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Sample records for age clinical stage

  1. Ages and Stages: Teen

    MedlinePlus

    ... Pediatrician Ages & Stages Prenatal Baby Toddler Preschool Gradeschool Teen Dating & Sex Fitness Nutrition Driving Safety School Substance Abuse Young Adult Healthy Children > Ages & Stages > Teen Teen Article Body Adolescence can be a rough ...

  2. Clinical manifestations and stages of Rett syndrome.

    PubMed

    Hagberg, Bengt

    2002-01-01

    The presentation and clinical diagnosis of Rett syndrome at various ages and stages are reviewed. In addition to the classical form, variability in phenotype between different atypical Rett forms is given. Obligatory, supportive, and differential diagnostic criteria are summarized. Long-term follow-up findings in ageing Rett women are addressed.

  3. Age, stage and senescence in plants

    PubMed Central

    Caswell, Hal; Salguero-Gómez, Roberto

    2013-01-01

    1. Senescence (an increase in the mortality rate or force of mortality, or a decrease in fertility, with increasing age) is a widespread phenomenon. Theories about the evolution of senescence have long focused on the age trajectories of the selection gradients on mortality and fertility. In purely age-classified models, these selection gradients are non-increasing with age, implying that traits expressed early in life have a greater impact on fitness than traits expressed later in life. This pattern leads inevitably to the evolution of senescence if there are trade-offs between early and late performance. 2. It has long been suspected that the stage- or size-dependent demography typical of plants might change these conclusions. In this paper, we develop a model that includes both stage- and age-dependence and derive the age-dependent, stage-dependent and age×stage-dependent selection gradients on mortality and fertility. 3. We applied this model to stage-classified population projection matrices for 36 species of plants, from a wide variety of growth forms (from mosses to trees) and habitats. 4. We found that the age-specific selection gradients within a life cycle stage can exhibit increases with age (we call these contra-senescent selection gradients). In later stages, often large size classes in plant demography, the duration of these contra-senescent gradients can exceed the life expectancy by several fold. 5. Synthesis. The interaction of age- and stage-dependence in plants leads to selection pressures on senescence fundamentally different from those found in previous, age-classified theories. This result may explain the observation that large plants seem less subject to senescence than most kinds of animals. The methods presented here can lead to improved analysis of both age-dependent and stage-dependent demographic properties of plant populations. PMID:23741075

  4. Treatment of vital and non-vital primary molar teeth by one-stage formocresol pulpotomy: clinical success and effect upon age at exfoliation.

    PubMed

    Roberts, J F

    1996-06-01

    The clinical success and effect upon the age at which teeth exfoliated was prospectively observed in 175 primary molars that had received formoceresol pulpotomies performed by one operator. The success rate among 142 vital teeth was 99.3% and among 33 non-vital teeth 84.8%. There was no significant effect upon age at exfoliation after either type of pulpal treatment.

  5. Development: Ages & Stages--Emerging Physical Skills

    ERIC Educational Resources Information Center

    Poole, Carla; Miller, Susan A.; Church, Ellen Booth

    2005-01-01

    In this article, the authors discuss how children develop their motor skills at different age levels. Newborn's movements are jerky and uncoordinated. Spending lots of floor time with a baby lying on her back or stomach helps her develop coordination, balance, and muscle strength during her earliest months. As locomotion enters a baby's life, she…

  6. Obesity, age, ethnicity, and clinical features of prostate cancer patients

    PubMed Central

    Wu, Victor J; Pang, Darren; Tang, Wendell W; Zhang, Xin; Li, Li; You, Zongbing

    2017-01-01

    Approximately 36.5% of the U.S. adults (≥ 20 years old) are obese. Obesity has been associated with type 2 diabetes mellitus, cardiovascular disease, stroke, and several types of cancer. The present study included 1788 prostate cancer patients who were treated with radical prostatectomy at the Ochsner Health System, New Orleans, Louisiana, from January, 2001 to March, 2016. The patient’s medical records were retrospectively reviewed. Body mass index (BMI), age, ethnicity (Caucasians versus African Americans), clinical stage, Gleason score, and prostate-specific antigen (PSA) levels were retrieved. The relative risk of the patients was stratified into low risk and high risk groups. Associative analyses found that BMI was associated with age, clinical stage, Gleason score, but not ethnicity, PSA levels, or the relative risk in this cohort. Age was associated with ethnicity, clinical stage, Gleason score, and PSA levels, as well as the relative risk. Ethnicity was associated with Gleason score and PSA levels as well as the relative risk, but not clinical stage. These findings suggest that obesity is associated with advanced prostate cancer with stage T3 or Gleason score ≥ 7 diseases, and age and ethnicity are important factors that are associated with the clinical features of prostate cancer patients. PMID:28337464

  7. Clinical pharmacology of old age syndromes

    PubMed Central

    Broadhurst, C; Wilson, K C M; Kinirons, M T; Wagg, A; Dhesi, J K

    2003-01-01

    Several syndromes occur in old age. They are often associated with increased mortality and in all there is a paucity of basic and clinical research. The recent developments in the clinical pharmacology of three common syndromes of old age (delirium, urinary incontinence, and falls) are discussed along with directions for future research. PMID:12919174

  8. [Performing madness: the clinic as stage].

    PubMed

    Herrn, Rainer; Friedland, Alexander

    2014-12-01

    In the second half of the nine- teenth century, clinical demonstrations became the dominant teaching method in psychiatry, playing a key role in medical-professional disputes, as well. This paper traces this widely used though historiographically neglected practice of knowledge implementation and mediation, as demonstrated in the psychiatric clinic of the Berlin Charité (Psychiatrische und Nervenklinik der Berliner Charité) from 1881 to 1927. Documentation of this practice, found within individual medical records, forms the basis of this research. The concept of 'theatricality' assists in uncovering the dramatic quality of the clinical demonstration: Psychiatric knowledge was not simply disseminated through such a practice; rather, such knowledge was first performatively created through the very logic of its presentation of exemplary patient histories, as well as through the examination and diagnostic positioning of its patients. The 'success' of such presentations depended on many variables, related to staff, time, place, and other situational factors. These include the presence of appropriate lecture halls, the availability and calculated selection of patients, and the employment of specific performative techniques by doctors for the sake of producing desired results. As one effect, clinical demonstrations also encouraged patients to both learn and rehearse behavior considered relevant to the particular diagnosis that was to be demonstrated.

  9. Automatic age-related macular degeneration detection and staging

    NASA Astrophysics Data System (ADS)

    van Grinsven, Mark J. J. P.; Lechanteur, Yara T. E.; van de Ven, Johannes P. H.; van Ginneken, Bram; Theelen, Thomas; Sánchez, Clara I.

    2013-03-01

    Age-related macular degeneration (AMD) is a degenerative disorder of the central part of the retina, which mainly affects older people and leads to permanent loss of vision in advanced stages of the disease. AMD grading of non-advanced AMD patients allows risk assessment for the development of advanced AMD and enables timely treatment of patients, to prevent vision loss. AMD grading is currently performed manually on color fundus images, which is time consuming and expensive. In this paper, we propose a supervised classification method to distinguish patients at high risk to develop advanced AMD from low risk patients and provide an exact AMD stage determination. The method is based on the analysis of the number and size of drusen on color fundus images, as drusen are the early characteristics of AMD. An automatic drusen detection algorithm is used to detect all drusen. A weighted histogram of the detected drusen is constructed to summarize the drusen extension and size and fed into a random forest classifier in order to separate low risk from high risk patients and to allow exact AMD stage determination. Experiments showed that the proposed method achieved similar performance as human observers in distinguishing low risk from high risk AMD patients, obtaining areas under the Receiver Operating Characteristic curve of 0.929 and 0.934. A weighted kappa agreement of 0.641 and 0.622 versus two observers were obtained for AMD stage evaluation. Our method allows for quick and reliable AMD staging at low costs.

  10. Advances take stage - Office of Cancer Clinical Proteomics Research

    Cancer.gov

    Regulatory advances in proteomics will be taking center stage at a Symposia scheduled to occur at the 2011 American Association for Clinical Chemistry (AACC) Annual Meeting. The symposium entitled "Enabling Translational Proteomics with NCI's Clinical Proteomic Technologies for Cancer" is scheduled for July 25, 2011 at AACC's annual Meeting.

  11. Can Screening With the Ages and Stages Questionnaire Detect Autism?

    PubMed Central

    Hardy, Sarah; Haisley, Lauren; Manning, Courtney; Fein, Deborah

    2015-01-01

    Objective Parents rely on pediatricians to monitor their child’s development. The American Academy of Pediatrics recommends routine developmental screening with both broadband and autism-specific instruments at specified ages. If broadband screeners can detect autism risk, this might minimize the burden of administering autism-specific screens to all children. The current study examines the ability of the Ages and Stages Questionnaire-Third Edition (ASQ-3) to identify children at risk for autism. We looked at ASQ-3 scores of children who screen positive on the Modified Checklist for Autism in Toddlers-Revised, children who continue to screen positive on the M-CHAT-R follow-up interview, and children diagnosed with ASD. Methods 2848 toddlers, aged 16–30 months, were screened with the ASQ-3 and M-CHAT-R across 20 pediatric sites. Children who screened positive on the M-CHAT-R and its follow-up interview were offered a diagnostic evaluation. Results Using the “monitor and/or fail” cutoff on any domain, the ASQ-3 identified 87% of the children who screened positive on the M-CHAT-R with follow-up and 95% (20/21) of those diagnosed with an ASD. “Monitor and/or Fail” on the Communication domain alone also identified 95% of the diagnosed children. Conclusions Scores below the “monitor” cutoff on the Communication domain of the ASQ-3 can indicate initial concern requiring autism-specific follow-up. If these results are confirmed with a sample large enough to separately examine toddlers of different ages and different cultural backgrounds, it may be feasible to implement a two-stage screening strategy, with autism specific screening reserved for those who are positive on a broad band screen. PMID:26348972

  12. Bone Mineral Density in Healthy Female Adolescents According to Age, Bone Age and Pubertal Breast Stage

    PubMed Central

    Moretto, M.R; Silva, C.C; Kurokawa, C.S; Fortes, C.M; Capela, R.C; Teixeira, A.S; Dalmas, J.C; Goldberg, T.B

    2011-01-01

    Objectives: This study was designed to evaluate bone mineral density (BMD) in healthy female Brazilian adolescents in five groups looking at chronological age, bone age, and pubertal breast stage, and determining BMD behavior for each classification. Methods: Seventy-two healthy female adolescents aged between 10 to 20 incomplete years were divided into five groups and evaluated for calcium intake, weight, height, body mass index (BMI), pubertal breast stage, bone age, and BMD. Bone mass was measured by bone densitometry (DXA) in lumbar spine and proximal femur regions, and the total body. BMI was estimated by Quetelet index. Breast development was assessed by Tanner’s criteria and skeletal maturity by bone age. BMD comparison according to chronologic and bone age, and breast development were analyzed by Anova, with Scheffe’s test used to find significant differences between groups at P≤0.05. Results: BMD (g·cm-2) increased in all studied regions as age advanced, indicating differences from the ages of 13 to 14 years. This group differed to the 10 and 11 to 12 years old groups for lumbar spine BMD (0.865±0.127 vs 0.672±0.082 and 0.689±0.083, respectively) and in girls at pubertal development stage B3, lumbar spine BMD differed from B5 (0.709±0.073 vs 0.936±0.130) and whole body BMD differed from B4 and B5 (0.867±0.056 vs 0.977±0.086 and 1.040±0.080, respectively). Conclusion: Bone mineralization increased in the B3 breast maturity group, and the critical years for bone mass acquisition were between 13 and 14 years of age for all sites evaluated by densitometry. PMID:21966336

  13. Health utility decreases with increasing clinical stage in amyotrophic lateral sclerosis.

    PubMed

    Jones, Ashley R; Jivraj, Naheed; Balendra, Rubika; Murphy, Caroline; Kelly, Joanna; Thornhill, Marie; Young, Carolyn; Shaw, Pamela J; Leigh, P Nigel; Turner, Martin R; Steen, I Nick; McCrone, Paul; Al-Chalabi, Ammar

    2014-06-01

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease typically causing death within three years. Understanding the impact of disease on patients using health utility at different stages of ALS would allow meaningful cost-benefit analysis of new potential therapies. A common health-related quality of life measurement, developed and validated for the UK, is the EQ-5D. Using clinical trial data from the LiCALS study, we calculated health utility using the EQ-5D for each King's ALS clinical stage from 214 patients. We analysed whether health utility, and other health-related measures, significantly changed between each of the clinical stages. Results showed that mean health utility decreased by 0.487 (the scale runs from 1 to - 0.594) between clinical stages 2A and 4. Emotional states, measured using the Hospital Anxiety and Depression Scale (HADS), showed worsening depression and anxiety scores as ALS progressed. Age of onset, disease onset, gender and treatment group were not predictors of EQ-5D, depression or anxiety. In conclusion, increasing severity of King's ALS Clinical Stage is associated with a progressive decrease in EQ-5D health utility. This is useful for cost-benefit analysis of new therapies and validates this ALS clinical staging system.

