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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. 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

  15. 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

  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. 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

  19. 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.

  20. 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

  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. 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

  6. 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

  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 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

  1. 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

  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 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

  17. 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

  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. 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

  1. 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

  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. 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

  9. 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

  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. 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

  16. 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

  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 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

  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. 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

  9. 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

  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. 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

  14. 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.

  15. 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

  16. 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

  17. 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

  18. 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

  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. 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

  1. 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

  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. 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

  8. 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

  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. 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…

  18. 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)

  19. 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.

  20. 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…

  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. 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.

  16. 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.

  17. 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

  18. 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

  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. 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

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  8. 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....

  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. 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

  15. 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

  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. 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.

  20. 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.

  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. Analysis of clinical efficacy of CyberKnife® treatment for locally advanced pancreatic cancer

    PubMed Central

    Song, Yongchun; Yuan, Zhiyong; Li, Fengtong; Dong, Yang; Zhuang, Hongqing; Wang, Jingsheng; Chen, Huaming; Wang, Ping

    2015-01-01

    Objective To evaluate the efficacy and safety of CyberKnife® treatment for locally-advanced pancreatic cancer (LAPC). Methods The efficacy of CyberKnife® treatment was analyzed in 59 LAPC patients treated between October 2006 and September 2014. The median tumor volume was 27.1 mL (13.0–125.145 mL). The median prescribed dose was 45 Gy (35–50 Gy), delivered in 5 fractions (3–8 fractions). The overall survival (OS) rates and freedom from local progression (FFLP) rates were estimated using the Kaplan–Meier survival curve. Results The median follow-up for all patients was 10.9 months (3.2–48.7 months) and 15.6 months (3.9–37.6 months) among surviving patients. The median OS was 12.5 months, and the 1-year and 2-year survival rates were 53.9% and 35.1%, respectively. The 1-year FFLP rate was 90.8% based on the computed tomography (CT) evaluation. Grade 1–2 acute and late-stage gastrointestinal (GI) reactions were observed in 61% of the patients. One patient experienced grade 3 toxicity. Conclusion Excellent clinical efficacy was obtained after treatment of LAPC using CyberKnife®, with minimal toxicity. PMID:26109866

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

    PubMed Central

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

    2014-01-01

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

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

    SciTech Connect

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

    1988-02-01

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

  12. 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.

  13. 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

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

    NASA Astrophysics Data System (ADS)

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

    2013-03-01

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

  15. Anatomical Localization of Lister's Tubercle and its Clinical and Surgical Importance.

    PubMed

    Ağır, Ismail; Aytekin, Mahmut Nedim; Küçükdurmaz, Fatih; Gökhan, Servan; Cavuş, Umut Yücel

    2014-01-01

    The dorsal tubercle of the radius, once called Lister's tubercle, is used as a landmark in wrist arthroscopy, wrist joint injections, and similar surgical and clinical procedures. However, there is no useful information in the reference anatomy books and literature. The aim of this study was to identify the anatomical localization of Lister's tubercle on the dorsum of radius in relation to the radial styloid process and the ulnar notch of radius and to demonstrate the clinical and surgical importance of these relationships. We studied 20 dried cadaver radius specimens. The distances from Lister's tubercle to the radial styloid process and to the ulnar notch were measured by using a digital micrometer caliber and the ratio of the two measures was calculated. The dorsal tubercle of the radius is variable in position and can be either closer to the radial styloid process or to the ulnar notch. The present study showed that in 11 of the radii the dorsal tubercle of the radius was nearer to the radial styloid process than the ulnar notch, while in 9 subjects it was nearer to the ulnar notch. This anatomical variation may be relevant for wrist injections, wrist artroscopy or wrist surgery. PMID:24843388

  16. Anatomical Localization of Lister’s Tubercle and its Clinical and Surgical Importance

    PubMed Central

    Ağır, İsmail; Aytekin, Mahmut Nedim; Küçükdurmaz, Fatih; Gökhan, Servan; Çavuş, Umut Yücel

    2014-01-01

    The dorsal tubercle of the radius, once called Lister’s tubercle, is used as a landmark in wrist arthroscopy, wrist joint injections, and similar surgical and clinical procedures. However, there is no useful information in the reference anatomy books and literature. The aim of this study was to identify the anatomical localization of Lister’s tubercle on the dorsum of radius in relation to the radial styloid process and the ulnar notch of radius and to demonstrate the clinical and surgical importance of these relationships. We studied 20 dried cadaver radius specimens. The distances from Lister’s tubercle to the radial styloid process and to the ulnar notch were measured by using a digital micrometer caliber and the ratio of the two measures was calculated. The dorsal tubercle of the radius is variable in position and can be either closer to the radial styloid process or to the ulnar notch. The present study showed that in 11 of the radii the dorsal tubercle of the radius was nearer to the radial styloid process than the ulnar notch, while in 9 subjects it was nearer to the ulnar notch. This anatomical variation may be relevant for wrist injections, wrist artroscopy or wrist surgery. PMID:24843388

  17. Toddlers at High Risk of Chemical Eye Burns

    MedlinePlus

    ... fullstory_160258.html Toddlers at High Risk of Chemical Eye Burns: Study Access to household cleaning products ... and 2 years have relatively high rates of chemical eye burns, with everyday cleaners a common cause, ...

  18. Understanding Suicide Risk: Identification of High Risk Groups during High Risk Times

    PubMed Central

    Overholser, James C.; Braden, Abby; Dieter, Lesa

    2012-01-01

    Background The assessment of suicide risk is a complex task for mental health professionals. Certain demographic groups are associated with completed suicide including males, divorced adults, and Caucasians. However, demographic variables alone provide a crude assessment of suicide risk. Psychiatric diagnosis and recent life events may improve the identification of high risk individuals. Method The current study evaluated 148 individuals who died by suicide compared to 257 adults who died suddenly from accidents or medical problems. Psychological autopsy was used to assess Axis I psychiatric diagnosis and recent stressful life events. Results Suicide completers were significantly more likely than comparison subjects to have a depressive disorder, a substance abuse disorder, and to have experienced interpersonal conflict in the months leading up to their death. A discriminant function analysis revealed that the combination of demographic variables, recent stressful life events, and psychiatric diagnoses best discriminated between suicide completers and comparison subjects. Conclusions Proper assessment of suicide risk should include a comprehensive evaluation of demographic characteristics, recent life stressors, and psychiatric diagnosis. PMID:22140004

  19. Management of High-Risk Cutaneous Squamous Cell Carcinoma

    PubMed Central

    Jennings, Lorraine

    2010-01-01

    Cutaneous squamous cell carcinoma is an increasing public health concern, representing the second most common cancer in the United States. High-risk cutaneous squamous cell carcinoma represents a subgroup of this disease, where patients are at higher risk of metastasis and death. To date, there are no accepted criteria for defining or managing these patients. This review discusses the current state of knowledge of high-risk cutaneous squamous cell carcinoma and outlines reasonable management strategies based on available data. PMID:20725546

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

    NASA Astrophysics Data System (ADS)

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

    1993-05-01

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

  1. Hospital acquired pneumonia with high-risk bacteria is associated with increased pulmonary matrix metalloproteinase activity

    PubMed Central

    Schaaf, Bernhard; Liebau, Cornelia; Kurowski, Volkhard; Droemann, Daniel; Dalhoff, Klaus

    2008-01-01

    Background Neutrophil products like matrix metalloproteinases (MMP), involved in bacterial defence mechanisms, possibly induce lung damage and are elevated locally during hospital- acquired pneumonia (HAP). In HAP the virulence of bacterial species is known to be different. The aim of this study was to investigate the influence of high-risk bacteria like S. aureus and pseudomonas species on pulmonary MMPconcentration in human pneumonia. Methods In 37 patients with HAP and 16 controls, MMP-8, MMP-9 and tissue inhibitors of MMP (TIMP) were analysed by ELISA and MMP-9 activity using zymography in bronchoalveolar lavage (BAL). Results MMP-9 activity in mini-BAL was increased in HAP patients versus controls (149 ± 41 vs. 34 ± 11, p < 0.0001). In subgroup analysis, the highest MMP concentrations and activity were seen in patients with high-risk bacteria: patients with high-risk bacteria MMP-9 1168 ± 266 vs. patients with low-risk bacteria 224 ± 119 ng/ml p < 0.0001, MMP-9 gelatinolytic activity 325 ± 106 vs. 67 ± 14, p < 0.0002. In addition, the MMP-8 and MMP-9 concentration was associated with the state of ventilation and systemic inflammatory marker like CRP. Conclusion Pulmonary MMP concentrations and MMP activity are elevated in patients with HAP. This effect is most pronounced in patients with high-risk bacteria. Artificial ventilation may play an additional role in protease activation. PMID:18700005

  2. Pneumococcal Vaccination in High-Risk Individuals: Are We Doing It Right?

    PubMed

    Papadatou, Ioanna; Spoulou, Vana

    2016-05-01

    Controversy exists regarding the optimal use of the 23-valent pneumococcal conjugate vaccine for the protection of high-risk individuals, such as children and adults with immunocompromising conditions and the elderly. The effectiveness and immunogenicity of 23-valent pneumococcal polysaccharide vaccine (PPV23) are limited in such high-risk populations compared to the healthy, with meta-analyses failing to provide robust evidence on vaccine efficacy against invasive pneumococcal disease (IPD) or pneumonia. Moreover, several studies have demonstrated a PPV23-induced state of immune tolerance or hyporesponsiveness to subsequent vaccination, where the response to revaccination does not reach the levels achieved with primary vaccination. The clinical significance of hyporesponsiveness is not yet clarified, but attenuated humoral and cellular response could lead to reduced levels of protection and increased susceptibility to pneumococcal disease. As disease epidemiology among high-risk groups shows that we are still in need of maximum serotype coverage, the optimal use of PPV23 in the context of combined conjugate/polysaccharide vaccine schedules is an important priority. In this minireview, we discuss PPV23-induced hyporesponsiveness and its implications in designing highly effective vaccination schedules for the optimal protection for high-risk individuals. PMID:27009210

  3. Movement recognition technology as a method of assessing spontaneous general movements in high risk infants.

    PubMed

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

    2014-01-01

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

  4. High risk cohort study for psychiatric disorders in childhood: rationale, design, methods and preliminary results.

    PubMed

    Salum, Giovanni Abrahão; Gadelha, Ary; Pan, Pedro Mario; Moriyama, Tais Silveira; Graeff-Martins, Ana Soledade; Tamanaha, Ana Carina; Alvarenga, Pedro; Valle Krieger, Fernanda; Fleitlich-Bilyk, Bacy; Jackowski, Andrea; Sato, João Ricardo; Brietzke, Elisa; Polanczyk, Guilherme Vanoni; Brentani, Helena; de Jesus Mari, Jair; Do Rosário, Maria Conceição; Manfro, Gisele Gus; Bressan, Rodrigo Affonseca; Mercadante, Marcos Tomanik; Miguel, Eurípedes Constantino; Rohde, Luis Augusto

    2015-03-01

    The objective of this study is to present the rationale, methods, design and preliminary results from the High Risk Cohort Study for the Development of Childhood Psychiatric Disorders. We describe the sample selection and the components of each phases of the study, its instruments, tasks and procedures. Preliminary results are limited to the baseline phase and encompass: (i) the efficacy of the oversampling procedure used to increase the frequency of both child and family psychopathology; (ii) interrater reliability and (iii) the role of differential participation rate. A total of 9937 children from 57 schools participated in the screening procedures. From those 2512 (random = 958; high risk = 1554) were further evaluated with diagnostic instruments. The prevalence of any child mental disorder in the random strata and high-risk strata was 19.9% and 29.7%. The oversampling procedure was successful in selecting a sample with higher family rates of any mental disorders according to diagnostic instruments. Interrater reliability (kappa) for the main diagnostic instrument range from 0.72 (hyperkinetic disorders) to 0.84 (emotional disorders). The screening instrument was successful in selecting a sub-sample with "high risk" for developing mental disorders. This study may help advance the field of child psychiatry and ultimately provide useful clinical information. PMID:25469819

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

    PubMed Central

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

    2015-01-01

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

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

    SciTech Connect

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

    2012-12-01

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

  7. Neoadjuvant Chemotherapy prior to Radical Prostatectomy for Patients with High-Risk Prostate Cancer: A Systematic Review

    PubMed Central

    Kourmpetis, Vasileios; Fokaefs, Eleftherios; Perimenis, Petros

    2013-01-01

    High-risk prostate cancer represents a pretentious clinical problem since a significant number of its patients will relapse and progress after radical prostatectomy. Neoadjuvant chemotherapy may be valuable since its efficacy in hormone-resistant prostate cancer has been established. In this paper, we report studies of neoadjuvant chemotherapies that have been used in high-risk patients prior to radical prostatectomy. Even though the results regarding the prognostic surrogates are not significant, the effects on clinical and pathological outcomes are promising, while toxicity in most of the studies is in the expected field. PMID:23509625

  8. Identification of high-risk communities for unattended out-of-hospital cardiac arrests using GIS.

    PubMed

    Semple, Hugh M; Cudnik, Michael T; Sayre, Michael; Keseg, David; Warden, Craig R; Sasson, Comilla

    2013-04-01

    Improving survival rates for out of hospital cardiac arrest (OHCA) at the neighborhood level is increasingly seen as priority in US cities. Since wide disparities exist in OHCA rates at the neighborhood level, it is necessary to locate neighborhoods where people are at elevated risk for cardiac arrest and target these for educational outreach and other mitigation strategies. This paper describes a GIS-based methodology that was used to identify communities with high risk for cardiac arrests in Franklin County, Ohio during the period 2004-2009. Prior work in this area used a single criterion, i.e., the density of OHCA events, to define the high-risk areas, and a single analytical technique, i.e., kernel density analysis, to identify the high-risk communities. In this paper, two criteria are used to identify the high-risk communities, the rate of OHCA incidents and the level of bystander CPR participation. We also used Local Moran's I combined with traditional map overlay techniques to add robustness to the methodology for identifying high-risk communities for OHCA. Based on the criteria established for this study, we successfully identified several communities that were at higher risk for OHCA than neighboring communities. These communities had incidence rates of OHCA that were significantly higher than neighboring communities and bystander rates that were significantly lower than neighboring communities. Other risk factors for OHCA were also high in the selected communities. The methodology employed in this study provides for a measurement conceptualization of OHCA clusters that is much broader than what has been previously offered. It is also statistically reliable and can be easily executed using a GIS. PMID:22983677

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

    PubMed Central

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

    2013-01-01

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

  10. Immunogenicity and tolerability of inactivated flu vaccine in high risk and healthy children.

    PubMed

    Avila Aguero, María Luisa; Soriano-Fallas, Alejandra; Umaña-Sauma, María de los Angeles; Ulloa-Gutierrez, Rolando; Arnoux, Sabine

    2007-01-01

    We conducted this open study to evaluate the immunogenicity and safety of the inactivated influenza vaccine, Imovax Gripe in 154 children between 6 and 36 months of age at high risk of influenza-related complications, and in a reference group of 64 healthy children. The study was conducted over two flu seasons, in which the vaccine contained the same A strains but different B strains. The results for the A/H3N2 and A/H1N1 strains from the two flu seasons were pooled, but those for the B strains were not. Anti-hemagglutinin (HA) antibody titers were determined before, and one month after each vaccination, and safety was evaluated based on diary card reporting any adverse event observed, either included or not in the list of "solicited events". Within each group of vaccines, the seroconversion rates, seroprotection rates, and ratio of post- to prevaccination geometric mean titers (GMTR) for the A/H3N2 and the A/H1N1 strains fulfilled all requirements of the criteria of the European Union Committee for Proprietary Medicinal Products (CPMP). The immune responses in high-risk and in healthy children were similar, and consistent with those observed in previous studies conducted in healthy children. The vaccine was equally well tolerated by all study groups. Reactogenicity was low and similar in both high-risk and healthy children. Overall from 9.5% to 15.4% of at-risk children and 12% of healthy children reported a solicited local reaction; 23.0 to 28.8% of high-risk and 25.3% of healthy children reported a solicited systemic reaction. The study results provide support for vaccination of children at high-risk of influenza related complications. PMID:17891930

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

    SciTech Connect

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

    2014-03-15

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

  12. Dosimetric correlation of acute and late toxicities in high-risk prostate cancer patients treated with three-dimensional conformal radiotherapy followed by intensity modulated radiotherapy boost

    PubMed Central

    Kapoor, Rakesh; Bansal, Anshuma; Kumar, Narendra; Oinam, Arun S.

    2016-01-01

    Introduction: In prostate cancer, higher radiation doses are often related to higher local control rates. However, the clinical effect of these higher doses on normal tissue toxicities is generally overlooked. We dosimetrically analyze sequential intensity modulated radiotherapy (IMRT) plans in high-risk prostate cancer patients and correlate them with acute and late normal tissue toxicities. Materials and Methods: Twenty-five high-risk prostate cancer patients were planned with three-dimensional conformal radiotherapy to a dose of 50 Gy delivered in 25 fractions in 5 weeks, followed by seven-field IMRT boost, to a dose of 24 Gy delivered in 12 fractions in 2.5 weeks, along with hormonal therapy. Acute and late toxicities were analyzed using Radiation Therapy Oncology Group toxicity criteria. Student's t-test was used for correlating doses received by normal tissues with toxicity grade. Five-year disease-free survival (DFS) and biochemical relapse-free survival (RFS) were evaluated using Kaplan–Meier analysis. Results: Median follow-up of patients was 65 months. Of 25 patients, two developed acute Grade 2 rectal toxicity. Only 1 patient developed acute Grade 2 bladder toxicity. Late Grade 2 and 3 rectal toxicity was seen in 2 and 1 patient, respectively. Late Grade 2 and 3 bladder toxicity was seen in 1 patient each. Grade 2 or more acute rectal toxicity correlated significantly with rectal volume receiving >70 Gy (P = 0.04). The 5-year DFS and biochemical RFS was 70.2% and 79.2%, respectively. One patient failed locally and seven failed at distant sites. Conclusion: Sequential IMRT with a dose of 74 Gy and maximum androgen blockade is well tolerated in high-risk patients in Indian setup with adequate control rates. PMID:27555679

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  15. [Therapeutic local anesthesia for the management of atypical odontalgia. A clinical case series].

    PubMed

    Türp, Jens Christoph

    2005-01-01

    The management of patients diagnosed with atypical odontalgia (AO) is a challenging task. The aim of this longitudinal clinical case series was to document the effect of a 4% carticaine solution without epinephrine among ten patients with AO. Once or on two successive days, 1.7 ml of the local anesthetics was injected buccally in the area of the perceived pain. Pain intensity was recorded four times daily by each participant, beginning at least two weeks prior to the treatment and ending at least four weeks thereafter. The main outcome parameter was pain reduction (in percent) four weeks after treatment compared to the average pain intensity before the injection(s). In addition, study participants were asked to rate their satisfaction with the treatment. Four weeks after treatment, seven of the ten patients experienced significantly less pain than before. Among five individuals, there was a significant pain decrease (about 30% or more). Patient satisfaction was not significantly associated with the amount of pain reduction. Considering the limited treatment options and their side effects, injections with epinephrine-free carticaine seem to be a measure worth to be taken into consideration. Although results gained from uncontrolled case series have to be interpreted with caution, the findings of this observational study sound promising. PMID:16342641

  16. High-risk coronary atheroma: the interplay between ischemia, plaque burden, and disease progression.

    PubMed

    Puri, Rishi; Nicholls, Stephen J; Ellis, Stephen G; Tuzcu, E Murat; Kapadia, Samir R

    2014-04-01

    Necropsy studies have outlined the morphological characteristics of high-risk, or "vulnerable," coronary plaque segments, demonstrating the presence of inflammatory infiltrate and various compositional elements in patients who succumbed to fatal intracoronary thrombosis. However, accumulating evidence in vivo relates the overall burden of atherosclerosis, its rate of progression, and its subsequent ischemic potential with the risk for incident clinical events. These observations, coupled with the efficacy of contemporary medical therapies in reducing clinical event rates, have important implications for trial design of future human in vivo evaluations of vulnerable coronary plaque. PMID:23994415

  17. Outcome of High-Risk Myelodysplastic Syndrome After Azacitidine Treatment Failure

    PubMed Central

    Prébet, Thomas; Gore, Steven D.; Esterni, Benjamin; Gardin, Claude; Itzykson, Raphael; Thepot, Sylvain; Dreyfus, François; Rauzy, Odile Beyne; Recher, Christian; Adès, Lionel; Quesnel, Bruno; Beach, C.L.; Fenaux, Pierre; Vey, Norbert

    2011-01-01

    Purpose Azacitidine (AZA) is the current standard of care for high-risk (ie, International Prognostic Scoring System high or intermediate 2) myelodysplastic syndrome (MDS), but most patients will experience primary or secondary treatment failure. The outcome of these patients has not yet been described. Patients and Methods Overall, 435 patients with high-risk MDS and former refractory anemia with excess blasts in transformation (RAEB-T) were evaluated for outcome after AZA failure. The cohort of patients included four data sets (ie, AZA001, J9950, and J0443 trials and the French compassionate use program). Results The median follow-up after AZA failure was 15 months. The median overall survival was 5.6 months, and the 2-year survival probability was 15%. Increasing age, male sex, high-risk cytogenetics, higher bone marrow blast count, and the absence of prior hematologic response to AZA were associated with significantly worse survival in multivariate analysis. Data on treatment administered after AZA failure were available for 270 patients. Allogeneic stem-cell transplantation and investigational agents were associated with a better outcome when compared with conventional clinical care. Conclusion Outcome after AZA failure is poor. Our results should serve as a basis for designing second-line clinical trials in this population. PMID:21788559

  18. Clinical factors of post-chemoradiotherapy as valuable indicators for pathological complete response in locally advanced rectal cancer

    PubMed Central

    Peng, Jianhong; Lin, Junzhong; Qiu, Miaozhen; Wu, Xiaojun; Lu, Zhenhai; Chen, Gong; Li, Liren; Ding, Peirong; Gao, Yuanhong; Zeng, Zhifan; Zhang, Huizhong; Wan, Desen; Pan, Zhizhong

    2016-01-01

    OBJECTIVES: Pathological complete response has shown a better prognosis for patients with locally advanced rectal cancer after preoperative chemoradiotherapy. However, correlations between post-chemoradiotherapy clinical factors and pathologic complete response are not well confirmed. The aim of the current study was to identify post-chemoradiotherapy clinical factors that could serve as indicators of pathologic complete response in locally advanced rectal cancer. METHODS: This study retrospectively analyzed 544 consecutive patients with locally advanced rectal cancer treated at Sun Yat-sen University Cancer Center from December 2003 to June 2014. All patients received preoperative chemoradiotherapy followed by surgery. Univariate and multivariate regression analyses were performed to identify post-chemoradiotherapy clinical factors that are significant indicators of pathologic complete response. RESULTS: In this study, 126 of 544 patients (23.2%) achieved pathological complete response. In multivariate analyses, increased pathological complete response rate was significantly associated with the following factors: post-chemoradiotherapy clinical T stage 0-2 (odds ratio=2.098, 95% confidence interval=1.023-4.304, p=0.043), post-chemoradiotherapy clinical N stage 0 (odds ratio=2.011, 95% confidence interval=1.264-3.201, p=0.003), interval from completion of preoperative chemoradiotherapy to surgery of >7 weeks (odds ratio=1.795, 95% confidence interval=1.151-2.801, p=0.010) and post-chemoradiotherapy carcinoembryonic antigen ≤2 ng/ml (odds ratio=1.579, 95% confidence interval=1.026-2.432, p=0.038). CONCLUSIONS: Post-chemoradiotherapy clinical T stage 0-2, post-chemoradiotherapy clinical N stage 0, interval from completion of chemoradiotherapy to surgery of >7 weeks and post-chemoradiotherapy carcinoembryonic antigen ≤2 ng/ml were independent clinical indicators for pathological complete response. These findings demonstrate that post-chemoradiotherapy clinical

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

    PubMed

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

    2015-12-01

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

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

    PubMed Central

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

    2015-01-01

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

  1. First experience with a new negative pressure incision management system on surgical incisions after cardiac surgery in high risk patients

    PubMed Central

    2011-01-01

    Background Sternal wound infection remains a serious potential complication after cardiac surgery. A recent development for preventing wound complications after surgery is the adjunctive treatment of closed incisions with negative pressure wound therapy. Suggested mechanisms of preventive action are improving the local blood flow, removing fluids and components in these fluids, helping keep the incision edges together, protecting the wound from external contamination and promoting incision healing. This work reports on our initial evaluation and clinical experience with the Prevena™Incision Management System, a recently introduced new negative pressure wound therapy system specifically developed for treating closed surgical incisions and helping prevent potential complications. We evaluated the new treatment on sternal surgical incisions in patients with multiple co-morbidities and consequently a high risk for wound complications. Methods The Prevena™incision management system was used in 10 patients with a mean Fowler risk score of 15.1 [Range 8-30]. The negative pressure dressing was applied immediately after surgery and left in place for 5 days with a continuous application of -125 mmHg negative pressure. Wounds and surrounding skin were inspected immediately after removal of the Prevena™ incision management system and at day 30 after surgery. Results Wounds and surrounding skin showed complete wound healing with the absence of skin lesions due to the negative pressure after removal of the Prevena™ dressing. No device-related complications were observed. No wound complications occurred in this high risk group of patients until at least 30 days after surgery. Conclusions The Prevena™system appears to be safe, easy to use and may help achieve uncomplicated wound healing in patients at risk of developing wound complications after cardiothoracic surgery. PMID:22145641

  2. Optimal Blood Pressure Goals in Patients With Hypertension at High Risk for Cardiovascular Events.

    PubMed

    Aronow, Wilbert S

    2016-01-01

    Existing epidemiologic and clinical trial data suggest that the blood pressure in patients with hypertension at high risk for cardiovascular events because of coronary artery disease, diabetes mellitus, chronic kidney disease, stroke, or heart failure should be reduced to <140/90 mm Hg in patients younger than 80 years and the systolic blood pressure be reduced to 140-145 mm Hg if tolerated in patients aged 80 years and older. Studies from patients with coronary artery disease, diabetes mellitus, chronic kidney disease, stroke, and heart failure will be discussed that support a blood pressure goal of <140/90 mm Hg in patients younger than 80 years at high risk for cardiovascular events. PMID:23591024

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

    PubMed

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

    2007-12-01

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

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

    PubMed

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

    2010-11-01

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

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

    PubMed

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

    2016-02-01

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

  6. A psychological profile of depressed and nondepressed women at high risk for breast cancer.

    PubMed

    Wellisch, D K; Lindberg, N M

    2001-01-01

    This study examines the difference on several demographic and psychosocial variables between women at high risk for breast cancer above and below the cut-off point of a depression measure (Center for Epidemiological Study Depression Scale). Data are presented for 430 consecutive patients from the UCLA Revlon Breast Center High Risk Clinic. Women scoring above the depression cut-off point were younger, had more relatives with breast cancer, reported more symptoms of anxiety, and had more self-perceived vulnerability to breast cancer. In addition, women above the depression cut-off point were more likely to be single, childless, to have not viewed the results of the surgical treatment of their relative, and to feel more anxiety regarding screening practices (mammography, pap smears, and breast self-examinations). PMID:11496022

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

    SciTech Connect

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

    2007-11-01

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

  8. An Automated System for Generating Situation-Specific Decision Support in Clinical Order Entry from Local Empirical Data

    ERIC Educational Resources Information Center

    Klann, Jeffrey G.

    2011-01-01

    Clinical Decision Support is one of the only aspects of health information technology that has demonstrated decreased costs and increased quality in healthcare delivery, yet it is extremely expensive and time-consuming to create, maintain, and localize. Consequently, a majority of health care systems do not utilize it, and even when it is…

  9. Spine radiosurgery for the local treatment of spine metastases: Intensity-modulated radiotherapy, image guidance, clinical aspects and future directions

    PubMed Central

    de Moraes, Fabio Ynoe; Taunk, Neil Kanth; Laufer, Ilya; Neves-Junior, Wellington Furtado Pimenta; Hanna, Samir Abdallah; de Andrade Carvalho, Heloisa; Yamada, Yoshiya

    2016-01-01

    Many cancer patients will develop spinal metastases. Local control is important for preventing neurologic compromise and to relieve pain. Stereotactic body radiotherapy or spinal radiosurgery is a new radiation therapy technique for spinal metastasis that can deliver a high dose of radiation to a tumor while minimizing the radiation delivered to healthy, neighboring tissues. This treatment is based on intensity-modulated radiotherapy, image guidance and rigid immobilization. Spinal radiosurgery is an increasingly utilized treatment method that improves local control and pain relief after delivering ablative doses of radiation. Here, we present a review highlighting the use of spinal radiosurgery for the treatment of metastatic tumors of the spine. The data used in the review were collected from both published studies and ongoing trials. We found that spinal radiosurgery is safe and provides excellent tumor control (up to 94% local control) and pain relief (up to 96%), independent of histology. Extensive data regarding clinical outcomes are available; however, this information has primarily been generated from retrospective and nonrandomized prospective series. Currently, two randomized trials are enrolling patients to study clinical applications of fractionation schedules spinal Radiosurgery. Additionally, a phase I clinical trial is being conducted to assess the safety of concurrent stereotactic body radiotherapy and ipilimumab for spinal metastases. Clinical trials to refine clinical indications and dose fractionation are ongoing. The concomitant use of targeted agents may produce better outcomes in the future. PMID:26934240

  10. The Effect of Radiation Timing on Patients With High-Risk Features of Parameningeal Rhabdomyosarcoma: An Analysis of IRS-IV and D9803

    SciTech Connect

    Spalding, Aaron C.; Hawkins, Douglas S.; Anderson, James R.; Lyden, Elizabeth; Laurie, Fran; Wolden, Suzanne L.; Arndt, Carola A.S.; Michalski, Jeff M.

    2013-11-01

    Purpose: Radiation therapy remains an essential treatment for patients with parameningeal rhabdomyosarcoma (PMRMS), and early radiation therapy may improve local control for patients with intracranial extension (ICE). Methods and Materials: To address the role of radiation therapy timing in PMRMS in the current era, we reviewed the outcome from 2 recent clinical trials for intermediate-risk RMS: Intergroup Rhabdomyosarcoma Study (IRS)-IV and Children's Oncology Group (COG) D9803. The PMRMS patients on IRS-IV with any high-risk features (cranial nerve palsy [CNP], cranial base bony erosion [CBBE], or ICE) were treated immediately at day 0, and PMRMS patients without any of these 3 features received week 6-9 radiation therapy. The D9803 PMRMS patients with ICE received day 0 X-Ray Therapy (XRT) as well; however, those with either CNP or CBBE had XRT at week 12. Results: Compared with the 198 PMRMS patients from IRS-IV, the 192 PMRMS patients from D9803 had no difference (P<.05) in 5-year local failure (19% vs 19%), failure-free-survival (70% vs 67%), or overall survival (75% vs 73%) in aggregate. The 5-year local failure rates by subset did not differ when patients were classified as having no risk features (None, 15% vs 19%, P=.25), cranial nerve palsy/cranial base of skull erosion (CNP/CBBE, 15% vs 28%, P=.22), or intracranial extension (ICE, 21% vs 15%, P=.27). The D9083 patients were more likely to have received initial staging by magnetic resonance imaging (71% vs 53%). Conclusions: These data support that a delay in radiation therapy for high-risk PMRMS features of CNP/CBBE does not compromise clinical outcomes.

  11. Stereotactic Body Radiotherapy for Localized Prostate Cancer: Interim Results of a Prospective Phase II Clinical Trial

    SciTech Connect

    King, Christopher R. Brooks, James D.; Gill, Harcharan; Pawlicki, Todd; Cotrutz, Cristian; Presti, Joseph C.

    2009-03-15

    Purpose: The radiobiology of prostate cancer favors a hypofractionated dose regimen. We report results of a prospective Phase II clinical trial of stereotactic body radiotherapy (SBRT) for localized prostate cancer. Methods and Materials: Forty-one low-risk prostate cancer patients with 6 months' minimum follow-up received 36.25 Gy in five fractions of 7.25 Gy with image-guided SBRT alone using the CyberKnife. The early (<3 months) and late (>6 months) urinary and rectal toxicities were assessed using validated quality of life questionnaires (International Prostate Symptom Score, Expanded Prostate Cancer Index Composite) and the Radiation Therapy Oncology Group (RTOG) toxicity criteria. Patterns of prostate-specific antigen (PSA) response are analyzed. Results: The median follow-up was 33 months. There were no RTOG Grade 4 acute or late rectal/urinary complications. There were 2 patients with RTOG Grade 3 late urinary toxicity and none with RTOG Grade 3 rectal complications. A reduced rate of severe rectal toxicities was observed with every-other-day vs. 5 consecutive days treatment regimen (0% vs. 38%, p = 0.0035). A benign PSA bounce (median, 0.4 ng/mL) was observed in 12 patients (29%) occurring at 18 months (median) after treatment. At last follow-up, no patient has had a PSA failure regardless of biochemical failure definition. Of 32 patients with 12 months minimum follow-up, 25 patients (78%) achieved a PSA nadir {<=}0.4 ng/mL. A PSA decline to progressively lower nadirs up to 3 years after treatment was observed. Conclusions: The early and late toxicity profile and PSA response for prostate SBRT are highly encouraging. Continued accrual and follow-up will be necessary to confirm durable biochemical control rates and low toxicity profiles.

