses are in ideal positions to screen patients for alcohol use. PMID:26626033

  15. 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

  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. RD3 loss dictates high-risk aggressive neuroblastoma and poor clinical outcomes

    PubMed Central

    Aravindan, Sheeja; Natarajan, Mohan; Azadi, Seifollah; Herman, Terence S.; Aravindan, Natarajan

    2015-01-01

    Clinical outcomes for high-risk neuroblastoma patients remains poor, with only 40–50% 5-Year overall survival (OS) and <10% long-term survival. The ongoing acquisition of genetic/molecular rearrangements in undifferentiated neural crest cells may endorse neuroblastoma progression. This study recognized the loss of Retinal Degeneration protein 3, RD3 in aggressive neuroblastoma, and identified its influence in better clinical outcomes and defined its novel metastasis suppressor function. The results showed ubiquitous expression of RD3 in healthy tissues, complete-loss and significant TNM-stage association of RD3 in clinical samples. RD3-loss was intrinsically associated with reduced OS, abridged relapse-free survival, aggressive stage etc., in neuroblastoma patient cohorts. RD3 was transcriptionally and translationally regulated in metastatic site-derived aggressive (MSDAC) cells (regardless of CSC status) ex vivo and in tumor manifolds from metastatic sites in reproducible aggressive disease models in vivo. Re-expressing RD3 in MSDACs reverted their metastatic potential both in vitro and in vivo. Conversely muting RD3 in neuroblastoma cells not only heightened invasion/migration but also dictated aggressive disease with metastasis. These results demonstrate the loss of RD3 in high-risk neuroblastoma, its novel, thus-far unrecognized metastasis suppressor function and further imply that RD3-loss may directly relate to tumor aggressiveness and poor clinical outcomes. PMID:26375249

  18. Endocrine therapy for breast cancer prevention in high-risk women: clinical and economic considerations.

    PubMed

    Groom, Amy G; Younis, Tallal

    2016-04-01

    The global burden of breast cancer highlights the need for primary prevention strategies that demonstrate both favorable clinical benefit/risk profile and good value for money. Endocrine therapy with selective estrogen-receptor modulators (SERMs) or aromatase inhibitors (AIs) has been associated with a favorable clinical benefit/risk profile in the prevention of breast cancer in women at high risk of developing the disease. The available endocrine therapy strategies differ in terms of their relative reductions of breast cancer risk, potential side effects, and upfront drug acquisition costs, among others. This review highlights the clinical trials of SERMs and AIs for the primary prevention of breast cancer, and the cost-effectiveness /cost-utility studies that have examined their "value for money" in various health care jurisdictions. PMID:26923683

  19. Clinical high risk and first episode schizophrenia: Auditory event-related potentials

    PubMed Central

    del Re, Elisabetta C.; Spencer, Kevin M.; Oribe, Naoya; Mesholam-Gately, Raquelle I.; Goldstein, Jill; Shenton, Martha E.; Petryshen, Tracey; Seidman, Larry J.; McCarley, Robert W.; Niznikiewicz, Margaret A.

    2014-01-01

    The clinical high risk (CHR) period is a phase denoting a risk for overt psychosis during which subacute symptoms often appear, and cognitive functions may deteriorate. To compare biological indices during this phase with those during first episode schizophrenia, we cross-sectionally examined sex- and age-matched clinical high risk (CHR, n=21), first episode schizophrenia patients (FESZ, n=20) and matched healthy controls (HC, n=25) on oddball and novelty paradigms and assessed the N100, P200, P3a and P3b as indices of perceptual, attentional and working memory processes. To our knowledge, this is the only such comparison using all of these event-related potentials (ERPs) in two paradigms. We hypothesized that the ERPs would differentiate between the three groups and allow prediction of a diagnostic group. The majority of ERPs were significantly affected in CHR and FESZ compared with controls, with similar effect sizes. Nonetheless, in logistic regression, only the P3a and N100 distinguished CHR and FESZ from healthy controls, suggesting that ERPs not associated with an overt task might be more sensitive to prediction of group membership. PMID:25557063

  20. Clinical high risk and first episode schizophrenia: auditory event-related potentials.

    PubMed

    del Re, Elisabetta C; Spencer, Kevin M; Oribe, Naoya; Mesholam-Gately, Raquelle I; Goldstein, Jill; Shenton, Martha E; Petryshen, Tracey; Seidman, Larry J; McCarley, Robert W; Niznikiewicz, Margaret A

    2015-02-28

    The clinical high risk (CHR) period is a phase denoting a risk for overt psychosis during which subacute symptoms often appear, and cognitive functions may deteriorate. To compare biological indices during this phase with those during first episode schizophrenia, we cross-sectionally examined sex- and age-matched clinical high risk (CHR, n=21), first episode schizophrenia patients (FESZ, n=20) and matched healthy controls (HC, n=25) on oddball and novelty paradigms and assessed the N100, P200, P3a and P3b as indices of perceptual, attentional and working memory processes. To our knowledge, this is the only such comparison using all of these event-related potentials (ERPs) in two paradigms. We hypothesized that the ERPs would differentiate between the three groups and allow prediction of a diagnostic group. The majority of ERPs were significantly affected in CHR and FESZ compared with controls, with similar effect sizes. Nonetheless, in logistic regression, only the P3a and N100 distinguished CHR and FESZ from healthy controls, suggesting that ERPs not associated with an overt task might be more sensitive to prediction of group membership. PMID:25557063

  1. The effects of HIV/AIDS intervention groups for high-risk women in urban clinics.

    PubMed Central

    Kelly, J A; Murphy, D A; Washington, C D; Wilson, T S; Koob, J J; Davis, D R; Ledezma, G; Davantes, B

    1994-01-01

    OBJECTIVE. This study reports the results of a behavior change intervention offered to women at high risk for human immunodeficiency virus (HIV) infection seen in an urban primary health care clinic. METHODS. Participants were 197 women randomly assigned to either an HIV/acquired immunodeficiency syndrome (AIDS) risk reduction group or a comparison group. Women in the HIV/AIDS intervention group attended five group sessions focusing on risk education; skills training in condom use, sexual assertiveness, problem solving, and risk trigger self-management; and peer support for change efforts. Women in the comparison group attended sessions on health topics unrelated to AIDS. RESULTS. At the 3-month follow-up, women in the HIV/AIDS intervention group had increased in sexual communication and negotiation skills. Unprotected sexual intercourse had declined significantly and condom use had increased from 26% to 56% of all intercourse occasions. Women in the comparison group showed no change. CONCLUSIONS. Socially disadvantaged women can be assisted in reducing their risk of contracting HIV infection. Risk reduction behavior change interventions should be offered routinely in primary health care clinics serving low-income and high-risk patients. PMID:7998630

  2. 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.

  3. 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

  4. 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

  5. Approval of High-Risk Medical Devices in the US: Implications for Clinical Cardiology

    PubMed Central

    Rome, Benjamin N.; Kramer, Daniel B.

    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 post-market surveillance and comparative effectiveness research remains imperative. PMID:24760423

  6. 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

  7. 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

  8. 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

  9. 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…

  10. Protective factors in Chinese university students at clinical high risk for psychosis.

    PubMed

    Shi, Jingyu; Wang, Lu; Yao, Yuhong; Chen, Fazhan; Su, Na; Zhao, Xudong; Zhan, Chenyu

    2016-05-30

    The role of protective factors in symptom formation and prognosis in schizophrenia has been shown in many studies, but research in the early phases of psychosis is limited, particularly among the nonclinical subjects. Protective factors associated with the severity of symptoms and clinical outcomes might be meaningful to the establishment of prevention systems and to the development of optimal psychosocial interventions prior to the onset of psychosis. The present study compares self-reported levels of self-esteem, social support and resilience of 32 university students at clinical high risk for psychosis (CHR) and 32 healthy controls in a longitudinal study design. Associations between protective factors with symptoms of psychosis were assessed in the CHR group. Individuals at CHR showed significantly lower self-esteem, social support and resilience compared to healthy controls. In the CHR group, lower social support and lower self-esteem were associated with more severe positive, negative and depressive symptoms. Multiple regression analyses revealed that self-esteem was the only significant determinant for negative, depressive symptoms and global functioning. In addition, we found that subjects who were fully recovered at a 6-month follow-up survey were greater resilient and showed lower depressive symptoms at baseline. The result implied that resilience intervention could be effective on early prevention of the onset of psychosis. Moreover, implications and limitations of this study will be discussed. PMID:27031594

  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. Molecular markers to complement sentinel node status in predicting survival in patients with high-risk locally invasive melanoma.

    PubMed

    Rowe, Casey J; Tang, Fiona; Hughes, Maria Celia B; Rodero, Mathieu P; Malt, Maryrose; Lambie, Duncan; Barbour, Andrew; Hayward, Nicholas K; Smithers, B Mark; Green, Adele C; Khosrotehrani, Kiarash

    2016-08-01

    Sentinel lymph node status is a major prognostic marker in locally invasive cutaneous melanoma. However, this procedure is not always feasible, requires advanced logistics and carries rare but significant morbidity. Previous studies have linked markers of tumour biology to patient survival. In this study, we aimed to combine the predictive value of established biomarkers in addition to clinical parameters as indicators of survival in addition to or instead of sentinel node biopsy in a cohort of high-risk melanoma patients. Patients with locally invasive melanomas undergoing sentinel lymph node biopsy were ascertained and prospectively followed. Information on mortality was validated through the National Death Index. Immunohistochemistry was used to analyse proteins previously reported to be associated with melanoma survival, namely Ki67, p16 and CD163. Evaluation and multivariate analyses according to REMARK criteria were used to generate models to predict disease-free and melanoma-specific survival. A total of 189 patients with available archival material of their primary tumour were analysed. Our study sample was representative of the entire cohort (N = 559). Average Breslow thickness was 2.5 mm. Thirty-two (17%) patients in the study sample died from melanoma during the follow-up period. A prognostic score was developed and was strongly predictive of survival, independent of sentinel node status. The score allowed classification of risk of melanoma death in sentinel node-negative patients. Combining clinicopathological factors and established biomarkers allows prediction of outcome in locally invasive melanoma and might be implemented in addition to or in cases when sentinel node biopsy cannot be performed. PMID:26990817

  13. 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

  14. Assessing Suicidal Ideation in Individuals at Clinical High Risk for Psychosis

    PubMed Central

    Gill, Kelly E.; Quintero, Jean M.; Poe, S. Lucy; Moreira, Alvaro D.; Brucato, Gary; Corcoran, Cheryl M.; Girgis, Ragy R.

    2015-01-01

    Background The majority of individuals with schizophrenia and other psychotic illnesses have had suicidal ideation at some point during the illness. However, little is known about the variation in level and intensity of suicidal ideation and symptoms in the attenuated stage of psychotic illness. Our aims were to assess prevalence of suicidal ideation in this at risk group, and to examine the severity and intensity of suicidal ideation, and their relation to symptoms. Methods Suicidal ideation was assessed in 42 clinical high-risk participants using the Columbia Suicide Severity Rating Scale (C-SSRS). We hypothesized prevalence rates would be similar to what was found in previous studies, and individuals with suicidal ideation would have higher positive and negative symptoms, with poorer functioning. We assessed levels of severity and intensity of suicidal ideation related to these symptoms, and examined how depressive symptoms affected these relationships. Results Nearly half (42.9%) of participants reported having current suicidal ideation. We found no relationship to positive symptoms. However, severity and intensity of suicidal ideation was found to be related to negative symptoms and level of functioning. When controlling for depressive symptoms during exploratory analysis, this relationship still emerged. Conclusions This study adds to the literature demonstrating the complex nature of suicidal ideation in psychotic illness. The C-SSRS has shown to be helpful in determining relationships between severity and intensity in suicidal ideation in relation to specific symptoms in a research setting. PMID:25960038

  15. 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.

  16. 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

  17. 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

  18. Neural Dysfunction in Cognitive Control Circuits in Persons at Clinical High-Risk for Psychosis.

    PubMed

    Colibazzi, Tiziano; Horga, Guillermo; Wang, Zhishun; Huo, Yuankai; Corcoran, Cheryl; Klahr, Kristin; Brucato, Gary; Girgis, Ragy; Gill, Kelly; Abi-Dargham, Anissa; Peterson, Bradley S

    2016-04-01

    Cognitive control, a set of functions that develop throughout adolescence, is important in the pathogenesis of psychotic disorders. Whether cognitive control has a role in conferring vulnerability for the development of psychotic illness is still unknown. The aim of this study was to investigate the neural systems supporting cognitive control in individuals deemed to be potentially prodromal for psychotic illness. We recruited 56 participants at clinical high-risk (CHR) for psychosis based on the Structured Interview for Psychosis-Risk Syndromes (SIPS) and 49 healthy controls. Twelve of the CHR participants eventually developed psychosis. We compared functional magnetic resonance imaging (fMRI) BOLD signal during the performance of the Simon task. We tested for differences between CHR individuals and controls in conflict-related functional activity. In the CHR group when compared with controls, we detected smaller conflict-related activations in several cortical areas, including the Dorsolateral Prefrontal Cortex (DLPFC). Furthermore, conflict-related activations in the DLPFC of those CHR individuals who ultimately developed psychosis (CHR converters) were smaller than in non-converters (CHR non-converters). Higher levels of conflict-related activation were associated with better social and role outcome. Risk for psychosis was associated at the neural level with reduced conflict-related brain activity. This neural phenotype appears correlated within the DLPFC with the development of psychosis and with functional outcome. PMID:26354046

  19. Impact of substance use on conversion to psychosis in youth at clinical high risk of psychosis.

    PubMed

    Buchy, Lisa; Perkins, Diana; Woods, Scott W; Liu, Lu; Addington, Jean

    2014-07-01

    Elevated rates of substance use (alcohol, tobacco, cannabis) have been reported in people at clinical high risk (CHR) of developing psychosis and there is some evidence that substance use may be higher in those who convert to a psychosis compared to non-converters. However little is known about the predictive value of substance use on risk of conversion to psychosis in those at CHR of psychosis. In the current study, 170 people at CHR of psychosis were assessed at baseline on severity of alcohol, tobacco and cannabis using the Alcohol and Drug Use Scale. Participants were recruited across three sites over a four year period as part of the Enhancing the Prospective Prediction of Psychosis (PREDICT) study. Predictors of conversion to psychosis were examined using Cox proportional hazards models. Results revealed that low use of alcohol, but neither cannabis use nor tobacco use at baseline, contributed to the prediction of psychosis in the CHR sample. Prediction algorithms incorporating combinations of additional baseline variables known to be associated with psychotic conversion may result in increased predictive power compared with substance use alone. PMID:24837058

  20. 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. PMID:26210694

  1. 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

  2. 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

  3. 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

  4. 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.

  5. Binocular Depth Perception in Individuals at Clinical High Risk for Psychosis: no evidence of dysfunction

    PubMed Central

    Barbato, Mariapaola; Addington, Jean

    2014-01-01

    Objective In the last decade the interest in the role of the visual system in schizophrenia has grown, with evidence pointing to dysfunction in bottom-up visual processing that leads to early visual processing deficits. A fundamental component of visual perception is binocular depth perception (BDP), i.e. depth perception derived by the difference between the images impressed upon the left and right retina. Two studies reported impaired BDP in schizophrenia and suggested a possible developmental deficit of brain structures involved in early visual processing. The aim of this study was to examine BDP in a young population at clinical high risk (CHR) of developing psychosis to determine if this dysfunction is present in this potentially pre-psychotic period. Methods Forty-two CHR participants and 44 healthy controls were assessed using a computerized test of depth perception; a subsample completed a test of stereopsis. The computerized test was comprised of two trial blocks, with four conditions at increasing level of difficulty, where participants were asked to discriminate the relative depth of two stimuli simultaneously presented on the screen. Results BDP was not impaired in the CHR group, whose performance was similar to that of the control group on both measures. For the CHR group performance in both tests was not correlated to positive symptoms. Conclusions These results indicate that BDP is preserved in individuals at CHR for psychosis and impaired BDP should not be considered a vulnerability marker for schizophrenia. Nevertheless future studies should verify BDP's potential power in predicting schizophrenia. PMID:24188117

  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. Management of high-risk popliteal vascular blunt trauma: clinical experience with 62 cases

    PubMed Central

    Pourzand, Ali; Fakhri, Bassir A; Azhough, Ramin; Hassanzadeh, Mohammad Ali; Hashemzadeh, Shahryar; Bayat, Amrollah M

    2010-01-01

    Purpose: The purpose of this study is to report the clinical and functional outcomes of patients, treated between 2004 and 2009, with high-risk popliteal vascular injuries due to compound fractures about the knee. Patients and methods: A retrospective analysis was conducted of prospectively collected data from Tabriz Medical Trauma Center. Our aim was to perform surgical revascularization as soon as the arterial injury was recognized. The mechanism of injury was blunt in the entire cohort of patients, and all of them had bone fractures about the knee. The treatment of arterial injury included vein graft interposition in 39 (63%), primary anastomosis in 20 (32.3%), and lateral repair in 3 (4.8%) patients. The patients were divided into 2 study groups: limb salvage group (group 1) and amputation group (group 2). Subgroup analysis consisted of univariate analysis comparing the 2 groups and multivariate analysis examining the factors associated negatively and positively with the primary endpoint, limb salvage. Results: In the entire cohort of patients, 60 patients (97%) were male and 2 were female (3%); the mean age was 34.1 years (16–49 years). The overall amputation rate in this study was 37.1% (23 amputations). Significant (P < 0.05) independent factors associated negatively with limb salvage were combined tibia and fibula fracture, concomitant artery and vein injury, ligation of venous injury, and lack of backflow after Fogarty catheter thrombectomy, while repair of popliteal artery and vein injury, when present, was associated with improved early limb salvage. For 40 patients, we adopt a liberal attitude toward open 4-compartment fasciotomy through both medially and laterally placed incisions. Conclusion: Expeditious recognition of vascular injury, transport to repair, and repair of associated venous injury when possible are necessary to optimize limb salvage. The importance of a high level of suspicion and low threshold for timely amputation has been emphasized

  8. Clinical Assessment of Autism in High-Risk 18-Month-Olds

    ERIC Educational Resources Information Center

    Brian, J.; Bryson, S. E.; Garon, N.; Roberts, W.; Smith, I. M.; Szatmari, P.; Zwaigenbaum, L.

    2008-01-01

    Earlier intervention improves outcomes for children with autism spectrum disorders (ASDs), but existing identification tools are at the limits of standardization with 18-month-olds. We assessed potential behavioural markers of ASD at 18 months in a high-risk cohort of infant siblings of children with ASD. Prospective data were collected using the…

  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. 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

  11. A Randomized Trial of Family Focused Therapy With Populations at Clinical High Risk for Psychosis: Effects on Interactional Behavior

    PubMed Central

    O’Brien, Mary P.; Miklowitz, David J.; Candan, Kristin A.; Marshall, Catherine; Domingues, Isabel; Walsh, Barbara C.; Zinberg, Jamie L.; De Silva, Sandra D.; Woodberry, Kristen A.; Cannon, Tyrone D.