  14. Reconsidering Clinical Staging Model: A Case of Genetic High Risk for Schizophrenia

    PubMed Central

    Lee, Tae Young; Kim, Minah; Kim, Sung Nyun

    2017-01-01

    The clinical staging model is considered a useful and practical method not only in dealing with the early stage of psychosis overcoming the debate about diagnostic boundaries but also in emerging mood disorder. However, its one limitation is that it cannot discriminate the heterogeneity of individuals at clinical high risk for psychosis, but lumps them all together. Even a healthy offspring of schizophrenia can eventually show clinical symptoms and progress to schizophrenia under the influence of genetic vulnerability and environmental stress even after the peak age of onset of schizophrenia. Therefore, individuals with genetic liability of schizophrenia may require a more intensive intervention than recommended by the staging model based on current clinical status. PMID:28096883

  15. The relationship between cognitive reserve and the clinical stage of HIV infection.

    PubMed

    Alvarez-Tostado, Pablo; Inozemtseva, Olga; Aguiñiga, Miguel A; López, Enrique; Matute, Esmeralda

    2016-01-01

    The objective of this study was to determine whether the effect of cognitive reserve (CR) on neuropsychological functioning differs according to the clinical stage of HIV infection. A sample of 34 HIV-positive individuals aged 23-49, with a minimum of 9 years of formal education, was assessed. Participants were grouped according to the Centers for Disease Control and Prevention's (CDC) clinical stages (A = 10, B = 16, C = 8). CR was calculated for each clinical stage group in accordance with estimates of premorbid IQ, years of education, and occupational attainment. The sum of these three variables was then transformed into z-scores. Individuals above the median were classified as having "High" CR (HCR), those below the median were classified as "Low" CR (LCR). Participants completed an evaluation of cognitive and executive functions based on selected, modified tasks from the HIV University of Miami Annotated Neuropsychological test in Spanish (HUMANS). Assessment included the following domains: attention, memory (visual, verbal, and working memory), executive functions (cognitive flexibility, switching), language (naming), and visual constructive skills (block design). HCR outperformed LCR in all cognitive domains. Comparison of HCR and LCR in each clinical stage revealed that the effect of CR was stronger in stage B than in stages A and C, suggesting that this effect does indeed vary among stages.

  16. Patients with Old Age or Proximal Tumors Benefit from Metabolic Syndrome in Early Stage Gastric Cancer

    PubMed Central

    Zhang, Ying; Liu, Jian-xin; Yu, Hong-mei; Liang, Wei-ping; Jin, Ying; Ren, Chao; He, Ming-ming; Chen, Wei-wei; Luo, Hui-yan; Wang, Zhi-qiang; Zhang, Dong-sheng; Wang, Feng-hua; Li, Yu-hong; Xu, Rui-hua

    2014-01-01

    Background Metabolic syndrome and/or its components have been demonstrated to be risk factors for several cancers. They are also found to influence survival in breast, colon and prostate cancer, but the prognostic value of metabolic syndrome in gastric cancer has not been investigated. Methods Clinical data and pre-treatment information of metabolic syndrome of 587 patients diagnosed with early stage gastric cancer were retrospectively collected. The associations of metabolic syndrome and/or its components with clinical characteristics and overall survival in early stage gastric cancer were analyzed. Results Metabolic syndrome was identified to be associated with a higher tumor cell differentiation (P = 0.036). Metabolic syndrome was also demonstrated to be a significant and independent predictor for better survival in patients aged >50 years old (P = 0.009 in multivariate analysis) or patients with proximal gastric cancer (P = 0.047 in multivariate analysis). No association was found between single metabolic syndrome component and overall survival in early stage gastric cancer. In addition, patients with hypertension might have a trend of better survival through a good control of blood pressure (P = 0.052 in univariate analysis). Conclusions Metabolic syndrome was associated with a better tumor cell differentiation in patients with early stage gastric cancer. Moreover, metabolic syndrome was a significant and independent predictor for better survival in patients with old age or proximal tumors. PMID:24599168

  17. Oral squamous cell carcinoma among Yemenis: Onset in young age and presentation at advanced stage

    PubMed Central

    Al-Mohaya, Maha; Abdulhuq, Mahmoud; Al-Mandili, Ahmad; Al-Anazi, Yousef

    2012-01-01

    Objectives: Oral cancer represents a health burden worldwide. Up to 90% of oral cancer cases are squamous cell carcinomas (SCC). The data on oral SCC in Yemen are lacking. The objective of this study therefore was to describe and analyze the demographic, clinical and histological characteristics of Yemeni patients with oral SCC. Study Design: In this cross-sectional study, two sets of retrospective data for Yemeni cancer patients were obtained officially by two different registries. Patients with oral SCC were included. Their ages were dichotomized using 40 and 45 years alternately as individual cut-points for young and old patients. The patients` demographic, clinical and histological characteristics were statistically analyzed. Results: There were 457 Yemenis with oral SCC; 253 patients (55.4%) were men. The overall mean age was 58.15±14.11 years. The tongue was the most affected oral sub-site accounting for 53% of the reported cases. The well and moderately differentiated oral SCC accounted for 55.5% and 25.6% of the total cases respectively. Noteworthy, 62 patients (14%) were affected by the age of ?40; this increased to 105 patients (23%) aged ?45 years. Additionally, a high proportion of oral SCC patients (62%, 283) were diagnosed at advanced tumor stages (regional extension or metastasized). The distributions of histological grades and tumor stages in young and old patients were significantly different (P=0.006 and 0.026 respectively). Conclusion: The relative frequency of oral SCC among Yemeni young people is high. Unfortunately, most of oral SCC patients in Yemen were diagnosed at advanced stage. Key words:Oral squamous cell carcinoma, Yemen, young patients, advanced stage. PMID:24558559

  18. How to analyze tumor stage data in clinical research.

    PubMed

    Hu, Zhi-De; Zhou, Zhi-Rui; Qian, Shi

    2015-04-01

    Tumor staging serves as an important prognostic factor in cancer patient care. It also plays critical roles in cancer-related clinical research. Aimed to shed lights on how to analyze tumor staging related data and deliver proper interpretation, various statistical methods, from categorical data analysis to modeling techniques, were introduced through the examples. General guidelines were discussed for how to choose proper statistical test with key considerations of research aims, study design, measurement scale of data, proper data summary, type of associations, and underlying assumptions of statistical methods.

  19. Outcomes of laparoscopic fertility-sparing surgery in clinically early-stage epithelial ovarian cancer

    PubMed Central

    Park, Jin-Young; Lee, Yoo-Young; Kim, Tae-Joong; Kim, Byoung-Gie; Bae, Duk-Soo

    2016-01-01

    Objective Fertility-sparing surgery (FSS) is becoming an important technique in the surgical management of young women with early-stage epithelial ovarian cancer (EOC). We retrospectively evaluated the outcome of laparoscopic FSS in presumed clinically early-stage EOC. Methods We retrospectively searched databases of patients who received laparoscopic FSS for EOC between January 1999 and December 2012 at Samsung Medical Center. Women aged ≤40 years were included. The perioperative, oncological, and obstetric outcomes of these patients were evaluated. Results A total of 18 patients was evaluated. The median age of the patients was 33.5 years (range, 14 to 40 years). The number of patients with clinically stage IA and IC was 6 (33.3%) and 12 (66.7%), respectively. There were 7 (38.9%), 5 (27.8%), 3 (16.7%), and 3 patients (16.7%) with mucinous, endometrioid, clear cell, and serous tumor types, respectively. Complete surgical staging to preserve the uterus and one ovary with adnexa was performed in 4 patients (22.2%). Two out of them were upstaged to The International Federation of Gynecology and Obstetrics stage IIIA1. During the median follow-up of 47.3 months (range, 11.5 to 195.3 months), there were no perioperative or long term surgical complications. Four women (22.2%) conceived after their respective ovarian cancer treatments. Three (16.7%) of them completed full-term delivery and one is expecting a baby. One patient had disease recurrence. No patient died of the disease. Conclusion FSS in young patients with presumed clinically early-stage EOC is a challenging and cautious procedure. Further studies are urgent to determine the safety and feasibility of laparoscopic FSS in young patients with presumed clinically early-stage EOC. PMID:26768783

  20. The Edmonton Obesity Staging System for Pediatrics: A proposed clinical staging system for paediatric obesity

    PubMed Central

    Hadjiyannakis, Stasia; Buchholz, Annick; Chanoine, Jean-Pierre; Jetha, Mary M; Gaboury, Laurie; Hamilton, Jill; Birken, Catherine; Morrison, Katherine M; Legault, Laurent; Bridger, Tracey; Cook, Stephen R; Lyons, John; Sharma, Arya M; Ball, Geoff DC

    2016-01-01

    Traditionally, clinical recommendations for assessing and managing paediatric obesity have relied on anthropometric measures, such as body mass index (BMI), BMI percentile and/or BMI z-score, to monitor health risks and determine weight management success. However, anthropometric measures do not always accurately and reliably identify children and youth with obesity-related health risks or comorbidities. The authors propose a new clinical staging system (the Edmonton Obesity Staging System for Pediatrics, EOSS-P), adapted from the adult-oriented EOSS. The EOSS-P is used to stratify patients according to severity of obesity-related comorbidities and barriers to weight management into four graded categories (0 to 3) within four main health domains: metabolic, mechanical, mental health and social milieu (the 4Ms). The EOSS-P is based on common clinical assessments that are widely available and routinely completed by clinicians, and has the potential to provide clinical and prognostic information to help evaluate and inform the management of paediatric obesity. PMID:26941556

  1. Carpal tunnel syndrome severity staging using sonographic and clinical measures

    PubMed Central

    Roll, Shawn C.; Volz, Kevin R.; Fahy, Christine M.; Evans, Kevin D.

    2014-01-01

    Introduction Ultrasonography may be valuable in staging carpal tunnel syndrome severity, especially by combining multiple measures. This study aimed to develop a preliminary severity staging model using multiple sonographic and clinical measures. Methods Measures were obtained in 104 participants. Multiple categorization structures for each variable were correlated to diagnostic severity based on nerve conduction. Goodness-of-fit was evaluated for models using iterative combinations of highly correlated variables. Using the best-fit model, a preliminary scoring system was developed, and frequency of misclassification was calculated. Results The severity staging model with best fit (Rho 0.90) included patient-reported symptoms, functional deficits, provocative testing, nerve cross-sectional area, and nerve longitudinal appearance. An 8-point scoring scale classified severity accurately for 79.8% of participants. Discussion This severity staging model is a novel approach to carpal tunnel syndrome evaluation. Including more sensitive measures of nerve vascularity, nerve excursion, or other emerging techniques may refine this preliminary model. PMID:25287477

  2. Radionuclide scans not indicated for clinical Stage I melanoma

    SciTech Connect

    Evans, R.A.; Bland, K.I.; McMurtrey, M.J.; Ballantyne, A.J.

    1980-04-01

    One hundred and sixty-two scans of the liver and 160 scans of the brain were performed upon 230 patients with clinical Stage I melanoma. No patient was found to have a true-positive scan. However, there were two false-positive scans of the liver and two false-positive scans of the brain. One craniotomy, two arteriograms, and numerous follow-up scans were done to confirm that these scans were false-positive. The cost of the 322 screening scans was $23,964, and the expense of follow-up evaluation was considerably greater. The authors have discontinued the use of scans of the liver and brain in the evaluation of asymptomatic patients with Stage I melanoma.

  3. Decreased growth rate of P. falciparum blood stage parasitemia with age in a holoendemic population.

    PubMed

    Pinkevych, Mykola; Petravic, Janka; Chelimo, Kiprotich; Vulule, John; Kazura, James W; Moormann, Ann M; Davenport, Miles P

    2014-04-01

    In malaria holoendemic settings, decreased parasitemia and clinical disease is associated with age and cumulative exposure. The relative contribution of acquired immunity against various stages of the parasite life cycle is not well understood. In particular, it is not known whether changes in infection dynamics can be best explained by decreasing rates of infection, or by decreased growth rates of parasites in blood. Here, we analyze the dynamics of Plasmodium falciparum infection after treatment in a cohort of 197 healthy study participants of different ages. We use both polymerase chain reaction (PCR) and microscopy detection of parasitemia in order to understand parasite growth rates and infection rates over time. The more sensitive PCR assay detects parasites earlier than microscopy, and demonstrates a higher overall prevalence of infection than microscopy alone. The delay between PCR and microscopy detection is significantly longer in adults compared with children, consistent with slower parasite growth with age. We estimated the parasite multiplication rate from delay to PCR and microscopy detections of parasitemia. We find that both the delay between PCR and microscopy infection as well as the differing reinfection dynamics in different age groups are best explained by a slowing of parasite growth with age.