  12. Impact of a Parenting Program in a High-Risk, Multi-Ethnic Community: The PALS Trial

    ERIC Educational Resources Information Center

    Scott, Stephen; O'Connor, Thomas G.; Futh, Annabel; Matias, Carla; Price, Jenny; Doolan, Moira

    2010-01-01

    Background: Parenting programs have been shown to work when delivered to motivated ethnic majority parents in demonstration projects, but comparatively little is known about their impact when delivered to high-risk, multi-ethnic populations by routine local services. Methods: The Primary Age Learning Skills (PALS) trial was a randomized controlled…

  13. High Risk Drinking among Non-Affiliated College Students

    ERIC Educational Resources Information Center

    Smith, Margaret; Finneran, John; Droppa, Marj

    2014-01-01

    This study investigated the high risk drinking practices of unaffiliated college students who are not involved in formal athletics, fraternities, or sororities. Using a qualitative research design, the investigators interviewed students at a northeast public college in fall 2010 to learn about unaffiliated students' drinking experiences and…

  14. Confronting Worst Case Scenarios: Education and High Risk Offenders.

    ERIC Educational Resources Information Center

    Duguid, Stephen

    1997-01-01

    Predicted vs. actual recidivism of 119 high-risk offenders aged 20-29 who had completed postsecondary prison education was compared. Despite a low predicted success rate, they achieved higher grade point averages, acquired more postrelease education, and had less recidivism. Success factors included a culture of academic achievement and student…

  15. Distribution of influenza vaccine to high-risk groups.

    PubMed

    Ompad, Danielle C; Galea, Sandro; Vlahov, David

    2006-01-01

    Vaccine distribution programs have historically targeted individuals at high risk of complications due to influenza. Despite recommendations from the Advisory Committee on Immunization Practices, vaccination coverage among high-risk populations has been generally low. This review systematically summarizes the recent literature evaluating programs in different settings, from within medical settings to venue-based and community-based approaches, in an effort to identify successful program components. The published literature was identified by using the MEDLINE database from 1990 to 2006 covering studies that reported on interventions or programs aimed at vaccinating high-risk populations. The authors reviewed 56 studies. In the United States, the Healthy People 2010 goals included 90% vaccination coverage for adults aged > or = 65 years and 60% for high-risk adults aged 18-64 years. Only a handful of the studies reviewed managed to meet those goals. Interventions that increased vaccination coverage to Healthy People 2010 goals included advertising, provider and patient mailings, registry-based telephone calls, patient and staff education, standing orders coupled with standardized forms, targeting of syringe exchange customers, and visiting nurses. Few studies evaluated the impact of vaccination programs by race/ethnicity and socioeconomic status. Few studies targeted individuals outside of the health-care and social services sectors. Given the growing disparities in health and health-care access, understanding the way in which interventions can remedy disparities is crucial. PMID:16707648

  16. ORGANOPHOSPHATE PESTICIDE EXPOSURES - WHERE ARE THE HIGH RISK CHILDREN?

    EPA Science Inventory

    Methods to identify children at high-risk for organophosphate (OP) pesticide exposure are difficult to develop because biological markers reflect only recent "snapshots" of exposure due to the short half-life of OP compounds (generally about 24 hours). We conducted a series of p...

  17. Cumulative Experiences of Violence among High-Risk Urban Youth

    ERIC Educational Resources Information Center

    Taylor, Catherine A.; Boris, Neil W.; Heller, Sherryl Scott; Clum, Gretchen A.; Rice, Janet C.; Zeanah, Charles H.

    2008-01-01

    This study examines type-specific and cumulative experiences of violence among a vulnerable population of youth. Sixty high-risk, shelter-dwelling, urban youth were interviewed regarding their history of childhood maltreatment, exposure to community violence (ECV), and experience with intimate partner violence (IPV). Results show a high prevalence…

  18. Improving antenatal risk assessment in women exposed to high risks.

    PubMed

    Perry, Natasha; Newman, Louise K; Hunter, Mick; Dunlop, Adrian

    2015-01-01

    Antenatal substance use and related psychosocial risk factors are known to increase the likelihood of child protection involvement; less is known about the predictive nature of maternal reflective functioning (RF) in this population. This preliminary study assessed psychosocial and psychological risk factors for a group of substance dependent women exposed to high risks in pregnancy, and their impact on child protection involvement. Pregnant women on opiate substitution treatment (n = 11) and a comparison group (n = 15) were recruited during their third trimester to complete measures of RF (Pregnancy Interview), childhood trauma, mental health and psychosocial assessments. At postnatal follow-up, RF was reassessed (Parent Development Interview - Revised Short Version) and mother-infant dyads were videotaped to assess emotional availability (EA). Child protection services were contacted to determine if any concerns had been raised for infant safety. Significant between-group differences were observed for demographics, psychosocial factors, trauma and mental health symptoms. Unexpectedly, no significant differences were found for RF or EA between groups. Eight women in the 'exposed to high risks' group became involved with child protection services. Reflective functioning was not significantly associated with psychosocial risk factors, and therefore did not mediate the outcome of child protection involvement. Women 'exposed to high risks' were equally able to generate a model of their own and their infants' mental states and should not be seen within a deficit perspective. Further research is required to better understand the range of risk factors that predict child protection involvement in high risk groups. PMID:23982989

  19. Staying Alive! Training High-Risk Teams for Self Correction

    NASA Technical Reports Server (NTRS)

    Slack, Kelley; Noe, Raymond; Weaver, Sallie

    2011-01-01

    Research examining teams working in high-risk operations has been lacking. The present symposium showcases research on team training that helps to optimize team performance in environments characterized by life or death situations arising spontaneously after long periods of mundane activity by pulling experts from diverse areas of industry: space flight, health care, and medical simulation.

  20. The High-Risk (Disturbed and Disturbing) College Student

    ERIC Educational Resources Information Center

    Hollingsworth, Kathy R.; Dunkle, John H.; Douce, Louise

    2009-01-01

    The disturbed and disturbing college student causes the most vexing concerns for student affairs administrators. The Assessment-Intervention of Student Problems (AISP) model offers a useful and easily understood framework for dealing with the various challenges of this high-risk student population. This chapter focuses on changes that have…

  1. Alleviating Stress in Parents of High-Risk Preterm Infants.

    ERIC Educational Resources Information Center

    Lowenthal, Barbara

    1989-01-01

    Possible sources of stress for parents of preterm high-risk infants are reviewed from a research perspective. Stages of parental attachment to their premature baby are spelled out. Strategies for special education teachers to use in alleviating parental stress are described. (JDD)

  2. Prediction of Violence Perpetration Among High-Risk Youth

    ERIC Educational Resources Information Center

    Sussman, Steve; Skara, Silvana; Weiner, Michelle D.; Dent, Clyde W.

    2004-01-01

    Objectives: To prospectively examine demographic background, personality, perceived environment, and behavior as violence perpetration predictors in emerging adulthood among high-risk adolescents using problem-behavior theory as a conceptual perspective. Methods: Self-report questionnaires were administered 5 years apart to 676 participants.…

  3. Suicide Prevention for High-Risk Persons Who Refuse Treatment

    ERIC Educational Resources Information Center

    Motto, Jerome A.

    1976-01-01

    Patients (N=3,006) admitted to a psychiatric in-patient service because of a suicidal state were contacted to determine if post-discharge plans were followed. Half of those who refused treatment were contacted by telephone or letter on a set schedule. Evidence is that a high-risk population for suicide can be identified. (Author)

  4. Psychiatric Symptoms and Community Violence among High-Risk Patients: A Test of the Relationship at the Weekly Level

    ERIC Educational Resources Information Center

    Skeem, Jennifer L.; Schubert, Carol; Odgers, Candice; Mulvey, Edward P.; Gardner, William; Lidz, Charles

    2006-01-01

    Given the availability of violence risk assessment tools, clinicians are now better able to identify high-risk patients. Once these patients have been identified, clinicians must monitor risk state and intervene when necessary to prevent harm. Clinical practice is dominated by the assumption that increases in psychiatric symptoms elevate risk of…

  5. Multivariate prediction of emerging psychosis in adolescents at high risk for schizophrenia

    PubMed Central

    Shah, Jai; Eack, Shaun M; Montrose, Debra M; Tandon, Neeraj; Miewald, Jean M; Prasad, Konsale M; Keshavan, Matcheri S

    2012-01-01

    Background Accurate prediction of psychosis development in high-risk populations is an important but thus far elusive goal. Of the many diverse etiologic and risk factors identified thus far, few have been combined into prospective risk ascertainment models. We tested the predictive power of familial, neurobiological, socioenvironmental, cognitive and clinical risk factors through an integrative biopsychosocial model for emerging psychosis in young relatives at familial risk for schizophrenia. Methods 96 young first- and second- degree relatives of schizophrenia probands were followed for an average of 2.38 (SD = 0.98) years to examine their trajectory towards psychosis. Iterative structural equation modelling utilizing multiple etiologic and risk factors was employed to estimate their joint contribution to prediction of psychosis development. Results The rate of conversion to psychosis over the study period was 12.5%. In the final model, clinical measures of schizotypy were directly predictive of conversion, with early (familial, biological, socioenvironmental) and cognitive risk factors indirectly predictive of psychosis through increased baseline clinical symptomatology. Our model provided an excellent fit to the observed data, with sensitivity of 0.17, specificity of 0.99, positive predictive value of 0.67 and negative predictive value of 0.89. Conclusions Integrative modeling of multivariate data from familial, neurobiological, socioenvironmental, cognitive and clinical domains represents a powerful approach to prediction of psychosis development. The high specificity and low sensitivity found using a combination of such variables suggests that their utility may be in confirmatory testing among already selected high-risk individuals, rather than for initial screening. These findings also highlight the importance of data from a broad array of etiologic and risk factors, even within a familial high-risk population. With further refinement and validation, such

  6. Comparative clinical evaluation of transcutaneous electrical nerve stimulator over conventional local anesthesia in children seeking dental procedures: A clinical study

    PubMed Central

    Varadharaja, M.; Udhya, J.; Srinivasan, Ila; Sivakumar, Jambai Sampath Kumar; Karthik, Ramasamy Sundararajan; Manivanan, M.

    2014-01-01

    Aim: The aim of this study to evaluate the effectiveness of pain control by employing transcutaneous electrical nerve stimulator (TENS) over conventional injectable local anesthesia for children requiring restorative procedures under rubber dam. Materials and Methods: The study design considered was the split mouth design, in experiment (right) side, dental procedures under rubber dam was performed under TENS and in control (left) side, dental procedures under rubber dam was performed under conventional injectable local anesthetic (LA). The level of comfort and discomfort experienced during TENS and conventional LA was determined using visual analog scale (VAS) and heart rate. Result: Increase in mean heart rate associated with TENS (0.78%) was significantly less compared to increase in heart rate with administration of conventional local anesthesia (11.78%). In VAS, the mean values for pain indicate that minimum pain was felt with TENS, which was closely followed by LA. Conclusion: TENS can offer many safer and psychological advantages and is a valuable alternative to conventional LA for children. PMID:25210350

  7. Biological markers of Pseudomonas aeruginosa epidemic high-risk clones.

    PubMed

    Mulet, Xavier; Cabot, Gabriel; Ocampo-Sosa, Alain A; Domínguez, M Angeles; Zamorano, Laura; Juan, Carlos; Tubau, Fe; Rodríguez, Cristina; Moyà, Bartolomé; Peña, Carmen; Martínez-Martínez, Luis; Oliver, Antonio

    2013-11-01

    A limited number of Pseudomonas aeruginosa genotypes (mainly ST-111, ST-175, and ST-235), known as high-risk clones, are responsible for epidemics of nosocomial infections by multidrug-resistant (MDR) or extensively drug-resistant (XDR) strains worldwide. We explored the potential biological parameters that may explain the success of these clones. A total of 20 isolates from each of 4 resistance groups (XDR, MDR, ModR [resistant to 1 or 2 classes], and MultiS [susceptible to all antipseudomonals]), recovered from a multicenter study of P. aeruginosa bloodstream infections performed in 10 Spanish hospitals, were analyzed. A further set of 20 XDR isolates belonging to epidemic high-risk clones (ST-175 [n = 6], ST-111 [n = 7], and ST-235 [n = 7]) recovered from different geographical locations was also studied. When unknown, genotypes were documented through multilocus sequence typing. The biological parameters evaluated included twitching, swimming, and swarming motility, biofilm formation, production of pyoverdine and pyocyanin, spontaneous mutant frequencies, and the in vitro competition index (CI) obtained with a flow cytometry assay. All 20 (100%) XDR, 8 (40%) MDR, and 1 (5%) ModR bloodstream isolate from the multicenter study belonged to high-risk clones. No significant differences were observed between clonally diverse ModR and MultiS isolates for any of the parameters. In contrast, MDR/XDR high-risk clones showed significantly increased biofilm formation and mutant frequencies but significantly reduced motility (twitching, swimming, and swarming), production of pyoverdine and pyocyanin, and fitness. The defined biological markers of high-risk clones, which resemble those resulting from adaptation to chronic infections, could be useful for the design of specific treatment and infection control strategies. PMID:23979744

  8. Biological Markers of Pseudomonas aeruginosa Epidemic High-Risk Clones

    PubMed Central

    Mulet, Xavier; Cabot, Gabriel; Ocampo-Sosa, Alain A.; Domínguez, M. Angeles; Zamorano, Laura; Juan, Carlos; Tubau, Fe; Rodríguez, Cristina; Moyà, Bartolomé; Peña, Carmen; Martínez-Martínez, Luis

    2013-01-01

    A limited number of Pseudomonas aeruginosa genotypes (mainly ST-111, ST-175, and ST-235), known as high-risk clones, are responsible for epidemics of nosocomial infections by multidrug-resistant (MDR) or extensively drug-resistant (XDR) strains worldwide. We explored the potential biological parameters that may explain the success of these clones. A total of 20 isolates from each of 4 resistance groups (XDR, MDR, ModR [resistant to 1 or 2 classes], and MultiS [susceptible to all antipseudomonals]), recovered from a multicenter study of P. aeruginosa bloodstream infections performed in 10 Spanish hospitals, were analyzed. A further set of 20 XDR isolates belonging to epidemic high-risk clones (ST-175 [n = 6], ST-111 [n = 7], and ST-235 [n = 7]) recovered from different geographical locations was also studied. When unknown, genotypes were documented through multilocus sequence typing. The biological parameters evaluated included twitching, swimming, and swarming motility, biofilm formation, production of pyoverdine and pyocyanin, spontaneous mutant frequencies, and the in vitro competition index (CI) obtained with a flow cytometry assay. All 20 (100%) XDR, 8 (40%) MDR, and 1 (5%) ModR bloodstream isolate from the multicenter study belonged to high-risk clones. No significant differences were observed between clonally diverse ModR and MultiS isolates for any of the parameters. In contrast, MDR/XDR high-risk clones showed significantly increased biofilm formation and mutant frequencies but significantly reduced motility (twitching, swimming, and swarming), production of pyoverdine and pyocyanin, and fitness. The defined biological markers of high-risk clones, which resemble those resulting from adaptation to chronic infections, could be useful for the design of specific treatment and infection control strategies. PMID:23979744

  9. Intravascular optical imaging of high-risk plaques in vivo by targeting macrophage mannose receptors.

    PubMed

    Kim, Ji Bak; Park, Kyeongsoon; Ryu, Jiheun; Lee, Jae Joong; Lee, Min Woo; Cho, Han Saem; Nam, Hyeong Soo; Park, Ok Kyu; Song, Joon Woo; Kim, Tae Shik; Oh, Dong Joo; Gweon, DaeGab; Oh, Wang-Yuhl; Yoo, Hongki; Kim, Jin Won

    2016-01-01

    Macrophages mediate atheroma expansion and disruption, and denote high-risk arterial plaques. Therefore, they are substantially gaining importance as a diagnostic imaging target for the detection of rupture-prone plaques. Here, we developed an injectable near-infrared fluorescence (NIRF) probe by chemically conjugating thiolated glycol chitosan with cholesteryl chloroformate, NIRF dye (cyanine 5.5 or 7), and maleimide-polyethylene glycol-mannose as mannose receptor binding ligands to specifically target a subset of macrophages abundant in high-risk plaques. This probe showed high affinity to mannose receptors, low toxicity, and allowed the direct visualization of plaque macrophages in murine carotid atheroma. After the scale-up of the MMR-NIRF probe, the administration of the probe facilitated in vivo intravascular imaging of plaque inflammation in coronary-sized vessels of atheromatous rabbits using a custom-built dual-modal optical coherence tomography (OCT)-NIRF catheter-based imaging system. This novel imaging approach represents a potential imaging strategy enabling the identification of high-risk plaques in vivo and holds promise for future clinical implications. PMID:26948523

  10. Hemodynamic monitoring and management in high-risk surgery: a survey among Japanese anesthesiologists.

    PubMed

    Suehiro, Koichi; Tanaka, Katsuaki; Mukai, Akira; Joosten, Alexandre; Desebbe, Olivier; Alexander, Brenton; Cannesson, Maxime; Nishikawa, Kiyonobu

    2016-06-01

    The aim of this study was to assess the current practices of hemodynamic management in high-risk surgical patients among Japanese anesthesiologists. An invitation letter to the survey, which included 35 questions related to hemodynamic monitoring in high-risk surgery, was mailed to every hospital approved by the Japanese Society of Anesthesiologists (JSA) (1260 hospitals). Of the 692 JSA respondents, 573 completed the survey. Despite reporting a high rate of cardiac output (CO) and stroke volume variation (SVV) monitoring in JSA members (70 and 74 %, respectively), fluid goal-directed therapy was poorly implemented in high-risk surgery (7.4 %). Also, 47 % of the JSA respondents did not consistently perform CO optimization. SVV was more commonly used (76 %) as an indicator of volume expansion among JSA respondents, while central venous pressure was less frequently used (48 %). Despite a broader use of advanced hemodynamic monitoring, optimization of CO is still poorly protocolized and applied in Japan. The development of guidelines and protocols for hemodynamic management, including the establishment of strong evidence aimed at improving clinical outcomes, is needed to assist anesthesiologists in more universal adoption of perioperative CO optimization. PMID:26961821

  11. Intravascular optical imaging of high-risk plaques in vivo by targeting macrophage mannose receptors

    PubMed Central

    Kim, Ji Bak; Park, Kyeongsoon; Ryu, Jiheun; Lee, Jae Joong; Lee, Min Woo; Cho, Han Saem; Nam, Hyeong Soo; Park, Ok Kyu; Song, Joon Woo; Kim, Tae Shik; Oh, Dong Joo; Gweon, DaeGab; Oh, Wang-Yuhl; Yoo, Hongki; Kim, Jin Won

    2016-01-01

    Macrophages mediate atheroma expansion and disruption, and denote high-risk arterial plaques. Therefore, they are substantially gaining importance as a diagnostic imaging target for the detection of rupture-prone plaques. Here, we developed an injectable near-infrared fluorescence (NIRF) probe by chemically conjugating thiolated glycol chitosan with cholesteryl chloroformate, NIRF dye (cyanine 5.5 or 7), and maleimide-polyethylene glycol-mannose as mannose receptor binding ligands to specifically target a subset of macrophages abundant in high-risk plaques. This probe showed high affinity to mannose receptors, low toxicity, and allowed the direct visualization of plaque macrophages in murine carotid atheroma. After the scale-up of the MMR-NIRF probe, the administration of the probe facilitated in vivo intravascular imaging of plaque inflammation in coronary-sized vessels of atheromatous rabbits using a custom-built dual-modal optical coherence tomography (OCT)-NIRF catheter-based imaging system. This novel imaging approach represents a potential imaging strategy enabling the identification of high-risk plaques in vivo and holds promise for future clinical implications. PMID:26948523

  12. Midterm results of endovascular infrarenal abdominal aortic aneurysm repair in high-risk patients.

    PubMed

    Nagpal, A David; Forbes, Thomas L; Novick, Teresa V; Lovell, Marge B; Kribs, Stewart W; Lawlor, D Kirk; Harris, Kenneth A; DeRose, Guy

    2007-01-01

    Short-term and midterm clinical outcomes after endovascular repair of abdominal aortic aneurysms (AAAs) have been well documented. Evaluation of longer term outcomes is now possible. Here we describe our initial 100 high-risk patients treated with endovascular aneurysm repair (EVAR), all with a minimum of 5 years of follow-up. A retrospective review of prospectively recorded data in a departmental database was undertaken for the first 100 consecutive EVAR patients with a minimum of 5 years (range, 60-105 months) of follow-up performed between December 1997 and June 2001. Information was obtained from surgical follow-up visits and family doctors' offices. Endovascular repair of AAA in high-risk patients can be achieved with acceptably low postoperative mortality and morbidity. Longer term results in this high-risk cohort suggest that EVAR is effective in preventing aneurysm-related deaths at 5 years and beyond. All late mortalities were due to patients' comorbid diseases. PMID:17704332

  13. Validation of the High-Risk Pregnancy Stress Scale in a sample of hospitalized Greek high-risk pregnant women.

    PubMed

    Gourounti, Kleanthi; Karpathiotaki, Natassa; Karapanou, Vassiliki; Antzaklis, Panos; Daskalakis, Georgios

    2016-01-01

    The aim of the authors in this study was to determine the psychometric properties of the Greek adaptation of the High-Risk Pregnancy Stress Scale (HRPSS) in a sample of high-risk hospitalized pregnant women. The sample consisted of 133 high-risk pregnant women with gestational age from 9 to 37 weeks. Data were collected between February and June of 2014. HRPSS was "forward-backward" translated from English to Greek. Principal axis factoring with promax rotation was used to test the factor structure of the HRPSS. Measures of state anxiety (STAI) and depressive symptoms (EPDS) were used to assess the convergent validity of the HRPSS. Exploratory factor analysis suggested three factors: concerns of pregnancy, movement restriction, and isolation and restriction of external activities. Construct validity was confirmed by computing correlations between the HRPSS and constructions of anxiety and depressive symptoms. Internal consistency reliability was satisfactory (α = 0.813). The original factor structure of the HRPSS was only partly replicated. The results of the exploratory factor analysis suggested that a three-factor solution instead of a two-factor solution would be the most adequate. The HRPSS is an appropriate measure for assessing the levels of concerns regarding pregnancy outcome, movement restriction, isolation, and external activity restrictions in Greek high-risk pregnant women. PMID:26624018

  14. 78 FR 24750 - Scientific Information Request Therapies for Clinically Localized Prostate Cancer

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-26

    ... randomized controlled trials and observational studies relevant to the clinical outcomes. AHRQ is interested in receiving both citations and reprints. Information identifying unpublished randomized...

  15. Presence of ulceration, but not high risk zone location, correlates with unfavorable histopathological subtype in facial basal cell carcinoma

    PubMed Central

    Yalcin, Ozben; Sezer, Engin; Kabukcuoglu, Fevziye; Kilic, Ayse Irem; Sari, Ahu Gulcin; Cerman, Asli Aksu; Altunay, Ilknur Kivanc

    2015-01-01

    Background: Basal cell carcinoma (BCC) has been stratified into low- and high-risk according to their propensity for local recurrence. Risk factors for recurrence include histologic subtype, anatomic location (i.e. H-zone of the face), horizontal diameter, and patient health status. Objective: To assess if favorable (superficial, nodular, adenoid and trabecular) and unfavorable (infiltrative, morpheaform, micronodular, metatypical, basosquamous) histopathological subtypes of BCC do correlate with anatomic location on the face (facial high risk versus non-high risk zones). Methods: Histopathological specimens of all facial BCCs, which were histopathologically diagnosed in the Pathology Department of Şişli Etfal Training Hospital, between the years 2008 and 2014 were retrospectively studied. Histopathological aggressive and non-aggressive subtypes as well as the presence of ulceration were correlated with facial high-risk (i.e. H-zone) and low risk anatomical locations. Results: Of 184 BCC of unfavorable subtypes, 101 cases were identified in facial high-risk anatomical region (H-zone) compared to 83 cases at non H-zone (P = 0.553). On the other hand the ulceration rate was significantly higher for unfavorable histological subtypes than in the favorable histopathological subtype group (P = 0.042). Regarding anatomic site, ulceration frequency was not significantly different for the H-versus non-high risk zones (P = 0.335). Conclusions: A correlation of unfavorable histopathological subtype of BCC and high-risk anatomical location (i.e. H-zone) was not observed in our study. Our results however confirmed a significantly higher rate of ulceration in the subgroup of aggressive histopathological BCC forms. Thus, factors other than histopathological subtype (such as narrow excision margin related to difficult surgical technique in H-zone, microcirculation, vasculature and host inflammatory response) may be responsible for the high recurrence rate in facial H

  16. A comparative study-efficacy and safety of combined spinal epidural anesthesia versus spinal anesthesia in high-risk geriatric patients for surgeries around the hip joint

    PubMed Central

    Tummala, Vengamamba; Rao, Lella Nageswara; Vallury, Manoj Kumar; Sanapala, Anitha

    2015-01-01

    Context: Combined spinal epidural anesthesia (CSEA) has a significant advantage by enabling the use of low dose intrathecal local anesthetic, with knowledge that the epidural catheter may be used to extend the block as necessary. CSEA is useful in high-risk geriatric patients by providing greater hemodynamic stability. Aim: This study is designed to compare the clinical effects of CSEA versus spinal anesthesia in high-risk geriatric patients undergoing surgeries around the hip joint. Materials and Methods: Sixty patients aged >65 years, American Society of Anaesthesiology III and IV were randomly allocated into two equal groups. Group A (n = 30) received CSEA with 1 ml (5 mg) of 0.5% hyperbaric bupivacaine with 25 μg fentanyl through spinal route, and the expected incompleteness of spinal block was managed with small incremental dose of 0.5% isobaric bupivacaine through epidural catheter, 1–1.5 ml for every unblocked segment to achieve T10 sensory level. Group B (n = 30) received spinal anesthesia with 2.5 ml (12.5 mg) of 0.5% hyperbaric bupivacaine and 25 μg fentanyl. Result: Both the groups showed rapid onset, excellent analgesia and good quality motor block. Group A showed a significantly less incidence of hypotension (P < 0.01) along with the provision of prolonging analgesia as compared to Group B. Conclusion: CSEA is a safe, effective, reliable technique with better hemodynamic stability along with the provision of prolonging analgesia compared to spinal anesthesia for high-risk geriatric patients undergoing surgeries around the hip joint. PMID:26417125

  17. Glocal Clinical Registries: Pacemaker Registry Design and Implementation for Global and Local Integration – Methodology and Case Study

    PubMed Central

    da Silva, Kátia Regina; Costa, Roberto; Crevelari, Elizabeth Sartori; Lacerda, Marianna Sobral; de Moraes Albertini, Caio Marcos; Filho, Martino Martinelli; Santana, José Eduardo; Vissoci, João Ricardo Nickenig; Pietrobon, Ricardo; Barros, Jacson V.

    2013-01-01

    Background The ability to apply standard and interoperable solutions for implementing and managing medical registries as well as aggregate, reproduce, and access data sets from legacy formats and platforms to advanced standard formats and operating systems are crucial for both clinical healthcare and biomedical research settings. Purpose Our study describes a reproducible, highly scalable, standard framework for a device registry implementation addressing both local data quality components and global linking problems. Methods and Results We developed a device registry framework involving the following steps: (1) Data standards definition and representation of the research workflow, (2) Development of electronic case report forms using REDCap (Research Electronic Data Capture), (3) Data collection according to the clinical research workflow and, (4) Data augmentation by enriching the registry database with local electronic health records, governmental database and linked open data collections, (5) Data quality control and (6) Data dissemination through the registry Web site. Our registry adopted all applicable standardized data elements proposed by American College Cardiology / American Heart Association Clinical Data Standards, as well as variables derived from cardiac devices randomized trials and Clinical Data Interchange Standards Consortium. Local interoperability was performed between REDCap and data derived from Electronic Health Record system. The original data set was also augmented by incorporating the reimbursed values paid by the Brazilian government during a hospitalization for pacemaker implantation. By linking our registry to the open data collection repository Linked Clinical Trials (LinkedCT) we found 130 clinical trials which are potentially correlated with our pacemaker registry. Conclusion This study demonstrates how standard and reproducible solutions can be applied in the implementation of medical registries to constitute a re-usable framework

  18. Hemodynamic monitoring and management of patients undergoing high-risk surgery: a survey among Chinese anesthesiologists.

    PubMed

    Chen, Guo; Zuo, Yunxia; Yang, Lei; Chung, Elena; Cannesson, Maxime

    2014-09-01

    Hemodynamic monitoring and optimization improve postoperative outcome during high-risk surgery. However, hemodynamic management practices among Chinese anesthesiologists are largely unknown. This study sought to evaluate the current intraoperative hemodynamic management practices for high-risk surgery patients in China. From September 2010 to November 2011, we surveyed anesthesiologists working in the operating rooms of 265 hospitals representing 28 Chinese provinces. All questionnaires were distributed to department chairs of anesthesiology or practicing anesthesiologists. Once completed, the 29-item questionnaires were collected and analyzed. Two hundred and 10 questionnaires from 265 hospitals in China were collected. We found that 91.4% of anesthesiologists monitored invasive arterial pressure, 82.9% monitored central venous pressure (CVP), 13.3% monitored cardiac output (CO), 10.5% monitored mixed venous saturation, and less than 2% monitored pulse pressure variation (PPV) or systolic pressure variation (SPV) during high-risk surgery. The majority (88%) of anesthesiologists relied on clinical experience as an indicator for volume expansion and more than 80% relied on blood pressure, CVP and urine output. Anesthesiologists in China do not own enough attention on hemodynamic parameters such as PPV, SPV and CO during fluid management in high-risk surgical patients. The lack of CO monitoring may be attributed largely to the limited access to technologies, the cost of the devices and the lack of education on how to use them. There is a need for improving access to these technologies as well as an opportunity to create guidelines and education for hemodynamic optimization in China. PMID:25332709

  19. The Prostate Cancer Intervention Versus Observation Trial: VA/NCI/AHRQ Cooperative Studies Program #407 (PIVOT): design and baseline results of a randomized controlled trial comparing radical prostatectomy with watchful waiting for men with clinically localized prostate cancer.

    PubMed

    Wilt, Timothy J

    2012-12-01

    categorizations incorporating PSA levels, Gleason histologic grade, and tumor stage, it was found that approximately 40% had low-risk, 34% had medium-risk, and 21% had high-risk prostate cancer based on local histopathology. Comparison to our national sample of eligible men declining PIVOT participation as well as to men enrolled in the Scandinavian trial indicated that PIVOT enrollees are representative of men being diagnosed and treated in the United States and quite different from men in the Scandinavian trial. PIVOT enrolled an ethnically diverse population representative of men diagnosed with prostate cancer in the United States. Results will yield important information regarding the relative effectiveness and harms of surgery compared with WW for men with predominately PSA-detected clinically localized prostate cancer. PMID:23271771

  20. A phase II study evaluating neo-/adjuvant EIA chemotherapy, surgical resection and radiotherapy in high-risk soft tissue sarcoma

    PubMed Central

    2011-01-01

    Abstract Background The role of chemotherapy in high-risk soft tissue sarcoma is controversial. Though many patients undergo initial curative resection, distant metastasis is a frequent event, resulting in 5-year overall survival rates of only 50-60%. Neo-adjuvant and adjuvant chemotherapy (CTX) has been applied to achieve pre-operative cytoreduction, assess chemosensitivity, and to eliminate occult metastasis. Here we report on the results of our non-randomized phase II study on neo-adjuvant treatment for high-risk STS. Method Patients with potentially curative high-risk STS (size ≥ 5 cm, deep/extracompartimental localization, tumor grades II-III [FNCLCC]) were included. The protocol comprised 4 cycles of neo-adjuvant chemotherapy (EIA, etoposide 125 mg/m2 iv days 1 and 4, ifosfamide 1500 mg/m2 iv days 1 - 4, doxorubicin 50 mg/m2 day 1, pegfilgrastim 6 mg sc day 5), definitive surgery with intra-operative radiotherapy, adjuvant radiotherapy and 4 adjuvant cycles of EIA. Result Between 06/2005 and 03/2010 a total of 50 subjects (male = 33, female = 17, median age 50.1 years) were enrolled. Median follow-up was 30.5 months. The majority of primary tumors were located in the extremities or trunk (92%), 6% originated in the abdomen/retroperitoneum. Response by RECIST criteria to neo-adjuvant CTX was 6% CR (n = 3), 24% PR (n = 12), 62% SD (n = 31) and 8% PD (n = 4). Local recurrence occurred in 3 subjects (6%). Distant metastasis was observed in 12 patients (24%). Overall survival (OS) and disease-free survival (DFS) at 2 years was 83% and 68%, respectively. Multivariate analysis failed to prove influence of resection status or grade of histological necrosis on OS or DFS. Severe toxicities included neutropenic fever (4/50), cardiac toxicity (2/50), and CNS toxicity (4/50) leading to CTX dose reductions in 4 subjects. No cases of secondary leukemias were observed so far. Conclusion The current protocol is feasible for achieving local control rates, as well as OS and

  1. Gender Disparities in Latent Tuberculosis Infection in High-Risk Individuals: A Cross-Sectional Study

    PubMed Central

    Ting, Wen-Ying; Huang, Shiang-Fen; Lee, Ming-Che; Lin, Yung-Yang; Lee, Yu-Chin

    2014-01-01

    Male predominance in active tuberculosis (TB) is widely-reported globally. Gender inequalities in socio-cultural status are frequently regarded as contributing factors for disparities in sex in active TB. The disparities of sex in the prevalence of latent TB infection (LTBI) are less frequently investigated and deserve clarification. In this cross-sectional study conducted in a TB endemic area, we enrolled patients at high-risk for LTBI and progression from LTBI to active TB from 2011 to 2012. Diagnosis of LTBI was made by QuantiFERON-TB Gold In-Tube (QFT-GIT). Differences in sex in terms of prevalence of LTBI and clinical predictors for LTBI were investigated. Associations among age, smoking status, and sex disparities in LTBI were also analyzed. A total of 1018 high-risk individuals with definite QFT-GIT results were included for analysis, including 534 males and 484 females. The proportion of LTBI was significantly higher in males than in females (32.6% vs. 25.2%, p = 0.010). Differences in the proportion of LTBI between sexes were most prominent in older patients (age ≥55 years). In multivariate analysis, independent clinical factors associated with LTBI were age (p = 0.014), smoking (p = 0.048), and fibro-calcified lesions on chest radiogram (p = 0.009). Male sex was not an independent factor for LTBI (p = 0.88). When stratifying patients according to the smoking status, the proportion of LTBI remained comparable between sexes among smokers and non-smokers. In conclusion, although the proportion of LTBI is higher in men, there is no significant disparity in terms of sex in LTBI among high-risk individuals after adjusting for age, smoking status, and other clinical factors. PMID:25369472

  2. A Multi-Dimensional and Integrative Approach to Examining the High-Risk and Ultra-High-Risk Stages of Bipolar Disorder

    PubMed Central

    Lin, Kangguang; Xu, Guiyun; Wong, Nichol M.L.; Wu, Huawang; Li, Ting; Lu, Weicong; Chen, Kun; Chen, Xiaodong; Lai, Bingyin; Zhong, Liuxia; So, Kwok-fai; Lee, Tatia M.C.