    2013-01-01

    Objective This study investigated whether family focused therapy (FFT-CHR), an 18-session intervention that consisted of psychoeducation and training in communication and problem solving, brought about greater improvements in family communication than enhanced care (EC), a 3-session psychoeducational intervention, among individuals at clinical high risk for developing psychosis. Method This study was conducted within a randomized controlled trial across 8 sites. We examined 10-min problem-solving discussions at baseline and 6-month reassessment among 66 adolescents and young adults and their parents. Trained coders who were blind to treatment and time of assessment achieved high levels of interrater reliability when evaluating family discussions on categories of calm–constructive and critical– conflictual behavior. Results Individuals at high risk and their family members who participated in FFT-CHR demonstrated greater improvement from baseline to 6-month reassessment in constructive communication and decreases in conflictual behaviors during family interactions than those in EC. Participants in FFT-CHR showed greater increases from baseline to 6 months in active listening and calm communication and greater decreases in irritability and anger, complaints and criticism, and off-task comments compared to participants in EC. These changes occurred equally in high-risk participants and their family members. Conclusions A 6-month family skills training treatment can bring about significant improvement in family communication among individuals at high risk for psychosis and their parents. Future studies should examine the association between enhancements in family communication and reduced risk for the onset of psychosis among individuals at high risk. PMID:24188511

  12. Clinical decision making in a high-risk primary care environment: a qualitative study in the UK

    PubMed Central

    Heneghan, Carl; Thompson, Matthew; Balla, Margaret

    2012-01-01

    Objective Examine clinical reasoning and decision making in an out of hours (OOH) primary care setting to gain insights into how general practitioners (GPs) make clinical decisions and manage risk in this environment. Design Semi-structured interviews using open-ended questions. Setting A 2-month qualitative interview study conducted in Oxfordshire, UK. Participants 21 GPs working in OOH primary care. Results The most powerful themes to emerge related to dealing with urgent potentially high-risk cases, keeping patients safe and responding to their needs, while trying to keep patients out of hospital and the concept of ‘fire fighting’. There were a number of well-defined characteristics that GPs reported making presentations easy or difficult to deal with. Severely ill patients were straightforward, while the older people, with complex multisystem diseases, were often difficult. GPs stopped collecting clinical information and came to clinical decisions when high-risk disease and severe illness requiring hospital attention has been excluded; they had responded directly to the patient's needs and there was a reliable safety net in place. Learning points that GPs identified as important for trainees in the OOH setting included the importance of developing rapport in spite of time pressures, learning to deal with uncertainty and learning about common presentations with a focus on critical cues to exclude severe illness. Conclusions The findings support suggestions that improvements in primary care OOH could be achieved by including automated and regular timely feedback system for GPs and individual peer and expert clinician support for GPs with regular meetings to discuss recent cases. In addition, trainee support and mentoring to focus on clinical skills, knowledge and risk management issues specific to OOH is currently required. Investigating the stopping rules used for diagnostic closure may provide new insights into the root causes of clinical error in such a

  13. 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

  14. High-Dose-Rate Brachytherapy Alone for Localized Prostate Cancer in Patients at Moderate or High Risk of Biochemical Recurrence

    SciTech Connect

    Hoskin, Peter; Rojas, Ana; Lowe, Gerry; Bryant, Linda; Ostler, Peter; Hughes, Rob; Milner, Jessica; Cladd, Helen

    2012-03-15

    Purpose: To evaluate genitourinary (GU) and gastrointestinal (GI) morbidity and biochemical control of disease in patients with localized prostate adenocarcinoma treated with escalating doses per fraction of high-dose rate brachytherapy alone. Methods and Materials: A total of 197 patients were treated with 34 Gy in four fractions, 36 Gy in four fractions, 31.5 Gy in three fractions, or 26 Gy in two fractions. Median follow-up times were 60, 54, 36, and 6 months, respectively. Results: Incidence of early Grade {>=} 3 GU morbidity was 3% to 7%, and Grade 4 was 0% to 4%. During the first 12 weeks, the highest mean International Prostate Symptom Score (IPSS) value was 14, and between 6 months and 5 years it was 8. Grade 3 or 4 early GI morbidity was not observed. The 3-year actuarial rate of Grade 3 GU was 3% to 16%, and was 3% to 7% for strictures requiring surgery (4-year rate). An incidence of 1% Grade 3 GI events was seen at 3 years. Late Grade 4 GU or GI events were not observed. At 3 years, 99% of patients with intermediate-risk and 91% with high-risk disease were free of biochemical relapse (log-rank p = 0.02). Conclusions: There was no significant difference in urinary and rectal morbidity between schedules. Biochemical control of disease in patients with intermediate and high risk of relapse was good.

  15. Management of patients with chronic lymphocytic leukemia with a high risk of adverse outcome: the Mayo Clinic approach

    PubMed Central

    ZENT, CLIVE S.; KAY, NEIL E.

    2012-01-01

    Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) is usually an incidental diagnosis in patients with early–intermediate stage disease. However, most patients with a diagnosis of CLL will subsequently have significant morbidity and die from their disease and its complications. For these patients, CLL is not the ‘good leukemia’ with a predictably ‘benign’ outcome. Indeed, we can now identify a cohort of patients with high-risk CLL at diagnosis who will have rapid disease progression, poor response to treatment, and poor survival based on prognostic methods developed from an improved understanding of the biology of CLL. The concomitant development of improved treatments has led to risk-adjusted management approaches that could improve outcomes. We discuss the clinical and laboratory components of comprehensive risk evaluation of patients with CLL and our approach to the management of patients with a high to very high risk of disease progression and poor outcome. In addition, we review the challenges and prospects for improving prognostic precision and the development of new drugs to improve the treatment of patients with CLL with a high risk of adverse outcome. PMID:21649549

  16. Phase 3 clinical trial investigating the effect of selenium supplementation in men at high risk for prostate cancer

    PubMed Central

    Algotar, Amit M.; Stratton, M. Suzanne; Ahmann, Frederick. R.; Ranger-Moore, James; Nagle, Raymond B.; Thompson, Patricia A.; Slate, Elizabeth; Hsu, Chiu H.; Dalkin, Bruce L.; Sindhwani, Puneet; Holmes, Michael A.; Tuckey, John A.; Graham, David. L.; Parnes, Howard L.; Clark, Lawrence C.; Stratton, Steven P.

    2014-01-01

    Purpose This study was conducted to investigate the effect of Se supplementation on prostate cancer incidence in men at high risk for prostate cancer. Methods A Phase 3 randomized, double-blind, placebo-controlled clinical trial was conducted in 699 men at high risk for prostate cancer (prostate specific antigen (PSA) >4 ng/ml and/or suspicious digital rectal examination and/or PSA velocity >0.75ng/ml/year), but with a negative prostate biopsy. Participants were randomized to receive daily oral placebo (N = 232), 200 µg selenium (N =234), or 400 µg selenium (N=233) as selenized yeast. They were followed every six months for up five years. The time to diagnosis of prostate cancer was compared between treatment groups using the Cox-proportional hazards model. Result Compared to placebo, the hazard ratios [95% confidence intervals] for risk of developing prostate cancer in the selenium 200 µg/day or the selenium 400 µg/day group were 0.94 [0.52, 1.7] and 0.90 [0.48, 1.7] respectively. PSA velocity in the selenium arms was not significantly different from that observed in the placebo group (p=0.18 and p=0.17, respectively). Conclusion Selenium supplementation appeared to have no effect on the incidence of prostate cancer in men at high risk. In conjunction with results of other studies, these data indicate that selenium supplementation may not have a role in prostate cancer chemoprevention. PMID:22887343

  17. 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.

  18. 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.

  19. 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

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

    PubMed

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

    2014-12-15

    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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  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. PMID:25689542

  7. Childhood Onset Diagnoses in a Case Series of Teens at Clinical High Risk for Psychosis

    PubMed Central

    Mazzoni, Paola; Kimhy, David; Khan, Shamir; Posner, Kelly; Maayan, Lawrence; Eilenberg, Mara; Messinger, Julie; Kestenbaum, Clarice

    2009-01-01

    Abstract Reasons Schizophrenia is typically an adult neurodevelopmental disorder that has its antecedents in childhood and adolescence. Little is known about disorders “usually first diagnosed in infancy, childhood and adolescence” (e.g., childhood-onset disorders) in “prodromal” teens at heightened clinical risk for psychotic disorder. Main Findings Childhood-onset disorders were prevalent in putatively prodromal teens, including anxiety and disruptive disorders, attention-deficit/hyperactivity disorder (ADHD), and, surprisingly, elimination disorders. These may reflect developmental antecedents in psychotic disorders such as schizophrenia. Key Data and Statistics A case series of 9 teens (ages 13–17) identified as prodromal to psychosis were evaluated with the Kiddie Schedule for Affective Disorders and Schizophrenia–Present and Lifetime Version (K-SADS-PL). Childhood-onset diagnoses commonly endorsed (threshold or subthreshold) included ADHD (5/9), oppositional defiant disorder (5/9), enuresis or encopresis (4/9), conduct disorder (2/9), separation anxiety (3/9), and transient tic disorder (2/9). Enuresis was identified in 3 of the 4 older teens (ages 15–17). Major Conclusions An understanding of the childhood-onset disorders that occur in teens at risk for psychotic illnesses, such as schizophrenia, can shed light on the pathophysiology of schizophrenia and potentially inform early identification and intervention. PMID:20035596

  8. 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. PMID:26165958

  9. Hypofractionated Accelerated Radiotherapy Using Concomitant Intensity-Modulated Radiotherapy Boost Technique for Localized High-Risk Prostate Cancer: Acute Toxicity Results

    SciTech Connect

    Lim, Tee S.; Cheung, Patrick Loblaw, D. Andrew; Morton, Gerard; Sixel, Katharina E.; Pang, Geordi; Basran, Parminder; Zhang Liying; Tirona, Romeo; Szumacher, Ewa; Danjoux, Cyril; Choo, Richard; Thomas, Gillian

    2008-09-01

    Purpose: To evaluate the acute toxicities of hypofractionated accelerated radiotherapy (RT) using a concomitant intensity-modulated RT boost in conjunction with elective pelvic nodal irradiation for high-risk prostate cancer. Methods and Materials: This report focused on 66 patients entered into this prospective Phase I study. The eligible patients had clinically localized prostate cancer with at least one of the following high-risk features (Stage T3, Gleason score {>=}8, or prostate-specific antigen level >20 ng/mL). Patients were treated with 45 Gy in 25 fractions to the pelvic lymph nodes using a conventional four-field technique. A concomitant intensity-modulated radiotherapy boost of 22.5 Gy in 25 fractions was delivered to the prostate. Thus, the prostate received 67.5 Gy in 25 fractions within 5 weeks. Next, the patients underwent 3 years of adjuvant androgen ablative therapy. Acute toxicities were assessed using the Common Terminology Criteria for Adverse Events, version 3.0, weekly during treatment and at 3 months after RT. Results: The median patient age was 71 years. The median pretreatment prostate-specific antigen level and Gleason score was 18.7 ng/L and 8, respectively. Grade 1-2 genitourinary and gastrointestinal toxicities were common during RT but most had settled at 3 months after treatment. Only 5 patients had acute Grade 3 genitourinary toxicity, in the form of urinary incontinence (n = 1), urinary frequency/urgency (n = 3), and urinary retention (n = 1). None of the patients developed Grade 3 or greater gastrointestinal or Grade 4 or greater genitourinary toxicity. Conclusion: The results of the present study have indicated that hypofractionated accelerated RT with a concomitant intensity-modulated RT boost and pelvic nodal irradiation is feasible with acceptable acute toxicity.

  10. 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

  11. Generalized and Specific Cognitive Performance in Clinical High-Risk Cohorts: A Review Highlighting Potential Vulnerability Markers for Psychosis

    PubMed Central

    Brewer, Warrick J.; Wood, Stephen J.; Phillips, Lisa J.; Francey, Shona M.; Pantelis, Christos; Yung, Alison R.; Cornblatt, Barbara; McGorry, Patrick D.

    2006-01-01

    Cognitive deficits are a core feature of established psychotic illnesses. However, the association between cognition and emerging psychosis is less understood. While there is some evidence that cognitive deficits are present prior to the onset of psychosis, findings are not consistent. In this article we provide an overview of the more general cognitive findings available from genetic high-risk studies, retrospective studies, and birth cohort studies. We then focus the review on neuropsychological performance in clinically “at-risk” groups. Overall, general cognitive ability as assessed by established batteries appears to remain relatively intact in these ultra-high risk cohorts and is a poor predictor close to illness onset relative to other vulnerability factors. Further decline may occur with illness progression, more consistent with state relative to trait factors. In addition, most established cognitive tasks involve several relatively discrete cognitive subprocesses, where findings from general batteries of subtests may mask specific deficits. In this context, our review suggests that relatively specific olfactory identification and spatial working memory deficits exist prior to illness onset and may be more potent trait markers for psychosis than cognitively dense tasks such as verbal memory. Suggestions for further research address the importance of standardization of inclusion criteria and the maintenance of basic neuropsychological assessment to allow better comparison of findings across centers. Further, in order to better understand the aetiopathology of cognitive dysfunction in psychosis, more experimental, hypothesis-driven measures of discrete cognitive processes are required. Delineation of the relationship between specific cognitive ability and symptoms from data-driven approaches may improve our understanding of the role of cognition during psychosis onset. PMID:16782759

  12. 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

  13. Increased peripheral blood CD5+ B cells predict earlier conversion to MS in high-risk clinically isolated syndromes.

    PubMed

    Villar, Luisa M; Espiño, Mercedes; Roldán, Ernesto; Marín, Nieves; Costa-Frossard, Lucienne; Muriel, Alfonso; Alvarez-Cermeño, José C

    2011-06-01

    Clinically isolated syndrome patients (CIS) with oligoclonal IgG bands (OCGB) are at high risk for clinically definite multiple sclerosis (MS). However, the outcome for individual patients is unpredictable and the search for reliable blood markers predicting early conversion to multiple sclerosis (MS) has clinical relevance. CD5+ B cells (CD5+Bc) are involved in some autoimmune diseases. This study investigated whether high blood CD5+Bc percentage can predict CIS conversion to MS. Fifty-five consecutive CIS showing OCGB were prospectively studied. Every patient underwent a brain MRI study and a flow cytometry analysis of CD5+Bc percentage. Conversion to MS was studied during follow-up. The CD5+Bc percentage was assessed in 40 controls and a cut-off value of 3.5% (mean+2 SD) was calculated. A blood CD5+Bc percentage above this value predicted earlier conversion to MS in the whole group (hazard ratio [HR]: 3.40; 95% confidence interval [CI]: 1.69-6.68; p=0.0005) and in CIS patients fulfilling three or more Barkhof-Tintoré criteria plus OCGB, who showed higher risk for MS (HR: 3.79; 95% CI: 1.86-15.32; p=0.0018). Multivariate analysis also showed a predictive value for high blood CD5+Bc count (HR: 4.3; 95% CI: 1.9-9.5; p<0.0001). It was concluded that high percentages of CD5+Bc independently associate with increased risk of early conversion to MS in CIS patients with OCGB and Barkhof-Tintoré criteria. PMID:21436320

  14. 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

  15. The I1307K APC mutation in a high-risk clinic setting: a follow-up study.

    PubMed

    Regev, M; Barzilai, S-Eisenberg; Figer, A; Zidan, J; Fidder, H H; Friedman, E

    2005-04-01

    While the I1307K APC mutation clearly confers an increased lifetime risk for colorectal cancer, there is a paucity of data on the natural history of colonic neoplasia in symptomatic and asymptomatic mutation carriers. In this study, 51 Jewish I1307K APC mutation carriers were identified in a high-risk familial cancer clinic over a 4-year period, of whom 29 (56.8%) (four males and 25 females) were successfully telephone interviewed for 0.5-5 years (mean 2.4 +/- 1.4) after initial genetic testing. Of these 29 cases, one individual was diagnosed with colon cancer at the age of 45 years, five had adenomatous polyps (mean number of polyps = 1.8), 11 had breast cancer (mean age at diagnosis 49.5 +/- 10.5 years), and 12 were asymptomatic, at the time of the testing. During the follow-up period, new colonic polyps were diagnosed in three mutation carriers, two with previously diagnosed colon cancer and polyps and only one of the asymptomatic mutation carriers, and two additional previously affected patients had new cancer diagnoses: gastric cancer and melanoma. From this descriptive study, it seems that the short-term risk for colonic polyps in I1307K APC mutation is low, primarily affecting patients with previously diagnosed colon tumors. PMID:15733272

  16. Clinical evaluation of Krimidanta Pratishedha (anti-caries) activity of Triphaladi Gandusha in high risk dental caries patients

    PubMed Central

    Atara, Achyuta G.; Manjusha, R.; Shukla, Vinay J.; Vaghela, Dharmendra B.; Rooparalia, Brijesh

    2014-01-01

    Background: Dental caries is the most common complaint encountered in clinical practice. Virtually every adult in the world has experience of dental caries. It affects almost 80% of the population. It is now being viewed in dual perspective- “caries as a disease” and “caries as a lesion”. Aims: To evaluate the efficacy of Triphaladi Gandusha for its anti-caries activity and improvement in Oral Hygiene Index in high risk patients of dental caries and to compare the efficacy of prevalent method of mouth rinsing and classical method of Gandusha. Materials and Methods: The study was conducted in 40 patients, 20 in each Group-1 and 2. Group -1 was given prepared Triphaladi mouthwash (mouth rinse) while Group-2 was given Triphaladi Kwath for Gandusha (retention). Results: The effect of treatment was assessed by subjective and objective parameters (like salivary pH, buffering capacity and microbial count). Triphaladi Gandusha (retention) in Group - 2 provided better results in the improvement of Ruja (toothache), Dantaharsha (tooth sensitivity), Sarambha (inflammation), pH of saliva, microbial count in salivary sample. And Triphaladi Mouthwash in Group - 1 provided better results in Srava (discharge), bad breath, pH of saliva and buffering capacity of salivary sample. There was no improvement in Chidrata (cavity formation), Krishnata (discoloration) and Chaladanta (mobility) with Triphaladi Gandusha and mouthwash. Conclusion: Study concluded that although both groups were effective, but Gandusha group patients’ got better relief in subjective symptoms compared to mouthwash group. PMID:25364198

  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. 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

  19. 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.