  4. Reference values of blood parameters in beef cattle of different ages and stages of lactation.

    PubMed Central

    Doornenbal, H; Tong, A K; Murray, N L

    1988-01-01

    Reference (normal) values for 12 blood serum components were determined for 48 Shorthorn cows (2-10 years old) and their 48 calves, 357 crossbred cows (12-14 years old), 36 feedlot bulls and 36 feedlot steers. In addition, hemoglobin, hematocrit, triiodothyronine, thyroxine and cortisol levels were determined for the crossbred cows, and feedlot bulls and steers. Reference values were tabulated according to sex, age and stage of lactation. Serum concentrations of urea, total protein and bilirubin, and serum activity of aspartate aminotransferase and lactate dehydrogenase increased with age (P less than 0.05), while calcium, phosphorus and alkaline phosphatase decreased with age (P less than 0.05) from birth to the age of ten years. The Shorthorn cows had the highest levels of glucose at parturition (P less than 0.05) with decreasing levels during lactation. Creatinine concentration decreased during lactation and increased during postweaning. Both lactate dehydrogenase and aspartate aminotransferase levels increased (P less than 0.05) during lactation. Urea and uric acid were present at higher concentrations in lactating than nonlactating cows (P less than 0.05). The values reported, based on a wide age range and large number of cattle, could serve as clinical guides and a basis for further research. PMID:3349406

  5. Atrophy patterns in early clinical stages across distinct phenotypes of Alzheimer's disease.

    PubMed

    Ossenkoppele, Rik; Cohn-Sheehy, Brendan I; La Joie, Renaud; Vogel, Jacob W; Möller, Christiane; Lehmann, Manja; van Berckel, Bart N M; Seeley, William W; Pijnenburg, Yolande A; Gorno-Tempini, Maria L; Kramer, Joel H; Barkhof, Frederik; Rosen, Howard J; van der Flier, Wiesje M; Jagust, William J; Miller, Bruce L; Scheltens, Philip; Rabinovici, Gil D

    2015-11-01

    Alzheimer's disease (AD) can present with distinct clinical variants. Identifying the earliest neurodegenerative changes associated with each variant has implications for early diagnosis, and for understanding the mechanisms that underlie regional vulnerability and disease progression in AD. We performed voxel-based morphometry to detect atrophy patterns in early clinical stages of four AD phenotypes: Posterior cortical atrophy (PCA, "visual variant," n=93), logopenic variant primary progressive aphasia (lvPPA, "language variant," n=74), and memory-predominant AD categorized as early age-of-onset (EOAD, <65 years, n=114) and late age-of-onset (LOAD, >65 years, n=114). Patients with each syndrome were stratified based on: (1) degree of functional impairment, as measured by the clinical dementia rating (CDR) scale, and (2) overall extent of brain atrophy, as measured by a neuroimaging approach that sums the number of brain voxels showing significantly lower gray matter volume than cognitively normal controls (n=80). Even at the earliest clinical stage (CDR=0.5 or bottom quartile of overall atrophy), patients with each syndrome showed both common and variant-specific atrophy. Common atrophy across variants was found in temporoparietal regions that comprise the posterior default mode network (DMN). Early syndrome-specific atrophy mirrored functional brain networks underlying functions that are uniquely affected in each variant: Language network in lvPPA, posterior cingulate cortex-hippocampal circuit in amnestic EOAD and LOAD, and visual networks in PCA. At more advanced stages, atrophy patterns largely converged across AD variants. These findings support a model in which neurodegeneration selectively targets both the DMN and syndrome-specific vulnerable networks at the earliest clinical stages of AD.

  6. Clinical investigation into the initial diagnosis and treatment of 539 patients with stage IV lung cancer

    PubMed Central

    Shao, Qian; Liu, Shanshan; Wang, Wei; Zhang, Yingjie; Li, Fengxiang; Li, Jianbin

    2017-01-01

    Objective The aim of the study was to analyze clinical data, including the types of pathologic classification, metastatic organs, treatment strategy, and prognosis of patients with stage IV lung cancer. Methods A retrospective analysis of the clinical features of 539 patients with stage IV lung cancer who were initially diagnosed and treated in 2009 was conducted. There were 146 cases of single organ metastases and 393 cases of multiple organ metastases. The Kaplan-Meier method and multivariate Cox regression analysis were performed to analyze the influence of age, pathological classification, metastatic organs, and treatment strategy on overall survival. Results The 1-, 2-, and 3-year survival rates were 64.2% (n=346), 19.7% (n=106), and 1.5% (n=8), respectively. Metastases to the liver and pleura predicted poor prognosis, although bone metastases predicted relatively good prognosis. The prognosis of single brain metastasis was relatively better than that of multiple brain metastases. Multi-factor analysis showed that the patient’s age, different metastatic organs, the numbers of metastatic organs, and different treatment were independent risk factors for survival. Conclusion The prognosis for patients with stage IV lung cancer is poor. Patient’s age, the type and number of metastatic organs, and method of treatment are the main factors affecting survival. PMID:28203086

  7. The 2-stage liver transplant: 3 clinical scenarios.

    PubMed

    Gedik, Ender; Bıçakçıoğlu, Murat; Otan, Emrah; İlksen Toprak, Hüseyin; Işık, Burak; Aydın, Cemalettin; Kayaalp, Cüneyt; Yılmaz, Sezai

    2015-04-01

    The main goal of 2-stage liver transplant is to provide time to obtain a new liver source. We describe our experience of 3 patients with 3 different clinical conditions. A 57-year-old man was retransplanted successfully with this technique due to hepatic artery thrombosis. However, a 38-year-old woman with fulminant toxic hepatitis and a 5-year-old-boy with abdominal trauma had poor outcome. This technique could serve as a rescue therapy for liver transplant patients who have toxic liver syndrome or abdominal trauma. These patients required intensive support during long anhepatic states. The transplant team should decide early whether to use this technique before irreversible conditions develop.

  8. Staging and treatment of clinically occult breast cancer.

    PubMed

    Schwartz, G F; Feig, S A; Rosenberg, A L; Patchefsky, A S; Schwartz, A B

    1984-03-15

    Five hundred fifty-seven biopsies were performed for clinically occult mammary lesions, detected by mammography as clustered calcifications or nonpalpable masses within the breast. One hundred seventy-five cancers were demonstrated within this group, including 106 invasive carcinomas, 10 microinvasive carcinomas, 45 in situ ductal carcinomas, and 14 lobular carcinomas in situ (lobular neoplasia). No patient with in situ or microinvasive carcinoma had evidence of axillary node metastases in 33 specimens studied. However, a disturbingly high proportion of those patients with invasive carcinomas, approximately 35%, had histologically confirmed axillary node metastases, despite the small size of the primary tumors. These observations suggest that the use of the term "minimal" cancer is misleading when applied to invasive carcinoma. Staging systems for breast cancer have been imprecise when referring to nonpalpable lesions. Cancers detected as clustered calcifications only or as areas of parenchymal distortion without an accompanying mass are properly considered as T-0 cancers, with a suggested T-0(m) to indicate that the lesion was detected by mammography. However, when the mammogram indicates the presence of a mass that proves to be malignant, although the clinical examination may have been negative, the cancer should be staged according to the size of the mass on the mammogram, with the notation that it was detected by mammography, e.g., T-1(m), T-2(m), etc. The incidence of axillary node metastases even in these so-called occult cancers is significant, so that recommendations for treatment for any invasive cancer, regardless of its size, must take these observations into account. Similarly, the incidence of multifocal sites of cancer within the breast, even in the noninvasive cancers encountered, must be remembered when treatment is suggested.

  9. Biophysical properties of the clinical-stage antibody landscape

    PubMed Central

    Jain, Tushar; Sun, Tingwan; Durand, Stéphanie; Hall, Amy; Houston, Nga Rewa; Nett, Juergen H.; Sharkey, Beth; Bobrowicz, Beata; Caffry, Isabelle; Yu, Yao; Cao, Yuan; Lynaugh, Heather; Brown, Michael; Baruah, Hemanta; Gray, Laura T.; Krauland, Eric M.; Xu, Yingda; Vásquez, Maximiliano; Wittrup, K. Dane

    2017-01-01

    Antibodies are a highly successful class of biological drugs, with over 50 such molecules approved for therapeutic use and hundreds more currently in clinical development. Improvements in technology for the discovery and optimization of high-potency antibodies have greatly increased the chances for finding binding molecules with desired biological properties; however, achieving drug-like properties at the same time is an additional requirement that is receiving increased attention. In this work, we attempt to quantify the historical limits of acceptability for multiple biophysical metrics of “developability.” Amino acid sequences from 137 antibodies in advanced clinical stages, including 48 approved for therapeutic use, were collected and used to construct isotype-matched IgG1 antibodies, which were then expressed in mammalian cells. The resulting material for each source antibody was evaluated in a dozen biophysical property assays. The distributions of the observed metrics are used to empirically define boundaries of drug-like behavior that can represent practical guidelines for future antibody drug candidates. PMID:28096333

  10. "Life Stage-Specific" Variations in Performance in Response to Age Stereotypes

    ERIC Educational Resources Information Center

    Hehman, Jessica A.; Bugental, Daphne Blunt

    2013-01-01

    In a test of life stage-specific responses to age-based stigma, older (n = 54, ages 62-92) and younger (n = 81, ages 17-22) adults were told that a task (Weschler Adult Intelligence Scale-III block design) required either (a) speed/contemporary knowledge (YA; "youth advantage") or (b) life experience/wisdom (OA; "age…

  11. [Predictive value of Ages & Stages Questionnaires for cognitive performance at early years of schooling].

    PubMed

    Schonhaut B, Luisa; Pérez R, Marcela; Castilla F, Ana María; Castro M, Sonia; Salinas A, Patricia; Armijo R, Iván

    2017-02-01

    The Ages and Stages questionnaires (ASQ) has been recently validated in our country for developmental screening. The objective of this study is evaluate the validity of ASQ to predict low cognitive performance in the early years of schooling.

  12. Age and the Association of Kidney Measures with Mortality and End-Stage Renal Disease

    PubMed Central

    Hallan, Stein I.; Matsushita, Kunihiro; Sang, Yingying; Mahmoodi, Bakhtawar K.; Black, Corri; Ishani, Areef; Kleefstra, Nanne; Naimark, David; Roderick, Paul; Tonelli, Marcello; Wetzels, Jack F.M.; Astor, Brad C.; Gansevoort, Ron T.; Levin, Adeera; Wen, Chi-Pang; Coresh, Josef

    2014-01-01

    Context Chronic kidney disease (CKD) is prevalent in older individuals, but the risk implications of low estimated glomerular filtration rate (eGFR) and high albuminuria across the full age range are controversial. Objective To evaluate possible effect modification (interaction) of age on the association of estimated GFR and albuminuria with clinical risk examining both relative and absolute risk. Design, Setting, Participants We investigated 2,051,244 participants from 33 general population or high-risk (of vascular disease) cohorts and 13 CKD cohorts from Asia, Australesia, Europe, and North/South America conducted during 1972–2011 with mean follow-up time of 5.8 years (range 0–31 years). Main Outcome Measures Hazard ratios (HRs) of mortality and end-stage renal disease (ESRD) according to eGFR and albuminuria were meta-analyzed across age categories after adjusting for sex, race, cardiovascular disease, diabetes, systolic blood pressure, cholestserol, body mass index, and smoking. Absolute risks were estimated using HRs and average incidence rates. Results Mortality (112,325 deaths) and ESRD (8,411 events) risk were higher at lower eGFR and higher albuminuria in every age category. In general/high-risk cohorts, relative mortality risk for reduced eGFR decreased with increasing age: e.g., adjusted HRs (95% CI) at eGFR 45 vs. 80 ml/min/1.73m2 were 3.50 (2.55–4.81), 2.21 (2.02–2.41), 1.59 (1.42–1.77), and 1.35 (1.23–1.48) in age categories 18–54, 55–64, 65–74 and 75+ years, respectively (P-values for age interaction <0.05). Absolute risk differences for the same comparisons were higher at older age (9.0 [95% CI, 6.0–12.8], 12.2 [10.3–14.3], 13.3 [9.0–18.6], and 27.2 [13.5–45.5] excess deaths per 1,000 person-years, respectively). For increased albuminuria, reduction of relative risk with increasing age were less evident, while differences in absolute risk were higher in the older age categories (7.5 [95% CI, 4.3–11.9], 12.2 [7.9–17

  13. Differentiation stage of myeloma plasma cells: biological and clinical significance.

    PubMed

    Paiva, B; Puig, N; Cedena, M T; de Jong, B G; Ruiz, Y; Rapado, I; Martinez-Lopez, J; Cordon, L; Alignani, D; Delgado, J A; van Zelm, M C; Van Dongen, J J M; Pascual, M; Agirre, X; Prosper, F; Martín-Subero, J I; Vidriales, M-B; Gutierrez, N C; Hernandez, M T; Oriol, A; Echeveste, M A; Gonzalez, Y; Johnson, S K; Epstein, J; Barlogie, B; Morgan, G J; Orfao, A; Blade, J; Mateos, M V; Lahuerta, J J; San-Miguel, J F

    2017-02-01

    The notion that plasma cells (PCs) are terminally differentiated has prevented intensive research in multiple myeloma (MM) about their phenotypic plasticity and differentiation. Here, we demonstrated in healthy individuals (n=20) that the CD19-CD81 expression axis identifies three bone marrow (BM)PC subsets with distinct age-prevalence, proliferation, replication-history, immunoglobulin-production, and phenotype, consistent with progressively increased differentiation from CD19+CD81+ into CD19-CD81+ and CD19-CD81- BMPCs. Afterwards, we demonstrated in 225 newly diagnosed MM patients that, comparing to normal BMPC counterparts, 59% had fully differentiated (CD19-CD81-) clones, 38% intermediate-differentiated (CD19-CD81+) and 3% less-differentiated (CD19+CD81+) clones. The latter patients had dismal outcome, and PC differentiation emerged as an independent prognostic marker for progression-free (HR: 1.7; P=0.005) and overall survival (HR: 2.1; P=0.006). Longitudinal comparison of diagnostic vs minimal-residual-disease samples (n=40) unraveled that in 20% of patients, less-differentiated PCs subclones become enriched after therapy-induced pressure. We also revealed that CD81 expression is epigenetically regulated, that less-differentiated clonal PCs retain high expression of genes related to preceding B-cell stages (for example: PAX5), and show distinct mutation profile vs fully differentiated PC clones within individual patients. Together, we shed new light into PC plasticity and demonstrated that MM patients harbouring less-differentiated PCs have dismal survival, which might be related to higher chemoresistant potential plus different molecular and genomic profiles.