    2015-01-01

    Background Validating the high-risk (HR) and ultra-high-risk (UHR) stages of bipolar disorder (BP) may help enable early intervention strategies. Methods We followed up with 44 offspring of parents with BP, subdividing into the HR and UHR categories. The offspring were aged 8–28 years and were free of any current DSM-IV diagnoses. Our multilevel, integrative approach encompassed gray matter (GM) volumes, brain network connectivity, neuropsychological performance, and clinical outcomes. Findings Compared with the healthy controls (HCs) (n = 33), the HR offspring (n = 26) showed GM volume reductions in the right orbitofrontal cortex. Compared with the HR offspring, the UHR offspring (n = 18) exhibited increased GM volumes in four regions. Both the HR and UHR offspring displayed abnormalities in the inferior occipital cortex regarding the measures of degree and centrality, reflecting the connections and roles of the region, respectively. In the UHR versus the HR offspring, the UHR offspring exhibited upwards-shifted small world topologies that reflect high clustering and efficiency in the brain networks. Compared with the HCs, the UHR offspring had significantly lower assortativity, which was suggestive of vulnerability. Finally, processing speed, visual–spatial, and general function were impaired in the UHR offspring but not in the HR offspring. Interpretation The abnormalities observed in the HR offspring appear to be inherited, whereas those associated with the UHR offspring represent stage-specific changes predisposing them to developing the disorder. PMID:26425699

  3. Identifying patients at high risk of breast cancer recurrence: strategies to improve patient outcomes

    PubMed Central

    Martei, Yehoda M; Matro, Jennifer M

    2015-01-01

    Identifying patients at high risk of breast cancer recurrence has important implications not only for enabling the ability to provide accurate information to patients but also the potential to improve patient outcomes. Patients at high recurrence risk can be offered appropriate treatment to improve the overall survival. However, the major challenge is identifying patients with early-stage breast cancer at lower risk who may be spared potentially toxic therapy. The successful integration of molecular assays into clinical practice may address the problem of overtreatment and improve overall patient outcomes. PMID:26504408

  4. Fifteen-Year Biochemical Relapse-Free Survival, Cause-Specific Survival, and Overall Survival Following I{sup 125} Prostate Brachytherapy in Clinically Localized Prostate Cancer: Seattle Experience

    SciTech Connect

    Sylvester, John E.; Grimm, Peter D.; Wong, Jason; Galbreath, Robert W.; Merrick, Gregory; Blasko, John C.

    2011-10-01

    Purpose: To report 15-year biochemical relapse-free survival (BRFS), cause-specific survival (CSS), and overall survival (OS) outcomes of patients treated with I{sup 125} brachytherapy monotherapy for clinically localized prostate cancer early in the Seattle experience. Methods and Materials: Two hundred fifteen patients with clinically localized prostate cancer were consecutively treated from 1988 to 1992 with I{sup 125} monotherapy. They were prospectively followed as a tight cohort. They were evaluated for BRFS, CSS, and OS. Multivariate analysis was used to evaluate outcomes by pretreatment clinical prognostic factors. BRFS was analyzed by the Phoenix (nadir + 2 ng/mL) definition. CSS and OS were evaluated by chart review, death certificates, and referring physician follow-up notes. Gleason scoring was performed by general pathologists at a community hospital in Seattle. Time to biochemical failure (BF) was calculated and compared by Kaplan-Meier plots. Results: Fifteen-year BRFS for the entire cohort was 80.4%. BRFS by D'Amico risk group classification cohort analysis was 85.9%, 79.9%, and 62.2% for low, intermediate, and high-risk patients, respectively. Follow-up ranged from 3.6 to 18.4 years; median follow-up was 15.4 years for biochemically free of disease patients. Overall median follow-up was 11.7 years. The median time to BF in those who failed was 5.1 years. CSS was 84%. OS was 37.1%. Average age at time of treatment was 70 years. There was no significant difference in BRFS between low and intermediate risk groups. Conclusion: I{sup 125} monotherapy results in excellent 15-year BRFS and CSS, especially when taking into account the era of treatment effect.

  5. Adjuvant treatment in patients at high risk of recurrence of thymoma: efficacy and safety of a three-dimensional conformal radiation therapy regimen

    PubMed Central

    Perri, Francesco; Pisconti, Salvatore; Conson, Manuel; Pacelli, Roberto; Della Vittoria Scarpati, Giuseppina; Gnoni, Antonio; D’Aniello, Carmine; Cavaliere, Carla; Licchetta, Antonella; Cella, Laura; Giuliano, Mario; Schiavone, Concetta; Falivene, Sara; Di Lorenzo, Giuseppe; Buonerba, Carlo; Ravo, Vincenzo; Muto, Paolo

    2015-01-01

    Background The clinical benefits of postoperative radiation therapy (PORT) for patients with thymoma are still controversial. In the absence of defined guidelines, prognostic factors such as stage, status of surgical margins, and histology are often considered to guide the choice of adjuvant treatment (radiotherapy and/or chemotherapy). In this study, we describe our single-institution experience of three-dimensional conformal PORT administered as adjuvant treatment to patients with thymoma. Methods Twenty-two consecutive thymoma patients (eleven male and eleven female) with a median age of 52 years and treated at our institution by PORT were analyzed. The patients were considered at high risk of recurrence, having at least one of the following features: stage IIB or III, involved resection margins, or thymic carcinoma histology. Three-dimensional conformal PORT with a median total dose on clinical target volume of 50 (range 44–60) Gy was delivered to the tumor bed by 6–20 MV X-ray of the linear accelerator. Follow-up after radiotherapy was done by computed tomography scan every 6 months for 2 years and yearly thereafter. Results Two of the 22 patients developed local recurrence and four developed distant metastases. Median overall survival was 100 months, and the 3-year and 5-year survival rates were 83% and 74%, respectively. Median disease-free survival was 90 months, and the 5-year recurrence rate was 32%. On univariate analysis, pathologic stage III and presence of positive surgical margins had a significant impact on patient prognosis. Radiation toxicity was mild in most patients and no severe toxicity was registered. Conclusion Adjuvant radiotherapy achieved good local control and showed an acceptable toxicity profile in patients with high-risk thymoma. PMID:26089683

  6. A study of Minnesota's high-risk health insurance pool.

    PubMed

    Zellner, B B; Haugen, D K; Dowd, B

    1993-01-01

    This is a report of a study of Minnesota's high-risk health insurance pool for "medically uninsurable" persons. The study consisted of a survey of current and past enrollees carried out in the Spring of 1990 and an analysis of the claims and membership files for 1988 and 1989. The main policy conclusion we reached is that Minnesota's high-risk pool is an adequate approach to the problem raised by risk segmentation on the basis of health status, providing that enrollment remains a small fraction of the population. The recent high, enrollment growth rates the Minnesota risk pool has experienced raise the possibility that basic structural reforms of the nongroup and small-group health insurance markets are needed. PMID:8314605

  7. Applying the lessons of high risk industries to health care.

    PubMed

    Hudson, P

    2003-12-01

    High risk industries such as commercial aviation and the oil and gas industry have achieved exemplary safety performance. This paper reviews how they have managed to do that. The primary reasons are the positive attitudes towards safety and the operation of effective formal safety management systems. The safety culture provides an important explanation of why such organisations perform well. An evolutionary model of safety culture is provided in which there is a range of cultures from the pathological through the reactive to the calculative. Later, the proactive culture can evolve towards the generative organisation, an alternative description of the high reliability organisation. The current status of health care is reviewed, arguing that it has a much higher level of accidents and has a reactive culture, lagging behind both high risk industries studied in both attitude and systematic management of patient risks. PMID:14645741

  8. Optimization of molecular radiotherapy with [131I]-meta Iodobenzylguanidine for high-risk neuroblastoma.

    PubMed

    Gaze, M N; Gains, J E; Walker, C; Bomanji, J B

    2013-03-01

    Molecular radiotherapy with [131I]-meta Iodobenzylguanidine ([131I]-mIBG) for neuroblastoma has been in clinical use for nearly 30 years. In this time, its role has changed from being an exclusively palliative treatment to one where the intent of treatment is often curative. To achieve this, the treatment has been brought forward from the relapse setting, to the beginning as induction therapy, as a possibility for salvage of those with chemo-refractory disease or as part of consolidation schedules. With the routine use of hemopoietic support, higher than previously standard administered activities are now commonly used. Other attempts to improve outcomes include the concomitant use of chemotherapy and radiation sensitisers and novel formulations such as no-carrier added [131I]-mIBG. Unfortunately, none of these strategies has been evaluated in a randomized controlled trial, so whether the theoretical benefits of these innovative approaches are seen clinically remains a matter of conjecture. Despite the prevalent belief in using higher administered activities, dosimetry has been under-used, hampering the ability to detect the benefit of this strategy. To properly evaluate concepts aiming at the optimisation of molecular radiotherapy with [131I]-mIBG for high-risk neuroblastoma, careful dosimetry in well-designed randomized clinical trials is essential. Only in this way will it be possible for [131I]-mIBG to be used to its best advantage in the complex multimodality treatment schedules required for high-risk neuroblastoma. PMID:23474636

  9. Identifying Older Chinese Immigrants at High Risk for Osteoporosis

    PubMed Central

    Lauderdale, Diane S; Kuohung, Victoria; Chang, Suey-Lee; Chin, Marshall H

    2003-01-01

    BACKGROUND Data about whether Asian Americans are a high-risk or a low-risk group for osteoporosis are limited and inconsistent. Few previous studies have recognized that the heterogeneity of the Asian American population, with respect to both nativity (foreign- vs U.S.-born) and ethnicity, may be related to osteoporosis risk. OBJECTIVE To assess whether older foreign-born Chinese Americans living in an urban ethnic enclave are at high risk of osteoporosis and to refer participants at high risk for follow-up care. DESIGN Cross-sectional survey and osteoporosis screening, undertaken as a collaborative project by the Chinese American Service League and researchers at the University of Chicago. SETTING Chicago's Chinatown. PARTICIPANTS Four hundred sixty-nine immigrant Chinese American men and women aged 50 and older. MEASUREMENTS AND MAIN RESULTS Chinese Americans in this urban setting are generally recent immigrants from south China with limited education and resources: mean age at immigration was 54, 56% had primary only or no education, and 57% reported “fair” or “poor” self-rated health. Eighteen percent are uninsured and 55% receive Medicaid. Bone mineral density (BMD) of the calcaneus was estimated using quantitative ultrasound. Immigrant Chinese women in the study had lower average BMD than reference data for white women or U.S.-born Asian Americans. BMD for immigrant Chinese men in the study was similar to white men at ages 50 to 69, and lower at older ages. Low body mass index, low educational attainment and older age at immigration were all associated with lower BMD. CONCLUSIONS Foreign-born Chinese Americans may be a high-risk group for osteoporosis. PMID:12848833

  10. Outcomes of parental investment in high-risk children.

    PubMed

    Bugental, Daphne Blunt; Corpuz, Randy; Samec, Rachel

    2013-09-01

    This study assesses the combined effects of children's early medical risk (e.g., preterm status) and parental investment levels (time spent in provision of care to target children as opposed to other family members) on children's response to novel, potentially distressing stimuli. While engaged in play activities, children were exposed to stimuli that were either neutral (a speaker on television with a calm voice) or threatening (a speaker with an angry voice). A significant interaction between children's risk status and parental investment was found only for threatening stimuli. High-risk children with high-investing parents showed high visual engagement with potentially threatening responses, whereas high-risk children with low-investing parents were more likely to show visual avoidance. No comparable effects were found for low-risk children. Findings were interpreted as showing that high-risk children with a history of high parental investment are more likely to attend to potentially threatening events, an adaptive response in the presence of reliable support. PMID:23465334

  11. Evaluating complications of local anesthesia administration and reversal with phentolamine mesylate in a portable pediatric dental clinic.

    PubMed

    Boynes, Sean G; Riley, Amah E; Milbee, Sarah; Bastin, Meghan R; Price, Maylyn E; Ladson, Andrea

    2013-08-01

    This study sought to identify and quantify complications with local anesthetic administration and reversal on consecutive patients seen for comprehensive dental care in a school-based, portable dental clinic, and includes data on the patients seen by the participating portable dental providers. In 923 dental visits where local anesthetic was administered, a standardized form was used to gain further information and identify any complications; this was accompanied by a questionnaire for the student's teacher, in order to quantify the student's distraction and disruption ratings following the dental visit. After statistical analysis of the 923 consecutive cases, the overall complication rate was 5.3%. All of the complications were considered to be mild or moderate, and there were no severe event reports. The complications encountered most frequently (n = 49) were associated with self-inflicted soft tissue injury. The results of this study indicate that comprehensive care with local anesthesia delivered by a school-based portable dental clinic has a low risk of complications. Whereas safe administration of dental care is achievable with or without phentolamine mesylate as a local anesthetic reversal agent, its use was determined to improve safety outcomes. Three factors appeared to directly increase the incidence of complications: the administration of an inferior alveolar nerve block, attention deficit disorder, and obesity. Teacher evaluations demonstrated that children receiving care by a portable dental team were able to reorient back to classwork and were not disruptive to classmates. PMID:23928444

  12. Prophylactic Ketoconazole Shampoo for Tinea Capitis in a High-Risk Pediatric Population

    PubMed Central

    Bookstaver, P. Brandon; Watson, Holly J.; Winters, Shauna D.; Carlson, Adrian L.; Schulz, Richard M.

    2011-01-01

    OBJECTIVES Although topical agents for the treatment of tinea capitis decrease viable fungal elements and reduce shedding, their use as a prophylactic agent has not been investigated. This study evaluated the effectiveness of a prophylactic ketoconazole shampoo (Nizoral 2%) protocol to reduce the number of clinically evident tinea capitis infections in a high-risk African American, urban population. METHODS We conducted a retrospective analysis of a ketoconazole prophylaxis protocol that was implemented at an urban pediatric clinic for medically fragile children. Patients at high risk for tinea capitis received twice-weekly ketoconazole shampoo. The primary outcome of the study was a reduction in the number of documented tinea capitis infections between the 12-month preprotocol and 12-month postprotocol periods. A secondary outcome included the evaluation of predisposing risk factors for acquiring tinea infections. RESULTS Ninety-seven patients, with a mean age of 8.06 years, were included. Most patients (78%) were African American. There were a total of 13 tinea capitis infections during the 12-month preprotocol period. During the 12-month postprotocol period, 41 infections were documented: 37 (90.2%) in the prophylaxis group and 4 (9.8%) in the nonprophylaxis group. The average numbers of per-patient infections in the postprotocol period were 0.79 and 0.08 in the prophylaxis and nonprophylaxis groups, respectively. Initiation of prophylaxis did not reduce tinea capitis infections (p=NS). Previous history of infection and a high level of care were significant predictors of infections (p<0.05). CONCLUSIONS Improved hygiene, adherence to prescribed treatment regimens, and prevention of recurrent environmental exposure to surviving fomites should be stressed in high-risk patients and supersede the need for an antifungal (ketoconazole shampoo) prophylaxis protocol. PMID:22479162

  13. Candidate Risks Indicators for Bipolar Disorder: Early Intervention Opportunities in High-Risk Youth

    PubMed Central

    Jones, Steven; Goodday, Sarah; Bentall, Richard

    2016-01-01

    Background: Psychiatric illnesses like bipolar disorder are increasingly understood to be neurodevelopmental disorders with clinical, psychological, and biological indicators recognizable long before the emergence of the full-blown syndromes. Methods: This paper is a selective review of findings from studies of high-risk children of affected parents that inform the knowledge of illness risk and development markers of bipolar disorder. We specifically focus on candidate clinical, biological, and psychological risk indicators that could serve as targets for future early intervention and prevention studies. Results: There is convergent evidence from prospective studies that bipolar disorder typically debuts as depressive episodes after puberty. In some high-risk children, sleep and anxiety disorders precede mood disorders by several years and reflect an increased vulnerability. An association between early exposure to adversity (eg, exposure to parental illness, neglect from mother) and increased risk of psychopathology may be mediated through increased stress reactivity evident at both behavioral and biological levels. Inter-related psychological processes including reward sensitivity, unstable self-esteem, rumination, and positive self-appraisal are risk factors for mood disorders. Disturbances in circadian rhythm and immune dysfunction are associated with mood disorders and may be vulnerability markers influenced by these other risk factors. Conclusions: There is accruing evidence of a number of measurable and potentially modifiable markers of vulnerability and developing illness in youth at familial risk for bipolar disorder. Longitudinal studies of multiple biological and psychological risk processes in high-risk offspring, both individually and together, will improve our understanding of illness onset and lead to the development of specific early interventions. PMID:26116493

  14. Sorafenib Neoadjuvant Therapy in the Treatment of High Risk Renal Cell Carcinoma

    PubMed Central

    Zhang, Yushi; Li, Yongqiang; Deng, Jianhua; Ji, Zhigang; Yu, Hongyan; Li, Hanzhong

    2015-01-01

    Objective To evaluate the clinical efficacy of sorafenib as preoperative neoadjuvant therapy in patients with high risk renal cell carcinoma (RCC). Materials and Methods Clinical data of 18 patients with high risk RCC who received surgery done successfully after preoperative neoadjuvant therapy with sorafenib in Peking Union Medical College Hospital (PUMCH) from April 2007 to October 2013 have been reviewed and analyzed in this study. Results Among the 18 patients there were 13 male and 5 female, with a median age of 54.6 years. The objective response rate (ORR) of the operation on the selected patients is very high (94.4%), including 4 cases (22.2%) of partial response (PR) and 13 cases (72.2%) of stable disease (SD). After preoperative sorafenib treatment, the average tumor size of the 18 patients decreased from 7.8 cm (ranging from 3.6 to 19.2 cm) to 6.2 cm (ranging from 2.4 to 16.8 cm), and the median value of average tumor CT value decreased from 61HU to 52 HU. Among the 5 patients who had IVC tumor thrombi, the grades of tumor thrombi in 2 patients who were grade II before sorafenib treatment became grade I and grade 0 respectively, 2 patients of grade III both became grade II. Conclusion Preoperative neoadjuvant therapy with sorafenib for high risk RCC patients can significantly decrease primary tumor volume as well as tumor thrombus, which could help the nephron-sparing surgery (NSS) or radical nephrectomy to be done successfully. PMID:25647522

  15. High-Dose-Rate Interstitial Brachytherapy as Monotherapy for Clinically Localized Prostate Cancer: Treatment Evolution and Mature Results

    SciTech Connect

    Zamboglou, Nikolaos; Tselis, Nikolaos; Baltas, Dimos; Buhleier, Thomas; Martin, Thomas; Milickovic, Natasa; Papaioannou, Sokratis; Ackermann, Hanns; Tunn, Ulf W.

    2013-03-01

    Purpose: To report the clinical outcome of high-dose-rate (HDR) interstitial (IRT) brachytherapy (BRT) as sole treatment (monotherapy) for clinically localized prostate cancer. Methods and Materials: Between January 2002 and December 2009, 718 consecutive patients with clinically localized prostate cancer were treated with transrectal ultrasound (TRUS)-guided HDR monotherapy. Three treatment protocols were applied; 141 patients received 38.0 Gy using one implant in 4 fractions of 9.5 Gy with computed tomography-based treatment planning; 351 patients received 38.0 Gy in 4 fractions of 9.5 Gy, using 2 implants (2 weeks apart) and intraoperative TRUS real-time treatment planning; and 226 patients received 34.5 Gy, using 3 single-fraction implants of 11.5 Gy (3 weeks apart) and intraoperative TRUS real-time treatment planning. Biochemical failure was defined according to the Phoenix consensus, and toxicity was evaluated using Common Toxicity Criteria for Adverse Events version 3. Results: The median follow-up time was 52.8 months. The 36-, 60-, and 96-month biochemical control and metastasis-free survival rates for the entire cohort were 97%, 94%, and 90% and 99%, 98%, and 97%, respectively. Toxicity was scored per event, with 5.4% acute grade 3 genitourinary and 0.2% acute grade 3 gastrointestinal toxicity. Late grade 3 genitourinary and gastrointestinal toxicities were 3.5% and 1.6%, respectively. Two patients developed grade 4 incontinence. No other instance of grade 4 or greater acute or late toxicity was reported. Conclusion: Our results confirm IRT-HDR-BRT is safe and effective as monotherapy for clinically localized prostate cancer.

  16. [Ophthalmic complications and local anesthesia. Pathophysiology and types of eye complications after intraoral dental anesthesia, and clinical recommendations].

    PubMed

    von Arx, Thomas; Lozanoff, Scott; Zinkernagel, Martin

    2014-01-01

    The present article reviews the different types of ophthalmologic complications following administration of intraoral local anesthesia. Since the first report by Brain in 1936, case reports about that topic have been published regularly in the literature. However, clinical studies evaluating the incidence of ophthalmologic complications after intraoral local anesthesia are rarely available. Previous data point to a frequency ranging from 0.03% to 0.13%. The most frequently described ophthalmologic complications include diplopia (double vision), ptosis (drooping of upper eyelid), and mydriasis (dilatation of pupil). Disorders that rather affect periorbital structures than the eye directly include facial paralysis and periorbital blanching (angiospasm). Diverse pathophysiologic mechanisms and causes have been reported in the literature, with the inadvertent intravascular administration of the local anesthetic considered the primary reason. The agent as well as the vasopressor is transported retrogradely via arteries or veins to the orbit or to periorbital structures (such as the cavernous sinus) with subsequent anesthesia of nerves and paralysis of muscles distant from the oral cavity. In general the ophthalmologic complications begin shortly after administration of the local anesthesia, and disappear once the local anesthesia has subsided. PMID:25428546

  17. Hypofractionated Concomitant Intensity-Modulated Radiotherapy Boost for High-Risk Prostate Cancer: Late Toxicity

    SciTech Connect

    Quon, Harvey; Cheung, Patrick C.F.; Loblaw, D. Andrew; Morton, Gerard; Pang, Geordi; Szumacher, Ewa; Danjoux, Cyril; Choo, Richard; Thomas, Gillian; Kiss, Alex; Mamedov, Alexandre; Deabreu, Andrea

    2012-02-01

    Purpose: To report the acute and late toxicities of patients with high-risk localized prostate cancer treated using a concomitant hypofractionated, intensity-modulated radiotherapy boost combined with long-term androgen deprivation therapy. Methods and Materials: A prospective Phase I-II study of patients with any of the following: clinical Stage T3 disease, prostate-specific antigen level {>=}20 ng/mL, or Gleason score 8-10. A dose of 45 Gy (1.8 Gy/fraction) was delivered to the pelvic lymph nodes with a concomitant 22.5 Gy prostate intensity-modulated radiotherapy boost, to a total of 67.5 Gy (2.7 Gy/fraction) in 25 fractions within 5 weeks. Image guidance was performed using three gold seed fiducials. The National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0, and Radiation Therapy Oncology Group late morbidity scores were used to assess the acute and late toxicities, respectively. Biochemical failure was determined using the Phoenix definition. Results: A total of 97 patients were treated and followed up for a median of 39 months, with 88% having a minimum of 24 months of follow-up. The maximal toxicity scores were recorded. The grade of acute gastrointestinal toxicity was Grade 0 in 4%, 1 in 59%, and 2 in 37%. The grade of acute urinary toxicity was Grade 0 in 8%, 1 in 50%, 2 in 39%, and 3 in 4%. The grade of late gastrointestinal toxicity was Grade 0 in 54%, 1 in 40%, and 2 in 7%. No Grade 3 or greater late gastrointestinal toxicities developed. The grade of late urinary toxicity was Grade 0 in 82%, 1 in 9%, 2 in 5%, 3 in 3%, and 4 in 1% (1 patient). All severe toxicities (Grade 3 or greater) had resolved at the last follow-up visit. The 4-year biochemical disease-free survival rate was 90.5%. Conclusions: A hypofractionated intensity-modulated radiotherapy boost delivering 67.5 Gy in 25 fractions within 5 weeks combined with pelvic nodal radiotherapy and long-term androgen deprivation therapy was well tolerated, with low rates

  18. Pragmatic fluid optimization in high-risk surgery patients: when pragmatism dilutes the benefits.

    PubMed

    Reuter, Daniel A

    2012-01-01

    There is increasing evidence that hemodynamic optimization by fluid loading, particularly when performed in the early phase of surgery, is beneficial in high-risk surgery patients: it leads to a reduction in postoperative complications and even to improved long-term outcome. However, it is also true that goal- directed strategies of fluid optimization focusing on cardiac output optimization have not been applied in the clinical routine of many institutions. Reasons are manifold: disbelief in the level of evidence and on the accuracy and practicability of the required monitoring systems, and economics. The FOCCUS trial examined perioperative fluid optimization with a very basic approach: a standardized volume load with 25 ml/kg crystalloids over 6 hours immediately prior to scheduled surgery in high-risk patients. The hypothesis was that this intervention would lead to a compensation of preoperative fluid deficit caused by overnight fasting, and would result in improved perioperative fluid homeostasis with less postoperative complications and earlier hospital discharge. However, the primary study endpoints did not improve significantly. This observation points towards the facts that: firstly, the differentiation between interstitial fluid deficit caused by fasting and intravascular volume loss due to acute blood loss must be recognized in treatment strategies; secondly, the type of fluid replacement may play an important role; and thirdly, protocolized treatment strategies should also always be tailored to suit the patients' individual needs in every individual clinical situation. PMID:22410167

  19. Treatment of a High-Risk Diabetic Patient with Peripheral Vascular Disease and Osteomyelitis.

    PubMed

    Allen, Latricia L; Kalmar, Garrett; Driver, Vickie R

    2016-06-01

    We report a case of calcaneal osteomyelitis that was surgically resected from a patient with diabetes and peripheral vascular disease. A 91-year-old male with history of type 2 diabetes, peripheral vascular disease, balloon angioplasty, and recent (2 months ago) stent of the superficial femoral artery presented to the emergency department with a left heel wound infection probed to bone. The patient reported having been on intravenous Zosyn for several months via an outside infectious disease provider for clinical suspicion of osteomyelitis, but noted no improvement. This report includes information regarding the clinical examination and imaging findings, which were used to assess this high-risk patient. Our patient underwent a partial calcanectomy and completed a 6-week course of intravenous antibiotics. The purpose of this case report is to illustrate limb preservation in a high-risk patient with compromised vascular supply who underwent a partial calcanectomy for treatment of calcaneal osteomyelitis. The patient underwent surgical resection of the calcaneus without complications and healed unremarkably with the ability to ambulate while wearing an ankle foot orthosis with a custom shoe. This report was authorized for publication as an educational report to contribute to generalizable knowledge and does not include any patient health information. PMID:27423990

  20. Effectiveness of splinting and splinting plus local steroid injection in severe carpal tunnel syndrome: A Randomized control clinical trial

    PubMed Central

    Khosrawi, Saeid; Emadi, Masoud; Mahmoodian, Amir Ebrahim

    2016-01-01

    Background: The Study aimed to compare the effectiveness of two commonly used conservative treatments, splinting and local steroid injection in improving clinical and nerve conduction findings of the patients with severe carpal tunnel syndrome (CTS). Materials and Methods: In this randomized control clinical trial, the patients with severe CTS selected and randomized in two interventional groups. Group A was prescribed to use full time neutral wrist splint and group B was injected with 40 mg Depo-Medrol and prescribed to use the full time neutral wrist splint for 12 weeks. Clinical and nerve conduction findings of the patients was evaluated at baseline, 4 and 12 weeks after interventions. Results: Twenty-two and 21 patients were allocated in group A and B, respectively. Mean of clinical symptoms and functional status scores, nerve conduction variables and patients’ satisfaction score were not significant between group at baseline and 4 and 12 weeks after intervention. Within the group comparison, there was significant improvement in the patients’ satisfaction, clinical and nerve conduction items between the baseline level and 4 weeks after intervention and between the baseline and 12 weeks after intervention (P < 0.01). The difference was significant for functional status score between 4 and 12 weeks after intervention in group B (P = 0.02). Conclusion: considering some findings regarding the superior effect of splinting plus local steroid injection on functional status scale and median nerve distal motor latency, it seems that using combination therapy could be more effective for long-term period specially in the field of functional improvement of CTS. PMID:26962518

  1. [Progress of clinical application of functional MRI in the localization of brain language area].