  20. White Matter Microstructure in Individuals at Clinical High Risk of Psychosis: A Whole-Brain Diffusion Tensor Imaging Study

    PubMed Central

    Clemm von Hohenberg, Christian; Pasternak, Ofer; Kubicki, Marek; Ballinger, Thomas; Vu, Mai-Anh; Swisher, Tali; Green, Katie; Giwerc, Michelle; Dahlben, Brian; Goldstein, Jill M.; Woo, Tsung-Ung W.; Petryshen, Tracey L.; Mesholam-Gately, Raquelle I.; Woodberry, Kristen A.; Thermenos, Heidi W.; Mulert, Christoph; McCarley, Robert W.; Seidman, Larry J.; Shenton, Martha E.

    2014-01-01

    Background: The study of individuals at clinical high risk (CHR) for psychosis provides an important opportunity for unraveling pathological mechanisms underlying schizophrenia and related disorders. A small number of diffusion tensor magnetic resonance imaging (DTI) studies in CHR samples have yielded anatomically inconsistent results. The present study is the first to apply tract-based spatial statistics (TBSS) to perform a whole-brain DTI analysis in CHR subjects. Methods: A total of 28 individuals meeting CHR criteria and 34 healthy controls underwent DTI. TBSS was used for a group comparison of fractional anisotropy (FA), as well as axial, radial, and mean diffusivity (AD, RD, and MD). Conversion to psychosis was monitored during a mean follow-up period of 12.3 months. Results: The rate of conversion to psychosis was relatively low (4%). TBSS revealed increased MD in several clusters in the right hemisphere, most notably in the superior longitudinal fasciculus (SLF), posterior corona radiata, and corpus callosum (splenium and body). Increased RD was restricted to a smaller area in the posterior parietal lobe. Conclusion: We present further evidence that white matter microstructure is abnormal in CHR individuals, even in a sample in which the vast majority do not transition to psychosis over the following year. In accord with previous studies on CHR individuals and patients with early-onset schizophrenia, our findings suggest an important pathological role for the parietal lobe and especially the SLF. The latter is known to undergo particularly dynamic microstructural changes during adolescence and early adulthood, a critical phase for the development of psychotic illness. PMID:23737549

  1. Stress-Induced Dopamine Response in Subjects at Clinical High Risk for Schizophrenia with and without Concurrent Cannabis Use

    PubMed Central

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

    2014-01-01

    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 [11C]-(+)-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

  2. Neoadjuvant chemotherapy in locally advanced nasopharyngeal carcinoma: Defining high-risk patients who may benefit before concurrent chemotherapy combined with intensity-modulated radiotherapy

    PubMed Central

    Du, Xiao-Jing; Tang, Ling-Long; Chen, Lei; Mao, Yan-Ping; Guo, Rui; Liu, Xu; Sun, Ying; Zeng, Mu-Sheng; Kang, Tie-Bang; Shao, Jian-Yong; Lin, Ai-Hua; Ma, Jun

    2015-01-01

    The purpose of this study was to create a prognostic model for distant metastasis in patients with locally advanced NPC who accept concurrent chemotherapy combined with intensity-modulated radiotherapy (CCRT) to identify high-risk patients who may benefit from neoadjuvant chemotherapy (NACT). A total of 881 patients with newly-diagnosed, non-disseminated, biopsy-proven locoregionally advanced NPC were retrospectively reviewed; 411 (46.7%) accepted CCRT and 470 (53.3%) accepted NACT followed by CCRT. Multivariate analysis demonstrated N2–3 disease, plasma Epstein–Barr virus (EBV) DNA > 4000 copies/mL, serum albumin ≤46 g/L and platelet count >300 k/cc were independent prognostic factors for distant metastasis in the CCRT group. Using these four factors, a prognostic model was developed, as follows: 1) low-risk group: 0–1 risk factors; and 2) high-risk group: 2–4 risk factors. In the high-risk group, patients who accepted NACT + CCRT had significantly higher distant metastasis-free survival and progression-free survival rates than the CCRT group (P = 0.001; P = 0.011). This simple prognostic model for distant metastasis in locoregionally advanced NPC may facilitate with the selection of high-risk patients who may benefit from NACT prior to CCRT. PMID:26564805

  3. A Clinical Algorithm to Identify HIV Patients at High Risk for Incident Active Tuberculosis: A Prospective 5-Year Cohort Study

    PubMed Central

    Lee, Susan Shin-Jung; Lin, Hsi-Hsun; Tsai, Hung-Chin; Su, Ih-Jen; Yang, Chin-Hui; Sun, Hsin-Yun; Hung, Chien-Chin; Sy, Cheng-Len; Wu, Kuan-Sheng; Chen, Jui-Kuang; Chen, Yao-Shen; Fang, Chi-Tai

    2015-01-01

    Background Predicting the risk of tuberculosis (TB) in people living with HIV (PLHIV) using a single test is currently not possible. We aimed to develop and validate a clinical algorithm, using baseline CD4 cell counts, HIV viral load (pVL), and interferon-gamma release assay (IGRA), to identify PLHIV who are at high risk for incident active TB in low-to-moderate TB burden settings where highly active antiretroviral therapy (HAART) is routinely provided. Materials and Methods A prospective, 5-year, cohort study of adult PLHIV was conducted from 2006 to 2012 in two hospitals in Taiwan. HAART was initiated based on contemporary guidelines (CD4 count < = 350/μL). Cox regression was used to identify the predictors of active TB and to construct the algorithm. The validation cohorts included 1455 HIV-infected individuals from previous published studies. Area under the receiver operating characteristic (ROC) curve was calculated. Results Seventeen of 772 participants developed active TB during a median follow-up period of 5.21 years. Baseline CD4 < 350/μL or pVL ≥ 100,000/mL was a predictor of active TB (adjusted HR 4.87, 95% CI 1.49–15.90, P = 0.009). A positive baseline IGRA predicted TB in patients with baseline CD4 ≥ 350/μL and pVL < 100,000/mL (adjusted HR 6.09, 95% CI 1.52–24.40, P = 0.01). Compared with an IGRA-alone strategy, the algorithm improved the sensitivity from 37.5% to 76.5%, the negative predictive value from 98.5% to 99.2%. Compared with an untargeted strategy, the algorithm spared 468 (60.6%) from unnecessary TB preventive treatment. Area under the ROC curve was 0.692 (95% CI: 0.587–0.798) for the study cohort and 0.792 (95% CI: 0.776–0.808) and 0.766 in the 2 validation cohorts. Conclusions A validated algorithm incorporating the baseline CD4 cell count, HIV viral load, and IGRA status can be used to guide targeted TB preventive treatment in PLHIV in low-to-moderate TB burden settings where HAART is routinely provided to all PLHIV. The

  4. MRP1 overexpression determines poor prognosis in prospectively treated patients with localized high-risk soft tissue sarcoma of limbs and trunk wall: an ISG/GEIS study.

    PubMed

    Martin-Broto, Javier; Gutierrez, Antonio M; Ramos, Rafael F; Lopez-Guerrero, José A; Ferrari, Stefano; Stacchiotti, Silvia; Picci, Piero; Calabuig, Silvia; Collini, Paola; Gambarotti, Marco; Bague, Silvia; Dei Tos, Angelo P; Palassini, Elena; Luna, Pablo; Cruz, Josefina; Cubedo, Ricardo; Martinez-Trufero, Javier; Poveda, Andres; Casali, Paolo G; Fernandez-Serra, Antonio; Lopez-Pousa, Antonio; Gronchi, Alessandro

    2014-01-01

    Patients with localized high-risk soft tissue sarcomas (STS) of the limbs and trunk wall still have a considerable metastatic recurrence rate of more than 50%, in spite of adjuvant chemotherapy. This drug-ceiling effect of chemotherapy in sarcoma setting could be explained, at least partially, by multidrug resistance (MDR) mechanisms. The aim of this study was to ascertain whether mRNA and protein expression of ABCB1 (P-glycoprotein), ABCC1 (MRP1), and GSTA1 (glutathione S-transferase pi) was prognostic in localized high-risk STS. Immunohistochemistry and reverse transcriptase-PCR studies were performed from biopsies at the time of diagnosis. Patients of this series were prospectively enrolled into a phase III trial that compared three versus five cycles of epirubicin plus ifosfamide. The series of 102 patients found 41 events of recurrence and 37 of death with a median follow-up of 68 months. In univariate analysis, variables with a statistically significant relationship with relapse-free survival (RFS) were: MRP1 expression (5-year RFS rate of 23% in positive cases and 63% in negative cases, P = 0.029), histology (5-year RFS rate of 74% in undifferentiated pleomorphic sarcoma and 43% in synovial sarcoma, P = 0.028), and ABCC1 expression (5-year RFS rate of 33% in overexpression and 65% in downregulation, P = 0.012). Combined ABCC1/MRP1 was the only independent prognostic factor for both RFS (HR = 2.704, P = 0.005) and overall survival (HR = 2.208, P = 0.029). ABCC1/MRP1 expression shows robust prognostic relevance in patients with localized high-risk STS treated with anthracycline-based chemotherapy, which is the standard front line treatment in STS. This finding deserves attention as it points to a new targetable protein in STS. PMID:24145283

  5. A retrospective study of focal segmental glomerulosclerosis: clinical criteria can identify patients at high risk for recurrent disease after first renal transplantation

    PubMed Central

    2013-01-01

    Background Focal segmental glomerulosclerosis (FSGS) is a frequent cause of end-stage renal disease. Renal transplantation in patients with FSGS is often complicated by disease recurrence, which is associated with poor outcome. There are no tests that reliably predict recurrence of FSGS after transplantation. The aim of this study was to evaluate if clinical criteria can identify patients at high risk for recurrent disease. Methods We retrospectively studied 94 patients who received a first renal transplant at a median age of 37 years (range 5–69 years). Patients were assigned to one of three groups: familial or genetic FSGS (group I; n=18), secondary FSGS (group II; n=10) and idiopathic FSGS (group III; n=66). Pretransplant clinical characteristics were analyzed to determine predictors of a recurrence after transplantation. Results FSGS only recurred in patients with idiopathic FSGS (group III; 42%). Patients with a recurrence had a significantly lower serum albumin, higher 24-hour proteinuria and higher estimated glomerular filtration rate at diagnosis. Serum albumin at diagnosis was the only independent predictor of a recurrence in patients with idiopathic FSGS. Patients with recurrent FSGS had more acute rejection episodes (54% vs. 27%, P =0.02) and lower five year graft survival compared to patients without a recurrence (50 vs. 82%, P <0.01). Conclusions Clinical criteria allow identification of patients at high risk of recurrent FSGS after renal transplantation. This information can be used in the counseling and management of patients with FSGS. PMID:23433074

  6. Preventing Perinatal Depression in High Risk Women: Moving the Mothers and Babies Course from Clinical Trials to Community Implementation.

    PubMed

    Le, Huynh-Nhu; Perry, Deborah F; Mendelson, Tamar; Tandon, S Darius; Muñoz, Ricardo F

    2015-10-01

    A growing research literature highlights the public health need for preventive interventions to reduce symptoms and incidence of perinatal depression among vulnerable populations. The Mothers and Babies (MB) course is a cognitive-behavioral intervention designed to teach mood regulation skills to English- and Spanish-speaking low-income women at high risk for perinatal depression. We describe the development of the MB course and evaluate the extent to which research findings support efficacy, effectiveness, and dissemination based on the Society for Prevention Research Standards Committee's standards of evidence. Our review of research and implementation activities suggests that the MB intervention demonstrates promising evidence for efficacy in reducing depressive symptoms; empirical support for prevention of major depressive episodes is still preliminary. Work is in progress to evaluate program effectiveness and prepare for broad dissemination and implementation. The MB course shows promise as an intervention for low-income women at risk for perinatal mood issues. Spanish and English intervention materials have been developed that can be delivered in different settings (hospitals, home visiting), in different dosages (6, 8, or 12 sessions), and via different modalities (group, individual). Evaluating the MB course against current standards is intended to inform other prevention intervention development research. PMID:25673369

  7. 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

  8. Self-Disorders and Clinical High Risk for Psychosis: An Empirical Study in Help-Seeking Youth Attending Community Mental Health Facilities.

    PubMed

    Raballo, Andrea; Pappagallo, Elena; Dell' Erba, Alice; Lo Cascio, Nella; Patane', Martina; Gebhardt, Eva; Boldrini, Tommaso; Terzariol, Laura; Angelone, Massimiliano; Trisolini, Alberto; Girardi, Paolo; Fiori Nastro, Paolo

    2016-07-01

    Anomalous subjective experiences involving an alteration of the basic sense of self (ie, Self-disorder [SD]) are emerging as a core marker of schizophrenia spectrum disorders with potential impact on current early detection strategies as well. In this study, we wished to field-test the prevalence of SD in a clinical sample of adolescent/young adult help-seekers at putative risk for psychosis attending standard community mental health facilities in Italy. Participants (n = 47), aged between 14 and 25, underwent extensive psychopathological evaluations with current semi-structured tools to assess Clinical High Risk (CHR) state (ie, Structured Interview for Prodromal Syndromes/Scale of Prodromal Symptoms [SIPS/SOPS], Schizophrenia Proneness Instrument-Adult/Child and Youth [SPI-A/CY]). SD aggregated in CHR subjects as compared to the non-CHR and revealed substantial association with sub-psychotic symptoms (SIPS), subjective experience of cognitive and cognitive-perceptual vulnerability (basic symptoms) and functional level (Global Assessment of functioning). Moreover, a combination of the 2 approaches (ie, CHR plus SD) enabled further "closing-in" on a subgroup of CHR with lower global functioning. The results confirm SD's relevance for the early profiling of youths at potential high risk for psychosis. PMID:26757754

  9. 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

  10. 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.

  11. 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

  12. Clinical Protocols to Reduce High Risk Drinking in College Students: The College Drinking Prevention Curriculum for Health Care Providers

    ERIC Educational Resources Information Center

    Fleming, Michael

    2002-01-01

    The goal of this curriculum is to help all health care professionals -- physicians, nurses, nurse practitioners, physician assistants, social workers, health educators, counselors, psychologists, and others who work with college students -- identify and treat students who are at-risk or are having alcohol-related problems. The clinical methods…

  13. Implementation and Operational Research: A Cost-Effective, Clinically Actionable Strategy for Targeting HIV Preexposure Prophylaxis to High-Risk Men Who Have Sex With Men

    PubMed Central

    Cinti, Sandro K.; Hutton, David W.

    2016-01-01

    Background: Preexposure prophylaxis (PrEP) is effective at preventing HIV infection among men who have sex with men (MSM), but there is uncertainty about how to identify high-risk MSM who should receive PrEP. Methods: We used a mathematical model to assess the cost-effectiveness of using the HIV Incidence Risk Index for MSM (HIRI-MSM) questionnaire to target PrEP to high-risk MSM. We simulated strategies of no PrEP, PrEP available to all MSM, and eligibility thresholds set to HIRI-MSM scores between 5 and 45, in increments of 5 (where a higher score predicts greater HIV risk). Based on the iPrEx, IPERGAY, and PROUD trials, we evaluated PrEP efficacies from 44% to 86% and annual costs from $5900 to 8700. We designate strategies with incremental cost-effectiveness ratio (ICER) ≤$100,000/quality-adjusted life-year (QALY) as “cost-effective.” Results: Over 20 years, making PrEP available to all MSM is projected to prevent 33.5% of new HIV infections, with an ICER of $1,474,000/QALY. Increasing the HIRI-MSM score threshold reduces the prevented infections, but improves cost-effectiveness. A threshold score of 25 is projected to be optimal (most QALYs gained while still being cost-effective) over a wide range of realistic PrEP efficacies and costs. At low cost and high efficacy (IPERGAY), thresholds of 15 or 20 are optimal across a range of other input assumptions; at high cost and low efficacy (iPrEx), 25 or 30 are generally optimal. Conclusions: The HIRI-MSM provides a clinically actionable means of guiding PrEP use. Using a score of 25 to determine PrEP eligibility could facilitate cost-effective use of PrEP among high-risk MSM who will benefit from it most. PMID:26977749

  14. Universal HIV screening at a major metropolitan TB clinic: HIV prevalence and high-risk behaviors among TB patients.

    PubMed Central

    Weis, S E; Foresman, B; Cook, P E; Matty, K J

    1999-01-01

    OBJECTIVES: This study assessed the outcome of implementing a policy of universal screening of patients with tuberculosis (TB) for HIV infection at a major metropolitan public health TB clinic. METHODS: HIV serologic testing was completed on 768 (93%) of 825 eligible patients. Ninety-eight HIV-positive cases (13%) were compared with 670 HIV-negative cases. The presence of adult HIV risk factors was determined by structured interview and review of medical records. RESULTS: One or more HIV risk factors were present in 93% of HIV-positive cases and 42% of HIV-negative cases. CONCLUSIONS: The metropolitan TB clinic is well suited for HIV screening, and HIV-antibody testing and counseling should be provided to all TB patients. PMID:9987468

  15. Phase 2 clinical trial of 5-azacitidine, valproic acid, and all-trans retinoic acid in patients with high-risk acute myeloid leukemia or myelodysplastic syndrome

    PubMed Central

    Raffoux, Emmanuel; Cras, Audrey; Recher, Christian; Boëlle, Pierre-Yves; de Labarthe, Adrienne; Turlure, Pascal; Marolleau, Jean-Pierre; Reman, Oumedaly; Gardin, Claude; Victor, Maud; Maury, Sébastien; Rousselot, Philippe; Malfuson, Jean-Valère; Maarek, Odile; Daniel, Marie-Thérèse; Fenaux, Pierre; Degos, Laurent; Chomienne, Christine; Chevret, Sylvie; Dombret, Hervé

    2010-01-01

    In this Phase 2 study, we evaluated the efficacy of combination of 5-azacitidine (AZA), valproic acid (VPA), and all-trans retinoic acid (ATRA) in patients with high-risk acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Treatment consisted of six cycles of AZA and VPA for 7 days, followed by ATRA for 21 days. Sixty-five patients were enrolled (median age, 72 years; 55 AML including 13 relapsed/refractory patients, 10 MDS; 30 unfavorable karyotypes). Best responses included 14 CR and 3 PR (26%), 75% of the responders and 36% of the non-responders achieving an erythroid response. Median overall survival (OS) was 12.4 months. Untreated patients had a longer OS than relapsed/refractory patients. In patients who fulfilled the 6 planned cycles, OS did not appear to depend on CR/PR achievement, suggesting that stable disease while on-treatment would be a surrogate for survival with this approach. During therapy, early platelet response and demethylation of the FZD9, ALOX12, HPN, and CALCA genes were associated with clinical response. Finally, there was no evidence for the restoration of an ATRA-induced differentiation during therapy. Epigenetic modulation deserves prospective comparisons to conventional care in patients with high-risk AML, at least in those presenting previously untreated disease and low blast count. PMID:21293051

  16. 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

  17. 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. PMID:26168262

  18. Eye Care Utilization among a High-Risk Diabetic Population Seen in a Public Hospital’s Clinics

    PubMed Central

    MacLennan, Paul A.; McGwin, Gerald; Heckemeyer, Christine; Lolley, Virginia R.; Hullett, Sandral; Saaddine, Jinan; Shrestha, Sundar S.; Owsley, Cynthia

    2015-01-01

    Objective Little is known regarding eye care utilization among low income persons with diabetes, especially African Americans. Methods A retrospective cohort study with two-years of follow-up examined eye care utilization among adult diabetes patients seen in 2007 in the internal medicine clinic of a large, urban, county hospital that serves primarily low income, non-Hispanic African American patients. Patients with a history of retinopathy and macular edema or a current diagnosis indicating ophthalmic complications were excluded. Eye care utilization was defined dichotomously as whether or not patients had a visit to the eye clinic for any eye care examination or procedure. We estimated crude and adjusted rate ratios (aRRs) and 95% confidence intervals (CIs) for the association between eye care utilization and selected clinical and demographic characteristics. Results There were 867 patients with diabetes identified: 61.9% women, 76.2% non-Hispanic African American, 61.3% indigent, and average age 51.8 years. Eye care utilization was 33.2% within one-year and 45.0% within two-years. For patients 19–39 years of age compared to those 65+ years, significantly decreased eye care utilization was observed within one-year (aRR=0.48, 95% CI 0.27–0.84) and within two-years (aRR=0.61, 95% CI 0.38–0.99). Conclusions Overall eye care utilization was low. Additional education efforts to increase the perception of need among urban minority populations may be enhanced if focused on younger people with diabetes. PMID:24310149

  19. Local Sea Level Changes: Assessing and Accounting for the Risk Associated With the Low-Probability, High-Risk Tail of the Risk Spectrum

    NASA Astrophysics Data System (ADS)

    Plag, H. P.