  14. COPD, stage and treatment in a large outpatient clinic

    PubMed Central

    Holm, Claire Præst; Holm, Jakob; Nørgaard, Annette; Godtfredsen, Nina

    2017-01-01

    ABSTRACT Some COPD patients suffer from frequent exacerbations despite triple inhalation treatment. These frequent exacerbators should be identified, as exacerbations often lead to decreasing lung function and increasing mortality. Roflumilast reduces exacerbations in patients with a previous history of exacerbations. Our aim was to describe COPD patient characteristics and compare roflumilast treatment eligible to non-eligible patients. An observational cross-section study was conducted. Patients were included from a large COPD outpatient clinic. Information regarding COPD patient characteristics was registered on a standardized form and lung function was measured. Patients were categorized according to the GOLD classification. Eligibility for roflumilast treatment was assessed and patient characteristics compared between groups. 547 patients were included. Most patients (54%) were in GOLD group D. 62 patients (11.3%) met the criteria for treatment with roflumilast. Among the patients eligible for roflumilast treatment, only 14 patients (22.6%) were receiving treatment. There were no significant differences in FEV1, number of exacerbations, hospitalization due to exacerbation, MRC grade, age, smoking status and medication use between patients receiving roflumilast and not treated eligible patients. Our study documents low use of roflumilast treatment. In view of the established effect of roflumilast we think that this treatment should be considered more consistently as an option among COPD patients fulfilling the criteria for this therapy. PMID:28326174

  15. Update on Merkel Cell Carcinoma: Epidemiology, Etiopathogenesis, Clinical Features, Diagnosis, and Staging.

    PubMed

    Llombart, B; Requena, C; Cruz, J

    2017-03-01

    Merkel cell carcinoma (MCC) is a rare, highly aggressive tumor, and local or regional disease recurrence is common, as is metastasis. MCC usually develops in sun-exposed skin in patients of advanced age. Its incidence has risen 4-fold in recent decades as the population has aged and immunohistochemical techniques have led to more diagnoses. The pathogenesis of MCC remains unclear but UV radiation, immunosuppression, and the presence of Merkel cell polyomavirus in the tumor genome seem to play key roles. This review seeks to update our understanding of the epidemiology, etiology, pathogenesis, and clinical features of MCC. We also review histologic and immunohistochemical features required for diagnosis. MCC staging is discussed, given its great importance in establishing a prognosis for these patients.

  16. Treatment results in women with clinical stage I and pathologic stage II endometrial carcinoma.

    PubMed

    Jobsen, J J; Schutter, E M; Meerwaldt, J H; Van Der Palen, J; Van Der Sijde, R; Ten Cate, L N

    2001-01-01

    The aim of this study is to report survival and results of therapy and possible prognostic factors in women with pathologic stage II endometrial carcinoma. Forty-two patients with pathologic stage II endometrial carcinoma were treated at the department of Radiation Oncology of the Medisch Spectrum Twente between 1987 and 1998. All patients received external radiotherapy following standard surgical procedures and no adjuvant systemic therapy was given. From the 42 patients 21 had a pathologic stage IIA and 21 stage IIB. The median follow-up was 62 months. The overall recurrence rate was 21.5% (9/42). Seven patients had distant metastasis, of which three also had locoregional recurrence, vaginal vault and/or pelvic. The presence of myometrial invasion (> (1/2)) and/or lymph-angioinvasion showed a significant relation with distant metastasis (P = 0.017). Stage IIB showed more recurrences, 33% (7/21). There was a significant different 5-year disease specific survival for stage IIA and IIB, respectively, 95% and 74% (P = 0.0311). Patients with a differentiation grade 3 and stage IIB showed a significantly poorer (P = 0.003) 5-year survival of 48.6% (P = 0.003). Results obtained in the present series of patients are in accordance with the literature. The present treatment policy seems justified, except for patients with pathologic stage IIB and grade 3, in which a more aggressive treatment should be considered.

  17. C5b-9 Staining Correlates With Clinical and Tumor Stage in Gastric Adenocarcinoma

    PubMed Central

    Chen, Jian; Yang, Wei-jun; Sun, Hai-jian; Wu, Yu-zhang

    2016-01-01

    The complement system is a critical part of the immune response, acting in defense against viral infections, clearance of immune complexes, and maintenance of tissue homeostasis. Upregulated expression of the terminal complement complex, C5b-9, has been observed on various tumor cells, such as stomach carcinoma cells, and on cells in the necrotic regions of these tumors as well; however, whether and how C5b-9 is related to gastric cancer progression and severity remains unknown. In this study, human gastric adenocarcinoma (HGAC) tissues (n=47 cases) and patient-matched adjacent nontumoral parenchyma (n=20 cases) were evaluated by tissue microarray and immunohistochemistry. The HGAC tissues showed upregulated C5b-9 expression. Multinomial logistic regression and likelihood ratio testing showed that overexpression of C5b-9 in HGAC tissue was significantly correlated with clinical stage (P=0.007) and tumor stage (P=0.005), but not with tumor distant organ metastasis, lymphoid nodal status, sex, or age. Patients with late-stage gastric adenocarcinoma had a higher amount of tumor cells showing positive staining for C5b-9 than patients with early-stage disease. These results may help in diagnosis and assessment of disease severity of human gastric carcinoma. PMID:26186252

  18. Aging and the kidney: clinical implications.

    PubMed

    Epstein, M

    1985-04-01

    Beyond the age of 30, kidney size begins to decrease, and there are accompanying decreases in total renal blood flow, outer cortical flow, glomerular filtration rate and the ability both to conserve and to excrete sodium. There is also a decline in concentrating ability and possibly in diluting ability. These changes make the elderly patient more susceptible both to hyponatremic and to hypernatremic states.

  19. Aging and facial changes--documenting clinical signs, part 1: clinical changes of the aging face.

    PubMed

    Nkengne, Alex; Bertin, Christiane

    2012-01-01

    The process of aging induces the transformation of the face with changes that are usually classified as either chronological or photo induced and that affect the shape, the texture, and the color of the face. Facial shape is mainly transformed by the evolution of bones and soft tissues (muscles, fat, and skin) in addition to noticeable effects of gravity. Skin texture is mainly determined by wrinkles, which arise from atrophy of the skin layers, elastosis, and facial expressions. Skin color is related to the distribution of skin chromophores and the structure of the dermis, which affects light scattering. All facial changes are dependant on sex, ethnicity, and lifestyle. They affect self-perception and social interactions and can sometimes be slowed down or reversed using appropriate clinical procedures (e.g., dermatological, surgical, and cosmetic interventions).

  20. Aging and facial changes--documenting clinical signs, part 1: clinical changes of the aging face.

    PubMed

    Nkengne, Alex; Bertin, Christiane

    2013-01-01

    The process of aging induces the transformation of the face with changes that are usually classified as either chronological or photo-induced and that affect the shape, the texture, and the color of the face. Facial shape is mainly transformed by the evolution of bones and soft tissues (muscles, fat, and skin) in addition to noticeable effects of gravity. Skin texture is mainly determined by wrinkles, which arise from atrophy of the skin layers, elastosis, and facial expressions. Skin color is related to the distribution of skin chromophores and the structure of the dermis, which affects light scattering. All facial changes are dependant on sex, ethnicity, and lifestyle. They affect self-perception and social interactions and can sometimes be slowed down or reversed using appropriate clinical procedures (eg, dermatological, surgical, cosmetic interventions).

  1. Reassessing the NTCTCS Staging Systems for Differentiated Thyroid Cancer, Including Age at Diagnosis

    PubMed Central

    McLeod, Donald S.A.; Jonklaas, Jacqueline; Brierley, James D.; Ain, Kenneth B.; Cooper, David S.; Fein, Henry G.; Haugen, Bryan R.; Ladenson, Paul W.; Magner, James; Ross, Douglas S.; Skarulis, Monica C.; Steward, David L.; Xing, Mingzhao; Litofsky, Danielle R.; Maxon, Harry R.

    2015-01-01

    Background: Thyroid cancer is unique for having age as a staging variable. Recently, the commonly used age cut-point of 45 years has been questioned. Objective: This study assessed alternate staging systems on the outcome of overall survival, and compared these with current National Thyroid Cancer Treatment Cooperative Study (NTCTCS) staging systems for papillary and follicular thyroid cancer. Methods: A total of 4721 patients with differentiated thyroid cancer were assessed. Five potential alternate staging systems were generated at age cut-points in five-year increments from 35 to 70 years, and tested for model discrimination (Harrell's C-statistic) and calibration (R2). The best five models for papillary and follicular cancer were further tested with bootstrap resampling and significance testing for discrimination. Results: The best five alternate papillary cancer systems had age cut-points of 45–50 years, with the highest scoring model using 50 years. No significant difference in C-statistic was found between the best alternate and current NTCTCS systems (p = 0.200). The best five alternate follicular cancer systems had age cut-points of 50–55 years, with the highest scoring model using 50 years. All five best alternate staging systems performed better compared with the current system (p = 0.003–0.035). There was no significant difference in discrimination between the best alternate system (cut-point age 50 years) and the best system of cut-point age 45 years (p = 0.197). Conclusions: No alternate papillary cancer systems assessed were significantly better than the current system. New alternate staging systems for follicular cancer appear to be better than the current NTCTCS system, although they require external validation. PMID:26203804

  2. Clinical trials in predementia stages of Alzheimer disease.

    PubMed

    Pillai, Jagan A; Cummings, Jeffrey L

    2013-05-01

    Effective treatments of Alzheimer disease (AD) dementia are an urgent necessity. There is a growing consensus that effective disease-modifying treatment before the onset of clinical dementia and slowing the progression of mild symptoms are needed after recent setbacks in AD therapeutics. The identification of at-risk and preclinical AD populations is becoming important for targeting primary and secondary prevention clinical trials in AD. This article reviews the strategies and challenges in targeting at-risk and preclinical AD populations for a new generation of AD clinical trials. Design, outcome measures, and complexities in successfully completing a clinical trial targeting this population are reviewed.

  3. Considerations in the design of clinical trials for cognitive aging.

    PubMed

    Reiman, Eric M; Brinton, Roberta Diaz; Katz, Russell; Petersen, Ronald C; Negash, Selam; Mungas, Dan; Aisen, Paul S

    2012-06-01

    What will it take to develop interventions for the treatment of age-related cognitive decline? Session V of the Summit provided perspectives on the design of clinical trials to evaluate promising but unproven interventions, and some of the steps needed to accelerate the discovery and evaluation of promising treatments. It considered strategies to further characterize the biological and cognitive changes associated with normal aging and their translation into the development of new treatments. It provided regulatory, scientific, and clinical perspectives about neurocognitive aging treatments, their potential benefits and risks, and the strategies and endpoints needed to evaluate them in the most rapid, rigorous, and clinically meaningful way. It considered lessons learned from the study of Alzheimer's disease, the promising roles of biomarkers in neurocognitive aging research, and ways to help galvanize the scientific study and treatment of neurocognitive aging.

  4. One-stage and two-stage designs for phase II clinical trials with survival endpoints.

    PubMed

    Whitehead, John

    2014-09-28

    This work is motivated by trials in rapidly lethal cancers or cancers for which measuring shrinkage of tumours is infeasible. In either case, traditional phase II designs focussing on tumour response are unsuitable. Usually, tumour response is considered as a substitute for the more relevant but longer-term endpoint of death. In rapidly lethal cancers such as pancreatic cancer, there is no need to use a surrogate, as the definitive endpoint is (sadly) available so soon. In uveal cancer, there is no counterpart to tumour response, and so, mortality is the only realistic response available. Cytostatic cancer treatments do not seek to kill tumours, but to mitigate their effects. Trials of such therapy might also be based on survival times to death or progression, rather than on tumour shrinkage. Phase II oncology trials are often conducted with all study patients receiving the experimental therapy, and this approach is considered here. Simple extensions of one-stage and two-stage designs based on binary responses are presented. Outcomes based on survival past a small number of landmark times are considered: here, the case of three such times is explored in examples. This approach allows exact calculations to be made for both design and analysis purposes. Simulations presented here show that calculations based on normal approximations can lead to loss of power when sample sizes are small. Two-stage versions of the procedure are also suggested.