    PubMed

    Zhang, Nan; Lu, Junfeng; Wu, Jinsong

    2016-02-01

    For surgical operation in the functional area in the brain, it's commonly demanded to resect the lesion to the maximal extent on the basis of preserve the normal neural function, thus the precise localization of functional area is extremely important. As for the advantages of being widely available, easy to grasp and non-invasive, the functional MRI (fMRI) has come into wide use, while the application of language fMRI is still in the initial stage. It's important to choose appropriate fMRI task according to the individual condition of the subject, the commonly-adopted tasks include verb generation, picture naming, word recognition, word generation, etc. However, the effectiveness of using fMRI to localize language area is not totally satisfactory, adopting multiple task is an effective approach to improve the sensitivity of this technique. The application of resting state fMRI in the localization of language area and the further research of the role of fMRI in localizing the Chinese language area are the important future directions. PMID:26876086

  2. Autonomic dysfunction in subjects at high risk for Parkinson's disease.

    PubMed

    Liepelt-Scarfone, Inga; Pilotto, Andrea; Müller, Katharina; Bormann, Christian; Gauss, Katharina; Wurster, Isabel; Streffer, Johannes; Berg, Daniela

    2015-12-01

    Aim of this project was to evaluate autonomic dysfunction in subjects proposed to be at high risk to develop Parkinson's disease (PD) compared to control subjects and PD patients at different disease stages. Combinations of substantia nigra hyperechogenicity (SN+) assessed by transcranial ultrasound (TCS), hyposmia, lifetime prevalence of depression and mild PD-specific motor signs were used to identify subjects at high risk for motor Parkinson's disease (HR-PD). Supine and standing blood pressure (BP), hearth rate (HR), orthostatic, urinary, sexual and bowel symptoms were evaluated in HR-PD, healthy control subjects and PD patients, divided into mild and advanced stages. The study group consisted of 113 PD patients (mild PD n = 71, advanced PD, n = 42), 40 HR-PD individuals and 50 controls. Compared to controls, HR-PD subjects complained more often about urinary (p = 0.002) and bowel dysfunction (p = 0.001) and had a higher diastolic BP drop after standing (p = 0.01). The cumulative number of autonomic symptoms differentiated PD as well as HR-PD significantly from controls (p < 0.001). Advanced PD patients presented often and severe orthostatic symptoms, not significantly different from mild PD after concomitant medication correction. Our results support the presence of urinary and bowel dysfunction in subjects at high risk for motor PD. Presence and severity of orthostatic symptoms was higher during stages and increase in advanced stages, at least partly due to increase in dopaminergic and conflicting medication. Understanding the progression of non-motor aspects in PD might offer the possibility to use them as targets for disease-modifying therapies. PMID:26530505

  3. Economic effects of aspergillosis management in high-risk patients.

    PubMed

    Leather, Helen

    2005-04-01

    Aspergillosis mortality has risen exponentially over the last 2 decades, related primarily to the availability of medical treatments and procedures that prolong the survival of patients with other disorders who are at high risk because of immunologic compromise. In addition to excess mortality, aspergillosis results in increased costs for hospitalization and treatment, including management of adverse events associated with conventional amphotericin B treatment. Compared with amphotericin B, the triazole antifungal voriconazole has excellent efficacy and a favorable side-effect profile. Reliable oral bioavailability of voriconazole may permit switching to an oral formulation in the inpatient setting and offers the possibility of earlier hospital discharge and potentially substantial cost savings. PMID:15889762

  4. Antiplatelet therapy in populations at high risk of atherothrombosis.

    PubMed

    Faxon, David P; Nesto, Richard W

    2006-05-01

    Atherothrombosis is the most common cause of an acute ischemic event. Antiplatelet agents form the cornerstone of atherothrombosis prevention. The purpose of this article is to review the use of antiplatelet agents in patients that are at particularly high risk of atherothrombotic events. To undertake this review, we searched the literature to identify key studies on the use of antiplatelet agents in this group of patients. Antiplatelet agents, such as aspirin and clopidogrel, play a fundamental role in the treatment and management of secondary thrombotic events. The routine use of aspirin is recommended, as it has been shown to reduce the risk of thrombotic events by approximately 25%. Additional benefit has been demonstrated with clopidogrel, both as a monotherapy and in combination with aspirin. In the CAPRIE trial, 19,185 patients with atherosclerotic vascular disease were randomized to receive clopidogrel (75 mg/day) or aspirin (325 mg/day) for a mean duration of follow-up of 1.91 years. Clopidogrel provided an additional 8.7% relative risk reduction in the primary composite endpoint of ischemic stroke, myocardial infraction or vascular death compared with aspirin. In the CURE trial, the addition of clopidogrel to background aspirin was associated with a 20% relative risk reduction in a composite of death from cardiovascular causes, nonfatal myocardial infarction or stroke compared with aspirin alone. In patients undergoing PCI as part of the PCI-CURE substudy, clopidogrel was associated with a 30% relative reduction in the incidence of cardiovascular events in the first 30 days after intervention compared with aspirin. The benefits of antiplatelet therapy continue to be investigated. Whether dual antiplatelet therapy is superior to aspirin monotherapy for high-risk primary prevention is unknown. The ongoing CHARISMA trial aims to determine the relative efficacies of aspirin monotherapy and aspirin/clopidogrel combination therapy in a broad range of high-risk

  5. Preoperative patient assessment: Identifying patients at high risk.

    PubMed

    Boehm, O; Baumgarten, G; Hoeft, A

    2016-06-01

    Postoperative mortality remains alarmingly high with a mortality rate ranging between 0.4% and 4%. A small subgroup of multimorbid and/or elderly patients undergoing different surgical procedures naturally confers the highest risk of complications and perioperative death. Therefore, preoperative assessment should identify these high-risk patients and stratify them to individualized monitoring and treatment throughout all phases of perioperative care. A "tailored" perioperative approach might help further reduce perioperative morbidity and mortality. This article aims to elucidate individual morbidity-specific risks. It further suggests approaches to detect patients at the risk of perioperative complications. PMID:27396802

  6. Fetal and umbilical Doppler ultrasound in high-risk pregnancies

    PubMed Central

    Alfirevic, Zarko; Stampalija, Tamara; Gyte, Gillian ML

    2014-01-01

    Background Abnormal blood flow patterns in fetal circulation detected by Doppler ultrasound may indicate poor fetal prognosis. It is also possible false positive Doppler ultrasound findings could encourage inappropriate early delivery. Objectives The objective of this review was to assess the effects of Doppler ultrasound used to assess fetal well-being in high-risk pregnancies on obstetric care and fetal outcomes. Search methods We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (September 2009) and the reference lists of identified studies. Selection criteria Randomised and quasi-randomised controlled trials of Doppler ultrasound for the investigation of umbilical and fetal vessels waveforms in high-risk pregnancies compared to no Doppler ultrasound. Data collection and analysis Two authors independently assessed the studies for inclusion, assessed risk of bias and carried out data extraction. Data entry was checked. Main results Eighteen completed studies involving just over 10,000 women were included. The trials were generally of unclear quality with some evidence of possible publication bias. The use of Doppler ultrasound in high-risk pregnancy was associated a reduction in perinatal deaths (risk ratio (RR) 0.71, 95% confidence interval (CI) 0.52 to 0.98, 16 studies, 10,225 babies, 1.2% versus 1.7 %, numbers needed to treat = 203; 95%CI 103 to 4352). There were also fewer inductions of labour (average RR 0.89, 95% CI 0.80 to 0.99, 10 studies, 5633 women, random effects) and fewer caesarean sections (RR 0.90, 95% CI 0.84 to 0.97, 14 studies, 7918 women). No difference was found in operative vaginal births (RR 0.95, 95% CI 0.80 to 1.14, four studies, 2813 women) nor in Apgar scores less than seven at five minutes (RR 0.92, 95% CI 0.69 to 1.24, seven studies, 6321 babies). Authors’ conclusions Current evidence suggests that the use of Doppler ultrasound in high-risk pregnancies reduced the risk of perinatal deaths and resulted in less

  7. Technology solutions for high-risk tasks in critical care.

    PubMed

    Baptiste, Andrea

    2007-06-01

    There are several high-risk nursing tasks in the critical care environment discussed in this article. These tasks include lateral transfers, repositioning patients up or side to side in bed, bed-to-chair or -wheelchair transfers, pericare of bariatric patients, toileting in bed, sustained limb holding for dressing wounds, and patient transport. Although many, if not all, of these tasks currently are performed manually, there are technological solutions available that undoubtedly can reduce the risks for caregiver and patient injuries. These solutions should be implemented in critical care to promote the safety of all involved in patient care. PMID:17512473

  8. Air pollution exposure: Who is at high risk?

    NASA Astrophysics Data System (ADS)

    Peled, Ronit

    2011-04-01

    This article reviews the sub-population groups who are at high risk and first to be harmed by air pollution coming from anthropogenic combustions. Epidemiological studies from the last few decades contributed to the understanding of the different levels of susceptibility to air pollution. Older people and young infants, people who suffer from allergies, pulmonary and heart diseases, pregnant women and newborn babies, and deprived populations that suffer from low socio-economic status have all been described as populations at risk. A better understanding of the role of air pollution on large as well as specific populations' health, will promote a better protection policy.

  9. Teamwork in high-risk environments analogous to space

    NASA Technical Reports Server (NTRS)

    Kanki, Barbara G.

    1990-01-01

    Mountaineering expeditions combine a number of factors which make them potentially good analogs to the planetary exploration facet of long-duration space missions. A study of mountain climbing teams was conducted in order to evaluate the usefulness of the environment as a space analog and to specifically identify the factors and issues surrounding teamwork and 'successful' team performance in two mountaineering environments. This paper focuses on social/organizational factors, including team size and structure, leadership styles and authority structure which were found in the sample of 22 climb teams (122 individuals). The second major issue discussed is the construction of a valid performance measure in this high-risk environment.

  10. High-Risk Cardiac Disease in Pregnancy: Part I.

    PubMed

    Elkayam, Uri; Goland, Sorel; Pieper, Petronella G; Silverside, Candice K

    2016-07-26

    The incidence of pregnancy in women with cardiovascular disease is rising, primarily due to the increased number of women with congenital heart disease reaching childbearing age and the changing demographics associated with advancing maternal age. Although most cardiac conditions are well tolerated during pregnancy and women can deliver safely with favorable outcomes, there are some cardiac conditions that have significant maternal and fetal morbidity and mortality. The purpose of this paper is to review the available published reports and provide recommendations on the management of women with high-risk cardiovascular conditions during pregnancy. PMID:27443437

  11. [Medical high-risk patient in the dental practice].

    PubMed

    Esser, E

    1992-01-01

    Cardiovaskular and pulmonary diseases, terminal renal failure, hepatitis B and C as well as the acquired immune deficiency syndrome, hemorrhagic diatheses, diabetes mellitus and hyperthyreosis are the major systemic diseases related to the practice of dentistry and require a modified treatment plan. Dental treatment during pregnancy may involve a risk for the woman and the fetus. The article outlines the most important aspects of interdisciplinary care for medial high-risk patients in the dental practice, refers to further readings and emphasizes the necessity of active continued education in the field of general medicine and specific emergency care. PMID:1535310

  12. Antiplatelet therapy in populations at high risk of atherothrombosis.

    PubMed Central

    Faxon, David P.; Nesto, Richard W.

    2006-01-01

    Atherothrombosis is the most common cause of an acute ischemic event. Antiplatelet agents form the cornerstone of atherothrombosis prevention. The purpose of this article is to review the use of antiplatelet agents in patients that are at particularly high risk of atherothrombotic events. To undertake this review, we searched the literature to identify key studies on the use of antiplatelet agents in this group of patients. Antiplatelet agents, such as aspirin and clopidogrel, play a fundamental role in the treatment and management of secondary thrombotic events. The routine use of aspirin is recommended, as it has been shown to reduce the risk of thrombotic events by approximately 25%. Additional benefit has been demonstrated with clopidogrel, both as a monotherapy and in combination with aspirin. In the CAPRIE trial, 19,185 patients with atherosclerotic vascular disease were randomized to receive clopidogrel (75 mg/day) or aspirin (325 mg/day) for a mean duration of follow-up of 1.91 years. Clopidogrel provided an additional 8.7% relative risk reduction in the primary composite endpoint of ischemic stroke, myocardial infraction or vascular death compared with aspirin. In the CURE trial, the addition of clopidogrel to background aspirin was associated with a 20% relative risk reduction in a composite of death from cardiovascular causes, nonfatal myocardial infarction or stroke compared with aspirin alone. In patients undergoing PCI as part of the PCI-CURE substudy, clopidogrel was associated with a 30% relative reduction in the incidence of cardiovascular events in the first 30 days after intervention compared with aspirin. The benefits of antiplatelet therapy continue to be investigated. Whether dual antiplatelet therapy is superior to aspirin monotherapy for high-risk primary prevention is unknown. The ongoing CHARISMA trial aims to determine the relative efficacies of aspirin monotherapy and aspirin/clopidogrel combination therapy in a broad range of high-risk

  13. Adjunctive Systemic and Local Antimicrobial Therapy in the Surgical Treatment of Peri-implantitis: A Randomized Controlled Clinical Trial.

    PubMed

    Carcuac, O; Derks, J; Charalampakis, G; Abrahamsson, I; Wennström, J; Berglundh, T

    2016-01-01

    The aim of the present randomized controlled clinical trial was to investigate the adjunctive effect of systemic antibiotics and the local use of chlorhexidine for implant surface decontamination in the surgical treatment of peri-implantitis. One hundred patients with severe peri-implantitis were recruited. Surgical therapy was performed with or without adjunctive systemic antibiotics or the local use of chlorhexidine for implant surface decontamination. Treatment outcomes were evaluated at 1 y. A binary logistic regression analysis was used to identify factors influencing the probability of treatment success, that is, probing pocket depth ≤5 mm, absence of bleeding/suppuration on probing, and no additional bone loss. Treatment success was obtained in 45% of all implants but was higher in implants with a nonmodified surface (79%) than those with a modified surface (34%). The local use of chlorhexidine had no overall effect on treatment outcomes. While adjunctive systemic antibiotics had no impact on treatment success at implants with a nonmodified surface, a positive effect on treatment success was observed at implants with a modified surface. The likelihood for treatment success using adjunctive systemic antibiotics in patients with implants with a modified surface, however, was low. As the effect of adjunctive systemic antibiotics depended on implant surface characteristics, recommendations for their use in the surgical treatment of peri-implantitis should be based on careful assessments of the targeted implant (ClinicalTrials.gov NCT01857804). PMID:26285807

  14. Cryosurgery would be An Effective Option for Clinically Localized Prostate Cancer: A Meta-analysis and Systematic Review.

    PubMed

    Gao, Liang; Yang, Lu; Qian, Shengqiang; Tang, Zhuang; Qin, Feng; Wei, Qiang; Han, Ping; Yuan, Jiuhong

    2016-01-01

    Cryosurgery (CS) has been used on patients with clinically localized PCa for more than 10 years. However, clinical studies evaluating its effectiveness and safety have reported conflicting results. This systematic assessment was performed to obtain comprehensive evidence regarding the potential benefits and safety of CS compared with those of radiotherapy (RT) and radical prostatectomy (RP), respectively. All controlled trials comparing CS with RT or RP and single-arm studies reporting results of CS therapy were identified through comprehensive searches of PubMed, the Cochrane Library and Embase. Ten publications from seven trials, with totally 1252 patients, were included in the meta-analysis, which revealed no significant differences in comparisons of CS vs RT and CS vs RP for overall survival and disease specific survival. However, a significantly lower disease-free survival could be observed for CS than RP. Moreover, a systematic review of literature focusing on comparative data of databases and materials of single-arm trials revealed satisfactory survival results in both primary and salvage CS. Our results showed that cryosurgery would be a relatively effective method for clinically localized prostate cancer with survival results comparable to radiotherapy and radical prostatectomy. However, the large percentage of complications caused by cryosurgery should be carefully monitored. PMID:27271239

  15. Cryosurgery would be An Effective Option for Clinically Localized Prostate Cancer: A Meta-analysis and Systematic Review

    PubMed Central

    Gao, Liang; Yang, Lu; Qian, Shengqiang; Tang, Zhuang; Qin, Feng; Wei, Qiang; Han, Ping; Yuan, Jiuhong

    2016-01-01

    Cryosurgery (CS) has been used on patients with clinically localized PCa for more than 10 years. However, clinical studies evaluating its effectiveness and safety have reported conflicting results. This systematic assessment was performed to obtain comprehensive evidence regarding the potential benefits and safety of CS compared with those of radiotherapy (RT) and radical prostatectomy (RP), respectively. All controlled trials comparing CS with RT or RP and single-arm studies reporting results of CS therapy were identified through comprehensive searches of PubMed, the Cochrane Library and Embase. Ten publications from seven trials, with totally 1252 patients, were included in the meta-analysis, which revealed no significant differences in comparisons of CS vs RT and CS vs RP for overall survival and disease specific survival. However, a significantly lower disease-free survival could be observed for CS than RP. Moreover, a systematic review of literature focusing on comparative data of databases and materials of single-arm trials revealed satisfactory survival results in both primary and salvage CS. Our results showed that cryosurgery would be a relatively effective method for clinically localized prostate cancer with survival results comparable to radiotherapy and radical prostatectomy. However, the large percentage of complications caused by cryosurgery should be carefully monitored. PMID:27271239

  16. [Activity and Future Perspective of Local Independent Clinical Trial Group (OGSG)].

    PubMed

    Tsujinaka, Toshimasa

    2016-04-01

    Osaka Gastrointestinal Cancer Chemotherapy Study Group (OGSG) was established in 2000 and has been conducting investigator initiated multi-institutional collaboration trials regarding the treatment of gastrointestinal cancer, especially using chemotherapeutic agents. Although organization of OGSG has been renovated to perform post-marketing clinical trials with high quality, OGSG is now facing severe financial crisis because of shortage of donation from pharmaceutical companies. Here, present problems and future perspectives are discussed. PMID:27220796

  17. [Home care for the high-risk newborn infant].

    PubMed

    Puddu, M

    2010-06-01

    With increased survival of extremely low birth weigh (ELBW) and very ill infants, a lot of them are discharged with unresolved medical issues that complicate their subsequent care. Infants born preterm with low birth weight who require neonatal intensive care experience a much higher rate of hospital readmission and death during the first year after birth compared with healthy term infants. Despite initial hospital care which is one of the most expensive of all kind of hospitalization, home care services are sometimes still sparse though the high risk of this group for failure to thrive, respiratory problems, developmental delays, parenting problems. In addition, societal and economic forces have come to bear on the timing and process of discharge and home care. Moreover it takes time for the family of a high-risk infant to prepare to care for their infant in a home setting and to obtain the necessary support services and mobilize community resources. Careful preparation for discharge, good follow-up and medical home after discharge may reduce these risks. PMID:21090070

  18. High-Risk Human Papillomavirus Targets Crossroads in Immune Signaling

    PubMed Central

    Tummers, Bart; Van Der Burg, Sjoerd H.

    2015-01-01

    Persistent infections with a high-risk type human papillomavirus (hrHPV) can progress to cancer. High-risk HPVs infect keratinocytes (KCs) and successfully suppress host immunity for up to two years despite the fact that KCs are well equipped to detect and initiate immune responses to invading pathogens. Viral persistence is achieved by active interference with KCs innate and adaptive immune mechanisms. To this end hrHPV utilizes proteins encoded by its viral genome, as well as exploits cellular proteins to interfere with signaling of innate and adaptive immune pathways. This results in impairment of interferon and pro-inflammatory cytokine production and subsequent immune cell attraction, as well as resistance to incoming signals from the immune system. Furthermore, hrHPV avoids the killing of infected cells by interfering with antigen presentation to antigen-specific cytotoxic T lymphocytes. Thus, hrHPV has evolved multiple mechanisms to avoid detection and clearance by both the innate and adaptive immune system, the molecular mechanisms of which will be dealt with in detail in this review. PMID:26008697

  19. Prognostic Factors Affecting Locally Recurrent Rectal Cancer and Clinical Significance of Hemoglobin

    SciTech Connect

    Rades, Dirk Kuhn, Hildegard; Schultze, Juergen; Homann, Nils; Brandenburg, Bernd; Schulte, Rainer; Krull, Andreas; Schild, Steven E.; Dunst, Juergen

    2008-03-15

    Purpose: To investigate potential prognostic factors, including hemoglobin levels before and during radiotherapy, for associations with survival and local control in patients with unirradiated locally recurrent rectal cancer. Patients and Methods: Ten potential prognostic factors were investigated in 94 patients receiving radiotherapy for recurrent rectal cancer: age ({<=}68 vs. {>=}69 years), gender, Eastern Cooperative Oncology Group performance status (0-1 vs. 2-3), American Joint Committee on Cancer (AJCC) stage ({<=}II vs. III vs. IV), grading (G1-2 vs. G3), surgery, administration of chemotherapy, radiation dose (equivalent dose in 2-Gy fractions: {<=}50 vs. >50 Gy), and hemoglobin levels before (<12 vs. {>=}12 g/dL) and during (majority of levels: <12 vs. {>=}12 g/dL) radiotherapy. Multivariate analyses were performed, including hemoglobin levels, either before or during radiotherapy (not both) because these are confounding variables. Results: Improved survival was associated with better performance status (p < 0.001), lower AJCC stage (p = 0.023), surgery (p = 0.011), chemotherapy (p = 0.003), and hemoglobin levels {>=}12 g/dL both before (p = 0.031) and during (p < 0.001) radiotherapy. On multivariate analyses, performance status, AJCC stage, and hemoglobin levels during radiotherapy maintained significance. Improved local control was associated with better performance status (p = 0.040), lower AJCC stage (p = 0.010), lower grading (p = 0.012), surgery (p < 0.001), chemotherapy (p < 0.001), and hemoglobin levels {>=}12 g/dL before (p < 0.001) and during (p < 0.001) radiotherapy. On multivariate analyses, chemotherapy, grading, and hemoglobin levels before and during radiotherapy remained significant. Subgroup analyses of the patients having surgery demonstrated the extent of resection to be significantly associated with local control (p = 0.011) but not with survival (p = 0.45). Conclusion: Predictors for outcome in patients who received radiotherapy for

  20. Localized Low-Dose Radiotherapy for Follicular Lymphoma: History, Clinical Results, Mechanisms of Action, and Future Outlooks

    SciTech Connect

    Ganem, Gerard; Cartron, Guillaume; Girinsky, Theodore; Haas, Rick L.M.; Cosset, Jean Marc; Solal-Celigny, Philippe

    2010-11-15

    The extreme radiosensitivity of indolent lymphomas was reported in the early years of radiotherapy (RT). The efficacy of low-dose total body irradiation (1.5-2 Gy) was particularly demonstrative. Higher doses were considered appropriate for localized disease. The optimal (or conventional) dose of curative RT derived from the early studies was determined to be 30-35 Gy. Nevertheless, in older series addressing the tumoricidal radiation dose in non-Hodgkin's lymphomas, investigators noted that a significant number of 'nodular' lymphomas were controlled with a dose of <22 Gy for >3 years. The idea of reintroducing localized low-dose radiotherapy (LDRT) for indolent non-Hodgkin's lymphomas came from a clinical observation. The first study showing the high efficacy of LDRT (4 Gy in two fractions of 2 Gy within 3 days) in selected patients with chemoresistant, indolent, non-Hodgkin's lymphomas was published in 1994. Since this first report, at least eight series of patients treated with localized LDRT have been published, showing a 55% complete response rate in irradiated sites, with a median duration of 15-42 months. How LDRT induces lymphoma cell death remains partly unknown. However, some important advances have recently been reported. Localized LDRT induces an apoptosis of follicular lymphoma cells. This apoptotic cell death elicits an immune response mediated by macrophages and dendritic cells. Follicular lymphoma is probably an ideal model to explore these mechanisms. This review also discusses the future of LDRT for follicular lymphoma.

  1. Clarification of the circulatory patho-physiology of anaesthesia - implications for high-risk surgical patients.

    PubMed

    Wolff, Christopher B; Green, David W

    2014-12-01

    The paper examines the effects of anaesthesia on circulatory physiology and their implications regarding improvement in perioperative anaesthetic management. Changes to current anaesthetic practice, recommended recently, such as the use of flow monitoring in high risk patients, are already beginning to have an impact in reducing complications but not mortality [1]. Better understanding of the patho-physiology should help improve management even further. Analysis of selected individual clinical trials has been used to illustrate particular areas of patho-physiology and how changes in practice have improved outcome. There is physiological support for the importance of achieving an appropriate rate of oxygen delivery (DO2), particularly following induction of anaesthesia. It is suggested that ensuring adequate DO2 during anaesthesia will avoid development of oxygen debt and hence obviate the need to induce a high, compensatory, DO2 in the post-operative period. In contrast to the usual assumptions underlying strategies requiring a global increase in blood flow [1] by a stroke volume near maximization strategy, blood flow control actually resides entirely at the tissues not at the heart. This is important as the starting point for understanding failed circulatory control as indicated by 'volume dependency'. Local adjustments in blood flow at each individual organ - auto-regulation - normally ensure the appropriate local rate of oxygen supply, i.e. local DO2. Inadequate blood volume leads to impairment of the regulation of blood flow, particularly in the individual tissues with least capable auto-regulatory capability. As demonstrated by many studies, inadequate blood flow first occurs in the gut, brain and kidney. The inadequate blood volume which occurs with induction of anaesthesia is not due to blood volume loss, but probably results from redistribution due to veno-dilation. The increase in venous capacity renders the existing blood volume inadequate to maintain

  2. Intensity-modulated pelvic radiation therapy and simultaneous integrated boost to the prostate area in patients with high-risk prostate cancer: a preliminary report of disease control.

    PubMed

    Saracino, Biancamaria; Petrongari, Maria Grazia; Marzi, Simona; Bruzzaniti, Vicente; Sara, Gomellini; Arcangeli, Stefano; Arcangeli, Giorgio; Pinnarò, Paola; Giordano, Carolina; Ferraro, Anna Maria; Strigari, Lidia

    2014-10-01

    The aim of the study was to report the clinical results in patients with high-risk prostate cancer treated with pelvic intensity-modulated radiation therapy (IMRT) and simultaneous integrated boost (SIB) to the prostate area. A total of 110 patients entered our study, 37 patients presented with localized prostate cancer and radiological evidence of node metastases or ≥15% estimated risk of lymph node (LN) involvement, while 73 patients underwent postoperative adjuvant or salvage irradiation for biochemical or residual/recurrent disease, LN metastases, or high risk of harboring nodal metastases. All patients received androgen deprivation therapy (ADT) for 2 years. The median follow-up was 56.5 months. For the whole patient group, the 3- and 5-year freedom from biochemical failure were 82.6% and 74.6%, respectively, with a better outcome in patients treated with radical approach. The 3- and 5-year freedom from local failure were 94.4% and 90.2%, respectively, while the 3- and 5-year distant metastasis-free survival were 87.8% and 81.7%, respectively. For all study patients, the rate of freedom from G2 acute rectal, intestinal, and urinary toxicities was 60%, 77%, and 61%, respectively. There was no G3 acute toxicity, ≥G2 late intestinal toxicity, or G3 late urinary or rectal toxicity. The 3- and 5-year ≥G2 freedom from late rectal toxicity rate were 98% and 95%, respectively, while the 3- and 5-year ≥G2 freedom from late urinary toxicity rate were 95% and 88%, respectively. The study concludes that pelvic IMRT and SIB to the prostatic area in association with 2-year ADT was a well-tolerated technique, providing high disease control in patients with prostate cancer requiring LN treatment. PMID:24976538

  3. Intensity-modulated pelvic radiation therapy and simultaneous integrated boost to the prostate area in patients with high-risk prostate cancer: a preliminary report of disease control

    PubMed Central

    Saracino, Biancamaria; Petrongari, Maria Grazia; Marzi, Simona; Bruzzaniti, Vicente; Sara, Gomellini; Arcangeli, Stefano; Arcangeli, Giorgio; Pinnarò, Paola; Giordano, Carolina; Ferraro, Anna Maria; Strigari, Lidia

    2014-01-01

    The aim of the study was to report the clinical results in patients with high-risk prostate cancer treated with pelvic intensity-modulated radiation therapy (IMRT) and simultaneous integrated boost (SIB) to the prostate area. A total of 110 patients entered our study, 37 patients presented with localized prostate cancer and radiological evidence of node metastases or ≥15% estimated risk of lymph node (LN) involvement, while 73 patients underwent postoperative adjuvant or salvage irradiation for biochemical or residual/recurrent disease, LN metastases, or high risk of harboring nodal metastases. All patients received androgen deprivation therapy (ADT) for 2 years. The median follow-up was 56.5 months. For the whole patient group, the 3- and 5-year freedom from biochemical failure were 82.6% and 74.6%, respectively, with a better outcome in patients treated with radical approach. The 3- and 5-year freedom from local failure were 94.4% and 90.2%, respectively, while the 3- and 5-year distant metastasis-free survival were 87.8% and 81.7%, respectively. For all study patients, the rate of freedom from G2 acute rectal, intestinal, and urinary toxicities was 60%, 77%, and 61%, respectively. There was no G3 acute toxicity, ≥G2 late intestinal toxicity, or G3 late urinary or rectal toxicity. The 3- and 5-year ≥G2 freedom from late rectal toxicity rate were 98% and 95%, respectively, while the 3- and 5-year ≥G2 freedom from late urinary toxicity rate were 95% and 88%, respectively. The study concludes that pelvic IMRT and SIB to the prostatic area in association with 2-year ADT was a well-tolerated technique, providing high disease control in patients with prostate cancer requiring LN treatment. PMID:24976538

  4. Adherence to drug–drug interaction alerts in high-risk patients: a trial of context-enhanced alerting

    PubMed Central

    Duke, Jon D; Li, Xiaochun; Dexter, Paul

    2013-01-01

    Objective Drug–drug interaction (DDI) alerting is an important form of clinical decision support, yet physicians often fail to attend to critical DDI warnings due to alert fatigue. We previously described a model for highlighting patients at high risk of a DDI by enhancing alerts with relevant laboratory data. We sought to evaluate the effect of this model on alert adherence in high-risk patients. Methods A 6-month randomized controlled trial involving 1029 outpatient physicians was performed. The target interactions were all DDIs known to cause hyperkalemia. Alerts in the intervention group were enhanced with the patient's most recent potassium and creatinine levels. The control group received unmodified alerts. High -risk patients were those with baseline potassium >5.0 mEq/l and/or creatinine ≥1.5 mg/dl (132 μmol/l). Results We found no significant difference in alert adherence in high-risk patients between the intervention group (15.3%) and the control group (16.8%) (p=0.71). Adherence in normal risk patients was significantly lower in the intervention group (14.6%) than in the control group (18.6%) (p<0.01). In neither group did physicians increase adherence in patients at high risk. Conclusions Physicians adhere poorly to hyperkalemia-associated DDI alerts even in patients with risk factors for a clinically significant interaction, and the display of relevant laboratory data in these alerts did not improve adherence levels in the outpatient setting. Further research is necessary to determine optimal strategies for conveying patient-specific DDI risk. PMID:23161895

  5. Reducing sexual risk behavior among high risk couples in Northern India

    PubMed Central

    Jones, Deborah; Bagga, Rashmi; Nehra, Ritu; Deepika; Sethi, Sunil; Walia, Kamini; Kumar, Mahendra; Villar-Loubet, Olga; Lopez, Maria; Weiss, Stephen M.

    2013-01-01

    Purpose This study sought to assess the feasibility of conducting a group, culturally tailored behavioral intervention and its impact on sexual barrier use, self efficacy, knowledge, conflict resolution and coping among high risk heterosexual couples in Northern India. Method This pilot study was conducted at the Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India from February 2008 to January 2009. Thirty sexually active high risk couples were drawn from a convenience sample of PGIMER patients attending infectious disease and family planning clinics. Couples participated in one month of 3 weekly gender concordant behavioral intervention groups and were individually administered assessments pre- and post-intervention. The intervention was tailored to the Northern Indian context, and addressed sexual barrier use, HIV/STI transmission and cognitive behavioral skill building focusing on sexual negotiation and communication. Results Participants were a mean age of 32 (men) and 29 (women) years, and the majority had at least 10 years of education. At baseline, the majority reported inconsistent condom use (<100% of the time) (64% of women, 59% of men). Post-intervention, nearly all participants reported consistent use (100% of the time) (100% of men, 97% of women). Participants also reported decreased verbal aggression, increased self efficacy and increased HIV-related knowledge, and women increased their use of positive coping tactics. Conclusions Results highlight the potential to successfully utilize a group intervention to discuss sensitive issues such as sexual risk behavior among both men and women. Strategies to improve condom use and communication without increasing intimate partner violence in high risk couples may be an important adjunct to preventing the development of a generalized epidemic in India. PMID:22648338

  6. Detecting the Psychosis Prodrome Across High-Risk Populations Using Neuroanatomical Biomarkers

    PubMed Central

    Koutsouleris, Nikolaos; Riecher-Rössler, Anita; Meisenzahl, Eva M.; Smieskova, Renata; Studerus, Erich; Kambeitz-Ilankovic, Lana; von Saldern, Sebastian; Cabral, Carlos; Reiser, Maximilian; Falkai, Peter; Borgwardt, Stefan

    2015-01-01

    To date, the MRI-based individualized prediction of psychosis has only been demonstrated in single-site studies. It remains unclear if MRI biomarkers generalize across different centers and MR scanners and represent accurate surrogates of the risk for developing this devastating illness. Therefore, we assessed whether a MRI-based prediction system identified patients with a later disease transition among 73 clinically defined high-risk persons recruited at two different early recognition centers. Prognostic performance was measured using cross-validation, independent test validation, and Kaplan-Meier survival analysis. Transition outcomes were correctly predicted in 80% of test cases (sensitivity: 76%, specificity: 85%, positive likelihood ratio: 5.1). Thus, given a 54-month transition risk of 45% across both centers, MRI-based predictors provided a 36%-increase of prognostic certainty. After stratifying individuals into low-, intermediate-, and high-risk groups using the predictor’s decision score, the high- vs low-risk groups had median psychosis-free survival times of 5 vs 51 months and transition rates of 88% vs 8%. The predictor’s decision function involved gray matter volume alterations in prefrontal, perisylvian, and subcortical structures. Our results support the existence of a cross-center neuroanatomical signature of emerging psychosis enabling individualized risk staging across different high-risk populations. Supplementary results revealed that (1) potentially confounding between-site differences were effectively mitigated using statistical correction methods, and (2) the detection of the prodromal signature considerably depended on the available sample sizes. These observations pave the way for future multicenter studies, which may ultimately facilitate the neurobiological refinement of risk criteria and personalized preventive therapies based on individualized risk profiling tools. PMID:24914177

  7. Determinants of Mental Health Care Utilization in a Suicide High-risk Group With Suicidal Ideation

    PubMed Central

    2016-01-01

    Objectives: The suicide rate in Korea is increasing every year, and is the highest among the Organization for Economic Cooperation and Development countries. Psychiatric patients in particular have a higher risk of suicide than other patients. This study was performed to evaluate determinants of mental health care utilization among individuals at high risk for suicide. Methods: Korea Health Panel data from 2009 to 2011 were used. Subjects were individuals at high risk of suicide who had suicidal ideation, a past history of psychiatric illness, or had utilized outpatient services for a psychiatric disorder associated with suicidal ideation within the past year. The chi-square test and hierarchical logistic regression were used to identify significant determinants of mental health care utilization. Results: The total number of subjects with complete data on the variables in our model was 989. Individuals suffering from three or more chronic diseases used mental health care more frequently. Mental health care utilization was higher in subjects who had middle or high levels of educational attainment, were receiving Medical Aid, or had a large family size. Conclusions: It is important to control risk factors in high-risk groups as part of suicide prevention strategies. The clinical approach, which includes community-based intervention, entails the management of reduction of suicidal risk. Our study identified demographic characteristics that have a significant impact on mental health care utilization and should be considered in the development of suicide prevention strategies. Further studies should examine the effect of mental health care utilization on reducing suicidal ideation. PMID:26841887

  8. Concurrent Androgen Deprivation Therapy During Salvage Prostate Radiotherapy Improves Treatment Outcomes in High-Risk Patients

    SciTech Connect

    Soto, Daniel E.; Passarelli, Michael N.; Daignault, Stephanie; Sandler, Howard M.