    2014-12-01

    Stakeholders in the coastal zone, particularly the urban coasts, are turning to science to get information on future Local Sea Level (LSL) rise. Many scientists and scientific committees respond to this request with a range of plausible trajectories (RPT) defined by a number of possible trajectories each corresponding to a certain scenario. Often these assessments take a starting point in the small number of global sea level trajectories provided by the IPCC. This approach is inherently deterministic. The resulting RPT, which can be quite large, is considered as reflecting "uncertainty in LSL projections." Non-scientists often use the RPT to select a preferred and much narrower sub-RPT, for which they plan, or they use the "large uncertainty" to justify not taking any measures. In response to societal needs, science focuses on a reduction of the uncertainties through improved deterministic models. This approach has a number of problems: (1) The complexity of LSL as the outcome of many local, regional and global earth system processes, including anthropogenic processes, renders a deterministic approach to prediction invalid. (2) Most assessments of the RPT account for an incomplete set of relevant earth system processes, and for each processes make assumptions that (often arbitrarily) constrain the contribution from this process. (3) LSL is an inherently probabilistic variable that has a broad probability density function (PDF), with a complex dependency of this PDF on the PDFs of the many contributing processes. In particular, the contribution from the large ice sheets has a PDF with low-probability high-impact tails that are generally neglected in deterministic LSL projections and in the sub-RPT used for coastal planning. A fully probabilistic assessment of the risk associated with LSL rise indicates that the standard deterministic assessment not only neglect most of the low-probability, high-risk tail of the PDF but also medium-probability, high-risk parts. This

  20. Tool for Rapid & Easy Identification of High Risk Diabetic Foot: Validation & Clinical Pilot of the Simplified 60 Second Diabetic Foot Screening Tool

    PubMed Central

    Woodbury, M. Gail; Sibbald, R. Gary; Ostrow, Brian; Persaud, Reneeka; Lowe, Julia M.

    2015-01-01

    Background Most diabetic foot amputations are caused by ulcers on the skin of the foot i.e. diabetic foot ulcers. Early identification of patients at high risk for diabetic foot ulcers is crucial. The ‘Simplified 60-Second Diabetic Foot Screening Tool’ has been designed to rapidly detect high risk diabetic feet, allowing for timely identification and referral of patients needing treatment. This study aimed to determine the clinical performance and inter-rater reliability of ‘Simplified 60 Second Diabetic Foot Screening Tool’ in order to evaluate its applicability for routine screening. Methods and Findings The tool was independently tested by n=12 assessors with n=18 Guyanese patients with diabetes. Inter-rater reliability was assessed by calculating Cronbach’s alpha for each of the assessment items. A minimum value of 0.60 was considered acceptable. Reliability scores of the screening tool assessment items were: ‘monofilament test’ 0.98; ‘active ulcer’ 0.97; ‘previous amputation’ 0.97; ‘previous ulcer’ 0.97; ‘fixed ankle’ 0.91; ‘deformity’ 0.87; ‘callus’ 0.87; ‘absent pulses’ 0.87; ‘fixed toe’ 0.80; ‘blisters’ 0.77; ‘ingrown nail’ 0.72; and ‘fissures’ 0.55. The item ‘stiffness in the toe or ankle’ was removed as it was observed in only 1.3% of patients. The item ‘fissures’ was also removed due to low inter-rater reliability. Clinical performance was assessed via a pilot study utilizing the screening tool on n=1,266 patients in an acute care setting in Georgetown, Guyana. In total, 48% of patients either had existing diabetic foot ulcers or were found to be at high risk for developing ulcers. Conclusions Clinicians in low and middle income countries such as Guyana can use the Simplified 60-Second Diabetic Screening Tool to facilitate early detection and appropriate treatment of diabetic foot ulcers. Implementation of this screening tool has the potential to decrease diabetes related disability and

  1. Uptake of tamoxifen in consecutive premenopausal women under surveillance in a high-risk breast cancer clinic

    PubMed Central

    Donnelly, L S; Evans, D G; Wiseman, J; Fox, J; Greenhalgh, R; Affen, J; Juraskova, I; Stavrinos, P; Dawe, S; Cuzick, J; Howell, A

    2014-01-01

    Background: Randomised trials of tamoxifen versus placebo indicate that tamoxifen reduces breast cancer risk by approximately 33%, yet uptake is low. Approximately 10% of women in our clinic entered the IBIS-I prevention trial. We assess the uptake of tamoxifen in a consecutive series of premenopausal women not in a trial and explore the reasons for uptake through interviews. Methods: All eligible women between 33 and 46 years at ⩾17% lifetime risk of breast cancer and undergoing annual mammography in our service were invited to take a 5-year course of tamoxifen. Reasons for accepting (n=15) or declining (n=15) were explored using semi-structured interviews. Results: Of 1279 eligible women, 136 (10.6%) decided to take tamoxifen. Women >40 years (74 out of 553 (13.4%)) and those at higher non-BRCA-associated risk were more likely to accept tamoxifen (129 out of 1109 (11.6%)). Interviews highlighted four themes surrounding decision making: perceived impact of side effects, the impact of others' experience on beliefs about tamoxifen, tamoxifen as a ‘cancer drug', and daily reminder of cancer risk. Conclusions: Tamoxifen uptake was similar to previously ascertained uptake in a randomised controlled trial (IBIS-I). Concerns were similar in women who did or did not accept tamoxifen. Decision making appeared to be embedded in the experience of significant others. PMID:24594998

  2. 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

  3. Frequency and pattern of childhood symptom onset reported by first episode schizophrenia and clinical high risk youth

    PubMed Central

    Woodberry, Kristen A.; Serur, Rachael A.; Hallinan, Sean B.; Mesholam-Gately, Raquelle I.; Giuliano, Anthony J.; Wojcik, Joanne D.; Keshavan, Matcheri S.; Frazier, Jean A.; Goldstein, Jill M.; Shenton, Martha E.; McCarley, Robert W.; Seidman, Larry J.

    2014-01-01

    Background Psychosis prevention and early intervention efforts in schizophrenia have focused increasingly on sub-threshold psychotic symptoms in adolescents and young adults. Although many youth report symptom onset prior to adolescence, the childhood incidence of prodromal-level symptoms in those with schizophrenia or related psychoses is largely unknown. Methods This study reports on the retrospective recall of prodromal-level symptoms from 40 participants in a first-episode of schizophrenia (FES) and 40 participants at “clinical high risk” (CHR) for psychosis. Onset of positive and non-specific symptoms was captured using the Structured Interview for Prodromal Syndromes. Frequencies are reported according to onset during childhood (prior to age 13), adolescence (13–17), or adulthood (18 +). Results Childhood-onset of attenuated psychotic symptoms was not rare. At least 11% of FES and 23% of CHR reported specific recall of childhood-onset of unusual or delusional ideas, suspiciousness, or perceptual abnormalities. Most recalled experiencing non-specific symptoms prior to positive symptoms. CHR and FES did not differ significantly in the timing of positive and non-specific symptom onset. Other than being younger at assessment, those with childhood onset did not differ demographically from those with later onset. Conclusion Childhood-onset of initial psychotic-like symptoms may be more common than previous research has suggested. Improved characterization of these symptoms and a focus on their predictive value for subsequent schizophrenia and other major psychoses are needed to facilitate screening of children presenting with attenuated psychotic symptoms. Accurate detection of prodromal symptoms in children might facilitate even earlier intervention and the potential to alter pre-illness trajectories. PMID:24924404

  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. A Phase I Trial of Samarium-153-Lexidronam Complex for Treatment of Clinically Nonmetastatic High-Risk Prostate Cancer: First Report of a Completed Study

    SciTech Connect

    Valicenti, Richard K.; Trabulsi, Edouard; Intenzo, Charles; Lavarino, Jorosali; Xu Yihuan; Chervoneva, Inna

    2011-03-01

    Purpose: We completed a Phase I trial to determine the maximum tolerated dose of samarium-153 EDTMP ({sup 153}Sm) with hormonal therapy (HT) and radiation therapy (RT) in high-risk clinically nonmetastatic prostate cancer. Methods and Materials: High-risk M0 prostate cancer patients (prostate-specific antigen >20 ng/mL, Gleason score >7, or >T3) were eligible for this prospective trial of dose-escalated radioactive {sup 153}Sm-EDTMP (.25-2.0 mCi/kg) as primary or postoperative therapy. After 1 month of HT, we administered {sup 153}Sm-EDTMP followed by 4 more months of HT, 46.8 Gy to the pelvic region and 23.4 Gy to the prostate target (TD = 70.2 Gy). The primary endpoint was Grade III toxicity or higher by the National Cancer Institute Common Toxicity Criteria. Results: Twenty-nine patients enrolled (median prostate-specific antigen = 8.2 ng/mL, 27/29 (93%) T stage {>=}T2b, 24/29 (83%) had Gleason >7) and received {sup 153}Sm-EDTMP (.25 mCi/kg, 4 patients; 0.5 mCi/kg, 4 patients; 0.75 mCi/kg, 6 patients; 1.0 mCi/kg, 6 patients; 1.5 mCi/kg, 5 patients; 2.0mCi/kg, 4 patients). Twenty-eight patients underwent all planned therapy without delays (1 patient required surgery before the start of RT). With a median follow-up time of 23 months, there were 2 patients (7 %) experiencing Grade III hematologic toxicity. There were no other Grade III or IV side effects. Conclusions: Our trial demonstrates that 2 mCi/kg {sup 153}Sm -EDTMP with HT and RT was safe and feasible in men with high-risk M0 prostate cancer. A Phase II study to test this treatment is currently underway by the Radiation Therapy Oncology Group.

  6. Clinical Evaluation of a GP5+/6+-Based Luminex Assay Having Full High-Risk Human Papillomavirus Genotyping Capability and an Internal Control

    PubMed Central

    Cuschieri, K.; de Koning, M. N. C.; van Doorn, L. J.; Snijders, P. J. F.; Meijer, C. J. L. M.; Quint, W. G. V.; Arbyn, M.

    2014-01-01

    The LMNX genotyping kit HPV GP (LMNX) is based on the clinically validated GP5+/6+ PCR, with a genotyping readout as an alternative for the more established enzyme immunoassay (EIA) detection of 14 targeted high-risk human papillomavirus (HPV) types. LMNX is additionally provided with an internal control probe. Here, we present an analysis of the clinical performance of the LMNX using a sample panel and infrastructure provided by the international VALGENT (Validation of Genotyping Tests) project. This panel consisted of cervical specimens from approximately 1,000 women attending routine screening, “enriched” with 300 women with abnormal cytology. Cases were defined as women classified with cervical intraepithelial neoplasia (CIN) grade 2+ (CIN2+) (n = 102) or CIN3+ (n = 55) within the previous 18 months. Controls were women who had normal cytology results over two subsequent screening rounds at a 3-year interval (n = 746). The GP5+/6+-PCR EIA (EIA) was used as a comparator assay and showed sensitivities of 94.1% and 98.2% for CIN2+ and CIN3+, respectively, with a clinical specificity of 92.4% among women aged ≥30 years. The LMNX demonstrated clinical sensitivities of 96.1% for CIN2+ and of 98.2% for CIN3+ and a clinical specificity of 92.6% for women aged ≥30 years. The LMNX and EIA were in high agreement (Cohen's kappa = 0.969) for the detection of 14 hrHPVs in aggregate, and no significant difference was observed (McNemar's P = 0.629). The LMNX internal control detected 0.6% inadequate specimens. Based on our study results, we consider the LMNX, similarly to the EIA, useful for HPV-based cervical cancer screening. PMID:25210073

  7. 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. PMID:26842902

  8. 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

  9. 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

  10. Hemiarthroplasty in high risk elderly patient under epidural anesthesia with 0.75% ropivacaine-fentanyl versus 0.5% bupivacaine-fentanyl: Clinical trial

    PubMed Central

    Rastogi, Bhawna; Gupta, Kumkum; Rastogi, Avinash; Gupta, Prashant K.; Singhal, Apoorva B.; Singh, Ivesh

    2013-01-01

    Background: Anesthetic management of elderly patients is a challenge as aging makes them more susceptible to hemodynamic fluctuations during regional anesthesia. This study was aimed to compare the clinical efficacy of epidural 0.75% ropivacaine fentanyl (RF)– with 0.5% bupivacaine–fentanyl (BF) for hemiarthroplasty in high-risk elderly patients. Methods: Sixty elderly consented patients of either sex with American Society of Anesthesiologist ASA II and III, scheduled for elective hemiarthroplasty were randomized into two Groups of 30 patients to receive epidural study solution of 15 mL of 0.75% Ropivacaine or 0.5% Bupivacaine with 1 mL fentanyl (50 μg). The hemodynamic variability with onset and duration of sensory and motor blocks were recorded. The adequacy and quality of surgical anesthesia were assessed. The post-epidural nausea and vomiting, shivering, respiratory parameters, or any other side effects were also recorded. Results: There was no difference in the demographic profile between groups. The mean onset time to achieve sensory block to the T10 dermatome was rapid in the Group BF (12.4±6.9 vs. 17.5±3.7 min in Group RF). The mean time to achieve motor block was 17.5±3.4 min in Group BF versus 21.7±7.8 min in Group RF. The intraoperative hemodynamic fluctuations showed statistically significant differences between groups. The pruritis was observed in five patients but post-epidural shivering, nausea, vomiting, respiratory depression, or urinary retention were not observed in any patient. Conclusion: Epidural 0.75% Ropivacaine with fentanyl showed better clinical profile as compared to 0.5% Bupivacaine with fentanyl for hemiarthroplasty in elderly patients. PMID:23956712

  11. Awareness and knowledge of Human Papillomavirus (HPV) infection among high-risk men of Hispanic origin attending a Sexually Transmitted Infection (STI) clinic

    PubMed Central

    2012-01-01

    Background Genital Human papilloma virus (HPV) is one of the most commonly diagnosed Sexually Transmitted Infection (STIs) in men and women. Knowledge about HPV infection among men is limited. This study aims to determine correlates of adequate knowledge of HPV infection among men who attend an STI clinic in Puerto Rico. Methods A cross-sectional study of 206 men was conducted at an STI clinic in San Juan, PR. Adequate knowledge was defined as a score of at least 70% of correct responses among those men who reported having ever heard of HPV. Variables that achieved statistical significance in the bivariate analysis (p<0.05) were included in the multivariate logistic regression model. Results Although 52.5% of men reported having heard of HPV infection before the survey, only 29.3% of this sub-group had an adequate knowledge of HPV. Most men did not know that HPV is a risk factor for anal (38.7%), penile (50.0%) and oral (72.6%) cancer. Factors associated with adequate knowledge of HPV in age-adjusted models were being men who have sex with men (MSM) (OR=2.6;95%CI=1.1-6.1), self-report of genital warts (OR=3.2;95%CI=1.3-7.9) and herpes (OR=7.4;95% CI=2.2-25.1). MSM was marginally associated with adequate knowledge (OR=2.3;95% CI=0.9-5.9) and self-report of herpes remained significantly associated (OR=5.0;95%CI=1.3-18.4) in multivariate logistic regression analysis. Conclusions Awareness and knowledge of HPV was very low in this group of men. Interventions to increase knowledge and awareness in this group are necessary to promote preventive practices for HPV-related cancers in high-risk groups. PMID:23231727

  12. Developmental trajectories of clinically significant attention-deficit/hyperactivity disorder (ADHD) symptoms from grade 3 through 12 in a high-risk sample: Predictors and outcomes.

    PubMed

    Sasser, Tyler R; Kalvin, Carla B; Bierman, Karen L

    2016-02-01

    Developmental trajectories of clinically significant attention-deficit/hyperactivity (ADHD) symptoms were explored in a sample of 413 children identified as high risk because of elevated kindergarten conduct problems. Symptoms of inattention and hyperactivity-impulsivity were modeled simultaneously in a longitudinal latent class analyses, using parent reports collected in Grades 3, 6, 9, and 12. Three developmental trajectories emerged: (1) low levels of inattention and hyperactivity (low), (2) initially high but then declining symptoms (declining), and (3) continuously high symptoms that featured hyperactivity in childhood and early adolescence and inattention in adolescence (high). Multinomial logistic regressions examined child characteristics and family risk factors as predictors of ADHD trajectories. Relative to the low class, children in the high and declining classes displayed similar elevations of inattention and hyperactivity in early childhood. The high class was distinguished from the declining class by higher rates of aggression and hyperactivity at school and emotion dysregulation at home. In contrast, the declining class displayed more social isolation at home and school, relative to the low class. Families of children in both high and declining trajectory classes experienced elevated life stressors, and parents of children in the high class were also more inconsistent in their discipline practices relative to the low class. By late adolescence, children in the high class were significantly more antisocial than those in the low class, with higher rates of arrests, school dropout, and unemployment, whereas children in the declining class did not differ from those in the low trajectory class. The developmental and clinical implications of these findings are discussed. PMID:26854506

  13. Altered Thalamo-Cortical White Matter Connectivity: Probabilistic Tractography Study in Clinical-High Risk for Psychosis and First-Episode Psychosis.