  5. Colon trauma--clinical staging for surgical decision making. Analysis of 119 cases.

    PubMed

    Morgado, P J; Alfaro, R; Morgado, P J; León, P

    1992-10-01

    A retrospective study is presented of 119 patients admitted to the Central Hospital of the Venezuelan Institute of Social Security, in Caracas, between 1982 and 1990, with the diagnosis of colon trauma. Several parameters including age, etiology, time elapsed between the accident or assault and hospital admission, preoperative and postoperative hemoglobin and diastolic blood pressure, associated lesions, procedure practiced, complication rate, and hospital mortality are reviewed. The second and third decades of life appear most often involved. Most patients reached the hospital within the first four hours of the accident or assault. Anemia, sustained diastolic hypotension, and number of organs involved in addition to the colon were important prognostic factors for complications. Apparently the surgical procedure, with simple suture or resection, mostly without "protective" colostomy, was not very relevant. Hospital mortality was 2.4 percent. A staging system based on clinical conditions for decision making in the operating room was used in an attempt to inject some objectivity into the surgical approach.

  6. The Relationship among Pubertal Stage, Age, and Drinking in Adolescent Boys and Girls

    ERIC Educational Resources Information Center

    Faden, Vivian B.; Ruffin, Beverly; Newes-Adeyi, Gabriella; Chen, Chiung

    2010-01-01

    This study used data from the Third National Household and Nutrition Examination Survey (NHANES) to examine the association between pubertal status (Tanner staging for boys and girls and menarche for girls) and alcohol use in a nationally representative sample of youths ages 12 to 17. Logistic regression was used to model the relationship. In…

  7. Minuteman Stage III Operational Surveillance Program Seven-Year Testing Bondline Aging Study,

    DTIC Science & Technology

    1985-12-01

    Liner Gel Fraction at Various Motor Locations ......... . . 25 14 Liner Moisture at Various Motor Locations ............. ... 26 6 15 Motor TC 30005 ...PageI ,,. 18 Shore A Hardness Gradient of ANB-3066 Propellant at the Forward Equator ........ ...................... .. 30 19 Motor TC 30005 ...75 I 2 Matrix for Minuteman Stage III Bondline Aging Program ........ 76 3 Motor TC 30005 Material Properties Data, Forward

  8. Developmental Screening Using the Ages and Stages Questionnaire: Standardized versus Real-World Conditions

    ERIC Educational Resources Information Center

    San Antonio, Marianne C.; Fenick, Ada M.; Shabanova, Veronika; Leventhal, John M.; Weitzman, Carol C.

    2014-01-01

    Developmental screens are often used in nonstandardized conditions, such as pediatric waiting rooms, despite validation under standardized conditions. We examined the reproducibility of the Ages and Stages Questionnaire (ASQ), a developmental screening instrument commonly used in pediatric practices, under standardized versus nonstandardized…

  9. From stage to age in variable environments: life expectancy and survivorship.

    PubMed

    Tuljapurkar, Shripad; Horvitz, Carol C

    2006-06-01

    Stage-based demographic data are now available on many species of plants and some animals, and they often display temporal and spatial variability. We provide exact formulas to compute age-specific life expectancy and survivorship from stage-based data for three models of temporal variability: cycles, serially independent random variation, and a Markov chain. These models provide a comprehensive description of patterns of temporal variation. Our formulas describe the effects of cohort (birth) environmental condition on mortality at all ages, and of the effects on survivorship of environmental variability experienced over the course of life. This paper complements existing methods for time-invariant stage-based data, and adds to the information on population growth and dynamics available from stochastic demography.

  10. Strategies and Challenges in Clinical Trials Targeting Human Aging

    PubMed Central

    Newman, John C.; Milman, Sofiya; Hashmi, Shahrukh K.; Austad, Steve N.; Kirkland, James L.; Halter, Jeffrey B.

    2016-01-01

    Interventions that target fundamental aging processes have the potential to transform human health and health care. A variety of candidate drugs have emerged from basic and translational research that may target aging processes. Some of these drugs are already in clinical use for other purposes, such as metformin and rapamycin. However, designing clinical trials to test interventions that target the aging process poses a unique set of challenges. This paper summarizes the outcomes of an international meeting co-ordinated by the NIH-funded Geroscience Network to further the goal of developing a translational pipeline to move candidate compounds through clinical trials and ultimately into use. We review the evidence that some drugs already in clinical use may target fundamental aging processes. We discuss the design principles of clinical trials to test such interventions in humans, including study populations, interventions, and outcomes. As examples, we offer several scenarios for potential clinical trials centered on the concepts of health span (delayed multimorbidity and functional decline) and resilience (response to or recovery from an acute health stress). Finally, we describe how this discussion helped inform the design of the proposed Targeting Aging with Metformin study. PMID:27535968

  11. Age-stage, two-sex life table of Parapoynx crisonalis (Lepidoptera: Pyralidae) at different temperatures.

    PubMed

    Chen, Qi; Li, Ni; Wang, Xing; Ma, Li; Huang, Jian-Bin; Huang, Guo-Hua

    2017-01-01

    Parapoynx crisonalis is an important pest of many aquatic vegetables including water chestnuts. Understanding the relationship between temperature variations and the population growth rates of P. crisonalis is essential to predicting its population dynamics in water chestnuts ponds. These relationships were examined in this study based on the age-stage, two-sex life table of P. crisonalis developed in the laboratory at 21, 24, 27, 30, 33 and 36°C. The results showed that the values of Sxj (age-stage-specific survival rate), fxj (age-stage-specific fecundity), lx (age specific survival rate) and mx (age-specific fecundity) increased as the temperature rose from 21 to 27°C, then decreased from 30 to 36°C. Temperature also had a significant effect on the net reproductive rate (R0), gross reproductive rate (GRR), intrinsic rate of increase (r) and finite rate of increase (λ). The value of these parameters were at low levels at 21, 33, and 36°C. Further, the r value decreased as the temperature rose from 24 to 30°C, while the GRR reached its highest level at 27°C. The results indicated that optimal growth and development of P. crisonalis occurred at temperatures between 24°C to 30°C when compared to the lowest temperature (21°C) and higher temperatures of 33°C and 36°C.

  12. Dynamic changes of driver genes' mutations across clinical stages in nine cancer types.

    PubMed

    Li, Xia

    2016-07-01

    The driver genes play critical roles for tumorigenesis, and the number of identified driver genes reached plateau. But how they act during different cancer development stages is lack of knowledge. We investigated 138 driver genes' mutation changes across clinical stages using 3,477 cases in nine cancer types from the Cancer Genome Atlas (TCGA) and constructed their temporal order relationships. We also examined the codon changes for the widely mutated TP53 and PIK3CA in tumor stages. Combinations of one to three driver genes specifically dominated in each cancer. Across the clinical stages, we categorized three patterns for the behaviors of driver genes' mutation changes in the nine cancer types: recurrently mutated in all the stages and triggering other mutations; certain mutations lost meanwhile other mutations emerged; mutations dominated across entire stages, while other mutations gradually appeared or disappeared. We observed different codon changes dominated in different stages and revealed mutations recurrently occurring on the hotspot regions of the coding sequence may be the core factor for driver genes' tumorigenesis. Our results highlighted the dynamic changes of oncogenesis roles in different clinical stages and suggested different diagnostic decision making according to the clinical stages of patients.

  13. A modified varying-stage adaptive phase II/III clinical trial design.

    PubMed

    Dong, Gaohong; Vandemeulebroecke, Marc

    2016-07-01

    Conventionally, adaptive phase II/III clinical trials are carried out with a strict two-stage design. Recently, a varying-stage adaptive phase II/III clinical trial design has been developed. In this design, following the first stage, an intermediate stage can be adaptively added to obtain more data, so that a more informative decision can be made. Therefore, the number of further investigational stages is determined based upon data accumulated to the interim analysis. This design considers two plausible study endpoints, with one of them initially designated as the primary endpoint. Based on interim results, another endpoint can be switched as the primary endpoint. However, in many therapeutic areas, the primary study endpoint is well established. Therefore, we modify this design to consider one study endpoint only so that it may be more readily applicable in real clinical trial designs. Our simulations show that, the same as the original design, this modified design controls the Type I error rate, and the design parameters such as the threshold probability for the two-stage setting and the alpha allocation ratio in the two-stage setting versus the three-stage setting have a great impact on the design characteristics. However, this modified design requires a larger sample size for the initial stage, and the probability of futility becomes much higher when the threshold probability for the two-stage setting gets smaller. Copyright © 2016 John Wiley & Sons, Ltd.

  14. Transitions in Physiologic Coupling: Sleep Stage and Age Dependence of Cardio-respiratory Phase Synchronization

    NASA Astrophysics Data System (ADS)

    Bartsch, Ronny P.; Ivanov, Plamen Ch.

    2012-02-01

    Recent studies have focused on various features of cardiac and respiratory dynamics with the aim to better understand key aspects of the underlying neural control of these systems. We investigate how sleep influences cardio-respiratory coupling, and how the degree of this coupling changes with transitions across sleep stages in healthy young and elderly subjects. We analyze full night polysomnographic recordings of 189 healthy subjects (age range: 20 to 90 years). To probe cardio-respiratory coupling, we apply a novel phase synchronization analysis method to quantify the adjustment of rhythms between heartbeat and breathing signals. We investigate how cardio-respiratory synchronization changes with sleep-stage transitions and under healthy aging. We find a statistically significant difference in the degree of cardio-respiratory synchronization during different sleep stages for both young and elderly subjects and a significant decline of synchronization with age. This is a first evidence of how sleep regulation and aging influence a key nonlinear mechanism of physiologic coupling as quantified by the degree of phase synchronization between the cardiac and respiratory systems, which is of importance to develop adequate modeling approaches.

  15. Clinical staging in bitches with mammary tumors: Influence of type and histological grade

    PubMed Central

    Gundim, Lígia F.; de Araújo, Camila P.; Blanca, William T.; Guimarães, Ednaldo C.; Medeiros, Alessandra A.

    2016-01-01

    Breast tumors are the most common tumors in dogs and the study of disease prognostic factors is important for establishing the appropriate treatment protocols. The purpose of this study was to clinically stage mammary tumors of bitches and correlate the stages with histological type and grade. The tumors of 63 dogs were clinically staged based on the findings of tumor sizing, lymph node evaluation, and radiographic examination. After surgical excision, the tumors were classified histologically and graded. The relationship between the tumor grade, stage, and histological type was evaluated using a binomial test. Stage I tumors were the most numerous (31.75%), followed by tumors at stages II, III, IV, and V. Animals with histological grade I carcinomas presented stage I, II, or III tumors more frequently and stage IV and V tumors less frequently. The number of animals with simple carcinomas that were at stage I of the disease was greater than that at stage V. Carcinomas in the mixed tumors were less aggressive; however, the small number of animals in stage V of the disease made any statistical association impossible. The complex carcinomas presented with the invasion of the lymph nodes and less cellular differentiation in a larger number of animals than did simple carcinomas. Histological grading proved to be the best parameter for the prognostic evaluation of the breast carcinomas. PMID:27733787

  16. Bacterial vectors for active immunotherapy reach clinical and industrial stages

    PubMed Central

    Le Gouëllec, Audrey; Chauchet, Xavier; Polack, Benoit; Buffat, Laurent; Toussaint, Bertrand

    2012-01-01

    Active immunotherapy based on live attenuated bacterial vectors has matured in terms of industrial development and develops through a combination of three phenomena. First, active immunotherapy that stimulates an antigen-specific cytotoxic T-cell immune response has become a reality after several years of work. Second, there is still a need to identify vectors that can deliver antigens to the cytosol of antigen-presenting cells in vivo. Third, the recent progress in the understanding of bacterial lifestyle and in developing genetic engineering tools has enabled the design of bioengineered bugs that are capable of delivering antigens. Here, we review the mechanisms by which clinical bacterial vectors deliver antigens into the cytosol of antigen-presenting cells and summarize the development strategy of the three identified firms in this field. PMID:22894945

  17. Identification of morphological markers of sarcopenia at early stage of aging in skeletal muscle of mice.

    PubMed

    Sayed, Ramy K A; de Leonardis, Erika Chacin; Guerrero-Martínez, José A; Rahim, Ibtissem; Mokhtar, Doaa M; Saleh, Abdelmohaimen M; Abdalla, Kamal E H; Pozo, María J; Escames, Germaine; López, Luis C; Acuña-Castroviejo, Darío

    2016-10-01

    The gastrocnemius muscle (GM) of young (3months) and aged (12months) female wild-type C57/BL6 mice was examined by light and electron microscopy, looking for the presence of structural changes at early stage of the aging process. Morphometrical parameters including body and gastrocnemius weights, number and type of muscle fibers, cross section area (CSA), perimeter, and Feret's diameter of single muscle fiber, were measured. Moreover, lengths of the sarcomere, A-band, I-band, H-zone, and number and CSA of intermyofibrillar mitochondria (IFM), were also determined. The results provide evidence that 12month-old mice had significant changes on skeletal muscle structure, beginning with the reduction of gastrocnemius weight to body weight ratio, compatible with an early loss of skeletal muscle function and strength. Moreover, light microscopy revealed increased muscle fibers size, with a significant increase on their CSA, perimeter, and diameter of both type I and type II muscle fibers, and a reduction in the percentage of muscle area occupied by type II fibers. Enhanced connective tissue infiltrations, and the presence of centrally nucleated muscle fibers, were also found in aged mice. These changes may underlie an attempt to compensate the loss of muscle mass and muscle fibers number. Furthermore, electron microscopy discovered a significant age-dependent increase in the length of sarcomeres, I and H bands, and reduction on the overlapped actin/myosin length, supporting contractile force loss with age. Electron microscopy also showed an increased number and CSA of IFM with age, which may reveal more endurance at 12months of age. Together, mice at early stage of aging already show significant changes in gastrocnemius muscle morphology and ultrastructure that are suggestive of the onset of sarcopenia.