    2012-03-01

    Purpose: To determine whether concurrent androgen deprivation therapy (ADT) during salvage radiotherapy (RT) improves prostate cancer treatment outcomes. Methods and Materials: A total of 630 postprostatectomy patients were retrospectively identified who were treated with three-dimensional conformal RT. Of these, 441 were found to be treated for salvage indications. Biochemical failure was defined as prostate-specific antigen (PSA) of 0.2 ng/mL or greater above nadir with another PSA increase or the initiation of salvage ADT. Progression-free survival (PFS) was defined as the absence of biochemical failure, continued PSA rise despite salvage therapy, initiation of systemic therapy, clinical progression, or distant failure. Multivariate-adjusted Cox proportional hazards modeling was performed to determine which factors predict PFS. Results: Low-, intermediate-, and high-risk patients made up 10%, 24%, and 66% of patients, respectively. The mean RT dose was 68 Gy. Twenty-four percent of patients received concurrent ADT (cADT). Regional pelvic nodes were treated in 16% of patients. With a median follow-up of 3 years, the 3-year PFS was 4.0 years for cADT vs. 3.4 years for cADT patients (p = 0.22). Multivariate analysis showed that concurrent ADT (p = 0.05), Gleason score (p < 0.001), and pre-RT PSA (p = 0.03) were independent predictors of PFS. When patients were stratified by risk group, the benefits of cADT (hazard ratio, 0.65; p = 0.046) were significant only for high-risk patients. Conclusions: This retrospective study showed a PFS benefit of concurrent ADT during salvage prostate RT. This benefit was observed only in high-risk patients.

  9. Evaluation of the Modified Asthma Predictive Index in High-Risk Preschool Children

    PubMed Central

    Chang, Timothy S.; Lemanske, Robert F.; Guilbert, Theresa W.; Gern, James E.; Coen, Michael H.; Evans, Michael D.; Gangnon, Ronald E.; Page, C. David; Jackson, Daniel J.

    2013-01-01

    BACKGROUND Prediction of subsequent school-age asthma during the preschool years has proven challenging. OBJECTIVE To confirm in a post hoc analysis the predictive ability of the modified Asthma Predictive Index (mAPI) in a high-risk cohort and a theoretical unselected population. We also tested a potential mAPI modification with a 2-wheezing episode requirement (m2API) in the same populations. METHODS Subjects (n = 289) with a family history of allergy and/or asthma were used to predict asthma at age 6, 8, and 11 years with the use of characteristics collected during the first 3 years of life. The mAPI and the m2API were tested for predictive value. RESULTS For the mAPI and m2API, school-age asthma prediction improved from 1 to 3 years of age. The mAPI had high predictive value after a positive test (positive likelihood ratio ranging from 4.9 to 55) for asthma development at years 6, 8, and 11. Lowering the number of wheezing episodes to 2 (m2API) lowered the predictive value after a positive test (positive likelihood ratio ranging from 1.91 to 13.1) without meaningfully improving the predictive value of a negative test. Posttest probabilities for a positive mAPI reached 72% and 90% in unselected and high-risk populations, respectively. CONCLUSIONS In a high-risk cohort, a positive mAPI greatly increased future asthma probability (eg, 30% pretest probability to 90% posttest probability) and is a preferred predictive test to the m2API. With its more favorable positive posttest probability, the mAPI can aid clinical decision making in assessing future asthma risk for preschool-age children. PMID:24187656

  10. Lenalidomide maintenance for high-risk multiple myeloma after allogeneic hematopoietic cell transplantation.

    PubMed

    Alsina, Melissa; Becker, Pamela S; Zhong, Xiaobo; Adams, Alexia; Hari, Parameswaran; Rowley, Scott; Stadtmauer, Edward A; Vesole, David H; Logan, Brent; Weisdorf, Daniel; Qazilbash, Muzaffar; Popplewell, Leslie L; McClune, Brian; Bensinger, William; Riches, Marcie; Giralt, Sergio A; Pasquini, Marcelo C

    2014-08-01

    Allogeneic hematopoietic cell transplantation (alloHCT) with reduced-intensity conditioning is an appealing option for patients with high-risk multiple myeloma (MM). However, progression after alloHCT remains a challenge. Maintenance therapy after alloHCT may offer additional disease control and allow time for a graft-versus-myeloma effect. The primary objective of this clinical trial was to determine the tolerability and safety profile of maintenance lenalidomide (LEN) given on days 1 to 21 of 28 days cycles, with intrapatient dose escalation during 12 months/cycles after alloHCT. Thirty alloHCT recipients (median age, 54 years) with high-risk MM were enrolled at 8 centers between 2009 and 2012. The median time from alloHCT to LEN initiation was 96 days (range, 66 to 171 days). Eleven patients (37%) completed maintenance and 10 mg daily was the most commonly delivered dose (44%). Most common reasons for discontinuation were acute graft-versus-host disease (GVHD) (37%) and disease progression (37%). Cumulative incidence of grades III to IV acute GVHD from time of initiation of LEN was 17%. Outcomes at 18 months after initiation of maintenance were MM progression, 28%; transplantation-related mortality, 11%; and progression-free and overall survival, 63% and 78%, respectively. The use of LEN after alloHCT is feasible at lower doses, although it is associated with a 38% incidence of acute GVHD. Survival outcomes observed in this high-risk MM population warrant further study of this approach. PMID:24769014

  11. Risk of Diabetes among Patients Receiving Primary Androgen Deprivation Therapy for Clinically Localized Prostate Cancer

    PubMed Central

    Tsai, Huei-Ting; Keating, Nancy L.; Van Den Eeden, Stephen K.; Haque, Reina; Cassidy-Bushrow, Andrea E.; Yood, Marianne Ulcickas; Smith, Matthew R.; Potosky, Arnold L.

    2015-01-01

    Purpose Androgen deprivation therapy may increase diabetes risk. As the benefits of primary androgen deprivation therapy for localized prostate cancer are controversial, and most prostate cancer survivors are of advanced age with comorbidities, it is important to determine if primary androgen deprivation therapy increases the risk of diabetes and to determine the susceptibility factors. Materials and Methods We conducted a retrospective cohort study of 12,191 men diagnosed with incident localized prostate cancer during 1995 to 2008, age 35 to 100 years, and without diabetes or receipt of prostatectomy or radiation 1 year after diagnosis. Patients were enrolled in 1 of 3 managed health plans and followed through 2010. Primary androgen deprivation therapy was defined as androgen deprivation therapy within 1 year after diagnosis. Incident diabetes was ascertained using inpatient and outpatient diagnosis codes, diabetes medications and hemoglobin A1c values. We estimated primary androgen deprivation therapy associated diabetes risk using Cox proportional hazard models in conventional and propensity score analyses. Results Diabetes developed in 1,203 (9.9%) patients during followup (median 4.8 years) with incidence rates of 2.5 and 1.6 events per 100 person-years in the primary androgen deprivation therapy and nonprimary androgen deprivation therapy groups, respectively. Primary androgen deprivation therapy was associated with a 1.61-fold increased diabetes risk (95% CI 1.38–1.88). The number needed to harm was 29. The association was stronger in men age 70 or younger than in older men (HR 2.25 vs 1.40, p value for interaction = 0.008). Conclusions Primary androgen deprivation therapy may increase diabetes risk by 60% and should be used with caution when managing localized prostate cancer. Because of the consistent association between androgen deprivation therapy and greater diabetes risk across disease states, we recommend routine screening and lifestyle

  12. Localization and upregulation of survivin in cancer health disparities: a clinical perspective

    PubMed Central

    Khan, Salma; Ferguson Bennit, Heather; Asuncion Valenzuela, Malyn May; Turay, David; Diaz Osterman, Carlos J; Moyron, Ron B; Esebanmen, Grace E; Ashok, Arjun; Wall, Nathan R

    2015-01-01

    Survivin is one of the most important members of the inhibitors of apoptosis protein family, as it is expressed in most human cancers but is absent in normal, differentiated tissues. Lending to its importance, survivin has proven associations with apoptosis and cell cycle control, and has more recently been shown to modulate the tumor microenvironment and immune evasion as a result of its extracellular localization. Upregulation of survivin has been found in many cancers including breast, prostate, pancreatic, and hematological malignancies, and it may prove to be associated with the advanced presentation, poorer prognosis, and lower survival rates observed in ethnically diverse populations. PMID:26185415

  13. Factors associated with travel to non-local genitourinary medicine clinics for gonorrhoea: an analysis of patients diagnosed in London, 2009-10.

    PubMed

    Le Polain de Waroux, Olivier; Hughes, Gwenda; Maguire, Helen; Crook, Paul D

    2014-03-01

    We analysed factors associated with travelling to non-local genitourinary medicine clinics for gonorrhoea care in London. We used surveillance data on London residents attending genitourinary medicine clinics in 2009-10 and calculated distances between patients' areas of residence and both the nearest genitourinary medicine clinic and the clinic attended. Non-local clinics were attended by 5408 (46.7%) patients. Men having sex with men attended non-local services more than heterosexuals (OR 3.83, p < 0.001). Among heterosexual men, black Africans and black Caribbeans were more likely, and South Asians less likely, to attend non-local services compared to whites (OR [95%CI] 1.33 [1.04-1.72], 1.36 [1.11-1.67] and 0.46 [0.31-0.70] respectively). Similar associations, although not statistically significant, were found in women. People were more likely to attend local services if their local clinic provided walk-in and young people's services, weekend consultations and long opening hours. These findings could help design services meeting local population needs and facilitate prompt and equitable access to care. PMID:23970635

  14. Adjuvant chemo- and hormonal therapy in locally advanced breast cancer: a randomized clinical study

    SciTech Connect

    Schaake-Koning, C.; van der Linden, E.H.; Hart, G.; Engelsman, E.

    1985-10-01

    Between 1977 and 1980, 118 breast cancer patients with locally advanced disease, T3B-4, any N, M0 or T1-3, tumor positive axillary apex biopsy, were randomized to one of three arms: I: radiotherapy (RT) to the breast and adjacent lymph node areas; II: RT followed by 12 cycles of cyclophosphamide, methotrexate, 5 fluorouracil (CMF) and tamoxifen during the chemotherapy period; III: 2 cycles of adriamycin and vincristine (AV), alternated with 2 cycles of CMF, then RT, followed by another 4 cycles of AV, alternated with 4 CMF; tamoxifen during the entire treatment period. The median follow-up period was 5 1/2 years. The adjuvant chemo- and hormonal therapy did not improve the overall survival; the 5-year survival was 37% for all three treatment arms. There was no statistically significant difference in RFS between the three modalities, nor when arm I was compared to arm II and III together. LR was not statistically different over the three treatment arms. In 18 of the 24 patients with LR, distant metastases appeared within a few months from the local recurrence. The menopausal status did not influence the treatment results. Dose reduction in more than 4 cycles of chemotherapy was accompanied by better results. In conclusion: adjuvant chemo- and hormonal therapy did not improve RFS and overall survival. These findings do not support the routine use of adjuvant chemo- and endocrine therapy for inoperable breast cancer.

  15. Clinical diversity and chromosomal localization of X-linked cone dystrophy (COD1).

    PubMed Central

    Hong, H. K.; Ferrell, R. E.; Gorin, M. B.

    1994-01-01

    X-linked progressive cone dystrophy (COD1) causes progressive deterioration of visual acuity, deepening of central scotomas, macular changes, and bull's-eye lesions. The cone electroretinography (ERG) is variably abnormal in affected males, and the rod ERG may also be abnormal. The clinical picture of heterozygous females ranges from asymptomatic to a widespread spectrum of cone-mediated dysfunction. A prior linkage study demonstrated linkage between the COD1 locus and the marker locus DXS84, assigned to Xp21.1, with no recombination. In the present study, we have clinically characterized a large four-generation family with COD1 and have performed a linkage analysis using seven polymorphic markers on the short arm of the X chromosome. No recombination was observed between the disease and the marker loci DXS7 and MAOA, suggesting that the location of COD1 is in the region Xp11.3, distal to DXS84 and proximal to ARAF1. Images Figure 2 PMID:7977377

  16. Practical opportunities to improve early detection and prevention of colorectal cancer (CRC) in members of high-risk families.

    PubMed

    Patel, S G; Lowery, J T; Gatof, D; Ahnen, D J

    2015-03-01

    Colorectal cancer (CRC) incidence and mortality are steadily declining and CRC screening rates are increasing in the United States. Although this a very good news, several definable groups still have very low screening rates including younger (under age 50) members of high-risk CRC families. This opinion piece describes five strategies that could be incorporated into routine practice to improve identification and guideline-based screening in members of high-risk families. Routine incorporation of a simple family history screening tool and outreach to high-risk family members could substantially improve guideline-based screening in this population. Identification of CRCs and advanced adenomas in the endoscopy suite defines another group of high-risk families for similar outreach. Lynch syndrome families can be identified by testing CRCs and selected adenomas for microsatellite instability or loss of DNA repair protein expression. Finally, selective addition of aspirin to surveillance endoscopy can decrease the risk of new adenomas and CRCs. The rationale for these strategies as well as mechanisms for their implementation and evaluation in clinical practice is described. PMID:25698379

  17. Intravascular near-infrared fluorescence molecular imaging of atherosclerosis: toward coronary arterial visualization of biologically high-risk plaques

    PubMed Central

    Calfon, Marcella A.; Vinegoni, Claudio; Ntziachristos, Vasilis; Jaffer, Farouc A.

    2010-01-01

    New imaging methods are urgently needed to identify high-risk atherosclerotic lesions prior to the onset of myocardial infarction, stroke, and ischemic limbs. Molecular imaging offers a new approach to visualize key biological features that characterize high-risk plaques associated with cardiovascular events. While substantial progress has been realized in clinical molecular imaging of plaques in larger arterial vessels (carotid, aorta, iliac), there remains a compelling, unmet need to develop molecular imaging strategies targeted to high-risk plaques in human coronary arteries. We present recent developments in intravascular near-IR fluorescence catheter-based strategies for in vivo detection of plaque inflammation in coronary-sized arteries. In particular, the biological, light transmission, imaging agent, and engineering principles that underlie a new intravascular near-IR fluorescence sensing method are discussed. Intravascular near-IR fluorescence catheters appear highly translatable to the cardiac catheterization laboratory, and thus may offer a new in vivo method to detect high-risk coronary plaques and to assess novel atherosclerosis biologics. PMID:20210433

  18. Characterizing and Reaching High-Risk Drinkers Using Audience Segmentation

    PubMed Central

    Moss, Howard B.; Kirby, Susan D.; Donodeo, Fred

    2010-01-01

    Background Market or audience segmentation is widely used in social marketing efforts to help planners identify segments of a population to target for tailored program interventions. Market-based segments are typically defined by behaviors, attitudes, knowledge, opinions, or lifestyles. They are more helpful to health communication and marketing planning than epidemiologically-defined groups because market-based segments are similar in respect to how they behave or might react to marketing and communication efforts. However, market segmentation has rarely been used in alcohol research. As an illustration of its utility, we employed commercial data that describes the sociodemographic characteristics of high-risk drinkers as an audience segment; where they tend to live, lifestyles, interests, consumer behaviors, alcohol consumption behaviors, other health-related behaviors, and cultural values. Such information can be extremely valuable in targeting and planning public health campaigns, targeted mailings, prevention interventions and research efforts. Methods We describe the results of a segmentation analysis of those individuals who self-report consuming five or more drinks per drinking episode at least twice in the last 30-days. The study used the proprietary PRIZM™ audience segmentation database merged with Center for Disease Control and Prevention's (CDC) Behavioral Risk Factor Surveillance System (BRFSS) database. The top ten of the 66 PRIZM™ audience segments for this risky drinking pattern are described. For five of these segments we provide additional in-depth details about consumer behavior and the estimates of the market areas where these risky drinkers reside. Results The top ten audience segments (PRIZM clusters) most likely to engage in high-risk drinking are described. The cluster with the highest concentration of binge drinking behavior is referred to as the “Cyber Millenials.” This cluster is characterized as “the nation's tech-savvy singles

  19. Automated analysis of free speech predicts psychosis onset in high-risk youths

    PubMed Central

    Bedi, Gillinder; Carrillo, Facundo; Cecchi, Guillermo A; Slezak, Diego Fernández; Sigman, Mariano; Mota, Natália B; Ribeiro, Sidarta; Javitt, Daniel C; Copelli, Mauro; Corcoran, Cheryl M

    2015-01-01

    Background/Objectives: Psychiatry lacks the objective clinical tests routinely used in other specializations. Novel computerized methods to characterize complex behaviors such as speech could be used to identify and predict psychiatric illness in individuals. AIMS: In this proof-of-principle study, our aim was to test automated speech analyses combined with Machine Learning to predict later psychosis onset in youths at clinical high-risk (CHR) for psychosis. Methods: Thirty-four CHR youths (11 females) had baseline interviews and were assessed quarterly for up to 2.5 years; five transitioned to psychosis. Using automated analysis, transcripts of interviews were evaluated for semantic and syntactic features predicting later psychosis onset. Speech features were fed into a convex hull classification algorithm with leave-one-subject-out cross-validation to assess their predictive value for psychosis outcome. The canonical correlation between the speech features and prodromal symptom ratings was computed. Results: Derived speech features included a Latent Semantic Analysis measure of semantic coherence and two syntactic markers of speech complexity: maximum phrase length and use of determiners (e.g., which). These speech features predicted later psychosis development with 100% accuracy, outperforming classification from clinical interviews. Speech features were significantly correlated with prodromal symptoms. Conclusions: Findings support the utility of automated speech analysis to measure subtle, clinically relevant mental state changes in emergent psychosis. Recent developments in computer science, including natural language processing, could provide the foundation for future development of objective clinical tests for psychiatry. PMID:27336038

  20. Rationale and design of a multicenter prospective cohort study for the eVALuation and monitoring of HPV infections and relATEd cervical diseases in high-risk women (VALHIDATE study)

    PubMed Central

    2012-01-01

    Background Pap screening, an effective method for cervical cancer prevention, is now supported by molecular human papillomavirus (HPV) testing. Recently commercialised preventive vaccines also provide new tools for the primary prevention of cervical cancer. To determine appropriate prevention strategies, the Health General Direction, Lombardy Region, funded a project that aims to characterize and monitor HPV infections and related cervical diseases in high-risk women. Methods/design VALHIDATE is a 5-year multicentre open prospective cohort study. It will recruit 7000 consenting women aged 13–65 years to provide information about the local biomolecular epidemiology of HPV infection and cervical diseases in high-risk women recruited from nine clinical centres and one faith-based organisation. The study will estimate the overall and type-specific prevalence of HPV infection and cervical abnormalities. It also aims to compare standard Pap screening with biomolecular screening, and to assist in the design of targeted regional prevention programs directed specifically at high-risk groups. Three groups of high-risk women: 1000 HIV-infected women (aged 26–65 years), 1000 recent migrant women (aged 26–65 years) and 3000 young women (aged 13–26 years) and 1 control group: 2000 women (aged 26–45 years) attending a spontaneous screening program, will be recruited. Sample sizes will be revised after the first year. Adult participants will undergo conventional cervical cytology, HPV DNA screening and genotyping. Paediatric participants will undergo HPV DNA testing and genotyping of urine samples. HPV DNA, cytological abnormalities and HPV types will be analysed according to demographic, epidemiological, behavioural, and clinical data collected in an electronic case report form. Overall and stratified prevalences will be estimated to analyse the associations between HPV infection and selected characteristics. Logistic regression models will be used to estimate

  1. Measurement of localized tissue water - clinical application of bioimpedance spectroscopy in wound management

    NASA Astrophysics Data System (ADS)

    Ward, L. C.; Sharpe, K.; Edgar, D.; Finlay, V.; Wood, F.

    2013-04-01

    Wound healing is a complex process which can be impeded by the presence of accumulated cell fluid or oedema. A simple and convenient method for the assessment of wound oedema would aid improvement in patient care. In this proof of concept study we investigated whether bioelectrical impedance spectroscopy has the potential to provide such a tool. A number of important observations were made. Firstly, the method was highly reproducible and data can be obtained from electrodes located at different positions around the region of interest; important given the highly variable topography of surface wounds, e.g. burns. Secondly, the method was highly sensitive with the potential to detect changes of as little as 20 μl in extracellular fluid. Thirdly the relative changes in R0, R∞ and Ri following sub-cutaneous injections of saline were consistent with redistribution of water from the extracellular to intracellular space and /or removal from the local area as may occur during wound healing.

  2. Redefining High-Risk Prostate Cancer Based on Distant Metastases and Mortality After High-Dose Radiotherapy With Androgen Deprivation Therapy

    SciTech Connect

    Tendulkar, Rahul D.; Reddy, Chandana A.; Stephans, Kevin L.; Ciezki, Jay P.; Klein, Eric A.; Mahadevan, Arul; Kupelian, Patrick A.

    2012-03-15

    Purpose: Modern outcomes of high-dose external beam radiotherapy (EBRT) with androgen deprivation therapy (ADT) for high-risk (HR) prostate cancer are not well described. Methods and Materials: We identified 585 patients who met HR criteria by 2010 National Comprehensive Cancer Network guidelines, who were treated with EBRT consisting of {>=}74 Gy from 1996 to 2008 at Cleveland Clinic, of whom 95% received ADT. We analyzed biochemical relapse-free survival (bRFS), distant metastases-free survival (DMFS), and prostate cancer-specific mortality (PCSM). Results: The median EBRT dose was 78 Gy, and median ADT duration was 6 months. At 10 years, the bRFS was 50.2%, the DMFS was 71.6%, and the PCSM was 14.4%. On multivariate analysis, significant predictors of bRFS were biopsy Gleason score (bGS) of 8 to 10, stage T3, and prostate-specific antigen (PSA) concentration; predictors of DMFS were bGS of 8 to 10 and stage T3; the only predictor of PCSM was bGS of 8 to 10. The duration of ADT was not predictive of any endpoint. We identified an unfavorable high-risk (UHR) group of stage T1-T2 tumors consisting of bGS of 8 with PSA of >10 ng/ml or bGS of 9 to 10 with any PSA level; the remaining clinically localized cancers comprised the favorable high-risk (FHR) group. Comparing FHR, UHR, and stage T3 groups, the DMFS rates were 81.4%, 57.8%, and 59.1% (p < 0.0001), and the PCSM rates were 7.5%, 28.4%, and 20.6% at 10 years, respectively (p = 0.006). Conclusion: A bGS of 8 to 10 is the strongest predictor of bRFS, DMFS, and PCSM after high-dose EBRT with ADT. The duration of ADT did not correlate with outcome. Future studies should account for the heterogeneity in HR prostate cancer.

  3. High-risk diagnosis, social stress, and parent-child relationships: A moderation model.

    PubMed

    Bentley, Eryn; Millman, Zachary B; Thompson, Elizabeth; Demro, Caroline; Kline, Emily; Pitts, Steven C; DeVylder, Jordan E; Smith, Melissa Edmondson; Reeves, Gloria; Schiffman, Jason

    2016-07-01

    Stress is related to symptom severity among youth at clinical high-risk (CHR) for psychosis, although this relation may be influenced by protective factors. We explored whether the association of CHR diagnosis with social stress is moderated by the quality of parent-child relationships in a sample of 96 (36 CHR; 60 help-seeking controls) adolescents and young adults receiving mental health services. We examined self-reported social stress and parent-child relationships as measured by the Behavior Assessment System for Children, Second Edition (BASC-2), and determined CHR status from the clinician-administered Structured Interview for Psychosis-Risk Syndrome (SIPS). The social stress subscale, part of the clinical domain of the BASC-2, assesses feelings of stress and tension in personal relationships and the relations with parents subscale, part of the adaptive domain of the BASC-2, assesses perceptions of importance in family and quality of parent-child relationship. There was a modest direct relation between risk diagnosis and social stress. Among those at CHR, however, there was a significant relation between parent-child relationships and social stress (b=-0.73, t[92]=-3.77, p<0.001, f(2)=0.15) that was not observed among non-CHR individuals, suggesting that a positive parent-child relationship may be a protective factor against social stress for those at risk for psychosis. Findings provide additional evidence to suggest that interventions that simultaneously target both social stress and parent-child relationships might be relevant for adolescents and young adults at clinical high-risk for psychosis. PMID:27131911

  4. Clinical Outcome of Palliative Radiotherapy for Locally Advanced Symptomatic Gastric Cancer in the Modern Era

    PubMed Central

    Tey, Jeremy; Choo, Bok Ai; Leong, Cheng Nang; Loy, En Yun; Wong, Lea Choung; Lim, Keith; Lu, Jiade Jay; Koh, Wee Yao

    2014-01-01

    Abstract The purpose of this study was to report the outcomes of patients with symptomatic locally advanced/recurrent gastric cancer treated with radiotherapy (RT) using modern 3-dimensional conformal techniques. We retrospectively reviewed patients who had palliative RT for index symptoms of gastric bleeding, pain, and obstruction. Study endpoints included symptom response, median survival, and treatment toxicity. Of 115 patients with median age of 77 years, 78 (67.8%) patients had metastatic disease at the time of treatment. Index symptoms were gastric bleeding, pain, and obstruction in 89.6%, 9.2%, and 14.3% of patients, respectively. Dose fractionation regimen ranged from 8-Gy single fraction to 40 Gy in 16 fractions. One hundred eleven patients (93.3%) were computed tomography (CT) planned. Median follow-up was 85 days. Response rates for bleeding, pain, and obstruction were 80.6% (83/103), 45.5% (5/11), and 52.9% (9/17), respectively, and median duration of response was 99 days, 233 days, and 97 days, respectively. Median survival was 85 days. Actuarial 12-month survival was 15.3%. There was no difference in response rates between low (≤39 Gy) and high (>39 Gy) biologically effective dose (BED) regimens (α/β ratio = 10). Median survival was significantly longer in patients who responded to RT compared with patients who did not (113.5 vs 47 days, P < 0.001). Three patients (2.6%) had grade 3 Common Toxicity Criteria equivalent toxicity (nausea/vomiting/anorexia). External beam RT delivered using 3-dimensional conformal techniques is highly effective and well tolerated in the local palliation of gastric cancer, with palliation lasting the majority of patient’s lives. Short (≤39 Gy BED) RT schedules are adequate for effective symptom palliation. A phase II study of palliative gastric RT is ongoing. PMID:25396330

  5. Hemodynamic monitoring and care of the patient of high risk for anesthesia.

    PubMed Central

    Pietak, S P; Teasdale, S J

    1979-01-01

    Hemodynamic monitoring and care of the patient at high risk for anesthesia require a careful and systematic approach. During preoperative evaluation the patient at increased risk must be identified and correctable problems must be solved. The patient's current medications must be reviewed because they may influence the choice of anesthetic approach and may alter the physiologic response to the stresses commonly associated with anesthesia. In addition to conventional clinical and electrocardiographic monitoring, perioperative hemodynamic monitoring may be desirable for patients at special risk, who are likely to have significant associated medical problems or to undergo complicated surgical procedures. No ideal induction agent exists, and hypotension secondary to peripheral vasodilation or myocardial depression, or both, is a potential problem. Patients with an inordinately high risk may benefit from mechanical circulatory assistance prior to induction of anesthesia. Attention to oxygenation, blood volume replacement and the prevention of hypertensive episodes are particularly important during anesthesia so that optimal cardiac performance is ensured and ischemia avoided. The stresses during emergence from anesthesia contribute to lability of the cardiovascular status and hypoxemia. The period of risk does not conclude with immediate recovery from anesthesia but extends through the postoperative phase. Careful monitoring and attention to the control of pain, prevention of hypotension and hypertension, adequate oxygenation, early mobilization and resumption of the administration of cardiac medications are important factors in a successful outcome. PMID:497983

  6. Reaching and retaining high-risk HIV/AIDS clients through the Internet.

    PubMed

    Feldacker, Caryl; Torrone, Elizabeth; Triplette, Matthew; Smith, Justin C; Leone, Peter A

    2011-07-01

    The Internet is a popular way for people to meet casual sex partners. However, online outreach remains largely unexplored to promote voluntary counseling and testing for HIV. The Student Health Action Coalition's HIV testing program (SHAC-HIV) targets high-risk clients through tailored Internet outreach via chat rooms, social networking sites, and online forums. The SHAC-HIV model also demonstrates that nontraditional testing sites can provide low-cost, client-centered, high-quality services to support increased demand for HIV-testing services. Within the clinic, SHAC-HIV's testing model includes four major components: (a) reliance on a team of well-trained health sciences student volunteers; (b) rapid oral-fluid HIV tests; (c) universal, consent-based testing with client-centered health education and counseling; and (d) coordinated referrals for follow-up testing, treatment, and care. This approach reaches high-risk clients as well as undiagnosed infections. In 2007, there were nine confirmed positive results out of 389 tests, yielding a 2.3% positivity rate. This positivity percentage is higher than any other nontraditional testing site in North Carolina. This article describes the SHAC-HIV outreach and voluntary counseling and testing program with the aim of encouraging adoption of the model by other nontraditional testing sites. PMID:20160022

  7. Electrochemical chip-based genomagnetic assay for detection of high-risk human papillomavirus DNA.

    PubMed

    Bartosik, Martin; Durikova, Helena; Vojtesek, Borivoj; Anton, Milan; Jandakova, Eva; Hrstka, Roman

    2016-09-15

    Cervical cancer, being the fourth leading cause of cancer death in women worldwide, predominantly originates from a persistent infection with a high-risk human papillomavirus (HPV). Detection of DNA sequences from these high-risk strains, mostly HPV-16 and HPV-18, represents promising strategy for early screening, which would help to identify women with higher risk of cervical cancer. In developing countries, inadequate screening options lead to disproportionately high mortality rates, making a fast and inexpensive detection schemes highly important. Electrochemical sensors and assays offer an alternative to current methods of detection. We developed an electrochemical-chip based assay, in which target HPV DNA is captured via magnetic bead-modified DNA probes, followed by an antidigoxigenin-peroxidase detection system at screen-printed carbon electrode chips, enabling parallel measurements of eight samples simultaneously. We show sensitive detection in attomoles of HPV DNA, selective discrimination between HPV-16 and HPV-18 and good reproducibility. Most importantly, we show application of the assay into both cancer cell lines and cervical smears from patients. The electrochemical results correlated well with standard methods, making this assay potentially applicable in clinical practice. PMID:27132004

  8. Adjuvant Pelvic Radiotherapy vs. Sequential Chemoradiotherapy for High-Risk Stage I-II Endometrial Carcinoma

    PubMed Central

    El-Hadaad, Hend Ahmed; Wahba, Hanan Ahmed; Gamal, Anas Mohamed; Dawod, Tamer

    2012-01-01

    Objective To explore if the addition of adjuvant chemotherapy with paclitaxel and carboplatin to radiotherapy confers an advantage for overall survival (OAS), and progression free survival (PFS); to assess the incidence of relapses over standard pelvic radiotherapy; and to evaluate the related toxicity in high-risk stage I-II endometrial carcinoma Methods Medical records were reviewed to identify high-risk stage I-II endometrial carcinoma cases treated in the Clinical Oncology and Nuclear Medicine department between 2002 and 2008 with adjuvant radiotherapy alone (arm I) (57 patients) or with sequential carboplatin (AUC5-6) and paclitaxel (135−175 mg/m2) with radiotherapy (arm II) (51 patients). Radiotherapy was performed through the four-field box technique at doses of 45−50 Gy (1.8 Gy/day × 5 days/week). Results The toxicity was manageable and predominantly hematologic with a grade 3 neutropenia and thrombocytopenia in 9.8% and 6% of the patients in arm I and arm II, respectively, without febrile neutropenia. All patients experienced hair loss. Chemoradiotherapy arm was associated with a lower incidence rate of relapse (9.8% vs. 22.7%). After a median follow-up period of 48 months, the 5-year OAS and PFS rates for chemoradiotherapy-treated patients were significantly more favorable than those who did not receive chemotherapy (P=0.02 and 0.03, respectively). In arm I, the OAS and PFS rates were 73.7% and 66.7% compared with those in arm II, whose rates were 90.2% and 84.3%. Conclusions Adjuvant chemoradiation with paclitaxel and carboplatin improved the survival rates and decreased the recurrence rates in patients with high-risk stage I-II endometrial carcinoma. Chemotherapy was associated with an acceptable rate of toxicity. However, a prospective study with a larger number of patients is needed to define a standard adjuvant treatment for high-risk stage I-II endometrial carcinoma. PMID:23691474

  9. High risk groups in an oil shale workforce

    SciTech Connect

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

    1984-04-01

    The workforce risks of a hypothetical one million barrels-per-day oil shale industry were estimated. The risks for the different workforce segments were compared and high risk groups were identified. Accidents and injuries were statistically described by rates for fatalities, for accidents with days lost from work, and for accidents with no days lost from work. Workforce diseases analyzed were cancers, silicosis, pneumoconiosis, chronic bronchitis, chronic airway obstruction, and high frequency hearing loss. A comparison of the workforce groups under different risk measures (occurrence, fatality, and life-loss expectancy) was performed. The miners represented the group with the largest fatality and the most serious accident rate, although the estimated rates were below the average industry-wide underground mining experience. Lung disease from inhalation exposure of about the nuisance dust threshold limit value presents a significant risk for future concerns.