    PubMed

    Cho, Kang Ik K; Shenton, Martha E; Kubicki, Marek; Jung, Wi Hoon; Lee, Tae Young; Yun, Je-Yeon; Kim, Sung Nyun; Kwon, Jun Soo

    2016-05-01

    Disrupted thalamo-cortical connectivity is regarded as a core psychopathology in patients diagnosed with schizophrenia. However, whether the thalamo-cortical white matter connectivity is disrupted before the onset of psychosis is still unknown. To determine this gap in knowledge, the strength of thalamo-cortical white matter anatomical connectivity in subjects at clinical-high risk for psychosis (CHR) was compared to that of first-episode psychosis (FEP) and healthy controls. A total of 37 CHR, 21 FEP, and 37 matched healthy controls underwent diffusion-weighted magnetic resonance imaging to examine the number of probabilistic tractography "counts" representing thalamo-cortical white matter connectivity. We also investigated the relationship with psychopathology. For FEP, the connectivity between the thalamus and parietal cortex was significantly increased (F= 5.65,P< .05) compared to that of healthy controls. However, the connectivity between thalamus and orbitofrontal cortex was significantly reduced compared to both healthy controls (F= 11.86,P< .005) and CHR (F= 6.63,P< .05). Interestingly, CHR exhibited a similar pattern as FEP, albeit with slightly reduced magnitude. Compared to healthy controls, there was a significant decrease (F= 4.16,P< .05) in CHR thalamo-orbitofrontal connectivity. Also, the strength of the thalamo-orbitofrontal connectivity was correlated with the Global Assessment of Functioning score in CHR (r= .35,P< .05). This observed pattern of white matter connectivity disruptions in FEP and in CHR suggests that this pattern of disconnectivity not only highlights the involvement of thalamus but also might be useful as an early biomarker for psychosis. PMID:26598740

  14. 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

  15. Deficient Suppression of Default Mode Regions during Working Memory in Individuals with Early Psychosis and at Clinical High-Risk for Psychosis

    PubMed Central

    Fryer, Susanna L.; Woods, Scott W.; Kiehl, Kent A.; Calhoun, Vince D.; Pearlson, Godfrey D.; Roach, Brian J.; Ford, Judith M.; Srihari, Vinod H.; McGlashan, Thomas H.; Mathalon, Daniel H.

    2013-01-01

    Background: The default mode network (DMN) is a set of brain regions typically activated at rest and suppressed during extrinsic cognition. Schizophrenia has been associated with deficient DMN suppression, though the extent to which DMN dysfunction predates psychosis onset is unclear. This study examined DMN suppression during working memory (WM) performance in youth at clinical high-risk (CHR) for psychosis, early schizophrenia (ESZ) patients, and healthy controls (HC). We hypothesized that the DMN would show load-dependent suppression during WM retrieval in HC but not in ESZ, with CHR participants showing an intermediate pattern. Methods: fMRI data were collected from CHR (n = 32), ESZ (n = 22), and HC (n = 54) participants, ages 12–30. DMN regions were defined via seed-based connectivity analysis of resting-state fMRI data from an independent HC sample. Load-dependent deactivations of these DMN regions in response to WM probes were interrogated. Results: Healthy controls showed linear load-dependent increases in DMN deactivation. Significant Group-by-Load interactions were observed in DMN regions including medial prefrontal and lateral posterior parietal cortices. Group-by-Load effects in posterior DMN nodes resulted from less suppression at higher WM loads in ESZ relative to HC, with CHR differing from neither group. In medial prefrontal cortex, suppression of activity at higher WM loads was significantly diminished in both CHR and ESZ groups, relative to HC. In addition, investigation of dorsolateral prefrontal cortex (DLPFC) activations revealed that ESZ activated right DLPFC significantly more than HC, with CHR differing from neither group. Conclusion: While HC showed WM load-dependent modulation of DMN suppression, CHR individuals had deficient higher-load DMN suppression that was similar to, but less pronounced than, the distributed suppression deficits evident in ESZ patients. These results suggest that DMN dysregulation associated with

  16. 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

  17. The impact of psychosis on the course of cognition: a prospective, nested case-control study in individuals at clinical high-risk for psychosis

    PubMed Central

    Carrión, R. E.; McLaughlin, D.; Auther, A. M.; Olsen, R.; Correll, C. U.; Cornblatt, B. A.

    2015-01-01

    Background Although cognitive deficits in patients with schizophrenia are rooted early in development, the impact of psychosis on the course of cognitive functioning remains unclear. In this study a nested case-control design was used to examine the relationship between emerging psychosis and the course of cognition in individuals ascertained as clinical high-risk (CHR) who developed psychosis during the study (CHR+T). Method Fifteen CHR+T subjects were administered a neurocognitive battery at baseline and post-psychosis onset (8.04 months, S.D. = 10.26). CHR+T subjects were matched on a case-by-case basis on age, gender, and time to retest with a group of healthy comparison subjects (CNTL, n = 15) and two groups of CHR subjects that did not transition: (1) subjects matched on medication treatment (i.e. antipsychotics and antidepressants) at both baseline and retesting (Meds-matched CHR+NT, n = 15); (2) subjects unmedicated at both assessments (Meds-free CHR+NT, n = 15). Results At baseline, CHR+T subjects showed large global neurocognitive and intellectual impairments, along with specific impairments in processing speed, verbal memory, sustained attention, and executive function. These impairments persisted after psychosis onset and did not further deteriorate. In contrast, CHR+NT subjects demonstrated stable mild to no impairments in neurocognitive and intellectual performance, independent of medication treatment. Conclusions Cognition appears to be impaired prior to the emergence of psychotic symptoms, with no further deterioration associated with the onset of psychosis. Cognitive deficits represent trait risk markers, as opposed to state markers of disease status and may therefore serve as possible predictors of schizophrenia prior to the onset of the full illness. PMID:26169626

  18. 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.

  19. 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

  20. 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

  1. 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). PMID:23996532

  2. 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

  3. [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. PMID:26951731

  4. 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

  5. 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

  6. 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. PMID:25514466

  7. Perspectives on the clinical management of localized prostate cancer

    PubMed Central

    Nelson, Joel B

    2014-01-01

    If cure is necessary, is it possible and if cure is possible, is it necessary?’-Willet F. Whitmore Defined broadly, prostate cancer has two states: An indolent histological manifestation of a locally proliferative and invasive process or a clinically relevant, potentially lethal disease. Likewise, the management of clinically localized prostate cancer must address two questions: what sort of disease is this and what needs to be done. PMID:24589461

  8. 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

  9. 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

  10. 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

  11. Breast ductal lavage for biomarker assessment in high risk women: rationale, design and methodology of a randomized phase II clinical trial with nimesulide, simvastatin and placebo

    PubMed Central

    2012-01-01

    Background Despite positive results from large phase III clinical trials proved that it is possible to prevent estrogen-responsive breast cancers with selective estrogen receptor modulators and aromatase inhibitors, no significant results have been reached so far to prevent hormone non-responsive tumors. The Ductal Lavage (DL) procedure offers a minimally invasive method to obtain breast epithelial cells from the ductal system for cytopathologic analysis. Several studies with long-term follow-up have shown that women with atypical hyperplasia have an elevated risk of developing breast cancer. The objective of the proposed trial is to assess the efficacy and safety of a daily administration of nimesulide or simvastatin in women at higher risk for breast cancer, focused particularly on hormone non-responsive tumor risk. The primary endpoint is the change in prevalence of atypical cells and cell proliferation (measured by Ki67) in DL or fine needle aspirate samples, after 12 months of treatment and 12 months after treatment cessation. Methods-Design From 2005 to 2011, 150 women with a history of estrogen receptor negative ductal intraepithelial neoplasia or lobular intraepithelial neoplasia or atypical hyperplasia, or unaffected subjects carrying a mutation of BRCA1 or with a probability of mutation >10% (according to BRCAPRO) were randomized to receive nimesulide 100mg/day versus simvastatin 20mg/day versus placebo for one year followed by a second year of follow-up. Discussion This is the first randomized placebo controlled trial to evaluate the role of DL to study surrogate endpoints biomarkers and the effects of these drugs on breast carcinogenesis. In 2007 the European Medicines Agency limited the use of systemic formulations of nimesulide to 15 days. According to the European Institute of Oncology Ethics Committee communication, we are now performing an even more careful monitoring of the study participants. Preliminary results showed that DL is a feasible

  12. 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

  13. 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.

  14. Age matters in the prevalence and clinical significance of ultra-high-risk for psychosis symptoms and criteria in the general population: Findings from the BEAR and BEARS-kid studies

    PubMed Central

    Schimmelmann, Benno G; Michel, Chantal; Martz-Irngartinger, Alexandra; Linder, Caroline; Schultze-Lutter, Frauke

    2015-01-01

    Early detection of psychosis is an important topic in psychiatry. Yet, there is limited information on the prevalence and clinical significance of high-risk symptoms in children and adolescents as compared to adults. We examined ultra-high-risk (UHR) symptoms and criteria in a sample of individuals aged 8-40 years from the general population of Canton Bern, Switzerland, enrolled from June 2011 to May 2014. The current presence of attenuated psychotic symptoms (APS) and brief intermittent psychotic symptoms (BLIPS) and the fulfillment of onset/worsening and frequency requirements for these symptoms in UHR criteria were assessed using the Structured Interview for Psychosis Risk Syndromes. Additionally, perceptive and non-perceptive APS were differentiated. Psychosocial functioning and current non-psychotic DSM-IV axis I disorders were also surveyed. Well-trained psychologists performed assessments. Altogether, 9.9% of subjects reported APS and none BLIPS, and 1.3% met all the UHR requirements for APS. APS were related to more current axis I disorders and impaired psychosocial functioning, indicating some clinical significance. A strong age effect was detected around age 16: compared to older individuals, 8-15-year olds reported more perceptive APS, that is, unusual perceptual experiences and attenuated hallucinations. Perceptive APS were generally less related to functional impairment, regardless of age. Conversely, non-perceptive APS were related to low functioning, although this relationship was weaker in those below age 16. Future studies should address the differential effects of perceptive and non-perceptive APS, and their interaction with age, also in terms of conversion to psychosis. PMID:26043337

  15. Non-invasive cardiac assessment in high risk patients (The GROUND study): rationale, objectives and design of a multi-center randomized controlled clinical trial

    PubMed Central

    de Vos, Alexander M; Rutten, Annemarieke; van de Zaag-Loonen, Hester J; Bots, Michiel L; Dikkers, Riksta; Buiskool, Robert A; Mali, Willem P; Lubbers, Daniel D; Mosterd, Arend; Prokop, Mathias; Rensing, Benno J; Cramer, Maarten J; van Es, H Wouter; Moll, Frans L; van de Pavoordt, Eric D; Doevendans, Pieter A; Velthuis, Birgitta K; Mackaay, Albert J; Zijlstra, Felix; Oudkerk, Matthijs

    2008-01-01

    Background Peripheral arterial disease (PAD) is a common disease associated with a considerably increased risk of future cardiovascular events and most of these patients will die from coronary artery disease (CAD). Screening for silent CAD has become an option with recent non-invasive developments in CT (computed tomography)-angiography and MR (magnetic resonance) stress testing. Screening in combination with more aggressive treatment may improve prognosis. Therefore we propose to study whether a cardiac imaging algorithm, using non-invasive imaging techniques followed by treatment will reduce the risk of cardiovascular disease in PAD patients free from cardiac symptoms. Design The GROUND study is designed as a prospective, multi-center, randomized clinical trial. Patients with peripheral arterial disease, but without symptomatic cardiac disease will be asked to participate. All patients receive a proper risk factor management before randomization. Half of the recruited patients will enter the 'control group' and only undergo CT calcium scoring. The other half of the recruited patients (index group) will undergo the non invasive cardiac imaging algorithm followed by evidence-based treatment. First, patients are submitted to CT calcium scoring and CT angiography. Patients with a left main (or equivalent) coronary artery stenosis of > 50% on CT will be referred to a cardiologist without further imaging. All other patients in this group will undergo dobutamine stress magnetic resonance (DSMR) testing. Patients with a DSMR positive for ischemia will also be referred to a cardiologist. These patients are candidates for conventional coronary angiography and cardiac interventions (coronary artery bypass grafting (CABG) or percutaneous cardiac interventions (PCI)), if indicated. All participants of the trial will enter a 5 year follow up period for the occurrence of cardiovascular events. Sequential interim analysis will take place. Based on sample size calculations about

  16. 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.

  17. How I treat high-risk myeloma.

    PubMed

    Lonial, Sagar; Boise, Lawrence H; Kaufman, Jonathan

    2015-09-24

    The treatment of patients with myeloma has dramatically changed over the past decade due in part to the development of new agents and myeloma-specific targets. Despite these advancements, a group for whom the long-term benefit remains less clear are patients with genetically or clinically defined high-risk myeloma. In order to successfully treat these patients, it is important to first identify these patients, treat them with aggressive combination therapy, and employ the use of aggressive long-term maintenance therapy. Future directions include the use of new immune-based treatments (antibodies or cellular-based therapies) as well as target-driven approaches. Until these treatment approaches are better defined, this review will provide a potential treatment approach for standard- and high-risk myeloma that can be followed using agents and strategies that are currently available with the goal of improving progression-free and overall survival for these patients today. PMID:26272217

  18. 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

  19. 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

  20. 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

  1. Critical role of bevacizumab scheduling in combination with pre-surgical chemo-radiotherapy in MRI-defined high-risk locally advanced rectal cancer: results of the branch trial

    PubMed Central

    Avallone, Antonio; Pecori, Biagio; Bianco, Franco; Aloj, Luigi; Tatangelo, Fabiana; Romano, Carmela; Granata, Vincenza; Marone, Pietro; Leone, Alessandra; Botti, Gerardo; Petrillo, Antonella; Caracò, Corradina; Iaffaioli, Vincenzo R.; Muto, Paolo; Romano, Giovanni; Comella, Pasquale; Budillon, Alfredo; Delrio, Paolo

    2015-01-01

    Background We have previously shown that an intensified preoperative regimen including oxaliplatin plus raltitrexed and 5-fluorouracil/folinic acid (OXATOM/FUFA) during preoperative pelvic radiotherapy produced promising results in locally advanced rectal cancer (LARC). Preclinical evidence suggests that the scheduling of bevacizumab may be crucial to optimize its combination with chemo-radiotherapy. Patients and methods This non-randomized, non-comparative, phase II study was conducted in MRI-defined high-risk LARC. Patients received three biweekly cycles of OXATOM/FUFA during RT. Bevacizumab was given 2 weeks before the start of chemo-radiotherapy, and on the same day of chemotherapy for 3 cycles (concomitant-schedule A) or 4 days prior to the first and second cycle of chemotherapy (sequential-schedule B). Primary end point was pathological complete tumor regression (TRG1) rate. Results The accrual for the concomitant-schedule was early terminated because the number of TRG1 (2 out of 16 patients) was statistically inconsistent with the hypothesis of activity (30%) to be tested. Conversely, the endpoint was reached with the sequential-schedule and the final TRG1 rate among 46 enrolled patients was 50% (95% CI 35%–65%). Neutropenia was the most common grade ≥3 toxicity with both schedules, but it was less pronounced with the sequential than concomitant-schedule (30% vs. 44%). Postoperative complications occurred in 8/15 (53%) and 13/46 (28%) patients in schedule A and B, respectively. At 5 year follow-up the probability of PFS and OS was 80% (95%CI, 66%–89%) and 85% (95%CI, 69%–93%), respectively, for the sequential-schedule. Conclusions These results highlights the relevance of bevacizumab scheduling to optimize its combination with preoperative chemo-radiotherapy in the management of LARC. PMID:26320185

  2. 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.

  3. Detection of High-Risk Atherosclerotic Plaque

    PubMed Central

    Fleg, Jerome L.; Stone, Gregg W.; Fayad, Zahi A.; Granada, Juan F.; Hatsukami, Thomas S.; Kolodgie, Frank D.; Ohayon, Jacques; Pettigrew, Roderic; Sabatine, Marc S.; Tearney, Guillermo; Waxman, Sergio; Domanski, Michael J.; Srinivas, Pothur R.; Narula, Jagat

    2013-01-01

    The leading cause of major morbidity and mortality in most countries around the world is atherosclerotic cardiovascular disease, most commonly caused by thrombotic occlusion of a high-risk coronary plaque resulting in myocardial infarction or cardiac death, or embolization from a high-risk carotid plaque resulting in stroke. The lesions prone to result in such clinical events are termed vulnerable or high-risk plaques, and their identification may lead to the development of pharmacological and mechanical intervention strategies to prevent such events. Autopsy studies from patients dying of acute myocardial infarction or sudden death have shown that such events typically arise from specific types of atherosclerotic plaques, most commonly the thin-cap fibroatheroma. However, the search in human beings for vulnerable plaques before their becoming symptomatic has been elusive. Recently, the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study demonstrated that coronary plaques that are likely to cause future cardiac events, regardless of angiographic severity, are characterized by large plaque burden and small lumen area and/or are thin-cap fibroatheromas verified by radiofrequency intravascular ultrasound imaging. This study opened the door to identifying additional invasive and noninvasive imaging modalities that may improve detection of high-risk atherosclerotic lesions and patients. Beyond classic risk factors, novel biomarkers and genetic profiling may identify those patients in whom noninvasive imaging for vulnerable plaque screening, followed by invasive imaging for risk confirmation is warranted, and in whom future pharmacological and/or device-based focal or regional therapies may be applied to improve long-term prognosis. PMID:22974808

  4. 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

  5. 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.

  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. PMID:19024978

  7. Prospective study of surveillance testing for metastasis in 100 high-risk uveal melanoma patients.

    PubMed

    Piperno-Neumann, S; Servois, V; Mariani, P; Plancher, C; Lévy-Gabriel, C; Lumbroso-Le Rouic, L; Couturier, J; Asselain, B; Desjardins, L; Cassoux, N

    2015-06-01

    Despite advances in the local treatment of UM, half of patients develop metastases typically to the liver with poor survival. Microscopic complete surgical resection (R0) of liver metastases improves survival in high selected patients. Early identification of high-risk patients might allow detection of asymptomatic metastases, and increase R0 liver surgery rate. From October 2006 to December 2009, we conducted a prospective study to detect early minimal lesions with 6-monthly liver function tests (LFTs) and liver MRI in 100 high-risk patients. High risk was defined by primary tumor clinical or genomic criteria: thickness>8mm or diameter>15 mm, or extra-scleral extension, or monosomy 3 by FISH or aCGH. With a median follow-up of 49 months, the 5-year metastasis-free survival and overall survival were 47 and 33%, respectively. Of the 60 patients who became metastatic, 50 (83%) had exclusive liver metastasis. LFTs screening had no sufficient accurary, but biannual MRI showed high predictive value to detect metastasis and select patients eligible for curative surgery: 25/50 underwent laparotomy and among them, 8/25 (32%) had a R0 surgery. Median survival after metastasis was 14 months, mean survival reached 40 months in the R0 resected population. Six-monthly liver MRI screening is recommended in patients with large tumors or genomic high risk in order to detect early patient candidates to complete resection of liver metastases. PMID:25978872

  8. High-risk prostate cancer: the role of surgical management.

    PubMed

    Morlacco, Alessandro; Karnes, R Jeffrey

    2016-06-01

    High-risk prostate cancer (HR Pca) is a highly heterogeneous disease from a biological and clinical standpoint, and it carries a significant chance of morbidity and mortality. Despite the impact of PSA screening, a significant number of men continue to present with high risk disease and need adequate management: clinical evidence shows that a considerable fraction on men with HR PCa can be actually cured with either uni- or multi-modality approaches. Surgical treatment, once considered unfeasible in this setting, is acquiring more and more diffusion in modern clinical practice. Herein we discuss the main treatment strategies for high-risk prostate cancer, providing an expert opinion on the role of surgical management and its outcomes in the most recent literature. PMID:27155934

  9. 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.