  18. Aging Effects on Cardiac and Respiratory Dynamics in Healthy Subjects across Sleep Stages

    PubMed Central

    Schumann, Aicko Y.; Bartsch, Ronny P.; Penzel, Thomas; Ivanov, Plamen Ch.; Kantelhardt, Jan W.

    2010-01-01

    Study Objectives: Respiratory and heart rate variability exhibit fractal scaling behavior on certain time scales. We studied the short-term and long-term correlation properties of heartbeat and breathing-interval data from disease-free subjects focusing on the age-dependent fractal organization. We also studied differences across sleep stages and night-time wake and investigated quasi-periodic variations associated with cardiac risk. Design: Full-night polysomnograms were recorded during 2 nights, including electrocardiogram and oronasal airflow. Setting: Data were collected in 7 laboratories in 5 European countries. Participants: 180 subjects without health complaints (85 males, 95 females) aged from 20 to 89 years. Interventions: None. Measurements and Results: Short-term correlations in heartbeat intervals measured by the detrended fluctuation analysis (DFA) exponent α1 show characteristic age dependence with a maximum around 50–60 years disregarding the dependence on sleep and wake states. Long-term correlations measured by α2 differ in NREM sleep when compared with REM sleep and wake, besides weak age dependence. Results for respiratory intervals are similar to those for α2 of heartbeat intervals. Deceleration capacity (DC) decreases with age; it is lower during REM and deep sleep (compared with light sleep and wake). Conclusion: The age dependence of α1 should be considered when using this value for diagnostic purposes in post-infarction patients. Pronounced long-term correlations (larger α2) for heartbeat and respiration during REM sleep and wake indicate an enhanced control of higher brain regions, which is absent during NREM sleep. Reduced DC possibly indicates an increased cardiovascular risk with aging and during REM and deep sleep. Citation: Schumann AY; Bartsch RP; Penzel T; Ivanov PC; Kantelhardt JW. Aging effects on cardiac and respiratory dynamics in healthy subjects across sleep stages. SLEEP 2010;33(7):943-955. PMID:20614854

  19. Age-stage, two-sex life table of Parapoynx crisonalis (Lepidoptera: Pyralidae) at different temperatures

    PubMed Central

    Chen, Qi; Li, Ni; Wang, Xing; Ma, Li; Huang, Jian-Bin; Huang, Guo-Hua

    2017-01-01

    Parapoynx crisonalis is an important pest of many aquatic vegetables including water chestnuts. Understanding the relationship between temperature variations and the population growth rates of P. crisonalis is essential to predicting its population dynamics in water chestnuts ponds. These relationships were examined in this study based on the age-stage, two-sex life table of P. crisonalis developed in the laboratory at 21, 24, 27, 30, 33 and 36°C. The results showed that the values of Sxj (age-stage–specific survival rate), fxj (age-stage-specific fecundity), lx (age specific survival rate) and mx (age-specific fecundity) increased as the temperature rose from 21 to 27°C, then decreased from 30 to 36°C. Temperature also had a significant effect on the net reproductive rate (R0), gross reproductive rate (GRR), intrinsic rate of increase (r) and finite rate of increase (λ). The value of these parameters were at low levels at 21, 33, and 36°C. Further, the r value decreased as the temperature rose from 24 to 30°C, while the GRR reached its highest level at 27°C. The results indicated that optimal growth and development of P. crisonalis occurred at temperatures between 24°C to 30°C when compared to the lowest temperature (21°C) and higher temperatures of 33°C and 36°C. PMID:28264022

  20. Effect of Two-Stage Aging on Microstructure of 7075 Aluminum Alloys

    DTIC Science & Technology

    1981-04-01

    which particular microstructural characteristic is of greatest significance in the stress corrosion behavior of 7075 in a high strength condition. 2...is expected that RRA may provide less improvement in the stress corrosion behavior of 7050 than of I I 7075 . Data from these tests would allow...I v h EFFECT OF TWO-STAGE AGING ON MICROSTRUCTURE OF 7075 ALUMINUM ALLOYS RE- 627 "Final Report E April 1981 "by 7! Jonn M. Papazian OT i. Prepared

  1. Regional staging of white matter signal abnormalities in aging and Alzheimer's disease.

    PubMed

    Lindemer, Emily R; Greve, Douglas N; Fischl, Bruce R; Augustinack, Jean C; Salat, David H

    2017-01-01

    White matter lesions, quantified as 'white matter signal abnormalities' (WMSA) on neuroimaging, are common incidental findings on brain images of older adults. This tissue damage is linked to cerebrovascular dysfunction and is associated with cognitive decline. The regional distribution of WMSA throughout the cerebral white matter has been described at a gross scale; however, to date no prior study has described regional patterns relative to cortical gyral landmarks which may be important for understanding functional impact. Additionally, no prior study has described how regional WMSA volume scales with total global WMSA. Such information could be used in the creation of a pathologic 'staging' of WMSA through a detailed regional characterization at the individual level. Magnetic resonance imaging data from 97 cognitively-healthy older individuals (OC) aged 52-90 from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study were processed using a novel WMSA labeling procedure described in our prior work. WMSA were quantified regionally using a procedure that segments the cerebral white matter into 35 bilateral units based on proximity to landmarks in the cerebral cortex. An initial staging was performed by quantifying the regional WMSA volume in four groups based on quartiles of total WMSA volume (quartiles I-IV). A consistent spatial pattern of WMSA accumulation was observed with increasing quartile. A clustering procedure was then used to distinguish regions based on patterns of scaling of regional WMSA to global WMSA. Three patterns were extracted that showed high, medium, and non-scaling with global WMSA. Regions in the high-scaling cluster included periventricular, caudal and rostral middle frontal, inferior and superior parietal, supramarginal, and precuneus white matter. A data-driven staging procedure was then created based on patterns of WMSA scaling and specific regional cut-off values from the quartile analyses. Individuals with Alzheimer's disease

  2. A varying-stage adaptive phase II/III clinical trial design.

    PubMed

    Dong, Gaohong

    2014-04-15

    Currently, adaptive phase II/III clinical trials are typically carried out with a strict two-stage design. The first stage is a learning stage called phase II, and the second stage is a confirmatory stage called phase III. Following phase II analysis, inefficacious or harmful dose arms are dropped, then one or two promising dose arms are selected for the second stage. However, there are often situations in which researchers are in dilemma to make 'go or no-go' decision and/or to select 'best' dose arm(s), as data from the first stage may not provide sufficient information for their decision making. In this case, it is challenging to follow a strict two-stage plan. Therefore, we propose a varying-stage adaptive phase II/III clinical trial design, in which we consider whether there is a need to have an intermediate stage to obtain more data, so that a more informative decision could be made. Hence, the number of further investigational stages in our design is determined on the basis of data accumulated to the interim analysis. With respect to adaptations, we consider dropping dose arm(s), switching another plausible endpoint as the primary study endpoint, re-estimating sample size, and early stopping for futility. We use an adaptive combination test to perform final analyses. By applying closed testing procedure, we control family-wise type I error rate at the nominal level of α in the strong sense. We delineate other essential design considerations including the threshold parameters and the proportion of alpha allocated in the two-stage versus three-stage setting.

  3. Effects of Age Expectations on Oncology Social Workers' Clinical Judgment

    ERIC Educational Resources Information Center

    Conlon, Annemarie; Choi, Namkee G.

    2014-01-01

    Objective: This study examined the influence of oncology social workers' expectations regarding aging (ERA) and ERA with cancer (ERAC) on their clinical judgment. Methods: Oncology social workers (N = 322) were randomly assigned to one of four vignettes describing a patient with lung cancer. The vignettes were identical except for the patent's age…

  4. A clinically relevant frailty index for aging rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Frailty is a clinical syndrome that is increasingly prevalent during aging. Frailty involves the confluence of reduced strength, speed, physical activity, and endurance, and it is associated with adverse health outcomes. Frailty indices have been developed to diagnose frailty in older adult populati...

  5. Revisiting the Biomedicalization of Aging: Clinical Trends and Ethical Challenges

    ERIC Educational Resources Information Center

    Kaufman, Sharon R.; Shim, Janet K.; Russ, Ann J.

    2004-01-01

    Developments in the realms of medical innovation and geriatric clinical intervention impact our understanding of the nature of late life, the possibilities for health in advanced age, medical decision making, and family responsibility in ways that could not have been predicted 15 years ago. This essay begins to map new forms of biomedicalization…

  6. Age estimation by dental developmental stages in children and adolescents in Iceland.

    PubMed

    Vidisdottir, Sigridur Rosa; Richter, Svend

    2015-12-01

    Studies have shown that it is necessary to create a database for dental maturity for every population and compare it to others. The present study is the first one for dental development in the Icelandic population the age range being 4-24 years. It will help in forensic dental age estimation and will also help dentists, physicians, anthropologists, archaeologists and other professionals who rely on developmental age assessment in children and adolescents. In this present retrospective cross-sectional study, dental maturity was determined in 1100 Icelandic children and adolescents from orthopantomograms (OPGs). The first 100 were used for a pilot study and the remaining 1000 for the main study. A total of 23 subjects were excluded. The sample consisted of 508 girls and 469 boys from the age of 4-24 years and a dental developmental scoring system was used as a standard for determination of dental maturity stages. A total of 200 OPGs were studied both on the left and right side and the remaining on the right side. Dental maturity was established for all teeth and both genders, when the sample permitted, from the beginning of crown formation to the root apex closure. The Cronbach's Alpha reliability test showed high reliability, R=0.982. Girls in Iceland reach dental maturity root completed (stage 10, Rc) at 17.81 years of age for the maxillary and at 18.47 years for the mandibular teeth. Boys reach dental maturity root completed (stage 10, Rc) at 18.00 years of age in the maxilla and 17.63 in the mandible. There was no significant difference between left and right side (r=0.95-1.00) and there was no gender difference, except in root formation in maxillary and mandibular canines where girls reached root completed earlier than boys. A reliable database has been established in Iceland for tooth development in the age range of 4-24 years, which is compatible with international studies. These results will help forensic odontologists and other professionals to estimate with

  7. Interval estimation of binomial proportion in clinical trials with a two-stage design.

    PubMed

    Tsai, Wei-Yann; Chi, Yunchan; Chen, Chia-Min

    2008-01-15

    Generally, a two-stage design is employed in Phase II clinical trials to avoid giving patients an ineffective drug. If the number of patients with significant improvement, which is a binomial response, is greater than a pre-specified value at the first stage, then another binomial response at the second stage is also observed. This paper considers interval estimation of the response probability when the second stage is allowed to continue. Two asymptotic interval estimators, Wald and score, as well as two exact interval estimators, Clopper-Pearson and Sterne, are constructed according to the two binomial responses from this two-stage design, where the binomial response at the first stage follows a truncated binomial distribution. The mean actual coverage probability and expected interval width are employed to evaluate the performance of these interval estimators. According to the comparison results, the score interval is recommended for both Simon's optimal and minimax designs.

  8. Age estimation from stages of epiphyseal union in the presacral vertebrae.

    PubMed

    Cardoso, Hugo F V; Ríos, Luis

    2011-02-01

    The presacral vertebrae have various secondary centers of ossification, whose timing of fusion can be used for age estimation of human skeletal remains up to the middle to the latter third decade. However, detailed information about the age at which these secondary centers of ossification fuse has been lacking. In this study, the timing of epiphyseal union in presacral vertebrae was studied in a sample of modern Portuguese skeletons (57 females and 47 males) between the ages of 9 and 30, taken from the Lisbon documented skeletal collection. A detailed photographic record of these epiphyses and the age ranges for the different stages of epiphyseal union are provided. Partial union of epiphyses was observed from 11 to 27 years of age. In general, centers of ossification begin to fuse first in the cervical and lumbar vertebrae, followed by centers of ossification in the thoracic region. The first center of ossification to complete fusion is usually that of the mammillary process in lumbar vertebrae. This is usually followed by that of the transverse process, spinous transverse process, and annular ring, regardless of vertebra type. There were no statistically significant sex differences in timing of fusion, but there was a trend toward early maturation in females for some vertebra or epiphyses. Bilateral epiphyses did not show statistically significant differences in timing of fusion. This study offers information on timing of fusion of diverse epiphyseal locations useful for age estimation of complete or fragmented human skeletal remains.