  10. Prenatal diagnosis of osteochondrodysplasias in high risk pregnancy.

    PubMed

    Gordienko IYu; Grechanina EYa; Sopko, N I; Tarapurova, E N; Mikchailets, L P

    1996-05-01

    We collected data on 39 prenatally diagnosed osteochondrodysplasias. We detected 30 (76.9%) cases in the first and second trimesters, including 18 (46.2%) with two twins before the 24th week of gestation. Of 39 cases 11 (28.2%) had osteogenesis imperfecta (OI) type II. Verification of the prenatal diagnosis was attempted in 26 cases on the basis of the data obtained from ultrasonographs, radiographs, external examination, and autopsy protocols. The prenatal diagnosis was confirmed in 19 (73%) fetuses. In 13 cases verification was not possible because one or several investigations could not be performed. Counselling followed all identified cases with osteochondrodysplasia. We present the pedigree of two families indicating the possibility of early prenatal diagnosis of achondrogenesis type I and metatropic dysplasia. We propose indications for ultrasonographic anatomical screening with subsequent phenotype analysis in high risk pregnancy to provide for the prenatal detection of malformations and hereditary diseases. PMID:8723093

  11. Characteristics of Violence among High Risk Adolescent Girls

    PubMed Central

    Secor-Turner, Molly; Garwick, Ann; Sieving, Renee; Seppelt, Ann

    2013-01-01

    Introduction Recent evidence demonstrates increasing rates of violence involvement among adolescent girls. The objective of this study was to describe the types and sources of violence experienced within social contexts of adolescent girls at high risk for pregnancy. Method Qualitative data for this analysis are drawn from intervention summary reports of 116 girls participating in Prime Time, a youth development intervention for adolescent girls. Descriptive content analysis techniques were used to identify types and sources of violence experienced by girls within their daily contexts. Results Types of violence included physical fighting, witnessing violence, physical abuse, gang-related violence, verbal fighting, verbal abuse and sexual abuse. Sources of violence included family, peers and friends, romantic partners, community violence, and self-perpetrated. Many girls in this study experienced violence in multiple contexts. Discussion It is imperative that efforts to assess and prevent violence among adolescent girls pay attention to the social contexts in which these adolescents live. PMID:23623540

  12. Prevalence of Hearing Impairment in High Risk Infants.

    PubMed

    Vashistha, Ishika; Aseri, Yogesh; Singh, B K; Verma, P C

    2016-06-01

    Hearing impairment is prevalent in the general population, early intervention facilitates proper development. The aim of this study was to establish the prevalence of hearing impairment in high-risk infants born between 2013 and 2014. 100 newborns were evaluated using evoked otoacoustic emissions and distortion produce and auditory behavior. Tests were reported if the results were altered. If altered results persisted, the child was referred for impedance testing and when necessary for medical evaluation. Infants referred for BOA and OAE undergone Brainstem auditory evoked potential testing. Of 100 children, 85 children have hearing within normal limits. Hearing impairment was found in 15 out of which 7 had unilateral hearing loss and 8 had bilateral hearing loss. The high prevalence of hearing impairment in this population underlines the importance of early audiological testing. PMID:27340640

  13. Empowering High-Risk Clients to Attain a Better Quality of Life: A Career Resiliency Framework

    ERIC Educational Resources Information Center

    Rickwood, Rory R.; Roberts, Jillian; Batten, Suzanne; Marshall, Anne; Massie, Kendra

    2004-01-01

    Career counselors frequently encounter clients who are at high risk for career and life development difficulties. Research suggests there is a connection between resiliency and successful career development in high-risk clients. Many high-risk individuals have poor decision-making skills and lack motivation to succeed in life and career…

  14. Web Services-Based Access to Local Clinical Trial Databases: A Standards Initiative of the Association of American Cancer Institutes

    PubMed Central

    Stahl, Douglas C.; Evans, Richard M.; Afrin, Lawrence B.; DeTeresa, Richard M.; Ko, Dave; Mitchell, Kevin

    2003-01-01

    Electronic discovery of the clinical trials being performed at a specific research center is a challenging task, which presently requires manual review of the center’s locally maintained databases or web pages of protocol listings. Near real-time automated discovery of available trials would increase the efficiency and effectiveness of clinical trial searching, and would facilitate the development of new services for information providers and consumers. Automated discovery efforts to date have been hindered by issues such as disparate database schemas, vocabularies, and standards for intersystem exchange of high-level data, but adequate infrastructure now exists that makes possible the development of applications for near real-time automated discovery of trials. This paper describes the current state (design and implementation) of the Web Services Specification for Publication and Discovery of Clinical Trials as developed by the Technology Task Force of the Association of American Cancer Institutes. The paper then briefly discusses a prototype web service-based application that implements the specification. Directions for evolution of this specification are also discussed. PMID:14728248

  15. Identification of local clinical Candida isolates using CHROMagar Candida™ as a primary identification method for various Candida species.

    PubMed

    Madhavan, P; Jamal, F; Chong, P P; Ng, K P

    2011-08-01

    The objective of our study was to study the effectiveness of CHROMagar Candida™ as the primary identification method for various clinical Candida isolates, other than the three suggested species by the manufacturer. We studied 34 clinical isolates which were isolated from patients in a local teaching hospital and 7 ATCC strains. These strains were first cultured in Sabouraud dextrose broth (SDB) for 36 hours at 35ºC, then on CHROMagar plates at 30ºC, 35ºC and 37ºC. The sensitivity of this agar to identify Candida albicans, Candida dubliniensis, Candida tropicalis, Candida glabrata, Candida rugosa, Candida krusei and Candida parapsilosis ranged between 25 and 100% at 30ºC, 14% and 100% at 35ºC, 56% and 100% at 37ºC. The specificity of this agar was 100% at 30ºC, between 97% and 100% at 35ºC, 92% and 100% at 37ºC. The efficiency of this agar ranged between 88 and 100% at 30ºC, 83% and 100% at 35ºC, 88% and 100% at 37ºC. Each species also gave rise to a variety of colony colours ranging from pink to green to blue of different colony characteristics. Therefore, the chromogenic agar was found to be useful in our study for identifying clinical Candida isolates. PMID:22041745

  16. [Clinical and experimental study of burns treated locally with Chinese herbs].

    PubMed

    Wang, G D; Zhang, Y M; Xiong, X Y

    1991-12-01

    According to the multiple pharmacological functions of Chinese herbs for treating burns, the authors selected some traditional herbs to cure the burning wound, which had not only the function of improving the local microcirculation of the burned surface and their bactericidal action, but also the function of changing the bacterial growth milieu action. Coptis chinensis 40%, Herba Taraxaci 40%, Fructus Mume 10% and Salvia miltiorrhizae 10% were boiled, infiltrated and disinfected. The mixture thus made was called as Burn II, which were applied on the burned surface daily, 97.1% of 103 patients were cured. Through the experiment of 60 rabbits burned by irons, which were divided into 6 groups (n = 10 in each group) and each 2 groups infected respectively with Bacillus pyocyaneus, Bacillus Coli and Staphylococcus Aureus, took one of each infected group as control group. After 14 days, the infected burned surfaces which were applied with Burn II daily. The results showed that the effect of Burn II was not only significant, but also its usage was not highly restricted by the medical condition. PMID:1821339

  17. The EANM clinical and technical guidelines for lymphoscintigraphy and sentinel node localization in gynaecological cancers.

    PubMed

    Giammarile, Francesco; Bozkurt, M Fani; Cibula, David; Pahisa, Jaume; Oyen, Wim J; Paredes, Pilar; Olmos, Renato Valdes; Sicart, Sergi Vidal

    2014-07-01

    The accurate harvesting of a sentinel node in gynaecological cancer (i.e. vaginal, vulvar, cervical, endometrial or ovarian cancer) includes a sequence of procedures with components from different medical specialities (nuclear medicine, radiology, surgical oncology and pathology). These guidelines are divided into sectione entitled: Purpose, Background information and definitions, Clinical indications and contraindications for SLN detection, Procedures (in the nuclear medicine department, in the surgical suite, and for radiation dosimetry), and Issues requiring further clarification. The guidelines were prepared for nuclear medicine physicians. The intention is to offer assistance in optimizing the diagnostic information that can currently be obtained from sentinel lymph node procedures. If specific recommendations given cannot be based on evidence from original scientific studies, referral is made to "general consensus" and similar expressions. The recommendations are designed to assist in the practice of referral to, and the performance, interpretation and reporting of all steps of the sentinel node procedure in the hope of setting state-of-the-art standards for high-quality evaluation of possible metastatic spread to the lymphatic system in gynaecological cancer. The final result has been discussed by a group of distinguished experts from the EANM Oncology Committee and the European Society of Gynaecological Oncology (ESGO). The document has been endorsed by the SNMMI Board. PMID:24609929

  18. Epidermal Th22 and Tc17 cells form a localized disease memory in clinically healed psoriasis.

    PubMed

    Cheuk, Stanley; Wikén, Maria; Blomqvist, Lennart; Nylén, Susanne; Talme, Toomas; Ståhle, Mona; Eidsmo, Liv

    2014-04-01

    Psoriasis is a common and chronic inflammatory skin disease in which T cells play a key role. Effective treatment heals the skin without scarring, but typically psoriasis recurs in previously affected areas. A pathogenic memory within the skin has been proposed, but the nature of such site-specific disease memory is unknown. Tissue-resident memory T (TRM) cells have been ascribed a role in immunity after resolved viral skin infections. Because of their localization in the epidermal compartment of the skin, TRM may contribute to tissue pathology during psoriasis. In this study, we investigated whether resolved psoriasis lesions contain TRM cells with the ability to maintain and potentially drive recurrent disease. Three common and effective therapies, narrowband-UVB treatment and long-term biologic treatment systemically inhibiting TNF-α or IL-12/23 signaling were studied. Epidermal T cells were highly activated in psoriasis and a high proportion of CD8 T cells expressed TRM markers. In resolved psoriasis, a population of cutaneous lymphocyte-associated Ag, CCR6, CD103, and IL-23R expressing epidermal CD8 T cells was highly enriched. Epidermal CD8 T cells expressing the TRM marker CD103 responded to ex vivo stimulation with IL-17A production and epidermal CD4 T cells responded with IL-22 production after as long as 6 y of TNF-α inhibition. Our data suggest that epidermal TRM cells are retained in resolved psoriasis and that these cells are capable of producing cytokines with a critical role in psoriasis pathogenesis. We provide a potential mechanism for a site-specific T cell-driven disease memory in psoriasis. PMID:24610014

  19. Local bupivacaine for postoperative pain management in thyroidectomized patients: A prospective and controlled clinical study

    PubMed Central

    Dumlu, Ersin Gürkan; Tokaç, Mehmet; Öcal, Haydar; Durak, Doğukan; Kara, Halil; Kılıç, Mehmet; Yalçın, Abdussamed

    2016-01-01

    Objective We aimed to evaluate the effect of bupivacaine and to compare the routes of administration of bupivacaine in the management of postoperative incision site pain after thyroidectomy. Material and Methods Consecutive patients who were planned for thyroidectomy surgery were randomized into three groups of 30 patients each: Group 1 (control group): standard thyroidectomy surgery without additional intervention; Group 2 (paratracheal infiltration with bupivacaine): following thyroidectomy, 0.25% bupivacaine was applied on the surgical area; Group 3 (subcutaneous infiltration with bupivacaine): following thyroidectomy, 0.25% bupivacaine was injected into the cutaneous, subcutaneous region and fascia of the surgical area. Postoperative pain was evaluated by a visual analog scale (VAS) at 1st, 4th, and 12th hours after thyroidectomy. Total daily requirement for additional analgesia was recorded. Results The mean age of 90 patients was 44.37±13.42 years, and the female:male ratio was 62:28. There was no difference between study groups in terms of age, thyroid volume, TSH and T4 levels. VAS score of patients in paratracheal infiltration with bupivacaine group was significantly lower than control group patients at 1st, 4th and 12th hours following thyroidectomy (p=0.030, p=0.033, p=0.039, respectively). The need for analgesics was significantly lower in both paratracheal infiltration and subcutaneous infiltration groups than the control group (86.7%, 83.0%, and 73.3%, respectively, p=0.049). Conclusions Intraoperative local bupivacaine application is effective in decreasing postoperative pain in patients with thyroidectomy. PMID:27528810

  20. Minocycline Ointment as a Local Drug Delivery in the Treatment of Generalized Chronic Periodontitis - A Clinical Study

    PubMed Central

    Abbas, Sara; Ari, Geetha

    2016-01-01

    Introduction The primary goal in periodontal therapy includes removal of the etiological factors by mechanical periodontal treatment, which sometimes fail to eliminate the anaerobic infection at the base of the pocket and requires adjuvant chemical therapy. Aim The aim of the study was to evaluate the effectiveness of 2% minocycline ointment when used as an adjunct to periodontal flap surgery and post-operative maintenance period for the treatment of generalized chronic periodontitis. Materials and Methods The study included 30 subjects comprising of 60 posterior sextants in a split mouth design in which 30 sextants were treated as experimental and 30 sextants as control with a probing pocket depth≥6mm. In Group A (experimental group) 30 sextants were treated with open flap debridement followed by the application of minocycline ointment as a local drug delivery. In Group B (control group) 30 sextants were treated with open flap debridement alone. Minocycline hydrochloride ointment was applied on the 0 day and 3rd month. The clinical parameters such as plaque index, probing pocket depth, clinical attachment level and gingival bleeding index were recorded at 0 day, 3rd month and 6th month in both the groups. Paired and unpaired t-test were used to compare the means of the two groups. Results When Group A and Group B were compared, Group A showed significantly greater reduction in gingival bleeding index, probing pocket depth and gain in clinical attachment level than Group B, from 0 day to 3 months and from 0 day to 6 months. Group A showed significant reduction in plaque index than Group B when they were compared at 6 months. Conclusion The results demonstrate that there was significant reduction in the clinical parameters with improvement in the periodontal status on application of minocycline ointment as an adjunct to periodontal flap surgery in generalized chronic periodontitis. PMID:27504402

  1. Prognostic role of clinical, pathological and biological characteristics in patients with locally advanced breast cancer.

    PubMed Central

    Honkoop, A. H.; van Diest, P. J.; de Jong, J. S.; Linn, S. C.; Giaccone, G.; Hoekman, K.; Wagstaff, J.; Pinedo, H. M.

    1998-01-01

    Forty-two patients with clinical stage IIIA or IIIB breast cancer were treated with neoadjuvant chemotherapy followed by mastectomy and radiotherapy. The median follow-up was 32 months (range 10-72 months) and the median time to progression was 17 months (range 10-30 months). A multivariate analysis showed that a longer disease-free survival (DFS) was related to more chemotherapy cycles given (P = 0.003), a better pathological response to chemotherapy (P = 0.04) and fewer positive axillary lymph nodes (P = 0.05). A better overall survival (OS) was related to more chemotherapy cycles given (P = 0.03) and better pathological response to chemotherapy (P = 0.04). In patients with residual tumour after neoadjuvant chemotherapy, high levels of staining for Ki-67 was correlated with a worse DFS (P = 0.008). Other biological characteristics, including oestrogen receptor status, microvessel density (CD31 staining), P-glycoprotein (P-gp) staining and nuclear accumulation of p53, were not independent prognostic factors for either DFS or OS. If both P-gp and p53 were expressed, DFS and OS were worse in the uni- and multivariate analysis. The preliminary results of this phase II study suggest that coexpression of P-gp/p53 and a high level of staining for Ki-67 after chemotherapy are associated with a worse prognosis, and that prolonged neoadjuvant chemotherapy and the attainment of a pathological complete remission are important factors in determining outcome for patients with this disease. PMID:9484820

  2. Multiple Human Papillomavirus Infection Is Associated with High-Risk Infection in Male Genital Warts in Ulsan, Korea

    PubMed Central

    Moon, Kyung Hyun; Yang, Sung-Hak; Roh, Min Cheol; Lee, Sang Hoon; Kim, Je Won; Kim, In Kyu; Roh, Kyoung Ho

    2016-01-01

    Further understanding of male human papillomavirus (HPV) infection is necessary to prevent infection in men, as well as transmission to women. In our current study, we investigated patterns of HPV infection and genotype distributions in male genital warts using the Anyplex II HPV28 Detection kit. We reviewed the medical records of 80 male patients who presented to 5 neighborhood clinics in Ulsan, Korea, for the treatment of genital warts between April 2014 and January 2015. All patients underwent HPV genotyping. The prevalence and characteristics of HPV infection were analyzed, and the patterns of HPV infection according to age were assessed. Among the study patients, 13 (16.3%) were negative for HPV infection, 46 (57.3%) were infected with low-risk HPV, and 21 (26.3%) were infected with high-risk HPV. Patients with multiple HPV infection were more likely to have high-risk HPV infection (P = 0.001). The prevalence of HPV infection was much higher in samples obtained by tissue excision due to a definite lesion (P = 0.001). There were no differences in high-risk HPV infection (P = 0.459), multiple HPV infection (P = 0.185), and recurrence at diagnosis (P = 0.178) according to age. HPV-6 and HPV-11 were the most common type overall (39.7% and 13.8%, respectively). HPV-16 and HPV-18 were the most common high-risk infections (both 3.4%). HPV infection is not only commonly encountered in male genital warts, but is also accompanied by high-risk HPV and multiple infections. PMID:26955236

  3. Patterns and predictors of high-risk sexual behavior in female partners of HIV-infected men with hemophilia.

    PubMed

    Dublin, S; Rosenberg, P S; Goedert, J J

    1992-05-01

    This study sought to characterize and quantify the high-risk heterosexual activity in HIV-discordant couples. An analysis of cross-sectional and longitudinal questionnaire data from 217 HIV-negative female sexual partners of HIV-infected hemophiliac men were included in this study. There was a comparison of prevalence rates of anal sex, oral sex, vaginal intercourse with or without condoms, and use of other contraceptives between 1985-91. Logistic regression analysis of demographic, sexual, and clinical variables was used to predict unprotected vaginal sex. Actuarial estimates of semiannual relapse rates to unsafe sex were used. The proportion of women at low risk increases from 7 to 69% between 1985-91, mainly because more women were using condoms during all acts of vaginal intercourse. Other contraceptive practices did not change during this time. The proportion who engaged in oral or anal sex decreased from 26 to 13% and from 13% to 4%, respectively. Unprotected vaginal sex was more common among women who enrolled earlier, had less education, engaged in oral or anal sex, and among those whose partners had not had AIDS. Unprotected vaginal sex before enrollment was the strongest predictor of this high-risk activity during followup. 2-year rates of relapse to high-risk behavior were significantly higher among women who enrolled at high risk compared with those who enrolled at low risk (39 vs 8%, p=0.005). Although high risk sexual behavior become much less prevalent in this population between 1985-91, many continued to have unprotected vaginal sex occasionally. Counseling efforts should target couples who have been the most sexually active or have less education, and should emphasize not only initial risk reduction but also maintenance of low-risk behavior. PMID:1616653

  4. Evaluation of a Pharmacist-Specific Intervention on 30-Day Readmission Rates for High-Risk Patients with Pneumonia

    PubMed Central

    Carroll, Douglas N.; Pinner, Nathan A.

    2015-01-01

    Background: Pharmacist interventions have been shown to have an impact on reducing readmission rates, however further research is necessary to target resources to high-risk populations and determine the most effective bundle of interventions. Objective: To evaluate the effect of a pharmacist-bundled intervention on 30-day readmission rates for high-risk patients with pneumonia. Methods: A pilot study with a historical control conducted at a community, teaching-affiliated medical center. Up to 65 selected subjects were included if they had pneumonia and any of the following high-risk criteria: admission within 6 months, at least 5 scheduled home medications, chronic obstructive pulmonary disease (COPD), or heart failure. A retrospective chart review was conducted to compile the historical control group that received usual care between June and November 2013. Patients admitted from December 2013 through March 2014 were reviewed to receive a bundled intervention. The primary outcome was 30-day readmission rates. Risk factors and reasons for readmission, pharmacist clinical interventions, and the time interval between discharge and readmission were also evaluated. Results: A trend toward a reduced 30-day readmission rate was observed in the intervention group (n = 43) compared to those who received usual care (n = 65) (27.9% vs 40.0%; relative risk [RR], 0.6977; 95% CI, 0.3965–1.2278; P = .2119). The most commonly identified high-risk inclusion criteria were having at least 5 scheduled home medications and COPD. The time interval between discharge and readmission did not considerably differ between groups (10.8 vs 10.6 days). Conclusions: The pharmacist-bundled intervention was associated with a reduced 30-day readmission rate for high-risk patients with pneumonia. PMID:26823619

  5. Other important applications for beta-blockers in high-risk patients.

    PubMed

    Egan, Brent M; Chilton, Robert J

    2003-12-01

    Beta-blockers suppress the adverse effects of chronic activation of the sympathetic nervous system-which plays an important role in the progression of cardiovascular disease- and the drugs are also recommended as primary therapy in other diverse medical conditions that present treatment problems. For many patients with atrial fibrillation, a common condition that poses a high risk of stroke, heart rate control with beta-blockers is increasingly seen as a critical therapeutic component. Similarly, perioperative beta-blocker use provides clinical benefits in patients undergoing noncardiac surgery who are at risk of cardiac events. In migraine therapy, beta-blockers are well established as effective agents for prophylaxis, and beta-blockers may reduce levels of C-reactive protein, a sensitive marker of inflammation in cardiovascular disease. Reviewing the role of beta-blockers in several ancillary conditions should help illuminate various aspects of the complex progression of cardiovascular disease and clarify the drugs' various therapeutic benefits. PMID:19667668

  6. Dissemination of high-risk clones of extensively drug-resistant Pseudomonas aeruginosa in colombia.

    PubMed

    Correa, Adriana; Del Campo, Rosa; Perenguez, Marcela; Blanco, Victor M; Rodríguez-Baños, Mercedes; Perez, Federico; Maya, Juan J; Rojas, Laura; Cantón, Rafael; Arias, Cesar A; Villegas, Maria V

    2015-04-01

    The ability of Pseudomonas aeruginosa to develop resistance to most antimicrobials represents an important clinical threat worldwide. We report the dissemination in several Colombian hospitals of two predominant lineages of extensively drug-resistant (XDR) carbapenemase-producing P. aeruginosa strains. These lineages belong to the high-risk clones sequence type 111 (ST111) and ST235 and harbor blaVIM-2 on a class 1 integron and blaKPC-2 on a Tn4401 transposon, respectively. Additionally, P. aeruginosa ST1492, a novel single-locus variant of ST111, was identified. Clonal dissemination and the presence of mobile genetic elements likely explain the successful spread of XDR P. aeruginosa strains in Colombia. PMID:25605362

  7. Dissemination of High-Risk Clones of Extensively Drug-Resistant Pseudomonas aeruginosa in Colombia

    PubMed Central

    del Campo, Rosa; Perenguez, Marcela; Blanco, Victor M.; Rodríguez-Baños, Mercedes; Perez, Federico; Maya, Juan J.; Rojas, Laura; Cantón, Rafael; Arias, Cesar A.; Villegas, Maria V.

    2015-01-01

    The ability of Pseudomonas aeruginosa to develop resistance to most antimicrobials represents an important clinical threat worldwide. We report the dissemination in several Colombian hospitals of two predominant lineages of extensively drug-resistant (XDR) carbapenemase-producing P. aeruginosa strains. These lineages belong to the high-risk clones sequence type 111 (ST111) and ST235 and harbor blaVIM-2 on a class 1 integron and blaKPC-2 on a Tn4401 transposon, respectively. Additionally, P. aeruginosa ST1492, a novel single-locus variant of ST111, was identified. Clonal dissemination and the presence of mobile genetic elements likely explain the successful spread of XDR P. aeruginosa strains in Colombia. PMID:25605362

  8. Pediatric Bipolar Disorder: Combination Pharmacotherapy, Adverse Effects, and Treatment of High-Risk Youth.

    PubMed

    Chang, Kiki D

    2016-01-01

    Treating bipolar disorder in pediatric patients is challenging because data from rigorous trials of pharmacotherapy in this population are still not plentiful enough. Furthermore, the treatment of children and adolescents is complicated by the frequent need to combine pharmacotherapies to address all bipolar symptoms as well as this population's elevated risk for experiencing side effects. Additionally, young patients with depressive episodes who are at high risk for developing bipolar disorder need careful treatment to prevent or delay the emergence of mania. Despite these challenges, clinicians should evaluate the existing pediatric literature, extrapolate evidence obtained from adult patients, and draw from clinical experience to guide treatment decisions for children and adolescents with bipolar disorder. PMID:27570929

  9. Advances in haplo-identical stem cell transplantation in adults with high-risk hematological malignancies

    PubMed Central

    Ricci, Michael J; Medin, Jeffrey A; Foley, Ronan S

    2014-01-01

    Allogeneic bone marrow transplant is a life-saving procedure for adults and children that have high-risk or relapsed hematological malignancies. Incremental advances in the procedure, as well as expanded sources of donor hematopoietic cell grafts have significantly improved overall rates of success. Yet, the outcomes for patients for whom suitable donors cannot be found remain a significant limitation. These patients may benefit from a hematopoietic cell transplant wherein a relative donor is fully haplotype mismatched. Previously this procedure was limited by graft rejection, lethal graft-versus-host disease, and increased treatment-related toxicity. Recent approaches in haplo-identical transplantation have demonstrated significantly improved outcomes. Based on years of incremental pre-clinical research into this unique form of bone marrow transplant, a range of approaches have now been studied in patients in relatively large phase II trials that will be summarized in this review. PMID:25258660

  10. Advances in haplo-identical stem cell transplantation in adults with high-risk hematological malignancies.

    PubMed

    Ricci, Michael J; Medin, Jeffrey A; Foley, Ronan S

    2014-09-26

    Allogeneic bone marrow transplant is a life-saving procedure for adults and children that have high-risk or relapsed hematological malignancies. Incremental advances in the procedure, as well as expanded sources of donor hematopoietic cell grafts have significantly improved overall rates of success. Yet, the outcomes for patients for whom suitable donors cannot be found remain a significant limitation. These patients may benefit from a hematopoietic cell transplant wherein a relative donor is fully haplotype mismatched. Previously this procedure was limited by graft rejection, lethal graft-versus-host disease, and increased treatment-related toxicity. Recent approaches in haplo-identical transplantation have demonstrated significantly improved outcomes. Based on years of incremental pre-clinical research into this unique form of bone marrow transplant, a range of approaches have now been studied in patients in relatively large phase II trials that will be summarized in this review. PMID:25258660

  11. Active surveillance for acute flaccid paralysis in poliomyelitis high-risk areas in southern China.

    PubMed Central

    Chiba, Y.; Hikita, K.; Matuba, T.; Chosa, T.; Kyogoku, S.; Yu, J.; Wang, Z.

    2001-01-01

    OBJECTIVE: On 29 October 2000 poliomyelitis was officially declared to have been eradicated from the Western Pacific Region. This article describes the results of surveillance for cases of acute flaccid paralysis (AFP) in China during the final phase of the eradication effort. METHODS: We conducted hospital-based active surveillance in high-risk areas for poliomyelitis in 5 provinces of southern-China (Sichuan, Yunnan, Guizhou, Guangxi and Jiangxi) between 1995 and 1997 to determine the adequacy of reporting and laboratory diagnosis of cases of AFP. FINDINGS: A total of 1069 AFP cases occurring since 1993 were identified in 311 hospital visits. Less than 50% of AFP cases occurring in 1993 and 1994 had been reported by AFP surveillance, and laboratory diagnosis had been carried out on only a small proportion of these. However, improved cooperation between hospital sectors increased the rate of case reporting and laboratory diagnosis to 85% and 78%, respectively, in 1997. Despite this overall improvement, these two indicators were approximately 10-20% lower in Yunnan Province. Epidemiological analysis revealed that cases of clinical poliomyelitis accounted for as much as one-third of all AFP in 1993 and that some of these cases were clustered. Clusters were rarely observed after 1994. Active surveillance in the China-Myanmar border areas of Yunnan over 1995-96 detected 9 cross-border cases of clinical poliomyelitis, including 2 of wild poliomyelitis. Import of poliomyelitis was thus considered to have occurred frequently until 1996 in this border area of Yunnan. These data were important for the outbreak response immunization carried out in 1996 in the border prefectures of Yunnan. CONCLUSION: Our investigation confirmed a high level of AFP surveillance in poliomyelitis high-risk areas of the five provinces and provided valuable information on the interruption of wild poliovirus circulation in southern China that will be of use to countries in other regions that have

  12. Early Prodromal Symptoms Can Predict Future Psychosis in Familial High-Risk Youth

    PubMed Central

    Tandon, Neeraj; Montrose, Debra; Shah, Jai; Rajarethinam, RP; Diwadkar, Vaibhav A.; Keshavan, Matcheri S.