  10. Rationale for and Review of Neoadjuvant Therapy Prior to Radical Prostatectomy for Patients with High-Risk Prostate Cancer

    PubMed Central

    McKay, Rana R.; Choueiri, Toni K.; Taplin, Mary-Ellen

    2014-01-01

    Despite state of the art local therapy a significant portion of men with high-risk prostate cancer develop progressive disease. Neoadjuvant systemic therapy prior to radical prostatectomy (RP) is an approach which can potentially maximize survival outcomes in patients with localized disease. This approach is under investigation with a wide array of agents and provides an opportunity to assess pathologic and biologic activity of novel treatments. The aim of this review is to explore the past and present role of neoadjuvant therapy prior to definitive therapy with RP in patients with high-risk localized or locally advanced disease. The results of neoadjuvant ADT, including use of newer agents such as abiraterone and enzalutamide, are promising. Neoadjuvant chemotherapy, primarily with docetaxel, with or without ADT has also demonstrated efficacy in men with high-risk disease. Other novel agents targeting the vascular endothelial growth factor receptor (VEGFR), epidermal growth factor receptor (EGFR), platelet derived growth factor receptor (PDGFR), clusterin, and the immune system are currently under investigation and have led to variable results in early clinical trials. Despite optimistic data, approval of neoadjuvant therapy prior to RP in patients with high-risk prostate cancer will depend on positive results from well designed phase III trials. PMID:23943203

  11. Genetic variations in angiogenesis pathway genes associated with clinical outcome in localized gastric adenocarcinoma

    PubMed Central

    Lurje, G.; Husain, H.; Power, D. G.; Yang, D.; Groshen, S.; Pohl, A.; Zhang, W.; Ning, Y.; Manegold, P. C.; El-Khoueiry, A.; Iqbal, S.; Tang, L. H.; Shah, M. A.; Lenz, H.-J.

    2010-01-01

    Background: Angiogenesis has been attributed to be a well-recognized aspect of human cancer biology. As such, proteinase-activated receptor (PAR)-1, endostatin (ES) and interleukin-8 (IL-8) mediate the regulation of early-onset angiogenesis and in turn impact the process of tumor-growth and disease progression. Patients and methods: Formalin-fixed paraffin-embedded tissues were obtained from 137 patients with localized gastric cancer at University of Southern California and Memorial Sloan-Kettering Cancer Center medical facilities. DNA was extracted and genotyping was carried out using PCR–restriction fragment length polymorphism-based protocols. Results: In false discovery rate-adjusted univariate analysis, PAR-1 −506 ins/del (P < 0.001), ES +4349 G>A (P = 0.004), and IL-8 −251 T>A (P < 0.0001) were associated with time to tumor recurrence (TTR). Further, PAR-1 −506 ins/del and IL-8 −251 were associated with overall survival (OS). After adjusting for covariates, IL-8 remained significantly associated with TTR (adjusted P = 0.003) and OS (adjusted P = 0.049), whereas ES was significantly associated with TTR (adjusted P = 0.026). Conclusions: Polymorphisms in PAR-1, ES, and IL-8 may serve as independent molecular prognostic markers in patients with localized gastric adenocarcinoma. The assessment of the patients’ individual risk on the basis of interindividual genotypes may therefore help to identify patient subgroups at high risk for poor clinical outcome. PMID:19622587

  12. 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

  13. 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…

  14. 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

  15. [Local estrogen therapy--clinical implications--2012 update].

    PubMed

    Kokot-Kierepa, Marta; Bartuzi, Aleksandra; Kulik-Rechberger, Beata; Rechberger, Tomasz

    2012-10-01

    sustained-release intra-vaginal estradiol ring and a low-dose estradiol and estriol tablets are useful therapeutic options in the treatment of this condition. Moreover; a low dose treatment with a minimised systemic absorption rate may be considered in women with a history of breast cancer and associated severe vulvovaginal atrophy. It should be mentioned that vaginal lubricants once applied on a regular basis may also be effective in alleviating the symptoms of vaginal atrophy and should be offered to women wishing to avoid the use of local vaginal estrogen preparations and in cases where local estrogen therapy is contraindicated. Vaginal dehydroepiandrosterone (DHEA), vaginal testosterone, and tissue selective estrogen complexes are new, emerging therapies; however more clinical studies are necessary to confirm their efficacy and safety in the treatment of postmenopausal vulvovaginal atrophy. PMID:23383564

  16. Placental morphologic and functional imaging in high-risk pregnancies.

    PubMed

    Gudmundsson, Saemundur; Dubiel, Mariusz; Sladkevicius, Povilas

    2009-08-01

    The placenta is vital for fetal growth and development. Improvement in ultrasound and magnetic resonance imaging have improved our understanding of placental morphology that can be important as in the case of placental accrete/percreta. Functional imaging is presently mainly performed by the use of Doppler ultrasound and can give information on placental perfusion, which can be vital for clinical diagnosis. This review summarizes the present knowledge on placental imaging and it's clinical value in high-risk pregnancies. PMID:19631087

  17. Brachytherapy boost and cancer-specific mortality in favorable high-risk versus other high-risk prostate cancer

    PubMed Central

    Muralidhar, Vinayak; Xiang, Michael; Orio, Peter F.; Martin, Neil E.; Beard, Clair J.; Feng, Felix Y.; Hoffman, Karen E.

    2016-01-01

    Purpose Recent retrospective data suggest that brachytherapy (BT) boost may confer a cancer-specific survival benefit in radiation-managed high-risk prostate cancer. We sought to determine whether this survival benefit would extend to the recently defined favorable high-risk subgroup of prostate cancer patients (T1c, Gleason 4 + 4 = 8, PSA < 10 ng/ml or T1c, Gleason 6, PSA > 20 ng/ml). Material and methods We identified 45,078 patients in the Surveillance, Epidemiology, and End Results database with cT1c-T3aN0M0 intermediate- to high-risk prostate cancer diagnosed 2004-2011 treated with external beam radiation therapy (EBRT) only or EBRT plus BT. We used multivariable competing risks regression to determine differences in the rate of prostate cancer-specific mortality (PCSM) after EBRT + BT or EBRT alone in patients with intermediate-risk, favorable high-risk, or other high-risk disease after adjusting for demographic and clinical factors. Results EBRT + BT was not associated with an improvement in 5-year PCSM compared to EBRT alone among patients with favorable high-risk disease (1.6% vs. 1.8%; adjusted hazard ratio [AHR]: 0.56; 95% confidence interval [CI]: 0.21-1.52, p = 0.258), and intermediate-risk disease (0.8% vs. 1.0%, AHR: 0.83, 95% CI: 0.59-1.16, p = 0.270). Others with high-risk disease had significantly lower 5-year PCSM when treated with EBRT + BT compared with EBRT alone (3.9% vs. 5.3%; AHR: 0.73; 95% CI: 0.55-0.95; p = 0.022). Conclusions Brachytherapy boost is associated with a decreased rate of PCSM in some men with high-risk prostate cancer but not among patients with favorable high-risk disease. Our results suggest that the recently-defined “favorable high-risk” category may be used to personalize therapy for men with high-risk disease. PMID:26985191

  18. 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

  19. Underreporting High-Risk Prescribing Among Medicare Advantage Plans

    PubMed Central

    Cooper, Alicia L.; Kazis, Lewis E.; Dore, David D.; Mor, Vincent; Trivedi, Amal N.

    2016-01-01

    Background Although Medicare Advantage plans are required to report clinical performance using Healthcare Effectiveness Data and Information Set (HEDIS) quality indicators, the accuracy of plan-reported performance rates is unknown. Objective To compare calculated and reported rates of high-risk prescribing among Medicare Advantage plans. Design Cross-sectional comparison. Setting 172 Medicare Advantage plans. Patients A random sample of beneficiaries in 172 Medicare Advantage plans in 2006 (n = 177 227) and 2007 (n = 173 655). Measurements Plan-reported HEDIS rates of high-risk prescribing among elderly persons were compared with rates calculated from Medicare Advantage plans’ Part D claims by using the same measure specifications and source population. Results The mean rate of high-risk prescribing derived from Part D claims was 26.9% (95% CI, 25.9% to 28.0%), whereas the mean plan-reported rate was 21.1% (CI, 20.0% to 22.3%). Approximately 95% of plans underreported rates of high-risk prescribing relative to calculated rates derived from Part D claims. The differences in the calculated and reported rates negatively affected quality rankings for the plans that most accurately reported rates. For example, the 9 plans that reported rates of high-risk prescribing within 1 percentage point of calculated rates were ranked 43.4 positions lower when reported rates were used instead of calculated rates. Among 103 680 individuals present in both the sample of Part D claims and HEDIS data in 2006, Medicare Advantage plans incorrectly excluded 10.3% as ineligible for the HEDIS high-risk prescribing measure. Among those correctly included in the high-risk prescribing denominator, the reported rate of high-risk prescribing was 21.9% and the calculated rate was 26.2%. Limitation A single quality measure was assessed. Conclusion Medicare Advantage plans underreport rates of high-risk prescribing, suggesting a role for routine audits to ensure the validity of publicly reported

  20. Non-localization and localization ROC analyses using clinically based scoring

    NASA Astrophysics Data System (ADS)

    Paquerault, Sophie; Samuelson, Frank W.; Myers, Kyle J.; Smith, Robert C.

    2009-02-01

    . The results on the variance analysis differed from those observed in the other study setting. This investigation furthers our understanding of the relationships between non-localization-specific and localization-specific ROC assessment methodologies and their relevance to clinical practice.

  1. 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

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

    PubMed

    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; Gloeckner, 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

    2015-10-29

    Neuroblastoma is a malignant paediatric tumour of the sympathetic nervous system. 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 elusive. 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 type. 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

  3. Career goals in the high risk adolescent.

    PubMed

    Fleming, Charlene; Woods, Charles; Barkin, Shari L

    2006-10-01

    Possessing a career goal might serve as a protective factor for an adolescent's healthy development. This could be especially important in adolescents who engage in high risk behaviors. The relationship between high risk adolescents' future career goals and selected predictor variables were examined. Almost half (49%) the students indicated a career goal. Students who reported a job were 5.1-fold more likely to have listed a future career goal. Females, those aged 18 years, and those whose mothers were employed were twice as likely to have a career goal. Considerations for fostering career goals for high risk students are warranted. PMID:16968962

  4. 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

  5. High-risk sexual behaviors.

    PubMed

    Troussier, Thierry; Benghozi, Pierre; Ganem, Marc

    2012-01-01

    Adolescence is a time of life characterized by danger because of the many changes that occur, the many ties that are severed: ties to childhood, ties to the child's body as it begins to take on an adult appearance, ties to a once-familiar body image and psyche as hormones complete the transformation to adulthood, ties to an unconscious that is struggling to restructure itself anew. The creation of the romantic couple is a danger inherent in any human society. This text was written from the professional practices of each author in a multidisciplinary approach combining the approaches of public health, risk reduction, and sexual, psychological and clinical care of adolescents. How to help anticipate the dangers is to use preventive insurance verifying that security is guaranteed before committing. Risk-taking is accepting all the challenges that boost the self with oneself and with others. The risk is therefore also the commitment in love. It is still the risk to speak, to feel, to express feelings, choices, and refusal of unwanted sex. The ability of adolescents to play and defeat the risk by learning the ethical value not only to protect themselves from contracting AIDS, but also to protect others is part of the pedagogy of risk. This pedagogy of risk, as we have seen, includes three areas: information, care and initiation into love. Adolescents must be supported in their emergence by responsible people to protect them from the dangers ahead. The support is not only to prevent them from engaging in risky behavior, but to help them better manage their anxieties and support the fragility of their families in a network approach. Not knowing how to confront the risk stifles the chance of allowing the child to grow up to be independent and helps reassure parents who may resent being removed from the empowerment of their children. PMID:22846539

  6. 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

  7. High-risk corneal allografts: A therapeutic challenge.

    PubMed

    Yu, Tian; Rajendran, Vijayalakshmi; Griffith, May; Forrester, John V; Kuffová, Lucia

    2016-03-24

    Corneal transplantation is the most common surgical procedure amongst solid organ transplants with a high survival rate of 86% at 1-year post-grafting. This high success rate has been attributed to the immune privilege of the eye. However, mechanisms originally thought to promote immune privilege, such as the lack of antigen presenting cells and vessels in the cornea, are challenged by recent studies. Nevertheless, the immunological and physiological features of the cornea promoting a relatively weak alloimmune response is likely responsible for the high survival rate in "low-risk" settings. Furthermore, although corneal graft survival in "low-risk" recipients is favourable, the prognosis in "high-risk" recipients for corneal graft is poor. In "high-risk" grafts, the process of indirect allorecognition is accelerated by the enhanced innate and adaptive immune responses due to pre-existing inflammation and neovascularization of the host bed. This leads to the irreversible rejection of the allograft and ultimately graft failure. Many therapeutic measures are being tested in pre-clinical and clinical studies to counter the immunological challenge of "high-risk" recipients. Despite the prevailing dogma, recent data suggest that tissue matching together with use of systemic immunosuppression may increase the likelihood of graft acceptance in "high-risk" recipients. However, immunosuppressive drugs are accompanied with intolerance/side effects and toxicity, and therefore, novel cell-based therapies are in development which target host immune cells and restore immune homeostasis without significant side effect of treatment. In addition, developments in regenerative medicine may be able to solve both important short comings of allotransplantation: (1) graft rejection and ultimate graft failure; and (2) the lack of suitable donor corneas. The advances in technology and research indicate that wider therapeutic choices for patients may be available to address the worldwide

  8. Relapsing fever in pregnancy: analysis of high-risk factors.

    PubMed

    Melkert, P W

    1988-10-01

    The diagnosis of tick-borne relapsing fever was established in 27 pregnant patients by demonstration of Borrelia spirochaetes in a thick blood smear and the borrelia index was estimated to calculate the density of the spirochaetaemia. Clinical findings are described and compared with those reported from Rwanda. The results suggest that the density of the spirochaetaemia and the gestational age are the main high-risk factors. PMID:3191046

  9. Best self visualization method with high-risk youth.

    PubMed

    Schussel, Lorne; Miller, Lisa

    2013-08-01

    The healing process of the Best Self Visualization Method (BSM) is described within the framework of meditation, neuroscience, and psychodynamic theory. Cases are drawn from the treatment of high-risk youth, who have histories of poverty, survival of sexual and physical abuse, and/or current risk for perpetrating abuse. Clinical use of BSM is demonstrated in two case illustrations, one of group psychotherapy and another of individual therapy. PMID:23775428

  10. [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. PMID:23268886

  11. Intensive combined modality therapy including low-dose TBI in high-risk Ewing's sarcoma patients

    SciTech Connect

    Kinsella, T.J.; Glaubiger, D.; Diesseroth, A.; Makuch, R.; Waller, B.; Pizzo, P.; Glatstein, E.

    1983-12-01

    Twenty-four high-risk Ewing's sarcoma patients were treated on an intensive combined modality protocol including low-dose fractionated total body irradiaiton (TBI) and autologous bone marrow infusion (ABMI). Twenty patients (83%) achieved a complete clinical response to the primary and/or metastatic sites following induction therapy. The median disease-free interval was 18 months, and nine patients remain disease-free with a follow-up of 22 to 72 months. Local failure as a manifestation of initial relapse occurred in only three patients (15%), each having synchronous distant failure. Eight patients failed initially with only distant metastases, usually within 1-2 years following a complete clinical response. Two patterns of granulocyte recovery following consolidative therapy (including TBI and ABMI) were recognized. The time to platelet recovery was different for the groups with early and late granulocyte recovery. Patients with late recovery did not tolerate maintenance chemotherapy. However, there was no difference in disease-free and overall survival, when comparing the groups with early and late granulocyte recovery. It is concluded that these high-risk Ewing's sarcoma patients remain a poor-prognosis group in spite of intensive combined modality therapy including low-dose TBI. The control of microscopic systemic disease remains the major challenge to improving the cure rate. A new combined modality protocol with high-dose 'therapeutic' TBI (800 rad/2 fractions) is being used and the protocol design is outlined.

  12. 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.

  13. Pulsatile roller pump perfusion is safe in high risk patients.

    PubMed

    Kocakulak, M; Küçükaksu, S; Pişkin, E

    2004-05-01

    In this study, controllability, safety, blood cell depletion, and hemolysis of a pulsatile roller pump in high-risk patients was evaluated. Sarns 8000 roller pump (Sams, Terumo CVS, Ann Arbor, MI, USA) with a pulsatile control module was used as arterial pump in a clinical setting. Forty patients undergoing elective open heart surgery with high-risk either having chronically obstructive pulmonary disease or chronic renal failure were randomly included in the study to be operated on using pulsatile perfusion or non-pulsatile perfusion. Blood samples were withdrawn at induction of anesthesia, at the time of aortic clamping and de-clamping and at 1 hour and 24 hours following cessation of the bypass. Hematocrit and plasma free hemoglobin values were measured. We observed that the pulsatile roller pump perfusion and the extracorporeal circuit used in the clinical study is safe in high-risk patients undergoing cardiopulmonary bypass. We did not face any emboli, hemolysis, or technical problems. Pulsatile roller pump perfusion with Sarns 8000 heart-lung machine is a simple and reliable technique and can be easily applied during open heart surgery. PMID:15202823

  14. [Clinical testing of a new local corticoid: desoximethasone].