  9. Age and petrology of alkalic postshield and rejuvenated-stage lava from Kauai, Hawaii

    USGS Publications Warehouse

    Clague, D.A.; Dalrymple, G.B.

    1988-01-01

    At the top of the Waimea Canyon Basalt on the island of Kauai, rare flows of alkalic postshield-stage hawaiite and mugearite overlie tholeiitic flows of the shield stage. These postshield-stage flows are 3.92 Ma and provide a younger limit for the age of the tholeiitic shield stage. The younger Koloa Volcanics consist of widespread alkalic rejuvenated-stage flows and vents of alkalic basalt, basanite, nephelinite, and nepheline melilitite that erupted between 3.65 and 0.52 Ma. All the flows older than 1.7 Ma occur in the west-northwestern half of the island and all the flows younger than 1.5 Ma occur in the east-southeastern half. The lithologies have no spatial or chronological pattern. The flows of the Koloa Volcanics are near-primary magmas generated by variable small degrees of partial melting of a compositionally heterogeneous garnet-bearing source that has about two-thirds the concentration of P2O5, rare-earth elements, and Sr of the source of the Honolulu Volcanics on the island of Oahu. The same lithology in the Koloa and Honolulu Volcanics is generated by similar degrees of partial melting of distinct source compositions. The lavas of the Koloa Volcanics can be generated by as little as 3 percent to as much as 17 percent partial melting for nepheline melilitite through alkalic basalt, respectively. Phases that remain in the residue of the Honolulu Volcanics, such as rutile and phlogopite, are exhausted during formation of the Koloa Volcanics at all but the smallest degrees of partial melting. The mantle source for Kauai lava becomes systematically more depleted in 87Sr/86Sr as the volcano evolves from the tholeiitic shield stage to the alkalic postshield stage to the alkalic rejuvenated stage: at the same time, the lavas become systematically more enriched in incompatible trace elements. On a shorter timescale, the lavas of the Koloa Volcanics display the same compositional trends, but at a lower rate of change. The source characteristics of the Koloa

  10. Virtual anthropology: useful radiological tools for age assessment in clinical forensic medicine and thanatology.

    PubMed

    Dedouit, Fabrice; Saint-Martin, Pauline; Mokrane, Fatima-Zohra; Savall, Frédéric; Rousseau, Hervé; Crubézy, Eric; Rougé, Daniel; Telmon, Norbert

    2015-09-01

    Virtual anthropology consists of the introduction of modern slice imaging to biological and forensic anthropology. Thanks to this non-invasive scientific revolution, some classifications and staging systems, first based on dry bone analysis, can be applied to cadavers with no need for specific preparation, as well as to living persons. Estimation of bone and dental age is one of the possibilities offered by radiology. Biological age can be estimated in clinical forensic medicine as well as in living persons. Virtual anthropology may also help the forensic pathologist to estimate a deceased person's age at death, which together with sex, geographical origin and stature, is one of the important features determining a biological profile used in reconstructive identification. For this forensic purpose, the radiological tools used are multislice computed tomography and, more recently, X-ray free imaging techniques such as magnetic resonance imaging and ultrasound investigations. We present and discuss the value of these investigations for age estimation in anthropology.

  11. Stages of the pathologic process in Alzheimer disease: age categories from 1 to 100 years.

    PubMed

    Braak, Heiko; Thal, Dietmar R; Ghebremedhin, Estifanos; Del Tredici, Kelly

    2011-11-01

    Two thousand three hundred and thirty two nonselected brains from 1- to 100-year-old individuals were examined using immunocytochemistry (AT8) and Gallyas silver staining for abnormal tau; immunocytochemistry (4G8) and Campbell-Switzer staining were used for the detection ofβ-amyloid. A total of 342 cases was negative in the Gallyas stain but when restaged for AT8 only 10 were immunonegative. Fifty-eight cases had subcortical tau predominantly in the locus coeruleus, but there was no abnormal cortical tau (subcortical Stages a-c). Cortical involvement (abnormal tau in neurites) was identified first in the transentorhinal region (Stage 1a, 38 cases). Transentorhinal pyramidal cells displayed pretangle material (Stage 1b, 236 cases). Pretangles gradually became argyrophilic neurofibrillary tangles (NFTs) that progressed in parallel with NFT Stages I to VI. Pretangles restricted to subcortical sites were seen chiefly at younger ages. Of the total cases, 1,031 (44.2%) had β-amyloid plaques. The first plaques occurred in the neocortex after the onset of tauopathy in the brainstem. Plaques generally developed in the 40s in 4% of all cases, culminating in their tenth decade (75%). β-amyloid plaques and NFTs were significantly correlated (p < 0.0001). These data suggest that tauopathy associated with sporadic Alzheimer disease may begin earlier than previously thought and possibly in the lower brainstem rather than in the transentorhinal region.

  12. Bringing the law to the gerontological stage: a different look at movies and old age.

    PubMed

    Doron, Israel

    2006-01-01

    Films often portray the complexities of real-life aging issues, showing how they are apparently handled outside of and around the law or legal issues. Furthermore, films considering the aged and the social issues associated with aging also reveal how the law actually functions as a framework around and within which people develop customs, habits, and behaviors related to the issue of old age. Exposing these hidden socio-legal boundaries allows us to better understand both the films concerned and the place of law within our aging society. In an attempt to better understand these issues, this article deconstructs five relatively modern and well-known films. All feature aged protagonists, and all tell their stories against a background of legal issues that are only alluded to, and remain hidden "behind the scenes." Two main questions are addressed by this analysis: First, to what extent does the reality of old age as described in the films considered here reflect familiar social phenomena identified by empirical studies? And, second, to what extent does the legal infrastructure embedded in the narrative of these films reflect the legal regulations that govern the aged in today's society. The conclusions that arose from the analysis of the cinematic and the legal reality expressed in the films demonstrate that the current level of discourse on major issues in social gerontology ignores the importance and relevance of law. Therefore, it behooves us to "bring the Law to the gerontological stage," where the current situation as it actually exists can be analyzed and perhaps even changed.

  13. Survival of patients with colorectal cancer in Austria by sex, age, and stage.

    PubMed

    Haidinger, Gerald; Waldhoer, Thomas; Hackl, Monika; Vutuc, Christian

    2006-10-01

    This paper for the first time presents Austrian data on survival of patients, diagnosed from 1998 through 2002, with colon cancer and with rectal cancer. Cumulative relative survival rates were calculated by age, standardized for all ages and stages combined, and by age groups (< 50 years, 50-64 years, and =65 years) according to stages (localized, regional metastases and distant metastases). In carcinoma of the colon 5-year relative survival was 66 % in males and 64 % in females. In carcinoma of the rectum 5-year relative survival was 64 % in males and 67 % in females. Compared to the earlier results from the Tyrol (based on patients diagnosed from 1990 through 1994) the 5-year survival of patients with colon cancer increased from 55 % to 66 % in males and from 58 % to 64 % in females. In patients with rectal cancer 5-year survival increased from 44 % to 64 % in males and from 46 % to 67 % in females. This increase in part can be explained by a positive effect of early detection and of better treatment.

  14. Variation in Honey Bee Gut Microbial Diversity Affected by Ontogenetic Stage, Age and Geographic Location

    PubMed Central

    Hroncova, Zuzana; Havlik, Jaroslav; Killer, Jiri; Doskocil, Ivo; Tyl, Jan; Kamler, Martin; Titera, Dalibor; Hakl, Josef; Mrazek, Jakub; Bunesova, Vera; Rada, Vojtech

    2015-01-01

    Social honey bees, Apis mellifera, host a set of distinct microbiota, which is similar across the continents and various honey bee species. Some of these bacteria, such as lactobacilli, have been linked to immunity and defence against pathogens. Pathogen defence is crucial, particularly in larval stages, as many pathogens affect the brood. However, information on larval microbiota is conflicting. Seven developmental stages and drones were sampled from 3 colonies at each of the 4 geographic locations of A. mellifera carnica, and the samples were maintained separately for analysis. We analysed the variation and abundance of important bacterial groups and taxa in the collected bees. Major bacterial groups were evaluated over the entire life of honey bee individuals, where digestive tracts of same aged bees were sampled in the course of time. The results showed that the microbial tract of 6-day-old 5th instar larvae were nearly equally rich in total microbial counts per total digestive tract weight as foraging bees, showing a high percentage of various lactobacilli (Firmicutes) and Gilliamella apicola (Gammaproteobacteria 1). However, during pupation, microbial counts were significantly reduced but recovered quickly by 6 days post-emergence. Between emergence and day 6, imago reached the highest counts of Firmicutes and Gammaproteobacteria, which then gradually declined with bee age. Redundancy analysis conducted using denaturing gradient gel electrophoresis identified bacterial species that were characteristic of each developmental stage. The results suggest that 3-day 4th instar larvae contain low microbial counts that increase 2-fold by day 6 and then decrease during pupation. Microbial succession of the imago begins soon after emergence. We found that bacterial counts do not show only yearly cycles within a colony, but vary on the individual level. Sampling and pooling adult bees or 6th day larvae may lead to high errors and variability, as both of these stages may

  15. An experimental and clinical evaluation of lens transparency and aging.

    PubMed

    Lerman, S

    1983-05-01

    The normal human lens is a precisely formed structure containing about 65% water and 35% organic matter, the latter being mainly (greater than 90%) structural proteins. The lens becomes encapsulated at the 13 mm embryonic stage and is consequently divorced from a direct blood supply for life. It provides the investigator with an organ that exists in an environment analogous to a single-cell type of tissue culture system and can be reproduced in vitro. Since the cornea and lens are transparent one can directly monitor morphologic and biochemical aging changes in vivo. Recent developments now permit us to monitor certain molecular changes as well. Thus this organ can serve as a unique model for studying in vivo aging parameters. In vivo UV slit lamp densitography to monitor lens fluorescence provides us with a useful diagnostic and prognostic screening method to identify lens photodamage due to excess UV exposure (occupational or accidental), photosensitizers (e.g. psoralens) as well as the normal age related increase in lenticular fluorescence. Cortical opacities are also a common finding in older individuals. In vitro NMR (human and animal lenses) and in vivo (animal experiments) currently in progress are rapidly elucidating the physicochemical basis for the development of light scattering areas in the aging lens cortex. This review demonstrates the feasibility of utilizing biophysical methods, in particular, optical spectroscopy and NMR analyses to delineate and monitor specific age related parameters in the ocular lens, in vivo as well as in vitro.

  16. [Clinical diagnostics of ADHD in preschool-aged children].

    PubMed

    Merkt, Julia; Petermann, Franz

    2015-03-01

    Attention deficit hyperactivity disorder (ADHD) is one of the most prevalent psychiatric disorders in childhood and adolescence and has many negative consequences for both the child and the family. Early identification of children with ADHD would be helpful for the prevention of long-term consequences. This review appraises questionnaires and clinical interviews that can be used for the diagnosis of ADHD in preschool-aged children (3-5 years). We compare and discuss both German and international methods. The role of questionnaires and clinical interviews in the diagnostic process of ADHD is discussed.

  17. Design of adaptive two-stage double-arm clinical trials for dichotomous variables.

    PubMed

    Jiang, Zhiwei; Xue, Fubo; Li, Chanjuan; Wang, Ling; Cai, Hongwei; Zhang, Chunmao; Xia, Jielai

    2010-05-01

    It is well known that flexibility is one of the major advantages of an adaptive two-stage design, and the intended adaptation should be as preplanned as possible to maintain the integrity of the clinical trial. The design of adaptive two-stage double-arm clinical trials for dichotomous variables was proposed by simulation and forecasting procedure at the planning stage. To further ensure the integrity of the clinical trial, the sample size scheme for each scenario, which was supposed to be based on the first stage, was provided in the protocol by Monte Carlo simulation. In addition, the study parameters were determined by comparing the assessment indexes such as total sample size, expected sample size and the test power at the first stage. Furthermore, Fisher's combination test and pooled data analysis were considered and compared through the simulation. The latter, which has the larger overall power and the better overall type I error control, with the same sample size was adopted for further simulation and statistical analysis in the clinical trial.

  18. Comorbidity-Age Index: A Clinical Measure of Biologic Age Before Allogeneic Hematopoietic Cell Transplantation

    PubMed Central

    Sorror, Mohamed L.; Storb, Rainer F.; Sandmaier, Brenda M.; Maziarz, Richard T.; Pulsipher, Michael A.; Maris, Michael B.; Bhatia, Smita; Ostronoff, Fabiana; Deeg, H. Joachim; Syrjala, Karen L.; Estey, Elihu; Maloney, David G.; Appelbaum, Frederick R.; Martin, Paul J.; Storer, Barry E.