    2011-01-01

    Background Efforts to predict psychosis in individuals at high risk for schizophrenia have focused on the identification of sub-threshold clinical criteria and neurobiological markers, including neuropsychological assessment, structural and functional brain imaging, and psychophysiological testing. We sought to evaluate the relative utility of psychosis proneness measures for prospective prediction of psychotic disorders in a group of young relatives at familial risk for schizophrenia. Methods We examined the receiver operating characteristics of sub-threshold symptoms in predicting conversion to psychosis in a group of 97 young first- and second-degree relatives of persons with schizophrenia over a 2-year period. Towards this end, we utilized the Structured Interview of Prodromal Symptoms to derive measures of two of the four Scale of Prodromal Symptoms subscales (positive and disorganized) and the Chapman Magical Ideation and Perceptual Aberration scales. These four measures were, together, taken to reflect a putative index of psychosis proneness. Results Eleven of the 97 subjects developed a psychotic disorder over 2 years of follow-up. Seventeen of the 97 subjects tested positive on this index of psychosis proneness at baseline and of these 10 converted to psychosis. The sensitivity and specificity of the test were 91 percent and 92 percent respectively. The positive predictive value of the test was 59 percent and its negative predictive value was 99 percent. Addition of measures of cognitive or social function to the index decreased its predictive ability, reducing its specificity and/or sensitivity. Conclusions A relatively simple set of clinical measures can be utilized to prospectively identify familial high-risk individuals who convert to psychosis with high specificity and sensitivity. Implications for the proposed addition of an “Attenuated Psychosis Syndrome” in DSM-5 are discussed. PMID:22056319

  13. Early detection of tumor relapse/regrowth by consecutive minimal residual disease monitoring in high-risk neuroblastoma patients

    PubMed Central

    Hirase, Satoshi; Saitoh, Atsuro; Hartomo, Tri Budi; Kozaki, Aiko; Yanai, Tomoko; Hasegawa, Daiichiro; Kawasaki, Keiichiro; Kosaka, Yoshiyuki; Matsuo, Masafumi; Yamamoto, Nobuyuki; Mori, Takeshi; Hayakawa, Akira; Iijima, Kazumoto; Nishio, Hisahide; Nishimura, Noriyuki

    2016-01-01

    Neuroblastoma is an aggressive pediatric tumor accounting for ~15% of cancer-associated mortalities in children. Despite the current intensive therapy, >50% of high-risk patients experience tumor relapse or regrowth caused by the activation of minimal residual disease (MRD). Although several MRD detection protocols using various reverse transcription-quantitative polymerase chain reaction (RT-qPCR) markers have been reported to evaluate the therapeutic response and disease status of neuroblastoma patients, their clinical significance remains elusive. The present study reports two high-risk neuroblastoma patients, whose MRD was consecutively monitored using 11 RT-qPCR markers (CHRNA3, CRMP1, DBH, DCX, DDC, GABRB3, GAP43, ISL1, KIF1A, PHOX2B and TH) during their course of treatment. The two patients initially responded to the induction therapy and reached MRD-negative status. The patients' MRD subsequently became positive with no elevation of their urinary homovanillic acid, urinary vanillylmandelic acid and serum neuron-specific enolase levels at 13 or 19 weeks prior to the clinical diagnosis of tumor relapse or regrowth. The present cases highlight the possibility of consecutive MRD monitoring using 11 markers to enable an early detection of tumor relapse or regrowth in high-risk neuroblastoma patients. PMID:27446404

  14. Does sexual coercion play a role in the high-risk sexual behavior of adolescent and young adult women?

    PubMed

    Biglan, A; Noell, J; Ochs, L; Smolkowski, K; Metzler, C

    1995-12-01

    Sexual coercion and its relationship to high-risk sexual behavior were examined in five samples of young women. Sample 1 (N = 22) consisted of sexually active adolescents aged 15 to 19. Samples 2 (N = 206) and 3 (N = 70) were recruited from among patients at three sexually transmitted disease clinics. Sample 4 (N = 51) consisted of young homeless women living on the street in a large city. Sample 5 (N = 51) was recruited from among young women on a college campus. Across all samples, 44.4% of women indicated that they had been forced into some form of sexual activity against their will. Self-reports of sexually coercive experiences were consistently related to risky sexual behavior. It appears that many young women are coerced into engaging in high-risk sexual behavior. This implies the need for greater attention to male coercive sexual behavior and women's skills for coping with such behavior. PMID:8749985

  15. Overview of High-Risk Medical Device Innovation in Gastroenterology from 2000 to 2014: Enhancing the Pipeline.

    PubMed

    Saleem, Nasir; Xu, Shuai

    2016-08-01

    Medical devices are a critical component in the diagnosis and treatment of diseases of the alimentary tract. The United States Food and Drug Administration database was mined for high-risk medical device development via the pre-market approval (PMA) pathway from 2000 to 2014. In total, there were only nine GI (gastrointestinal) devices approved during this period. Furthermore, only one GI device was granted expedited review. The clinical studies leading to approval were mostly limited to non-blinded, non-randomized studies. Only a minority of pivotal studies defined and met their primary endpoints (27 %). Eight out of nine devices were required to undergo post-marketing studies. Ultimately, cardiology led with 157 total approvals in the time period studied. GI ranked 12 out of 18 across various medical and surgical specialties and accounted for <2 % of total PMA approvals. Future efforts should focus on spurring more high-risk device innovation in the field. PMID:27003144

  16. Clinical Trial of Prophylactic Extended-Field Carbon-Ion Radiotherapy for Locally Advanced Uterine Cervical Cancer (Protocol 0508)

    PubMed Central

    Wakatsuki, Masaru; Kato, Shingo; Kiyohara, Hiroki; Ohno, Tatsuya; Karasawa, Kumiko; Tamaki, Tomoaki; Ando, Ken; Tsujii, Hirohiko; Nakano, Takashi; Kamada, Tadashi; Shozu, Makio

    2015-01-01

    To evaluate the efficacy and the toxicity of prophylactic extended-field carbon-ion radiotherapy (C-ion RT, Protocol 0508) for locally advanced squamous cell carcinoma of the uterine cervix in phase I / II clinical trial. Between May 2006 and January 2012, 26 patients of Protocol 0508 were treated with C-ion RT. The numbers of patients with stage IIB, IIIB, and IVA disease were 13, 11, and 2, respectively. Twenty patients had pelvic lymph node metastases. Median tumor size was 6.1 cm (range, 4.0–10.0 cm). The treatment consisted of extended-field irradiation of 39.0 gray equivalents (GyE) in 13 fractions, and additional 15.0 GyE in 5 fractions was given to the gross tumor volume (GTV) and surrounding tissues. With regard to local boost, 18.0 GyE in 2 fractions was given to GTV only. Total dose to the cervical tumor was 72.0 GyE over 20 fractions. The median follow-up period was 37 months. Twenty-one patients had grade 1 or 2 acute gastrointestinal toxicity, but all patients completed the treatment on schedule. There were no grade 3 or higher late complications, with 8 patients having grade 1 or 2 toxicities, 1 had grade 2 gastrointestinal toxicity and 2 had grade 2 genitourinary toxicity. Four patients (15.4%) developed local recurrence, and 8 patients (30.8%) had distant metastases. The 2-year local control rate, progression-free survival rate and overall survival rate were 83.6%, 61.5% and 73.1%, respectively. There were no severe acute or late complications in this trial. Prophylactic extended-field C-ion RT for locally advanced squamous cell carcinoma of the uterine cervix was a safe treatment. Although the number of patients in this study was small, the results support further investigations to confirm the therapeutic efficacy and to avoid or reduce toxicity. Trial Registration UMIN-CTR UMIN000016169 PMID:25993047

  17. Professional drivers: protection needed for a high-risk occupation.

    PubMed Central

    Baker, S P; Wong, J; Baron, R D

    1976-01-01

    "On the job" motor vehicle deaths number more than 4,000 annually in the U.S. and comprise nearly one-third of all work-related deaths. Yet the Department of Labor has set no standards relating to on-the-road safety of the millions of workers whose jobs entail large amounts of driving, and Department of Transportation standards affecting occupational safety cover only drivers in interstate commerce. Drivers of some commercial vehicles, such as heavy trucks, are at special risk of injury because trucks have usually been exempted for many years from federal motor vehicle safety standards--such as standards for brakes and seatbelts--designed to prevent crashes or protect occupants in crashes. Observations based on a series of 150 fatal crashes involving tractor trailers illustrate the need for better protection of this large population of high-risk workers. Clarification of responsibility within the various federal agencies and application of available knowledge and technology are essential. PMID:937611

  18. Upper tract urothelial carcinoma: epidemiology, high risk populations and detection.

    PubMed

    Redrow, Grant P; Matin, Surena F

    2016-08-01

    Upper tract urothelial carcinoma (UTUC) is a rare but highly morbid genitourinary malignancy. In 2014 approximately 15,000 new cases were diagnosed in the United States. It accounts for approximately 5-10% of all urothelial cell carcinomas, and 10% of renal tumors. Recent research has increased understanding of the epidemiology of this disease, including several high-risk populations. Environmental exposure to tobacco as well as aristolochic acid, and other carcinogens significantly increase the development of UTUC. Additionally, the genetic condition of hereditary nonpolyposis colorectal carcinoma (HNPCC), also known as Lynch Syndrome (LS) is linked to development of UTUC. Advances in imaging, ureteroscopy, cytological techniques and pathological recognition have allowed for improved detection of primary tumors and recurrent disease. Non-invasive imaging with computed tomography (CT) and magnetic resonance imaging (MRI) now represent the gold standard in imaging detection and surveillance, while technological advances in ureteroscopy allow for minimally invasive approaches to obtain pathologic diagnosis anywhere within the upper tracts. This review will highlight these recent improvements to allow better understanding of who is affected by this rare and morbid disease, as well as the latest developments in detection and surveillance. PMID:27008468

  19. The genetic landscape of high-risk neuroblastoma

    PubMed Central

    Pugh, Trevor J.; Morozova, Olena; Attiyeh, Edward F.; Asgharzadeh, Shahab; Wei, Jun S.; Auclair, Daniel; Carter, Scott L.; Cibulskis, Kristian; Hanna, Megan; Kiezun, Adam; Kim, Jaegil; Lawrence, Michael S.; Lichenstein, Lee; McKenna, Aaron; Pedamallu, Chandra Sekhar; Ramos, Alex H.; Shefler, Erica; Sivachenko, Andrey; Sougnez, Carrie; Stewart, Chip; Ally, Adrian; Birol, Inanc; Chiu, Readman; Corbett, Richard D.; Hirst, Martin; Jackman, Shaun D.; Kamoh, Baljit; Khodabakshi, Alireza Hadj; Krzywinski, Martin; Lo, Allan; Moore, Richard A.; Mungall, Karen L.; Qian, Jenny; Tam, Angela; Thiessen, Nina; Zhao, Yongjun; Cole, Kristina A.; Diamond, Maura; Diskin, Sharon J.; Mosse, Yael P.; Wood, Andrew C.; Ji, Lingyun; Sposto, Richard; Badgett, Thomas; London, Wendy B.; Moyer, Yvonne; Gastier-Foster, Julie M.; Smith, Malcolm A.; Auvil, Jaime M. Guidry; Gerhard, Daniela S.; Hogarty, Michael D.; Jones, Steven J. M.; Lander, Eric S.; Gabriel, Stacey B.; Getz, Gad; Seeger, Robert C.; Khan, Javed; Marra, Marco A.; Meyerson, Matthew; Maris, John M.

    2013-01-01

    Neuroblastoma is a malignancy of the developing sympathetic nervous system that often presents with widespread metastatic disease, resulting in survival rates of less than 50%1. To determine the spectrum of somatic mutation in high-risk neuroblastoma, we studied 240 cases using a combination of whole exome, genome and transcriptome sequencing as part of the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) initiative. Here we report a low median exonic mutation frequency of 0.60 per megabase (0.48 non-silent), and remarkably few recurrently mutated genes in these tumors. Genes with significant somatic mutation frequencies included ALK (9.2% of cases), PTPN11 (2.9%), ATRX (2.5%, an additional 7.1% had focal deletions), MYCN (1.7%, a recurrent p.Pro44Leu alteration), and NRAS (0.83%). Rare, potentially pathogenic germline variants were significantly enriched in ALK, CHEK2, PINK1, and BARD1. The relative paucity of recurrent somatic mutations in neuroblastoma challenges current therapeutic strategies reliant upon frequently altered oncogenic drivers. PMID:23334666

  20. Germline RECQL mutations in high risk Chinese breast cancer patients.

    PubMed

    Kwong, Ava; Shin, Vivian Y; Cheuk, Isabella W Y; Chen, Jiawei; Au, Chun H; Ho, Dona N; Chan, Tsun L; Ma, Edmond S K; Akbari, Mohammad R; Narod, Steven A

    2016-06-01

    Recently, RECQL was reported as a new breast cancer susceptibility gene. RECQL belongs to the RECQ DNA helicase family which unwinds double strand DNA and involved in the DNA replication stress response, telomere maintenance and DNA repair. RECQL deficient mice cells are prone to spontaneous chromosomal instability and aneuploidy, suggesting a tumor-suppressive role of RECQL in cancer. In this study, RECQL gene mutation screening was performed on 1110 breast cancer patients who were negative for BRCA1, BRCA2, TP53 and PTEN gene mutations and recruited from March 2007 to June 2015 in the Hong Kong Hereditary and High Risk Breast Cancer Program. Four different RECQL pathogenic mutations were identified in six of the 1110 (0.54 %) tested breast cancer patients. The identified mutations include one frame-shift deletion (c.974_977delAAGA), two splicing site mutations (c.394+1G>A, c.867+1G>T) and one nonsense mutation (c.796C>T, p.Gln266Ter). Two of the mutations (c.867+1G>T and p.Gln266Ter) were seen in more than one patients. This study provides the basis for existing of pathogenic RECQL mutations in Southern Chinese breast cancer patients. The significance of rare variants in RECQL gene in the estimation of breast cancer risk warranted further investigation in larger cohort of patients and in other ethnic groups. PMID:27125668

  1. INSTRUMENTS OF HIGH RISK SEXUAL BEHAVIOR ASSESSMENT: A SYSTEMATIC REVIEW

    PubMed Central

    Mirzaei, Mojtaba; Ahmadi, Khodabakhsh; Saadat, Seyed-Hassan; Ramezani, Mohammad Arash

    2016-01-01

    Background: Sexual behavior is a complex activity affecting all aspects of human’s life. Risky sexual behaviors impose negative outcomes on family, relationships and health. Unsafe sex is the second most leading cause of disability adjusted life years worldwide. Valid and reliable tools for assessment of risky sexual behaviors are necessary for implementing preventive measures. Methods: we searched Medline and the Cochrane Library of Systematic Reviews, with the keywords of “risky sexual behavior assessment”, “sexual risk assessment”, “high risk sexual behavior”, “sexual risk taking”. By reviewing references of the articles, some complementary studies were added. Results: Assessment can be performed by questionnaire or non-questionnaire instruments. Questionnaires vary depending on their target population, evaluation of risky sexual behavior as a whole or focusing on an associated risk factor. In order to avoid usual biases in self reports, objective biomarker assessment of unprotected sex are employed. These markers include prostate specific antigen, chromosome Y DNA and Seminogelin. Conclusion: Risky sexual behavior can be assessed by various subjective and objective methods. While self-reports are more feasible, objective methods offer a higher degree of reliability. Further studies for finding more feasible methods of using biomarkers are recommended. PMID:27047267

  2. Decontamination of High-risk Animal and Zoonotic Pathogens

    PubMed Central

    Menrath, Andrea; Tomuzia, Katharina; Braeunig, Juliane; Appel, Bernd

    2013-01-01

    Preparedness for the decontamination of affected environments, premises, facilities, and products is one prerequisite for an immediate response to an animal disease outbreak. Various information sources provide recommendations on how to proceed in an outbreak situation to eliminate biological contaminants and to stop the spread of the disease. In order to facilitate the identification of the right decontamination strategy, we present an overview of relevant references for a collection of pathogenic agents. The choice of pathogens is based on a survey of lists containing highly pathogenic agents and/or biological agents considered to be potential vehicles for deliberate contamination of food, feed, or farm animals. European legislation and guidelines from national and international institutions were screened to find decontamination protocols for each of the agents. Identified recommendations were evaluated with regard to their area of application, which could be facilities and equipment, wastes, food, and other animal products. The requirements of a disinfectant for large-scale incidents were gathered, and important characteristics (eg, inactivating spectrum, temperature range, toxicity to environment) of the main recommended disinfectants were summarized to assist in the choice of a suitable and efficient approach in a crisis situation induced by a specific high-risk animal or zoonotic pathogen. The literature search revealed numerous relevant recommendations but also legal gaps for certain diseases, such as Q fever or brucellosis, and legal difficulties for the use of recommended disinfectants. A lack of information about effective disinfectants was identified for some agents. PMID:23971795

  3. Decontamination of high-risk animal and zoonotic pathogens.

    PubMed

    Frentzel, Hendrik; Menrath, Andrea; Tomuzia, Katharina; Braeunig, Juliane; Appel, Bernd

    2013-09-01

    Preparedness for the decontamination of affected environments, premises, facilities, and products is one prerequisite for an immediate response to an animal disease outbreak. Various information sources provide recommendations on how to proceed in an outbreak situation to eliminate biological contaminants and to stop the spread of the disease. In order to facilitate the identification of the right decontamination strategy, we present an overview of relevant references for a collection of pathogenic agents. The choice of pathogens is based on a survey of lists containing highly pathogenic agents and/or biological agents considered to be potential vehicles for deliberate contamination of food, feed, or farm animals. European legislation and guidelines from national and international institutions were screened to find decontamination protocols for each of the agents. Identified recommendations were evaluated with regard to their area of application, which could be facilities and equipment, wastes, food, and other animal products. The requirements of a disinfectant for large-scale incidents were gathered, and important characteristics (eg, inactivating spectrum, temperature range, toxicity to environment) of the main recommended disinfectants were summarized to assist in the choice of a suitable and efficient approach in a crisis situation induced by a specific high-risk animal or zoonotic pathogen. The literature search revealed numerous relevant recommendations but also legal gaps for certain diseases, such as Q fever or brucellosis, and legal difficulties for the use of recommended disinfectants. A lack of information about effective disinfectants was identified for some agents. PMID:23971795

  4. Improved results in high risk cadaveric kidney transplantation

    SciTech Connect

    Toledo-Pereyra, L.H.; Baskin, S.; McNichol, L.; Edford, G.; Whitten, J.; Allaben, R.

    1980-01-01

    In general, cadaver kidney transplantation survival remains at 40-50% for the first year after transplantation. To compare the beneficial effect of a new immunosuppressive protocol to standard therapy (azathioprine and prednisone), we have studied 30 high risk first cadaveric renal allograft recipients who were randomly selected before (Group A, n.15) and after (Group B, n.15) 10/79. At 12 mos, actuarial graft survival of Group B is 75% compared to 46% in Group A. Actuarial patient survival for Group B is 94% for one year compared to 60% in Group A. We feel that these improved results are related to basic changes in our immunosuppressive protocol. These changes consist of: 1. Low doses of azathioprine and prednisolone (less than 1 mg/kg) with rapid reduction to very low levels (less than 0.3 mg/kg); 2. ALG administration at 30 mg/kg/day for 14 times; 3. Rapid placement (one month) on alternate day steroid therapy; 4. Elimination of steroids for the treatment of rejection; 5. Use of ALG (20 mg/kg/day for 10 days) for the treatment of rejection; 6. Use of ALG combined with modified lymph node irradiation for third rejection episodes; and 7. Long-term intermittent ALG administration provided that kidney function continues to be normal. The best immunosuppressive protocol is clearly the one associated with less morbidity and improved quality of life after transplantation. Our current protocol (Group B) provides the best results.

  5. Neurophysiology for Detection of High Risk for Psychosis.

    PubMed

    Pantlin, Lara N; Davalos, Deana

    2016-01-01

    Schizophrenia is a complex and often disabling disorder that is characterized by a wide range of social, emotional, and cognitive deficits. Increasing research suggests that the greatest social and cognitive therapeutic impact comes from early identification. The present study applied a well-established neurophysiological paradigm in the schizophrenia literature, mismatch negativity (MMN), to college students identified as high risk (HR) for psychosis to investigate MMN as a potential biomarker for the onset of psychosis. The hypothesis was that HR would exhibit attenuated MMN amplitudes compared to controls, as has been established in individuals with chronic schizophrenia. Participants (N = 121) were separated into Group 1 (controls) (n 1 = 72) and Group 2 (HR) (n 2 = 49) based on the established cutoff score of the 16-item Prodromal Questionnaire. Participants then completed a time based MMN paradigm during which brain activity was recorded with EEG. For all electrode locations, controls demonstrated significantly more negative amplitudes than HR (Cz: F(1,119) = 8.09, p = .005; Fz: F(1, 119) = 5.74, p = .018; Pz: F(1,119) = 5.88, p = .017). Results suggested that MMN may assist in identifying those who appear high-functioning but may be at risk for later development of psychosis or cognitive and psychological difficulties associated with psychosis. PMID:27579180

  6. Neurophysiology for Detection of High Risk for Psychosis

    PubMed Central

    2016-01-01

    Schizophrenia is a complex and often disabling disorder that is characterized by a wide range of social, emotional, and cognitive deficits. Increasing research suggests that the greatest social and cognitive therapeutic impact comes from early identification. The present study applied a well-established neurophysiological paradigm in the schizophrenia literature, mismatch negativity (MMN), to college students identified as high risk (HR) for psychosis to investigate MMN as a potential biomarker for the onset of psychosis. The hypothesis was that HR would exhibit attenuated MMN amplitudes compared to controls, as has been established in individuals with chronic schizophrenia. Participants (N = 121) were separated into Group 1 (controls) (n1 = 72) and Group 2 (HR) (n2 = 49) based on the established cutoff score of the 16-item Prodromal Questionnaire. Participants then completed a time based MMN paradigm during which brain activity was recorded with EEG. For all electrode locations, controls demonstrated significantly more negative amplitudes than HR (Cz: F(1,119) = 8.09, p = .005; Fz: F(1, 119) = 5.74, p = .018; Pz: F(1,119) = 5.88, p = .017). Results suggested that MMN may assist in identifying those who appear high-functioning but may be at risk for later development of psychosis or cognitive and psychological difficulties associated with psychosis. PMID:27579180

  7. Pharmacological Management of High-risk Neuroblastoma in Children

    PubMed Central

    Ganeshan, Veena R.; Schor, Nina F.

    2015-01-01

    BACKGROUND Neuroblastoma is the most common extracranial solid tumor of childhood. It accounts for 15% of pediatric cancer deaths. Children with high-risk disease have a 3-year event-free survival rate of only 20%. Chemotherapy is the mainstay of the treatment of children with advanced neuroblastoma. OBJECTIVE To review and critically evaluate the pharmacotherapy of neuroblastoma. DATA SOURCES Peer-reviewed and review literature, 2000–2011. STUDY SELECTION All peer-reviewed, published human subjects studies of therapy for neuroblastoma in children were included. Animal model and in vitro studies were included only if they added to the understanding of the mechanism of a proposed or existing human neuroblastoma therapy. DATA SYNTHESIS Current therapeutic options for neuroblastoma involve insufficient differentiation of normal from neoplastic tissue. Critically needed new approaches will increasingly exploit targeting of therapy for unique characteristics of the neuroblastoma cell. CONCLUSIONS Pharmacotherapy for neuroblastoma still suffers from an inadequate therapeutic window. Enhancement of toxicity for tumor and safety for normal tissues will entail innovation in targeting neuroblastoma cells and rescuing or protecting normal tissue elements. PMID:21692548

  8. Temporal expression and localization patterns of variant surface antigens in clinical Plasmodium falciparum isolates during erythrocyte schizogony.

    PubMed

    Bachmann, Anna; Petter, Michaela; Tilly, Ann-Kathrin; Biller, Laura; Uliczka, Karin A; Duffy, Michael F; Tannich, Egbert; Bruchhaus, Iris

    2012-01-01

    Avoidance of antibody-mediated immune recognition allows parasites to establish chronic infections and enhances opportunities for transmission. The human malaria parasite Plasmodium falciparum possesses a number of multi-copy gene families, including var, rif, stevor and pfmc-2tm, which encode variant antigens believed to be expressed on the surfaces of infected erythrocytes. However, most studies of these antigens are based on in vitro analyses of culture-adapted isolates, most commonly the laboratory strain 3D7, and thus may not be representative of the unique challenges encountered by P. falciparum in the human host. To investigate the expression of the var, rif-A, rif-B, stevor and pfmc-2tm family genes under conditions that mimic more closely the natural course of infection, ex vivo clinical P. falciparum isolates were analyzed using a novel quantitative real-time PCR approach. Expression patterns in the clinical isolates at various time points during the first intraerythrocytic developmental cycle in vitro were compared to those of strain 3D7. In the clinical isolates, in contrast to strain 3D7, there was a peak of expression of the multi-copy gene families rif-A, stevor and pfmc-2tm at the young ring stage, in addition to the already known expression peak in trophozoites. Furthermore, most of the variant surface antigen families were overexpressed in the clinical isolates relative to 3D7, with the exception of the pfmc-2tm family, expression of which was higher in 3D7 parasites. Immunofluorescence analyses performed in parallel revealed two stage-dependent localization patterns of RIFIN, STEVOR and PfMC-2TM. Proteins were exported into the infected erythrocyte at the young trophozoite stage, whereas they remained inside the parasite membrane during schizont stage and were subsequently observed in different compartments in the merozoite. These results reveal a complex pattern of expression of P. falciparum multi-copy gene families during clinical progression

  9. Probability of Extraprostatic Disease According to the Percentage of Positive Biopsy Cores in Clinically Localized Prostate Cancer

    PubMed Central

    Valette, Thiago N.; Antunes, Alberto A.; Leite, Kátia Moreira; Srougi, Miguel

    2015-01-01

    ABSTRACT Objective Prediction of extraprostatic disease in clinically localized prostate cancer is relevant for treatment planning of the disease. The purpose of this study was to explore the usefulness of the percentage of positive biopsy cores to predict the chance of extraprostatic cancer. Materials and Methods We evaluated 1787 patients with localized prostate cancer submitted to radical prostatectomy. The percentage of positive cores in prostate biopsy was correlated with the pathologic outcome of the surgical specimen. In the final analysis, a correlation was made between categorical ranges of positive cores (10% intervals) and the risk of extraprostatic extension and/or bladder neck invasion, seminal vesicles involvement or metastasis to iliac lymph nodes. Student's t test was used for statistical analysis. Results For each 10% of positive cores we observed a progressive higher prevalence of extraprostatic disease. The risk of cancer beyond the prostate capsule for <10% positive biopsy cores was 7.4% and it increased to 76.2% at the category 90-100% positive cores. In patients with Gleason grade 4 or 5, the risk of extraprostatic cancer prostate was higher than in those without any component 4 or 5. Conclusion The percentage of positive cores in prostate biopsy can predict the risk of cancer outside the prostate. Our study shows that the percentage of positive prostate biopsy fragments helps predict the chance of extraprostatic cancer and may have a relevant role in the patient's management. PMID:26200538

  10. A Phase I/II Clinical Trial in Localized Prostate Cancer of an Adenovirus Expressing Nitroreductase with CB1984

    PubMed Central

    Patel, Prashant; Young, J Graham; Mautner, Vivien; Ashdown, Daniel; Bonney, Sarah; Pineda, Robert G; Collins, Stuart I; Searle, Peter F; Hull, Diana; Peers, Elizabeth; Chester, John; Wallace, D Michael; Doherty, Alan; Leung, Hing; Young, Lawrence S; James, Nicholas D

    2009-01-01

    We report a phase I/II clinical trial in prostate cancer (PCa) using direct intraprostatic injection of a replication defective adenovirus vector (CTL102) encoding bacterial nitroreductase (NTR) in conjunction with systemic prodrug CB1954. One group of patients with localized PCa scheduled for radical prostatectomy received virus alone, prior to surgery, in a dose escalation to establish safety, tolerability, and NTR expression. A second group with local failure following primary treatment received virus plus prodrug to establish safety and tolerability. Based on acceptable safety data and indications of prostate-specific antigen (PSA) responses, an extended cohort received virus at a single dose level plus prodrug. The vector was well tolerated with minimal side effects, had a short half-life in the circulation, and stimulated a robust antibody response. Immunohistochemistry of resected prostate demonstrated NTR staining in tumor and glandular epithelium at all dose levels [5 × 1010–1 × 1012 virus particles (vp)]. A total of 19 patients received virus plus prodrug and 14 of these had a repeat treatment; minimal toxicity was observed and there was preliminary evidence of change in PSA kinetics, with an increase in the time to 10% PSA progression in 6 out of 18 patients at 6 months. PMID:19367257

  11. Locally Advanced Rectal Cancer Patients Receiving Radio-Chemotherapy: A Novel Clinical-Pathologic Score Correlates With Global Outcome

    SciTech Connect

    Berardi, Rossana; Mantello, Giovanna; Scartozzi, Mario; Del Prete, Stefano; Luppi, Gabriele; Martinelli, Roberto; Fumagalli, Marco; Grillo-Ruggieri, Filippo; Bearzi, Italo; Mandolesi, Alessandra; Marmorale, Cristina; Cascinu, Stefano

    2009-12-01

    Purpose: To determine the importance of downstaging of locally advanced rectal cancer after neoadjuvant treatment. Methods and Materials: The study included all consecutive patients with locally advanced rectal cancer who underwent neoadjuvant treatment (chemotherapy and/or radiotherapy) in different Italian centers from June 1996 to December 2003. A novel score was used, calculated as the sum of numbers obtained by giving a negative or positive point, respectively, to each degree of increase or decrease in clinical to pathologic T and N status. Results: A total of 317 patients were eligible for analysis. Neoadjuvant treatments performed were as follows: radiotherapy alone in 75 of 317 patients (23.7%), radiotherapy plus chemotherapy in 242 of 317 patients (76.3%). Worse disease-free survival was observed in patients with a lower score (Score 1 = -3 to +3 vs. Score 2 = +4 to +7; p = 0.04). Conclusions: Our results suggest that a novel score, calculated from preoperative and pathologic tumor and lymph node status, could represent an important parameter to predict outcome in patients receiving neoadjuvant treatment for rectal cancer. The score could be useful to select patients for adjuvant chemotherapy after neoadjuvant treatment and surgery.

  12. Evaluation of a cloud-based local-read paradigm for imaging evaluations in oncology clinical trials for lung cancer

    PubMed Central

    Kobayashi, Naomi; Bonnard, Eric; Charbonnier, Colette; Yamamichi, Junta; Mizobe, Hideaki; Kimura, Shinya

    2015-01-01

    Background Although tumor response evaluated with radiological imaging is frequently used as a primary endpoint in clinical trials, it is difficult to obtain precise results because of inter- and intra-observer differences. Purpose To evaluate usefulness of a cloud-based local-read paradigm implementing software solutions that standardize imaging evaluations among international investigator sites for clinical trials of lung cancer. Material and Methods Two studies were performed: KUMO I and KUMO I Extension. KUMO I was a pilot study aiming at demonstrating the feasibility of cloud implementation and identifying issues regarding variability of evaluations among sites. Chest CT scans at three time-points from baseline to progression, from 10 patients with lung cancer who were treated with EGFR tyrosine kinase inhibitors, were evaluated independently by two oncologists (Japan) and one radiologist (France), through a cloud-based software solution. The KUMO I Extension was performed based on the results of KUMO I. Results KUMO I showed discordance rates of 40% for target lesion selection, 70% for overall response at the first time-point, and 60% for overall response at the second time-point. Since the main reason for the discordance was differences in the selection of target lesions, KUMO I Extension added a cloud-based quality control service to achieve a consensus on the selection of target lesions, resulting in an improved rate of agreement of response evaluations. Conclusion The study shows the feasibility of imaging evaluations at investigator sites, based on cloud services for clinical studies involving multiple international sites. This system offers a step forward in standardizing evaluations of images among widely dispersed sites. PMID:26668754

  13. Clinical implication of computed tomography findings in patients with locally advanced squamous cell carcinoma of the larynx and hypopharynx.

    PubMed

    Ryu, In Sun; Lee, Jeong Hyun; Roh, Jong-Lyel; Choi, Seung-Ho; Nam, Soon Yuhl; Kim, Sang Yoon; Cho, Kyung-Ja

    2015-10-01

    Accurate tumor staging including involvement of laryngeal cartilage is important to treatment planning. Clinicians rely on imaging findings and determine initial laryngectomy for T4-stage cancer with functionless larynx or extralaryngeal spread (ELS). We examined the accuracy and prognostic value of preoperative CT findings for tumor staging in patients with locally advanced laryngeal and hypopharyngeal cancer. Ninety-four consecutive patients with clinically T3-T4-stage squamous cell carcinoma of the larynx or hypopharynx who underwent curative resection of primary tumor were reviewed. Preoperative CT findings were interpreted by a radiologist without pathologic information. Pathologic findings were used as the gold standard for correlating radiographic findings. CT imaging identified 23 (72%) of 32 cases of pathologically documented thyroid cartilage penetration and 24 (73%) of 33 cases of pathologically documented ELS. The positive predictive values for thyroid cartilage penetration and ELS were 70 and 80%, respectively. Pretreatment CT imaging up-staged 6 of 46 pT3 cases and all of 8 pT2 cases, while it down-staged 7 of 40 pT4 cases. The accuracy for clinical staging by CT imaging was 78%. Subglottic extension of the CT image was an independent variable for predicting thyroid cartilage penetration and ELS (P = 0.014). Thyroid cartilage penetration with or without ELS on CT scans is significantly associated with unfavorable DFS outcome of patients (P = 0.020). CT imaging is suboptimal in diagnosing TCP or ELS of advanced laryngeal cancer, but may be useful to predict patient survival by identifying clinically TCP. PMID:25149290

  14. Stereotactic Body Radiation Therapy in Treating Patients With High Risk Locally Advanced Head and Neck Cancer

    ClinicalTrials.gov

    2016-03-04

    Recurrent Hypopharyngeal Squamous Cell Carcinoma; Recurrent Laryngeal Squamous Cell Carcinoma; Recurrent Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Recurrent Nasopharyngeal Keratinizing Squamous Cell Carcinoma; Recurrent Oral Cavity Squamous Cell Carcinoma; Recurrent Oropharyngeal Squamous Cell Carcinoma; Stage II Nasopharyngeal Keratinizing Squamous Cell Carcinoma; Stage III Hypopharyngeal Squamous Cell Carcinoma; Stage III Laryngeal Squamous Cell Carcinoma; Stage III Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage III Nasopharyngeal Keratinizing Squamous Cell Carcinoma; Stage III Oral Cavity Squamous Cell Carcinoma; Stage III Oropharyngeal Squamous Cell Carcinoma; Stage IVA Hypopharyngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Squamous Cell Carcinoma; Stage IVA Nasopharyngeal Keratinizing Squamous Cell Carcinoma; Stage IVA Oral Cavity Squamous Cell Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma; Stage IVB Hypopharyngeal Squamous Cell Carcinoma; Stage IVB Laryngeal Squamous Cell Carcinoma; Stage IVB Nasopharyngeal Keratinizing Squamous Cell Carcinoma; Stage IVB Oral Cavity Squamous Cell Carcinoma; Stage IVB Oropharyngeal Squamous Cell Carcinoma; Stage IVC Hypopharyngeal Squamous Cell Carcinoma; Stage IVC Laryngeal Squamous Cell Carcinoma; Stage IVC Nasopharyngeal Keratinizing Squamous Cell Carcinoma; Stage IVC Oral Cavity Squamous Cell Carcinoma; Stage IVC Oropharyngeal Squamous Cell Carcinoma

  15. Comorbidity and Inflammatory Markers May Contribute to Predict Mortality of High-Risk Patients With Chronic Obstructive Pulmonary Disease Exacerbation

    PubMed Central

    Kim, Yu Jin; Lim, Byeongwoo; Kyung, Sun Young; Park, Jeong-woong; Jeong, Sung Hwan

    2016-01-01

    Background Acute exacerbation of chronic obstructive pulmonary disease (COPD) causes not only an accelerated disease progression, but also an increased mortality rate. The purpose of this study was to analyze the factors associated with clinical features, comorbidities and mortality in patients at high risk for acute COPD exacerbation who had been hospitalized at least once in a year. Methods The study enrolled 606 patients who had been diagnosed with and were being treated for COPD at university affiliated hospital. Among them, there were 61 patients at high risk for acute exacerbation of COPD who had been hospitalized at least once in a year. A retrospective analysis was conducted to examine the factors affecting mortality. The analysis divided the patients into non-survivor and survivor groups, and reviewed their medical records for clinical aspects, comorbidities, pulmonary function tests and blood tests. Results In the high-risk group, the number of comorbidities at diagnosis (P = 0.020) and the Charlson comorbidity index value (P = 0.018) were higher in the non-survivor group than in the survivor group. During hospitalization, the non-survivor group had a significantly higher neutrophil (%) and a significantly lower lymphocyte (%) in complete blood count. Under stable conditions, the high-sensitivity C-reactive protein (hsCRP) concentration in blood plasma and neutrophil (%) were significantly higher (P = 0.025 and P = 0.036), while the lymphocyte (%) was significantly lower (P = 0.005) in the non-survivor group. A pulmonary function test revealed no statistically significant differences between the two groups. Conclusion The number of comorbidities, neutrophil (%), lymphocyte (%) in complete blood cell (CBC) and hsCRP in blood plasma concentration among the groups at high risk for COPD exacerbation are associated with increased mortality. PMID:27298662

  16. Dinutuximab for the treatment of pediatric patients with high-risk neuroblastoma.

    PubMed

    Mora, Jaume

    2016-01-01

    Neuroblastoma (NB) is the most common extra cranial solid tumor of childhood, with 60% of patients presenting with high risk (HR) NB by means of clinical, pathological and biological features. The 5-year survival rate for HR-NB remains below 40%, with the majority of patients suffering relapse from chemorefractory tumor. Immunotherapy is the main strategy against minimal residual disease and clinical experience has mostly focused on monoclonal antibodies (MoAb) against the glycolipid disialoganglioside GD2. Three anti-GD2 antibodies have been tested in the clinic including murine 14G2a, human-mouse chimeric ch14.18 and 3F8. Anti-GD2 MoAb induces cellular cytoxicity against NB and is most effective when effector cells like natural killer cells, granulocytes and macrophages are amplified by cytokines. The combination of cytokines IL-2 and GM-CSF with the anti-GD2 MoAb ch14.18 (Dinutuximab) has shown a significant improvement in outcome for HR-NB. The FDA and EMA approved dinutuximab (Unituxin(R)) in 2015 for the treatment of patients with HR-NB who achieved at least a partial response after multimodality therapy. PMID:26934530

  17. Recombinant activated factor VII in patients at high risk of bleeding.

    PubMed

    Kubisz, Peter; Stasko, Ján

    2004-01-01

    Currently, recombinant activated factor VII (rFVIIa) (NovoSeven) is indicated for the treatment of spontaneous and surgical bleeding in congenital haemophilia A and B patients with inhibitors to factors VIII (FVIII) and IX (FIX) >5 Bethesda units (BU) worldwide, and in patients with acquired haemophilia, congenital FVII deficiency and Glanzmann's thrombasthenia in Europe. Until April 2003, almost three-quarters of a milion doses of rFVIIa have been administered proving its efficacy and excellent safety record. According to results from initial clinical trials and a large number of case reports, the rFVIIa may be effective not only in treating haemophilia patients but also in treatment of bleeding in patients on oral anticoagulation or heparin, patients with liver diseases, von Willebrand disease (vWD), thrombocytopenia, various platelet defects, congenital or acquired deficiency of FVII, and in subjects without any pre-existing coagulopathy with diffuse life-threatening bleeding triggered by surgery or trauma. This review will briefly summarize rFVIIa mode of action in haemostasis, the current clinical experience with rFVIIa and focus on the alternative use of rFVIIa in patients at the high risk of bleeding in both spontaneous cases and clinical trials reports. PMID:15763970

  18. CT-Based Evaluation of Tumor Volume After Intra-Arterial Chemotherapy of Locally Advanced Carcinoma of the Oral Cavity: Comparison with Clinical Remission Rates

    SciTech Connect

    Rohde, Stefan Turowski, Bernd; Berkefeld, Joachim; Kovacs, Adorjan F.