    PubMed

    Camarasa, G

    1975-01-01

    In a double-blind comparative trial on 37 patients with symetric dermatoses, the clinical effect of desoximetasone (0.25%) has been compared to fluocinolone acetonide (0.2%). After 7 days of treatment an improvement or cure of the lesions could be seen in 34 patients treated with desoximetasone, and only on 22 patients treated with fluocinolone acetonide (0.2%). The better effect of desoximetasone was especially evident on erythema and pruritus. Differences between the drugs were statistically significant. PMID:132780

  15. 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

  16. Improved Clinical Outcomes With High-Dose Image Guided Radiotherapy Compared With Non-IGRT for the Treatment of Clinically Localized Prostate Cancer

    SciTech Connect

    Zelefsky, Michael J.; Kollmeier, Marisa; Cox, Brett; Fidaleo, Anthony; Sperling, Dahlia; Pei, Xin; Carver, Brett; Coleman, Jonathan; Lovelock, Michael; Hunt, Margie

    2012-09-01

    Purpose: To compare toxicity profiles and biochemical tumor control outcomes between patients treated with high-dose image-guided radiotherapy (IGRT) and high-dose intensity-modulated radiotherapy (IMRT) for clinically localized prostate cancer. Materials and Methods: Between 2008 and 2009, 186 patients with prostate cancer were treated with IGRT to a dose of 86.4 Gy with daily correction of the target position based on kilovoltage imaging of implanted prostatic fiducial markers. This group of patients was retrospectively compared with a similar cohort of 190 patients who were treated between 2006 and 2007 with IMRT to the same prescription dose without, however, implanted fiducial markers in place (non-IGRT). The median follow-up time was 2.8 years (range, 2-6 years). Results: A significant reduction in late urinary toxicity was observed for IGRT patients compared with the non-IGRT patients. The 3-year likelihood of grade 2 and higher urinary toxicity for the IGRT and non-IGRT cohorts were 10.4% and 20.0%, respectively (p = 0.02). Multivariate analysis identifying predictors for grade 2 or higher late urinary toxicity demonstrated that, in addition to the baseline Internatinoal Prostate Symptom Score, IGRT was associated with significantly less late urinary toxicity compared with non-IGRT. The incidence of grade 2 and higher rectal toxicity was low for both treatment groups (1.0% and 1.6%, respectively; p = 0.81). No differences in prostate-specific antigen relapse-free survival outcomes were observed for low- and intermediate-risk patients when treated with IGRT and non-IGRT. For high-risk patients, a significant improvement was observed at 3 years for patients treated with IGRT compared with non-IGRT. Conclusions: IGRT is associated with an improvement in biochemical tumor control among high-risk patients and a lower rate of late urinary toxicity compared with high-dose IMRT. These data suggest that, for definitive radiotherapy, the placement of fiducial markers

  17. 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.

  18. Student Assistance Programs and High Risk Youth.

    ERIC Educational Resources Information Center

    Casale, Jenni

    This manual discusses a method for developing a comprehensive drug abuse prevention and intervention program for students in special education. The first section contains introductory material regarding high risk students in general and implications for special education. The second section outlines material on specific types of high-risk…

  19. Teaching Art to High Risk Groups.

    ERIC Educational Resources Information Center

    Rossol, Monona

    The role of art therapy is considered in working with such high risk groups as the institutionalized, mentally retarded, elderly, visually impaired, physically handicapped, asthmatic, hyper- and hypo-active children, hearing impaired, and patients on mind altering drugs. The special risks of infectious diseases (such as serum hepatitis), and…

  20. The High Risk Freshman Chemist Revisited

    ERIC Educational Resources Information Center

    Pickering, Miles

    1977-01-01

    Reports on the long term comparison between a group of "high risk" college freshmen who were given a supplemental chemistry course and another group who did not have the course. The supplemental course was found to produce only a short term rise in students' grades. (MR)

  1. 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,...

  2. Rosuvastatin versus atorvastatin in achieving lipid goals in patients at high risk for cardiovascular disease in clinical practice: A randomized, open-label, parallel-group, multicenter study (DISCOVERY Alpha study)

    PubMed Central

    Binbrek, Azan S.; Elis, Avishay; Al-Zaibag, Muayed; Eha, Jaan; Keber, Irena; Cuevas, Ada M.; Mukherjee, Swati; Miller, Thomas R.

    2006-01-01

    Background: The majority of clinical trials investigating the clinical benefits of lipid-lowering therapies (LLTs) have focused on North American or western and nothern European populations. Therefore, it is timely to confirm the efficacy of these agents in other patient populations in routine clinical practice. Objective: The aim of the Direct Statin COmparison of low-density lipoprotein cholesterol (LDL-C) Values: an Evaluation of Rosuvastatin therapY (DISCOVERY) Alpha study was to compare the effects of rosuvastatin 10 mg with those of atorvastatin 10 mg in achieving LDL-C goals in the Third Joint Task Force of European and Other Societies on Cardiovascular Disease Prevention in Clinical Practice guidelines. Methods: This randomized, open-label, parallel-group study was conducted at 93 centers in eastern Europe (Estonia, Latvia, Romania, Russia, Slovenia), Central and South America (Chile, Dominican Republic, El Salvador, Guatemala, Honduras, Nicaragua, Panama), and the Middle East (Israel, Kuwait, Saudi Arabia, United Arab Emirates). Male and female patients aged ≥18 years with primary hypercholesterolemia (LDL-C level, >135 mg/dL if LLT-naive or ≥120 mg/dL if switching statins; triglyceride [TG] level, <400 mg/dL) and a 10-year coronary heart disease (CHD) risk >20% or a history of CHD or other established atherosclerotic disease were eligible for inclusion in the study. Patients were randomly assigned to receive rosuvastatin 10-mg or atorvastatin 10-mg tablets QD for 12 weeks. No formal statistical analyses or comparisons were performed on lipid changes between switched and LLT-naive patients because of the different lipid inclusion criteria for these patients. The primary end point was the proportion of patients achieving 1998 European LDL-C goals after 12 weeks of treatment. A subanalysis was performed to assess the effects of statins in patients who had received previous statin treatment versus those who were LLT-naive. Tolerability was assessed using

  3. 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

  4. 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

  5. Prognostic associations of 25 hydroxy vitamin D in NCIC CTG MA.21, a phase III adjuvant randomized clinical trial of three chemotherapy regimens in high-risk breast cancer.

    PubMed

    Lohmann, Ana Elisa; Chapman, Judy-Anne W; Burnell, Margot J; Levine, Mark Norman; Tsvetkova, Elena; Pritchard, Kathleen I; Gelmon, Karen A; O'Brien, Patti; Han, Lei; Rugo, Hope S; Albain, Kathy S; Perez, Edith A; Vandenberg, Theodore A; Chalchal, Haji I; Sawhney, Ravinder Pal Singh; Shepherd, Lois E; Goodwin, Pamela Jean

    2015-04-01

    Low vitamin D levels have been associated with poor breast cancer outcomes in observational studies. We examined the association of vitamin D blood levels with relapse-free survival (RFS), breast cancer-specific survival (BCSS), and overall survival (OS) in the MA.21 randomized clinical trial. Fasting blood was collected pre-chemotherapy in 934/2104 (44.4 %) of subjects; 25 hydroxy vitamin D was measured (radioimmunoassay, Diasorin) in one batch. Vitamin D was assessed as a transformed continuous factor, and categorically (quartiles and clinical classifications). Univariate and multivariate prognostic analyses (adjusted for treatment, stratification factors, and baseline imbalances) were performed using Cox models. Most patients were young (median 47.8 years), white (91.6 %) and premenopausal (69.4 %) with grade III (52 %), HER2 negative or missing (89.5 %), ER positive (61.9 %), T1-2 (89.4 %), N + (72.7 %) breast cancer. Compared to the full population, those with vitamin D levels were more likely to be white, PS 1 or 2, to have undergone mastectomy, and to have an ER + tumor. Mean vitamin D was 69.7 nmol/L (27.9 ng/ml) and did not vary by tumor subtype. The majority (80.5 %) had levels >50 nmol/L (20 ng/ml), considered adequate by Institute of Medicine. Continuous vitamin D was not multivariately associated with RFS, BCSS, or OS (p = 0.36, 0.26, 0.33, respectively); categorical vitamin D was also not associated with outcome. Vitamin D associations with RFS did not differ within ER/HER2 subgroups. There was no evidence that vitamin D blood level was associated with RFS, BCSS, and OS in MA.21; the majority of subjects had adequate vitamin D levels at study entry. PMID:25833209

  6. The evolution of a clinical database: from local to standardized clinical languages.

    PubMed

    Prophet, C M

    2000-01-01

    For more than twenty years, the University of Iowa Hospitals and Clinics Nursing Informatics (UIHC NI) has been developing a clinical database to support patient care planning and documentation in the INFORMM NIS (Information Network for Online Retrieval & Medical Management Nursing Information System). Beginning in 1992, the database content was revised to standardize orders and to incorporate the Standardized Nursing Languages (SNLs) of the North American Nursing Diagnosis Association (NANDA), Nursing Diagnosis Extension Classification (NDEC), Nursing Interventions Classification (NIC), and Nursing Outcomes Classification (NOC). This paper reports the results of the database revision as well as recent usage data, new user selection methods for clinical content, and the advantages of a database utilizing SNLs. PMID:11079966

  7. 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.

  8. 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

  9. 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.

  10. What is High Risk Surgery? Development of a List of High Risk Operations for Patients Age 65 and Older

    PubMed Central

    Schwarze, Margaret L.; Barnato, Amber E.; Rathouz, Paul J.; Zhao, Qianqian; Neuman, Heather B.; Winslow, Emily R.; Kennedy, Gregory D.; Hu, Yue-Yung; Dodgion, Christopher M.; Kwok, Alvin C.; Greenberg, Caprice C.

    2015-01-01

    list of “high risk” operations can be used to standardize the definition of high risk surgery in quality and outcomes-based studies and design targeted clinical interventions. PMID:25692282

  11. Gynecological surveillance in high risk women.

    PubMed

    Dilley, James; Gentry-Maharaj, Aleksandra; Menon, Usha

    2016-10-01

    In high-risk women, risk reducing surgery remains the cornerstone of prevention. However, the resulting premature menopause has led to continued efforts to develop effective screening strategies for those who wish to delay or avoid surgery. This review describes how the screening of women at risk of ovarian and endometrial cancer has evolved to its current state. Serial monitoring of CA125 is core to ovarian cancer screening and most recent studies have used the Risk of Ovarian Cancer Algorithm (ROCA) to interpret CA125 profile. The additional use of a second tumour marker, HE4, is reviewed. The results to date of key ovarian cancer screening studies in high-risk women are summarised ahead of their concluding findings due later in 2016. The role of both ultrasound and endometrial sampling in the management of women at increased risk of endometrial cancer is outlined. Exciting new methodology, which could help shape the future of screening is investigated. The article summarises the current recommendations and guidelines from recognised international bodies to aid the clinician with management of these women. PMID:26930388

  12. 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.

  13. 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

  14. Noninvasive cerebral perfusion imaging in high-risk neonates.

    PubMed

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

    2010-02-01

    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

  15. Management of dyslipidemia in the high-risk patient.

    PubMed

    Stein, Evan A

    2002-12-01

    Lipid-lowering agents have been shown to reduce morbidity and mortality associated with coronary heart disease (CHD), particularly in high-risk patients. The identification and treatment of these patients should therefore be a high priority for clinicians. Guidelines from medical organizations, such as the National Cholesterol Education Program Adult Treatment Panel (NCEP ATP) and the American Diabetes Association (ADA), suggest that patients with low-density lipoprotein cholesterol (LDL-C) levels > or =130 mg/dL, and perhaps even those with levels > or =100 mg/dL, should receive drug therapy. Optimal LDL-C levels have been set at <100 mg/dL and <115 mg/dL for high-risk patients by US and European guidelines, respectively. However, a recent survey shows that only about 20% of high-risk patients currently meet these goals. In order to achieve therapeutic targets for LDL-C, the statins are the foundation of treatment, as they are the most effective and best-tolerated form of lipid-lowering therapy. Other therapeutic options include bile acid sequestrants, niacin, and plant stanols, although seldom as monotherapy. Combination therapy with a statin and one of these other lipid-lowering agents can be useful in patients who are unable to achieve target lipid levels through monotherapy. There remains, however, a need for additional agents. Some of the new options for reducing LDL-C levels that may be available in the near future include 2 new statins, pitavastatin and rosuvastatin. In patients with heterozygous familial hypercholesterolemia, rosuvastatin, which is currently under review by the Food and Drug Administration (FDA), has been shown to produce significantly greater reductions in LDL-C than atorvastatin over its full dose range. In comparative clinical trials, it has also enabled more patients with primary hypercholesterolemia to meet lipid goals than atorvastatin, simvastatin, and pravastatin. Inhibitors of bile acid transport or cholesterol absorption may also

  16. [High Risk Federal Program Areas]: An Overview. High-Risk Series.

    ERIC Educational Resources Information Center

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

    This report reviews the status of government agencies and operations that have been identified as at "high risk" for waste, fraud, abuse, and mismanagement; describes successful progress in some agencies; and looks at recent reform legislation. Six categories being targeted include accountability of defense programs, ensuring that all revenues are…

  17. Virtual clinical trials using inserted pathology in clinical images: investigation of assumptions for local glandularity and noise

    NASA Astrophysics Data System (ADS)

    Rashidnasab, Alaleh; Elangovan, Premkumar; Mackenzie, Alistair; Dance, David R.; Young, Kenneth C.; Bosmans, Hilde; Wells, Kevin

    2015-03-01

    Virtual clinical trials have been proposed as a viable alternative to clinical trials for testing and comparing the performance of breast imaging systems. One of the main simulation methodologies used in virtual trials employs clinical images of patients in which simulated models of cancer are inserted using a physics-based template multiplication technique. The purpose of this work is to investigate two assumptions commonly considered in this simulation approach: Firstly, given the absence of useful depth information in a clinical situation, an average measure of the local breast glandularity is commonly used as an estimate of the breast composition at the insertion site; secondly, it is also assumed that any change in the relative noise in the image at the insertion site, after insertion of a mass, is negligible. In order to test the validity of these assumptions, spheres representing idealised masses and anthropomorphic computational breast phantoms with perfect prior knowledge of local tissue composition and distribution were used. Results from several region of interest (ROI) insertions demonstrated a lack of variation obtained in contrast with insertion depth using the template multiplication insertion method as compared to the true depth-wise variation contrast values obtained from voxel replacement in a heterogeneous phantom. It was also found that the amount of noise is underestimated by insertion of spherical masses using template multiplication method by 8% - 29% compared to voxel replacement for the test conditions. This resulted in up to 12% variation in contrast-to-noise-ratio (CNR) values between template multiplication and voxel replacement methods.

  18. 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.

  19. 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

  20. Preoperative Treatment of Locally Advanced Rectal Cancer: Assets and Drawbacks of Short Course and Long Course in Clinical Practice.

    PubMed

    Ngan, Samuel Y

    2016-07-01

    Preoperative short-course radiotherapy and preoperative long-course chemoradiotherapy are the standards of care for high-risk rectal cancer in different parts of the world. Both treatments are effective in local control and carry a low morbidity. The advantage of short course is its simplicity, whereas long course has the advantage of downsizing tumors thus increasing the chance of sphincter preservation. Although 2 randomized trials comparing short course and long course have been performed, the better form of preoperative treatment remains a subject of discussion. This article reviews the evidence supporting each approach, and it discusses their relative merits and future directions. PMID:27238469

  1. The Adoption and Discontinuation of Clinical Services by Local Health Departments

    PubMed Central

    Rodriguez, Hector P.

    2014-01-01

    Objectives. We identified factors associated with local health department (LHD) adoption and discontinuation of clinical services. Methods. We used multivariate regression with 1997 and 2008 LHD survey and area resource data to examine factors associated with LHDs maintaining or offering more clinical services (adopter) versus offering fewer services (discontinuer) over time and with the number of clinical services discontinued among discontinuers. Results. Few LHDs (22.2%) were adopters. The LHDs were more likely to be adopters if operating in jurisdictions with local boards of health and not in health professional shortage areas, and if experiencing larger percentage increase in non-White population and Medicaid managed care penetration. Discontinuer LHDs eliminated more clinical services in jurisdictions that decreased core public health activities’ scope over time, increased community partners’ involvement in these activities, had larger increases in Medicaid managed care penetration, and had lower LHD expenditures per capita over time. Conclusions. Most LHDs are discontinuing clinical services over time. Those that cover a wide range of core public health functions are less likely to discontinue services when residents lack care access. Thus, the impact of discontinuation on population health may be mitigated. PMID:24228663

  2. 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

  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. Clinical assessment of three-dimensional ultrasound prostate localization for external beam radiotherapy

    SciTech Connect

    Orton, Nigel P.; Jaradat, Hazim A.; Tome, Wolfgang A.

    2006-12-15

    Three-dimensional ultrasound localization has been performed for external beam prostate treatments at our institution since September 2001. This article presents data from the daily shifts for 221 patients and 5005 fractions, and the results of tests performed to assess the system's performance under clinical conditions. Three tests are presented: (1) To measure the accuracy of the shifts, eight patients treated on a helical tomotherapy machine were localized daily using both ultrasound (US) and a megavoltage computed tomography (MVCT) scan. Comparison of the shifts showed that US localization improved alignment for six of the eight patients when compared to alignment using skin marks alone. The mean US-MVCT vector for these six patients was 3.1{+-}1.3 mm, compared to 5.1{+-}2.1 mm between the MVCT and the skin marks. The other two patients were identified as poor candidates for US prior to their first treatment fraction. (2) To assess the extent of intrafraction motion, US localization was repeated after treatment for six patients and a total of 29 fractions. The mean intrafraction prostate shift was 1.9{+-}1.0 mm, and the shift was within the 3 mm localization uncertainty [Tome et al., Med. Phys. 29, 1781-1788 (2002); in New Technologies in Radiotion Oncology, edited by W. Schlegel, T. Bortfelde, and A. Grosu (Springer, Berlin, 2005)] of the system for 25 of 29 fractions. (3) To assess the interuser variation in shifts, four experienced operators independently localized five patients for five consecutive fractions. The standard deviation of the users' shifts was found to be approximately the same as the system's localization uncertainty. For shifts larger than the system localization uncertainty, the standard deviation of the users' shifts was nearly always much smaller than the mean shift. Taken together with the results of the US-MVCT comparison, this indicates that the shifts improved patient localization despite differences between users.

  5. 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

  6. 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.

  7. Stereotactic Ablative Radiotherapy for the Treatment of Clinically Localized Renal Cell Carcinoma

    PubMed Central

    Campbell, Scott P.; Song, Daniel Y.; Pierorazio, Phillip M.; Allaf, Mohamad E.; Gorin, Michael A.