    2007-02-15

    Purpose. To assess the volume of locally advanced tumors of the oral cavity and the oropharynx before and after intra-arterial (i.a.) chemotherapy by means of computed tomography and to compare these data with clinically determined treatment response of the same patient population. Methods. Eighty-eight patients with histologically proven, advanced carcinoma of the oral cavity and/or the oropharynx (local tumor stages T3/4) received neoadjuvant i.a. chemotherapy with cisplatin as part of a multimodal therapeutic regimen, comprising (1) local chemotherapy, (2) surgery, and (3) combined radio-chemotherapy. Three weeks after the intervention, residual disease was evaluated radiologically by measurement of the tumor volume and clinically by inspection and palpation of the primary tumor according to WHO criteria. Results. Comparison of treatment response according to radiological and clinical criteria respectively revealed complete remission in 5% vs. 8% (p < 0.05), partial remission in 30% vs. 31%, stable disease in 61% vs. 58%, and tumor progression in 5% vs. 2%. Conclusion. Radiological volumetry and clinical evaluation found comparable response rates after local chemotherapy. However, in patients with good response after local treatment, volumetric measurement with CT may help to distinguish between partial and complete remission. Thus, radiological tumor volumetry provides precise and differentiated information about tumor response and should be used as an additional tool in treatment monitoring after local chemotherapy.

  19. Therapeutic benefit of decitabine, a hypomethylating agent, in patients with high-risk primary myelofibrosis and myeloproliferative neoplasm in accelerated or blastic/acute myeloid leukemia phase.

    PubMed

    Badar, Talha; Kantarjian, Hagop M; Ravandi, Farhad; Jabbour, Elias; Borthakur, Gautam; Cortes, Jorge E; Pemmaraju, Naveen; Pierce, Sherry R; Newberry, Kate J; Daver, Naval; Verstovsek, Srdan

    2015-09-01

    Myeloproliferative neoplasm (MPN) transformed to acute myeloid leukemia (MPN-AML), MPN in accelerated phase (MPN-AP), and high-risk primary myelofibrosis (PMF) are associated with a poor response to therapy and very short survival. Several reports have suggested clinical activity of hypomethylating agents in these patients. We conducted a retrospective study of 21 patients with MPN-AML, 13 with MPN-AP and 11 with DIPSS-plus high-risk PMF treated with decitabine at our institution over the last 7 years and evaluated their clinical outcomes. Six patients (29%) with MPN-AML responded to decitabine (3 CR, 2 CRi, and 1 PR); median response duration was 7 months. The median overall survival (OS) was significantly higher in those who responded (10.5 vs 4 months). Among patients with MPN-AP, 8 patients (62%) benefited; the median response duration was 6.5 months. The median OS was 11.8 months in responders vs 4.7 months in non-responders. Among patients with DIPSS-plus high-risk PMF, 9 (82%) benefited; the median response duration was 9 months. The median OS was 32 months in responders vs 16.3 months in non-responders. Decitabine is a viable therapeutic option for patients with MPN-AML, MP-AP and high-risk PMF. Prospective clinical studies combining decitabine with other clinically active agents are needed to improve overall outcome. PMID:26183878

  20. The Effect of Brief Interventions on the Drinking Behaviour of Pregnant Women in a High-Risk Rural South African Community: A Cluster Randomised Trial

    ERIC Educational Resources Information Center

    Marais, Sandra; Jordaan, Esme; Viljoen, Dennis; Olivier, Leana; de Waal, Johanna; Poole, Caroline

    2011-01-01

    The purpose of this paper is to assess the impact of a series of brief interventions (BIs) on anti-natal alcohol consumption of women from a disadvantaged and high-risk background attending state health clinics in a rural district, Western Cape Province, South Africa. A pragmatic cluster randomised trial design was followed. All pregnant women,…

  1. Presence of high-risk clones of OXA-23-producing Acinetobacter baumannii (ST79) and SPM-1-producing Pseudomonas aeruginosa (ST277) in environmental water samples in Brazil.

    PubMed

    Turano, Helena; Gomes, Fernando; Medeiros, Micheli; Oliveira, Silvane; Fontes, Lívia C; Sato, Maria I Z; Lincopan, Nilton

    2016-09-01

    This study reports the presence of hospital-associated high-risk lineages of OXA-23-producing ST79 Acinetobacter baumannii and SPM-1-producing ST277 Pseudomonas aeruginosa in urban rivers in Brazil. These findings indicate that urban rivers can act as reservoirs of clinically important multidrug-resistant bacteria, which constitute a potential risk to human and animal health. PMID:27342783

  2. Phase 1 Trial of Neoadjuvant Radiation Therapy Before Prostatectomy for High-Risk Prostate Cancer

    SciTech Connect

    Koontz, Bridget F.; Quaranta, Brian P.; Pura, John A.; Lee, W.R.; Vujaskovic, Zeljko; Gerber, Leah; Haake, Michael; Anscher, Mitchell S.; Robertson, Cary N.; Polascik, Thomas J.; Moul, Judd W.

    2013-09-01

    Purpose: To evaluate, in a phase 1 study, the safety of neoadjuvant whole-pelvis radiation therapy (RT) administered immediately before radical prostatectomy in men with high-risk prostate cancer. Methods and Materials: Twelve men enrolled and completed a phase 1 single-institution trial between 2006 and 2010. Eligibility required a previously untreated diagnosis of localized but high-risk prostate cancer. Median follow-up was 46 months (range, 14-74 months). Radiation therapy was dose-escalated in a 3 × 3 design with dose levels of 39.6, 45, 50.4, and 54 Gy. The pelvic lymph nodes were treated up to 45 Gy with any additional dose given to the prostate and seminal vesicles. Radical prostatectomy was performed 4-8 weeks after RT completion. Primary outcome measure was intraoperative and postoperative day-30 morbidity. Secondary measures included late morbidity and oncologic outcomes. Results: No intraoperative morbidity was seen. Chronic urinary grade 2+ toxicity occurred in 42%; 2 patients (17%) developed a symptomatic urethral stricture requiring dilation. Two-year actuarial biochemical recurrence-free survival was 67% (95% confidence interval 34%-86%). Patients with pT3 or positive surgical margin treated with neoadjuvant RT had a trend for improved biochemical recurrence-free survival compared with a historical cohort with similar adverse factors. Conclusions: Neoadjuvant RT is feasible with moderate urinary morbidity. However, oncologic outcomes do not seem to be substantially different from those with selective postoperative RT. If this multimodal approach is further evaluated in a phase 2 setting, 54 Gy should be used in combination with neoadjuvant androgen deprivation therapy to improve biochemical outcomes.

  3. Massive Endoscopic Screening for Esophageal and Gastric Cancers in a High-Risk Area of China

    PubMed Central

    Xu, Kun; Lü, Lingshuang; Peng, Xianzhen; Wang, Min; Xu, Guisheng; Hua, Zhaolai; Wang, Jianping; Xue, Hengchuan; Wang, Jianming; Lu, Cheng

    2015-01-01

    Objective This study aims to describe the findings from a massive endoscopic screening program in a high-risk area of China and to evaluate the prognosis of patients diagnosed through endoscopic screening compared with those diagnosed at usual hospital visits because of illness. Methods In 2006, an early detection and treatment program was initiated in Yangzhong county, China. Local residents aged 40–69 years were eligible for free endoscopic screening. Endoscopic examination was performed with Lugol’s iodine staining, followed by biopsies. Patients diagnosed with esophageal or gastric cancer were referred for treatment and followed to assess their long-term survival status. Results From 2006 through 2012, we screened 12453 participants, including 5334 (42.8%) men and 7119 (57.2%) women. The average age was 52.8±8.0 years. We detected 166 patients with upper digestive tract cancers, including 106 cancers in the esophagus (detection rate: 0.85%) and 60 cancers in the stomach (detection rate: 0.48%). Of these patients, 98.11% with esophageal cancer and 100% with gastric cancer were defined as at the early stage. In the process of follow-up, 17 patients died from cancer-related causes, and the median survival time was greater than 85 months. The overall survival rates for 1, 3 and 5 years were 98.0%, 90.0% and 89.0%, respectively. A significant positive effect was observed for the long-term survival of patients diagnosed through massive endoscopic screening. Conclusions In a high-risk population, massive endoscopic screening can identify early stage carcinoma of esophageal and gastric cancers and improve patients’ prognosis through early detection and treatment. PMID:26699332

  4. Outcome of major spinal deformity surgery in high-risk patients: comparison between two departments

    PubMed Central

    Murans, Girts; Gustavsson, Bengt; Saraste, Helena

    2010-01-01

    Study design: Retrospective cohort study Objective: To describe the outcome and resource use in major spine surgery on high-risk patients, and analyze possible differences between two surgical departments. Methods: Data from the deformity register and medical records of 136 patients, median age 12-years, with neuromuscular and congenital spinal deformities with and without intraspinal pathology, surgically treated by one surgeon from 1997 through 2004 at two departments. H1 with a pediatric multidisciplinary team, and H2 with focus on adult spine. Variables at baseline: age, gender, diagnosis, curve size, and type of surgical procedure. Result variables included clinical and radiographic outcome, surgery time, length of intensive care and hospital stay, relative blood loss, and occurrence of complications during 2 or more years follow-up. Results: There was no perioperative or postoperative mortality, no spinal-cord damage, no neurological or ambulatory function deterioration. The overall complication rate was 36%, and the overall major complication rate was 15.4%. The mean loss of correction was 2° during the follow-up. There were statistically significant differences between the H1 and H2 departments. At H1, deformity correction was better and surgery time shorter. Infections were more frequent at H2 (P = .04; 6/65 at H1; 16/71 at H2), tendency (P = .06) of more department-related complications was higher at H2. Conclusions: Major spine surgery in high-risk patients can be performed safely and with good outcoms. Impact of organization and workplace culture on the outcome might be important and worth further study. PMID:22956923

  5. Next-generation personalised medicine for high-risk paediatric cancer patients - The INFORM pilot study.

    PubMed

    Worst, Barbara C; van Tilburg, Cornelis M; Balasubramanian, Gnana Prakash; Fiesel, Petra; Witt, Ruth; Freitag, Angelika; Boudalil, Miream; Previti, Christopher; Wolf, Stephan; Schmidt, Sabine; Chotewutmontri, Sasithorn; Bewerunge-Hudler, Melanie; Schick, Matthias; Schlesner, Matthias; Hutter, Barbara; Taylor, Lenka; Borst, Tobias; Sutter, Christian; Bartram, Claus R; Milde, Till; Pfaff, Elke; Kulozik, Andreas E; von Stackelberg, Arend; Meisel, Roland; Borkhardt, Arndt; Reinhardt, Dirk; Klusmann, Jan-Henning; Fleischhack, Gudrun; Tippelt, Stephan; Dirksen, Uta; Jürgens, Heribert; Kramm, Christof M; von Bueren, Andre O; Westermann, Frank; Fischer, Matthias; Burkhardt, Birgit; Wößmann, Wilhelm; Nathrath, Michaela; Bielack, Stefan S; Frühwald, Michael C; Fulda, Simone; Klingebiel, Thomas; Koscielniak, Ewa; Schwab, Matthias; Tremmel, Roman; Driever, Pablo Hernáiz; Schulte, Johannes H; Brors, Benedikt; von Deimling, Andreas; Lichter, Peter; Eggert, Angelika; Capper, David; Pfister, Stefan M; Jones, David T W; Witt, Olaf

    2016-09-01

    The 'Individualized Therapy for Relapsed Malignancies in Childhood' (INFORM) precision medicine study is a nationwide German program for children with high-risk relapsed/refractory malignancies, which aims to identify therapeutic targets on an individualised basis. In a pilot phase, reported here, we developed the logistical and analytical pipelines necessary for rapid and comprehensive molecular profiling in a clinical setting. Fifty-seven patients from 20 centers were prospectively recruited. Malignancies investigated included sarcomas (n = 25), brain tumours (n = 23), and others (n = 9). Whole-exome, low-coverage whole-genome, and RNA sequencing were complemented with methylation and expression microarray analyses. Alterations were assessed for potential targetability according to a customised prioritisation algorithm and subsequently discussed in an interdisciplinary molecular tumour board. Next-generation sequencing data were generated for 52 patients, with the full analysis possible in 46 of 52. Turnaround time from sample receipt until first report averaged 28 d. Twenty-six patients (50%) harbored a potentially druggable alteration with a prioritisation score of 'intermediate' or higher (level 4 of 7). Common targets included receptor tyrosine kinases, phosphoinositide 3-kinase-mammalian target of rapamycin pathway, mitogen-activated protein kinase pathway, and cell cycle control. Ten patients received a targeted therapy based on these findings, with responses observed in some previously treatment-refractory tumours. Comparative primary relapse analysis revealed substantial tumour evolution as well as one case of unsuspected secondary malignancy, highlighting the importance of re-biopsy at relapse. This study demonstrates the feasibility of comprehensive, real-time molecular profiling for high-risk paediatric cancer patients. This extended proof-of-concept, with examples of treatment consequences, expands upon previous personalised oncology endeavors

  6. Remote ischaemic preconditioning does not alter perioperative cytokine production in high-risk cardiac surgery

    PubMed Central

    Williams, Jenni M; Young, Paul; Pilcher, Janine; Weatherall, Mark; Miller, John Holmes; Beasley, Richard; La Flamme, Anne Camille

    2012-01-01

    Rationale Remote ischaemic preconditioning (RIPC) is a novel cardioprotective strategy that uses brief intermittent limb ischaemia to protect the myocardium and other organs from perioperative ischaemic damage. The precise mechanism through which this protective effect occurs is unknown, but potentially could be related to changes in blood-borne mediators such as cytokines. Objective To determine whether RIPC alters inflammatory cytokine expression in a double-blind, randomised, controlled trial of patients undergoing high-risk cardiac surgery. Methods and results Serum interleukin (IL)-6, IL-8, and IL-10 levels from 95 patients randomised to RIPC (n=47) or control treatment (n=48) were measured preoperatively, and 1, 2, 3, 6 and 12 h after cross-clamp removal. Systemic concentrations of all cytokines were increased from baseline following surgery, and, compared with simple procedures, complex surgeries were associated with significantly higher release of IL-6 (ratio of mean area under the curves 1.54 (95% CI 1.02 to 2.34), p=0.04) and IL-10 (1.97 (1.16 to 3.35), p=0.012). No significant difference in mean cytokine levels between the RIPC and control groups was detected at any time point, irrespective of the type of surgery undergone. Conclusions High levels of IL-6, IL-8 and IL-10 are produced during high-risk cardiac surgery, and RIPC does not alter these elevated perioperative cytokine concentrations. Identification of factors that influence the ability to induce RIPC-mediated cardioprotection should be the priority of future research. Trial registration is in the Australian New Zealand Clinical Trials Registry (http://www.anzctr.org.au; ACTRN12609000965202)

  7. Behavioral Parent Training in Infancy: A Window of Opportunity for High-Risk Families.

    PubMed

    Bagner, Daniel M; Coxe, Stefany; Hungerford, Gabriela M; Garcia, Dainelys; Barroso, Nicole E; Hernandez, Jennifer; Rosa-Olivares, Jose

    2016-07-01

    To meet the mental health needs of infants from high-risk families, we examined the effect of a brief home-based adaptation of Parent-child Interaction Therapy (PCIT) on improvements in infant and parent behaviors and reductions in parenting stress. Participants included 60 infants (55 % male; average age of 13.5 ± 1.31 months) who were recruited at a large urban primary care clinic and were included if their scores exceeded the 75th percentile on a brief screener of early behavior problems. Most infants were from an ethnic or racial minority background (98 %) and lived below the poverty line (60 %). Families were randomly assigned to receive the home-based parenting intervention or standard pediatric primary care. Observational and parent-report measures of infant and parenting behaviors were examined at pre- and post-intervention and at 3- and 6-month follow-ups. Infants receiving the intervention were more compliant with maternal commands at the 6-month follow-up and displayed lower levels of externalizing and internalizing behavior problems across post and follow-up assessments compared to infants in standard care. Mothers receiving the intervention displayed a significantly higher proportion of positive and lower proportion of negative behaviors with their infant during play compared to mothers in the standard care group. There were no significant group differences for parenting stress. Results provide initial evidence for the efficacy of this brief and home-based adaptation of PCIT for infants. These findings highlight the benefit of identification and intervention as early as possible to promote mental health for infants from high-risk families. PMID:26446726

  8. Identification of high risk DISC1 protein structural variants in patients with bipolar spectrum disorder.

    PubMed

    Song, Wenjia; Li, Wenyan; Noltner, Katie; Yan, Jin; Green, Elaine; Grozeva, Detelina; Jones, Ian R; Craddock, Nick; Longmate, Jeff; Feng, Jinong; Sommer, Steve S

    2010-12-17

    In a large Scottish pedigree, a balanced translocation t (1;11)(q42.1;q14.3) disrupting the DISC1 and DISC2 genes segregates with major mental illness, including schizophrenia and depression. A frame-shift carboxyl-terminal deletion was reported in DISC1 in an American family with schizophrenia, but subsequently found in two controls. Herein, we test one hypothesis utilizing a large scale case-control mutation analysis: uncommon DISC1 variants are associated with high risk for bipolar spectrum disorder. We have analyzed the regions of likely functional significance in the DISC1 gene in 504 patients with bipolar spectrum disorder and 576 ethnically similar controls. Five patients were heterozygous for ultra-rare protein structural variants not found in the 576 controls (p=0.02, one-sided Fisher's exact test) and shown to be ultra-rare by their absence in a pool of 10,000 control alleles. In our sample, ultra-rare (private) protein structural variants in DISC1 are associated with an estimated attributable risk of about 0.5% in bipolar spectrum disorder. These data are consistent with: (i) the high frequency of depression in the large Scottish family with a translocation disrupting DISC1; (ii) linkage disequilibrium analysis demonstrating haplotypes associated with relatively small increases in risk for bipolar disorder (<3-fold odds ratio). The data illustrate how low/moderate risk haplotypes that might be found by the HapMap project can be followed up by resequencing to identify protein structural variants with high risk, low frequency and of potential clinical utility. PMID:20850505

  9. Abnormal Heart Rate Turbulence Predicts Cardiac Mortality in Low, Intermediate and High Risk Older Adults

    PubMed Central

    Stein, Phyllis K.; Barzilay, Joshua I.

    2011-01-01

    Introduction We examined whether heart rate turbulence (HRT) adds to traditional risk factors for cardiac mortality in older adults at low, intermediate and high risk. Methods and Results N=1298, age ≥65 years, with 24-hour Holter recordings were studied. HRT, which quantifies heart rate response to ventricular premature contractions, was categorized as: both turbulence onset (TO) and turbulence slope (TS) normal; TO abnormal; TS abnormal; or both abnormal. Independent risks for cardiac mortality associated with HRT or, for comparison, elevated C-reactive protein (CRP) (>3.0 mg/L), were calculated using Cox regression analysis adjusted for traditional cardiovascular disease risk factors and stratified by the presence of no, isolated subclinical (i.e., intermediate risk) or clinical CVD. Having both TS and TO abnormal compared to both normal was associated with cardiac mortality in the low risk group [HR 7.9, 95% CI 2.8–22.5, (p<0.001)]. In the high and intermediate risk groups, abnormal TS and TO ([HR 2.2, 95% CI 1.5–4.0, p=0.016] and [HR 2.7, 95% CI 1.2–5.9, p=0.012]), respectively, were also significantly associated with cardiac mortality. In contrast, elevated CRP was associated with increased cardiac mortality risk only in low risk individuals [HR 2.5, 95% CI 1.3–5.1, p=0.009]. In the low risk group, the c-statistic was 0.706 for the base model, 0.725 for the base model with CRP, and 0.767 for the base model with HRT. Conclusions Abnormal HRT independently adds to risk stratification of low, intermediate and high risk individuals but appears to add especially to the stratification of those considered at low risk. PMID:21134026

  10. Reward learning in pediatric depression and anxiety: Preliminary findings in a high-risk sample

    PubMed Central

    Morris, Bethany H.; Bylsma, Lauren M.; Yaroslavsky, Ilya; Kovacs, Maria; Rottenberg, Jonathan

    2015-01-01

    Background Reward learning has been postulated as a critical component of hedonic functioning that predicts depression risk. Reward learning deficits have been established in adults with current depressive disorders, but no prior studies have examined the relationship of reward learning and depression in children. The present study investigated reward learning as a function of familial depression risk and current diagnostic status in a pediatric sample. Method The sample included 204 children of parents with a history of depression (n=86 high-risk offspring) or parents with no history of major mental disorder (n=118 low-risk offspring). Semi-structured clinical interviews were used to establish current mental diagnoses in the children. A modified signal detection task was used to assess reward learning. We tested whether reward learning was impaired in high-risk offspring relative to low-risk offspring. We also tested whether reward learning was impaired in children with current disorders known to blunt hedonic function (depression, social phobia, PTSD, GAD, n=13) compared to children with no disorders and to a psychiatric comparison group with ADHD. Results High- and low-risk youth did not differ in reward learning. However, youth with current anhedonic disorders (depression, social phobia, PTSD, GAD) exhibited blunted reward learning relative to nondisordered youth and those with ADHD. Conclusions Our results are a first demonstration that reward learning deficits are present among youth with disorders known to blunt anhedonic function and that these deficits have some degree of diagnostic specificity. We advocate for future studies to replicate and extend these preliminary findings. PMID:25826304

  11. Conflicting Readmission Rate Trends in a High-Risk Population: Implications for Performance Measurement

    PubMed Central

    Vann, Julie C. Jacobson; Jackson, Carlos T.

    2015-01-01

    Abstract The 30-day readmission rate is a common performance indicator for hospitals and accountable care entities. There is reason to question whether measuring readmissions as a function of hospital discharges is an appropriate measure of performance for initiatives that aim to improve overall cost and quality outcomes in a population. The objectives of this study were to compare trends in 30-day readmission rates per discharge to population-based measures of hospital admission and readmission frequency in a high-risk statewide Medicaid population over a 5-year period of quality improvement and care management intervention. Further, this study aimed to examine case-mix changes among hospitalized beneficiaries over time. This was a retrospective analysis of North Carolina Medicaid paid claims 2008 through 2012 for beneficiaries with multiple chronic or catastrophic conditions. Thirty-day readmission rates per discharge trended upward from 18.3% in 2008 to 18.7% in 2012. However, the rate of 30-day readmissions per 1000 beneficiaries declined from 123.3 to 110.7. Overall inpatient admissions per 1000 beneficiaries decreased from 579.4 to 518.5. The clinical complexity of hospitalized patients increased over the 5-year period. Although rates of hospital admissions and readmissions fell substantially in this high-risk population over 5 years, the 30-day readmission rate trend appeared unfavorable when measured as a percent of hospital discharges. This may be explained by more complex patients requiring hospitalization over time. The choice of metrics significantly affects the perceived effectiveness of improvement initiatives. Emphasis on readmission rates per discharge may be misguided for entities with a population health management focus. (Population Health Management 2015;18:351–357) PMID:25607449

  12. Synthetic ACTH in High Risk Patients with Idiopathic Membranous Nephropathy: A Prospective, Open Label Cohort Study

    PubMed Central

    van de Logt, Anne-Els; Beerenhout, Charles H.; Brink, Hans S.; van de Kerkhof, Jos J.; Wetzels, Jack F.; Hofstra, Julia M.

    2015-01-01

    New therapeutic agents are warranted in idiopathic membranous nephropathy. Synthetic ACTH may be advantageous with reported remission rates up to 85% and few side effects. We conducted a prospective open label cohort study from 2008 till 2010 (NCT00694863). We prospectively selected patients with idiopathic membranous nephropathy and high risk for progression (defined as βeta-2-microglobulin (β2m) excretion of >500 ng/min). For comparison, we selected matched historical controls treated with cyclophosphamide. The prospectively selected patients received intramuscular injections of synthetic ACTH during 9 months (maximal dose 1 mg twice a week). The primary endpoints concerned the feasibility and incidence of remissions as a primary event. Secondary endpoints included side effects of treatment and the incidence of remissions and relapses at long-term follow-up. Twenty patients (15 men) were included (age 54±14 years, serum creatinine 104 μmol/l [IQR 90–113], urine protein:creatinine ratio 8.7 g/10 mmol creatinine [IQR 4.3–11.1]). Seventeen patients (85%) completed treatment. 97% of injections were administered correctly. Cumulative remission rate was 55% (complete remission in 4 patients, partial remission 7 patients). In a group of historical controls treated with cyclophosphamide and steroids, 19 of 20 patients (95%) developed a remission (complete remission in 13 patients, partial remission in 6 patients) (p<0.01). The main limitation of our study is its small size and the use of a historical control group. We show that treatment with intramuscular injections of synthetic ACTH is feasible. Our data suggest that synthetic ACTH is less effective than cyclophosphamide in inducing a remission in high risk patients with idiopathic membranous nephropathy. The use of synthetic ACTH was also associated with many adverse events. Therefore, we advise against synthetic ACTH as standard treatment in membranous nephropathy. Trial Registration ClinicalTrials.gov NCT

  13. A Randomized Trial (Irish Clinical Oncology Research Group 97-01) Comparing Short Versus Protracted Neoadjuvant Hormonal Therapy Before Radiotherapy for Localized Prostate Cancer

    SciTech Connect

    Armstrong, John G.; Gillham, Charles M.; Dunne, Mary T.; Fitzpatrick, David A.; Finn, Marie A.; Cannon, Mairin E.; Taylor, Judy C.; O'Shea, Carmel M.; Buckney, Steven J.; Thirion, Pierre G.

    2011-09-01

    Purpose: To examine the long-term outcomes of a randomized trial comparing short (4 months; Arm 1) and long (8 months; Arm 2) neoadjuvant hormonal therapy before radiotherapy for localized prostate cancer. Methods and Materials: Between 1997 and 2001, 276 patients were enrolled and the data from 261 were analyzed. The stratification risk factors were prostate-specific antigen level >20 ng/mL, Gleason score {>=}7, and Stage T3 or more. The intermediate-risk stratum had one factor and the high-risk stratum had two or more. Staging was done from the bone scan and computed tomography findings. The primary endpoint was biochemical failure-free survival. Results: The median follow-up was 102 months. The overall survival, biochemical failure-free survival. and prostate cancer-specific survival did not differ significantly between the two treatment arms, overall or at 5 years. The cumulative probability of overall survival at 5 years was 90% (range, 87-92%) in Arm 1 and 83% (range, 80-86%) in Arm 2. The biochemical failure-free survival rate at 5 years was 66% (range, 62-71%) in Arm 1 and 63% (range, 58-67%) in Arm 2. Conclusion: No statistically significant difference was found in biochemical failure-free survival between 4 months and 8 months of neoadjuvant hormonal therapy before radiotherapy for localized prostate cancer.

  14. Randomized clinical trial of local anesthetic versus a combination of local anesthetic with self-hypnosis in the management of pediatric procedure-related pain.

    PubMed

    Liossi, Christina; White, Paul; Hatira, Popi

    2006-05-01

    A prospective controlled trial was conducted to compare the efficacy of an analgesic cream (eutectic mixture of local anesthetics, or EMLA) with a combination of EMLA with hypnosis in the relief of lumbar puncture-induced pain and anxiety in 45 pediatric cancer patients (age 6-16 years). The study also explored whether young patients can be taught and can use hypnosis independently as well as whether the therapeutic benefit depends on hypnotizability. Patients were randomized to 1 of 3 groups: local anesthetic, local anesthetic plus hypnosis, and local anesthetic plus attention. Results confirmed that patients in the local anesthetic plus hypnosis group reported less anticipatory anxiety and less procedure-related pain and anxiety and that they were rated as demonstrating less behavioral distress during the procedure. The level of hypnotizability was significantly associated with the magnitude of treatment benefit, and this benefit was maintained when patients used hypnosis independently. PMID:16719602

  15. Glycated haemoglobin and metabolic control of diabetes mellitus: external versus locally established clinical targets for primary care.

    PubMed Central

    Butler, C.; Peters, J.; Stott, N.

    1995-01-01

    OBJECTIVES--To examine current targets for glycated haemoglobin as a marker for metabolic control in diabetes mellitus in relation to datasets from several areas, and to consider whether target setting could be improved. DESIGN--Data collected from enhanced care records of general practices for a representative community based sample of people with diabetes. SETTING AND SUBJECTS--3022 people with diabetes on the lists of 37 general practices (total list size 222,550) in South Glamorgan in 1992; samples of glycated haemoglobin had been processed at two laboratories with different methodologies and reference ranges. MAIN OUTCOME MEASURES--Last glycated haemoglobin level measured in subjects for 1992 and published data from other studies considered in relation to existing goals and standards for the metabolic control of diabetes. RESULTS--An ascertainment rate for people with diabetes of 1.36% was obtained. The rate of data capture for haemoglobin A1 was 75.7%, and the mean level for study samples was 10.5% at one laboratory and 10.0% at the other (similar values to those of comparable studies). These mean levels of haemoglobin A1 in representative populations of people with diabetes are poor or very poor according to published standards, including those of the British Diabetic Association. These findings are set in the context of the psychology of goal setting and performance in complex clinical situations. CONCLUSION--Targets for clinical care that are set in the absence of normative data and local feasibility assessments should be treated with caution. Targets are more likely to enhance health care if target setters recognise the importance of psychological aspects of goal setting and motivation. PMID:7677834

  16. The Association Between Chemoradiation-related Lymphopenia and Clinical Outcomes in Patients With Locally Advanced Pancreatic Adenocarcinoma

    PubMed Central

    Wild, Aaron T.; Ye, Xiaobu; Ellsworth, Susannah G.; Smith, Jessica A.; Narang, Amol K.; Garg, Tanu; Campian, Jian; Laheru, Daniel A.; Zheng, Lei; Wolfgang, Christopher L.; Tran, Phuoc T.; Grossman, Stuart A.; Herman, Joseph M.

    2014-01-01

    Objectives Lymphopenia is a common consequence of chemoradiation therapy yet is seldom addressed clinically. This study was conducted to determine if patients with locally advanced pancreatic cancer (LAPC) treated with definitive chemoradiation develop significant lymphopenia and if this affec