    2015-01-01

    Thermal ablation is currently the most studied treatment option for medically inoperable patients with clinically localized renal cell carcinoma (RCC). Recent evidence suggests that stereotactic ablative radiotherapy (SABR) may offer an effective noninvasive alternative for these patients. In this review, we explore the current literature on SABR for the primary treatment of RCC and make recommendations for future studies so that an accurate comparison between SABR and other ablative therapies may be conducted. PMID:26640488

  8. 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

  9. High-risk sex offenders may not be high risk forever.

    PubMed

    Hanson, R Karl; Harris, Andrew J R; Helmus, Leslie; Thornton, David

    2014-10-01

    This study examined the extent to which sexual offenders present an enduring risk for sexual recidivism over a 20-year follow-up period. Using an aggregated sample of 7,740 sexual offenders from 21 samples, the yearly recidivism rates were calculated using survival analysis. Overall, the risk of sexual recidivism was highest during the first few years after release, and decreased substantially the longer individuals remained sex offense-free in the community. This pattern was particularly strong for the high-risk sexual offenders (defined by Static-99R scores). Whereas the 5-year sexual recidivism rate for high-risk sex offenders was 22% from the time of release, this rate decreased to 4.2% for the offenders in the same static risk category who remained offense-free in the community for 10 years. The recidivism rates of the low-risk offenders were consistently low (1%-5%) for all time periods. The results suggest that offense history is a valid, but time-dependent, indicator of the propensity to sexually reoffend. Further research is needed to explain the substantial rate of desistance by high-risk sexual offenders. PMID:24664250

  10. 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…

  11. 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…

  12. 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:…

  13. Longitudinal changes in hippocampal volume in the Edinburgh High Risk Study of Schizophrenia.

    PubMed

    Bois, C; Levita, L; Ripp, I; Owens, D C G; Johnstone, E C; Whalley, H C; Lawrie, S M

    2016-06-01

    Schizophrenia is associated with structural brain abnormalities that are likely to be present before disease onset. It remains unclear to what extent these represent general vulnerability indicators or are associated with the developing clinical state itself. It also remains unclear whether such state or trait alterations may be evident at any given time-point, or whether they progress over time. To investigate this, structural brain scans were acquired at two time-points (mean scan-interval 1.87years) in a cohort of young unaffected individuals at high familial risk of schizophrenia (baseline, n=142; follow-up, n=64) and healthy controls (baseline, n=36; follow-up, n=18). Sub-cortical reconstructions of the hippocampus and amygdala were generated using the longitudinal pipeline available with Freesurfer. The high risk cohort was subdivided into individuals that remained well during the study (HR[well], baseline, n=68; follow-up, n=30), transient and/or partial symptoms that were insufficient to support a formal diagnosis (HR[symp], baseline, n=57; follow-up, n=26) and individuals that subsequently developed schizophrenia according to ICD-10 criteria (HR[ill], baseline, n=17; follow-up, n=8). Longitudinal change in the hippocampus and amygdala was compared, focusing first on overall differences between high-risk individuals and controls and then on sub-group differences within the high-risk cohort. We found a significantly altered developmental trajectory for all high risk individuals compared to controls, with controls showing a significant increase in hippocampal volume over time compared to those at high risk. We did not find evidence of altered longitudinal trajectories based on clinical outcome within the high risk cohort. These results suggest that an altered developmental trajectory of hippocampal volume is associated with a general familial predisposition to develop schizophrenia, as this alteration was not related to subsequent clinical outcome. PMID

  14. 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

  15. Rates of violence in patients classified as high risk by structured risk assessment instruments

    PubMed Central

    Singh, Jay P.; Fazel, Seena; Gueorguieva, Ralitza; Buchanan, Alec

    2014-01-01

    Background Rates of violence in persons identified as high risk by structured risk assessment instruments (SRAIs) are uncertain and frequently unreported by validation studies. Aims To analyse the variation in rates of violence in individuals identified as high risk by SRAIs. Method A systematic search of databases (1995-2011) was conducted for studies on nine widely used assessment tools. Where violence rates in high-risk groups were not published, these were requested from study authors. Rate information was extracted, and binomial logistic regression was used to study heterogeneity. Results Information was collected on 13 045 participants in 57 samples from 47 independent studies. Annualised rates of violence in individuals classified as high risk varied both across and within instruments. Rates were elevated when population rates of violence were higher, when a structured professional judgement instrument was used and when there was a lower proportion of men in a study. Conclusions After controlling for time at risk, the rate of violence in individuals classified as high risk by SRAIs shows substantial variation. In the absence of information on local base rates, assigning predetermined probabilities to future violence risk on the basis of a structured risk assessment is not supported by the current evidence base. This underscores the need for caution when such risk estimates are used to influence decisions related to individual liberty and public safety. PMID:24590974

  16. 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.

  17. 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.

  18. Clinical and Epidemiologic Profile of Cutaneous Leishmaniasis in Colombian Children: Considerations for Local Treatment

    PubMed Central

    Blanco, Victor M.; Cossio, Alexandra; Martinez, Javier D.; Saravia, Nancy Gore

    2013-01-01

    Treatment alternatives have seldom been evaluated in children with cutaneous leishmaniasis (CL). We examine the clinical/epidemiological profile of children with CL considering international guidelines for local treatment. Descriptive analyses were conducted using International Center for Medical Research and Training (CIDEIM) case reports of parasitologically diagnosed patients ≤ 14 years of age from 2004 to 2010. Eligibility for local treatment based on World Health Organization/Pan American Health Organization (WHO/PAHO) criteria was determined. Among 380 children, 90% presented lesions of < 3 months duration, 54% presented single lesions < 30 mm in diameter, and 45% were ≤ 5 years old. Lesions on the head and neck were more frequent among children 0–5 years, and lesions below the head/neck were more frequent among 11- to 14-year-old children (P = 0.004). Using PAHO and WHO criteria, 26% and 53% of children, respectively, were eligible for local treatment. Recommended local treatments for New World CL have potential but limited applicability in children. Individual risk–benefit assessment and effectiveness data in children may increase eligibility. PMID:23798581

  19. 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. PMID:26133479

  20. 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

  1. Current status of local therapy in malignant gliomas--a clinical review of three selected approaches.

    PubMed

    Juratli, Tareq A; Schackert, Gabriele; Krex, Dietmar

    2013-09-01

    Malignant gliomas are the most frequently occurring, devastating primary brain tumors, and are coupled with a poor survival rate. Despite the fact that complete neurosurgical resection of these tumors is impossible in consideration of their infiltrating nature, surgical resection followed by adjuvant therapeutics, including radiation therapy and chemotherapy, is still the current standard therapy. Systemic chemotherapy is restricted by the blood-brain barrier, while methods of local delivery, such as with drug-impregnated wafers, convection-enhanced drug delivery, or direct perilesional injections, present attractive ways to circumvent these barriers. These methods are promising ways for direct delivery of either standard chemotherapeutic or new anti-cancer agents. Several clinical trials showed controversial results relating to the influence of a local delivery of chemotherapy on the survival of patients with both recurrent and newly diagnosed malignant gliomas. Our article will review the development of the drug-impregnated release, as well as convection-enhanced delivery and the direct injection into brain tissue, which has been used predominantly in gene-therapy trials. Further, it will focus on the use of convection-enhanced delivery in the treatment of patients with malignant gliomas, placing special emphasis on potential shortcomings in past clinical trials. Although there is a strong need for new or additional therapeutic strategies in the treatment of malignant gliomas, and although local delivery of chemotherapy in those tumors might be a powerful tool, local therapy is used only sporadically nowadays. Thus, we have to learn from our mistakes in the past and we strongly encourage future developments in this field. PMID:23694764

  2. 15 CFR 14.14 - High risk special award conditions.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 15 Commerce and Foreign Trade 1 2011-01-01 2011-01-01 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...

  3. 15 CFR 14.14 - High risk special award conditions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 15 Commerce and Foreign Trade 1 2013-01-01 2013-01-01 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...

  4. 15 CFR 14.14 - High risk special award conditions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 15 Commerce and Foreign Trade 1 2012-01-01 2012-01-01 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...

  5. 15 CFR 14.14 - High risk special award conditions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 15 Commerce and Foreign Trade 1 2014-01-01 2014-01-01 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...

  6. 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...

  7. 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....

  8. Social work services in a high-risk nursery.

    PubMed

    Sheridan, M S; Johnson, D R

    1976-05-01

    Why should a social worker be on the team of a neonatal intensive-care nursery? Helping parents cope with the crises that arise with high-risk births is only one important reason. Ameliorating staff stress is another. Also, by following up the high-risk babies, the social worker has an opportunity to play a preventive role. PMID:185126

  9. 40 CFR 35.6790 - High risk recipients.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... described in 40 CFR 31.12. Requirements for Administering a Superfund State Contract (SSC) ... 40 Protection of Environment 1 2014-07-01 2014-07-01 false High risk recipients. 35.6790 Section... Actions Other Administrative Requirements for Cooperative Agreements § 35.6790 High risk recipients....

  10. 40 CFR 35.6790 - High risk recipients.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... described in 40 CFR 31.12. Requirements for Administering a Superfund State Contract (SSC) ... 40 Protection of Environment 1 2012-07-01 2012-07-01 false High risk recipients. 35.6790 Section... Actions Other Administrative Requirements for Cooperative Agreements § 35.6790 High risk recipients....

  11. 40 CFR 35.6790 - High risk recipients.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... described in 40 CFR 31.12. Requirements for Administering a Superfund State Contract (SSC) ... 40 Protection of Environment 1 2011-07-01 2011-07-01 false High risk recipients. 35.6790 Section... Actions Other Administrative Requirements for Cooperative Agreements § 35.6790 High risk recipients....

  12. 40 CFR 35.6790 - High risk recipients.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... described in 40 CFR 31.12. Requirements for Administering a Superfund State Contract (SSC) ... 40 Protection of Environment 1 2013-07-01 2013-07-01 false High risk recipients. 35.6790 Section... Actions Other Administrative Requirements for Cooperative Agreements § 35.6790 High risk recipients....

  13. 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.

  14. Efficacy of Robotic-Assisted Prostatectomy in Localized Prostate Cancer: A Systematic Review of Clinical Trials

    PubMed Central

    Sandoval Salinas, Carolina; González Rangel, Andrés L.; Cataño Cataño, Juan G.; Fuentes Pachón, Juan C.; Castillo Londoño, Juan S.

    2013-01-01

    Background. Radical prostatectomy is an effective treatment for clinically localized prostate cancer. The three approaches in current use have been extensively compared in observational studies, which have methodological limitations. Objective. To compare the efficacy and safety of three radical prostatectomy approaches in patients with localized prostate cancer: open, laparoscopic, and robotic-assisted laparoscopic surgery. Materials and Methods. A systematic review of the literature was carried out. Databases MEDLINE, EMBASE, LILACS, and CENTRAL were searched for randomized clinical trials that directly compared two or more radical prostatectomy approaches. Selection criteria, methodological rigor, and risk of bias were evaluated by two independent researchers using Cochrane Collaboration's tools. Results. Three trials were included. In one study, laparoscopic surgery was associated with fewer blood loss and transfusion rates than the open procedure, in spite of longer operating time. The other two trials compared laparoscopic and robotic-assisted surgery in which no differences in perioperative outcomes were detected. Nevertheless, robotic-assisted prostatectomy showed more favorable erectile function and urinary continence recovery. Conclusion. At the present time, no clear advantage can be attributed to any of the existing prostatectomy approaches in terms of oncologic outcomes. However, some differences in patient-related outcomes favor the newer methods. Larger trials are required. PMID:24312127

  15. The abscopal effect of local radiotherapy: using immunotherapy to make a rare event clinically relevant

    PubMed Central

    Reynders, Kobe; Illidge, Tim; Siva, Shankar; Chang, Joe Y.; De Ruysscher, Dirk

    2016-01-01

    Background Recently, immunologic responses to localized irradiation are proposed as mediator of systemic effects after localized radiotherapy (called the abscopal effect). Here, we give an overview of both preclinical and clinical data about the abscopal effect in particular and link them with the immunogenic properties of radiotherapy. Methods We searched Medline and Embase with the search term “abscopal” from 1960 until July, 2014. Only papers that cover radiotherapy in an oncological setting were selected and only if no concurrent cytotoxic treatment was given. Targeted immune therapy was allowed. Results Twenty-three case reports, one retrospective study and 13 preclinical papers were selected. Eleven preclinical papers used a combination of immune modification and radiotherapy to achieve abscopal effects. Patient age range (28 to 83 years) and radiation dose (median total dose 32 Gy) varied. Fractionation size ranged from 1,2 Gy to 26 Gy. Time to documented abscopal response ranged between less than one and 24 months, with a median reported time of 5 months. Once an abscopal response was achieved, a median time of 13 months went by before disease progression occurred or the reported follow-up ended (range 3–39 months). Conclusion Preclinical data points heavily towards a strong synergy between radiotherapy and immune treatments. Recent case reports already illustrate that such a systemic effect of radiotherapy is possible when enhanced by targeted immune treatments. However, several issues concerning dosage, timing, patient selection and toxicity need to be resolved before the abscopal effect can become clinically relevant. PMID:25872878

  16. 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

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. Establishing a program for individuals at high risk for breast cancer.

    PubMed

    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

  3. 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.

  4. 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.

  5. [Administrative databases of the Local Health Unit: possible use for clinical governance of chronic kidney disease].

    PubMed

    Degli Esposti, Luca; Sturani, Alessandra; Quintaliani, Giuseppe; Buda, Stefano; Degli Esposti, Ezio

    2014-01-01

    Nowadays a large amount of medical data are available, although they are not always homogeneous, they arise from different backgrounds and are used for different purposes. The aggregation of these data could give huge boost to the epidemiology and, in particular, to nephrology. In many parts of Italy there is the aim to reorganize the hospital health care, as well as the territorial setting. In this framework, the role of nephrology is evaluated without data to support the ongoing decisions, therefore the linkage among the data stored in the administrative and clinical databases of the Local Health Unit could contribute to the planning of nephrological (but not only) activities, in order to ensure the best cost-effectiveness possible for each different reality. PMID:25030017

  6. Natural History, Growth Kinetics and Outcomes of Untreated Clinically Localized Renal Tumors Under Active Surveillance

    PubMed Central

    Crispen, Paul L.; Viterbo, Rosalia; Boorjian, Stephen A.; Greenberg, Richard E.; Chen, David Y.T.; Uzzo, Robert G.

    2010-01-01

    Background The growth kinetics of untreated solid organ malignancies are not defined. Radiographic active surveillance (AS) of renal tumors in patient unfit or unwilling to undergo intervention provides an opportunity to quantitate the natural history of untreated localized tumors. Here we report the radiographic growth kinetics of renal neoplasms during a period of surveillance. Methods We identified patients with enhancing renal masses who were radiographically observed for at least 12 months. Clinical and pathological records were reviewed to determine tumor growth kinetics and clinical outcomes. Tumor growth kinetics were expressed in terms of absolute and relative linear and volumetric growth. Results We identified 172 renal tumors in 154 patients under AS. Median tumor diameter and volume on presentation was 2.0 cm (mean 2.5, range 0.4 - 12.0) and 4.18 cm3 (mean 20.0, range 0.0033 – 904). Median duration of follow-up was 24 months (mean 31, range 12 – 156). A significant association between presenting tumor size and proportional growth was noted, with smaller tumors growing faster than larger tumors. 39% (68/173) of tumors underwent delayed intervention and 84% (57/68) were pathologically malignant. Progression to metastatic disease was noted in 1.3% (2/154) of patients. Conclusions We demonstrate the association between a tumor’s volume and subsequent growth with smaller tumors exhibiting significantly faster volumetric growth than larger tumors, consistent with Gompertzian kinetics. Surveillance of localized renal tumors is associated with a low rate of disease progression in the intermediate term and suggests potential over-treatment biases in select patients. PMID:19402168

  7. 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.

  8. Estimates of Commercial Population at High Risk for Cardiovascular Events: Impact of Aggressive Cholesterol Reduction

    PubMed Central

    Fitch, Kathryn; Goldberg, Sara W.; Iwasaki, Kosuke; Pyenson, Bruce S.; Kuznik, Andreas; Solomon, Henry A.

    2009-01-01

    Objectives To model the financial and health outcomes impact of intensive statin therapy compared with usual care in a high-risk working-age population (actively employed, commercially insured health plan members and their adult dependents). The target population consists of working-age people who are considered high-risk for cardiovascular disease events because of a history of coronary heart disease. Study Design Three-year event forecast for a sample population generated from the National Health and Nutrition Examination Survey data. Methods Using Framingham risk scoring system, the probability of myocardial infarction or stroke events was calculated for a representative sample population, ages 35 to 69 years, of people at high risk for cardiovascular disease, with a history of coronary heart disease. The probability of events for each individual was used to project the number of events expected to be generated for this population. Reductions in cardiovascular and stroke events reported in clinical trials with aggressive statin therapy were applied to these cohorts. We used medical claims data to model the cohorts' event costs. All results are adjusted to reflect the demographics of a typical working-age population. Results The high-risk cohort (those with coronary heart disease) comprises 4% of the 35- to 69-year-old commercially insured population but generates 22% of the risk for coronary heart disease and stroke. Reduced event rates associated with intensive statin therapy yielded a $58 mean medical cost reduction per treated person per month; a typical payer cost for a 30-day supply of intensive statin therapy is approximately $57. Conclusions Aggressive low-density lipoprotein cholesterol–lowering therapy for working-age people at high risk for cardiovascular events and with a history of heart disease appears to have a significant potential to reduce the rate of clinical events and is cost-neutral for payers. PMID:25126293

  9. 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.

  10. Intensified Surveillance for Early Detection of Breast Cancer in High-Risk Patients

    PubMed Central

    Bick, Ulrich

    2015-01-01

    Summary Efforts for early detection of breast cancer play an important role in the care of high-risk women. This will include both women with a pathological mutation in one of the known breast cancer susceptibility genes as well as women with a high breast cancer risk based on family history only. Due to the much higher incidence of breast cancer in premenopausal women with a genetic predisposition or a familial background, to be most effective, imaging-based breast surveillance should start at an age as early as 25–30 years. There is now ample evidence that magnetic resonance imaging (MRI) is by far the most sensitive imaging modality in young high-risk women. With high-risk multimodality screening at least 30% of breast cancers will be detected primarily by MRI and would have been missed at regular screening without MRI. Therefore, most high-risk breast surveillance programs now offer annual MRI to eligible high-risk women from age 25 to 30, usually supplemented by regular mammography starting at least from age 40. The inclusion of clinical breast exam (CBE) and/or ultrasound in the high-risk surveillance has little impact on the detection of additional cancers, but may improve compliance and reduce unnecessary callbacks for nonspecific findings on MRI. To reduce advanced stage interval cancers, especially in BRCA1/2 mutation carriers, some programs offer additional semiannual CBE and/or ultrasound or alternate MRI and mammography every 6 months. How long regular MRI should be continued in high-risk women is a matter of considerable debate. It appears feasible that MRI can safely be discontinued even in BRCA1/2 mutation carriers between the age of 60 and 70, especially if mammographic breast density is low. Even though several cohort studies have now demonstrated a very favorable stage distribution of breast cancers found in women undergoing high-risk surveillance with MRI, data on long-term survival and mortality in these patients is still rare. PMID:25960720