    2014-01-01

    Purpose Age has long been used as a major factor for assessing suitability for allogeneic hematopoietic cell transplantation (HCT). The HCT-comorbidity index (HCT-CI) was developed as a measure of health status to predict mortality risk after HCT. Whether age, comorbidities, or both should guide decision making for HCT is unknown. Patients and Methods Data from 3,033 consecutive recipients of HLA-matched grafts from five institutions contributed to this analysis. Patients were randomly divided into a training set to develop weights for age intervals and a validation set to assess the performance of prognostic models. Results In the training set, patients age 20 to 39 years, 40 to 49 years, 50 to 59 years, and ≥ 60 years had hazard ratios for nonrelapse mortality (NRM) of 1.21 (P = .29), 1.48 (P = .04), 1.75 (P = .004), and 1.84 (P = .005), respectively, compared with those age younger than 20 years. Consequently, age ≥ 40 years was assigned a weight of 1 to be added to the HCT-CI to constitute a composite comorbidity/age index. In the validation set, the composite comorbidity/age score had statistically significantly higher c-statistic estimates for prediction of NRM (0.664 v 0.556; P < .001) and survival (0.682 v 0.560; P < .001) compared with age, respectively. Patients with comorbidity/age scores of 0 to 2 had comparable mortality risks regardless of conditioning regimens. Patients with scores of 3 to 4 and ≥ 5 had statistically significant higher mortality risks after high-dose versus nonmyeloablative regimens. Conclusion Age is a poor prognostic factor. The proposed composite measure allows integration of both comorbidities and age into clinical decision making and comparative-effectiveness research of HCT. PMID:25154831

  19. Incidence of adenocarcinoma of the esophagus among white Americans by sex, stage, and age.

    PubMed

    Brown, Linda Morris; Devesa, Susan S; Chow, Wong-Ho

    2008-08-20

    Rapid increases in the incidence of adenocarcinoma of the esophagus have been reported among white men. We further explored the temporal patterns of this disease among white individuals by sex, stage, and age by use of data from the Surveillance, Epidemiology, and End Results program. We identified 22,759 patients from January 1, 1975, through December 31, 2004, with esophageal cancer, of whom 9526 were diagnosed with adenocarcinoma of the esophagus. Among white men, increases in the incidence of esophageal cancer were largely attributed to a 463% increase in the incidence of adenocarcinoma over this time period, from 1.01 per 100,000 person-years (95% confidence interval [CI] = 0.90 to 1.13) in 1975-1979 to 5.69 per 100,000 person-years (95% CI = 5.47 to 5.91) in 2000-2004. A similar rapid increase was also apparent among white women, among whom the adenocarcinoma rate increased 335%, from 0.17 (95% CI = 0.13 to 0.21) to 0.74 per 100,000 person-years (95% CI = 0.67 to 0.81), over the same time period. Adenocarcinoma rates rose among white men and women in all stage and age groups, indicating that these increases are real and not an artifact of surveillance.

  20. Optimal adaptive two-stage designs for early phase II clinical trials.

    PubMed

    Shan, Guogen; Wilding, Gregory E; Hutson, Alan D; Gerstenberger, Shawn

    2016-04-15

    Simon's optimal two-stage design has been widely used in early phase clinical trials for Oncology and AIDS studies with binary endpoints. With this approach, the second-stage sample size is fixed when the trial passes the first stage with sufficient activity. Adaptive designs, such as those due to Banerjee and Tsiatis (2006) and Englert and Kieser (2013), are flexible in the sense that the second-stage sample size depends on the response from the first stage, and these designs are often seen to reduce the expected sample size under the null hypothesis as compared with Simon's approach. An unappealing trait of the existing designs is that they are not associated with a second-stage sample size, which is a non-increasing function of the first-stage response rate. In this paper, an efficient intelligent process, the branch-and-bound algorithm, is used in extensively searching for the optimal adaptive design with the smallest expected sample size under the null, while the type I and II error rates are maintained and the aforementioned monotonicity characteristic is respected. The proposed optimal design is observed to have smaller expected sample sizes compared to Simon's optimal design, and the maximum total sample size of the proposed adaptive design is very close to that from Simon's method. The proposed optimal adaptive two-stage design is recommended for use in practice to improve the flexibility and efficiency of early phase therapeutic development.

  1. Genetics of Unilateral and Bilateral Age-Related Macular Degeneration Severity Stages

    PubMed Central

    Schick, Tina; Altay, Lebriz; Viehweger, Eva; Hoyng, Carel B.; den Hollander, Anneke I.; Felsch, Moritz; Fauser, Sascha

    2016-01-01

    Background Age-related macular degeneration (AMD) is a common disease causing visual impairment and blindness. Various gene variants are strongly associated with late stage AMD, but little is known about the genetics of early forms of the disease. This study evaluated associations of genetic factors and different AMD stages depending on unilateral and bilateral disease severity. Methods In this case-control study, participants were assigned to nine AMD severity stages based on the characteristics of each eye. 18 single nucleotide polymorphisms (SNPs) were genotyped and attempted to correlate with AMD severity stages by uni- and multivariate logistic regression analyses and trend analyses. Area under the receiver operating characteristic curves (AUC) were calculated. Results Of 3444 individuals 1673 were controls, 379 had early AMD, 333 had intermediate AMD and 989 showed late AMD stages. With increasing severity of disease and bilateralism more SNPs with significant associations were found. Odds ratios, especially for the main risk polymorphisms in ARMS2 (rs10490924) and CFH (rs1061170), gained with increasing disease severity and bilateralism (exemplarily: rs1061170: unilateral early AMD: OR = 1.18; bilateral early AMD: OR = 1.20; unilateral intermediate AMD: OR = 1.28; bilateral intermediate AMD: OR = 1.39, unilateral geographic atrophy (GA): OR = 1.50; bilateral GA: OR = 1.71). Trend analyses showed p<0.0001 for ARMS2 (rs10490924) and for CFH (rs1061170), respectively. AUC of risk models for various AMD severity stages was lowest for unilateral early AMD (AUC = 0.629) and showed higher values in more severely and bilaterally affected individuals being highest for late AMD with GA in one eye and neovascular AMD in the other eye (AUC = 0.957). Conclusion The association of known genetic risk factors with AMD became stronger with increasing disease severity, which also led to an increasing discriminative ability of AMD cases and controls. Genetic predisposition was

  2. Lung cancer staging: the value of PET depends on the clinical setting

    PubMed Central

    2014-01-01

    Background Although positron emission tomography (PET) imaging is widely recommended in the evaluation of patients with lung cancer, randomized controlled trials (RCTs) assessing this have demonstrated inconsistent results. We asked whether differences in the clinical context and endpoints could explain these discrepancies. Methods We used realist synthesis methods to analyze how contextual differences among RCTs affected the results. We focused on RCTs to minimize confounding yet permit evaluation of differences by comparing across studies. Results This analysis suggests that the impact of PET depends on the clinical setting. PET is of greatest benefit in identifying M1 disease in patients with a high chance of such involvement and when little traditional imaging [e.g., abdominal/pelvis computed tomography (CT) and bone scan] is used. Identification of N2,3 involvement by PET prior to resection is seen primarily when there is at least a moderate probability of such and the rate of invasive staging is high. The rate of N2 disease not identified preoperatively appears to increase if PET is used to avoid invasive mediastinal staging in clinical settings in which the risk of N2,3 involvement is moderately high. There is both a potential benefit in avoiding stage-inappropriate resection as well as a risk of missed (stage-appropriate) resection if PET findings are not evaluated carefully. Conclusions A blanket recommendation for PET may be too simplistic without considering nuances of the clinical setting. PMID:25589964

  3. Photoacoustic intra-operative nodal staging using clinically approved superparamagnetic iron oxide nanoparticles

    NASA Astrophysics Data System (ADS)

    Grootendorst, Diederik J.; Fratila, Raluca M.; Visscher, Martijn; Ten Haken, Bennie; van Wezel, Richard; Steenbergen, Wiendelt; Manohar, Srirang; Ruers, Theo J. M.

    2013-02-01

    Detection of tumor metastases in the lymphatic system is essential for accurate staging of various malignancies, however fast, accurate and cost-effective intra-operative evaluation of the nodal status remains difficult to perform with common available medical imaging techniques. In recent years, numerous studies have confirmed the additional value of superparamagnetic iron oxide dispersions (SPIOs) for nodal staging purposes, prompting the clearance of different SPIO dispersions for clinical practice. We evaluate whether a combination of photoacoustic (PA) imaging and a clinically approved SPIO dispersion, could be applied for intra-operative nodal staging. Metastatic adenocarcinoma was inoculated in Copenhagen rats for 5 or 8 days. After SPIO injection, the lymph nodes were photoacoustically imaged both in vivo and ex vivo whereafter imaging results were correlated with MR and histology. Results were compared to a control group without tumor inoculation. In the tumor groups clear irregularities, as small as 1 mm, were observed in the PA contrast pattern of the nodes together with an decrease of PA response. These irregularities could be correlated to the absence of contrast in the MR images and could be linked to metastatic deposits seen in the histological slides. The PA and MR images of the control animals did not show these features. We conclude that the combination of photoacoustic imaging with a clinically approved iron oxide nanoparticle dispersion is able to detect lymph node metastases in an animal model. This approach opens up new possibilities for fast intra-operative nodal staging in a clinical setting.

  4. Angiogenic inhibitors for older patients with advanced colorectal cancer: Does the age hold the stage?

    PubMed Central

    Aprile, Giuseppe; Fontanella, Caterina; Lutrino, Eufemia Stefania; Ferrari, Laura; Casagrande, Mariaelena; Cardellino, Giovanni Gerardo; Rosati, Gerardo; Fasola, Gianpiero

    2013-01-01

    Although major progress has been achieved in the treatment of advanced colorectal cancer (CRC) with the employment of antiangiogenic agents, several questions remain on the use of these drugs in older patients. Since cardiovascular, renal and other comorbidities are common in the elderly, an accurate assessment of the patients’ conditions should be performed before a treatment decision is made. Since most CRC patients enrolled in clinical trials testing antiangiogenic drugs were aged < 65 years, the efficacy and tolerability of these agents in elderly patients has not been adequately explored. Data suggest that patients with advanced CRC derive similar benefit from bevacizumab treatment regardless of age, but the advantage of other antiangiogenic drugs in the same class of patients appears more blurred. Literature data suggest that specific antiangiogenic-related toxicities such as hypertension or arterial thromboembolic events may be higher in the elderly than in the younger patients. In addition, it should be emphasized that the patients included in the clinical studies discussed herein were selected and therefore may not be representative of the usual elderly population. Advanced age alone should not discourage the use of bevacizumab. However, a careful patients’ selection and watchful monitoring of toxicities are required to optimize the use of antiangiogenics in this population. PMID:23847406

  5. The Living Stage Improvisational Theatre Demonstration Project for Orthopedically Handicapped Children, Ages 4-8. Overview, 1978-1981.

    ERIC Educational Resources Information Center

    Alexander, Robert; Haynes, Wendy

    The Living Stage Improvisational Theatre Demonstration Project (Washington, D.C.) conducts weekly workshops to enhance the creative expression and self esteem of orthopedically handicapped children, aged 4 to 8 years. The Living Stage program is designed to demonstrate that methods of improvisational theatre can have a positive impact on parental…

  6. Revisiting the Biomedicalization of Aging: Clinical Trends and Ethical Challenges

    PubMed Central

    Kaufman, Sharon R.; Shim, Janet K.; Russ, Ann J.

    2008-01-01

    Developments in the realms of medical innovation and geriatric clinical intervention impact our understanding of the nature of late life, the possibilities for health in advanced age, medical decision making, and family responsibility in ways that could not have been predicted 15 years ago. This essay begins to map new forms of biomedicalization in the U.S. and to underscore their emergence in a new ethical field. We suggest that a new kind of ethical knowledge is emerging through “routine” clinical care, and we offer examples from the following interventions: cardiac procedures, kidney dialysis, and kidney transplant. This new ethical knowledge is characterized by the difficulty of saying “no” to life-extending interventions, regardless of age. We explore the intensification of the biomedicalization of old age through a discussion of three features of the new ethical field: (a) the ways in which routine medical care overshadows choice; (b) the transformation of the technological imperative to a moral imperative; and (c) the coupling of hope with the normalization and routinization of life-extending interventions. We argue that societal expectations about longevity and standard medical care come together today in a shifting ethics of normalcy, with unexplored sociocultural ramifications. PMID:15611209

  7. A Comparative Analysis of Clinical and Molecular Factors with the Stage of Cervical Cancer in a Brazilian Cohort

    PubMed Central

    Amaro-Filho, Sergio M.; Golub, Jonathan E.; Nuovo, Gerard J.; Cunha, Cynthia B.; Levi, José E.; Villa, Luisa L.; Andrade, Cecília V.; Russomano, Fabio B.; Tristão, Aparecida; Pires, Andrea; Nicol, Alcina F.

    2013-01-01

    Cell cycle protein expression plays an important role in the pathophysiology of cervical cancer. However, few studies have attempted to correlate the use of these biomarkers with the clinical progression of the tumor. Objectives 1) To analyze the expression of Ki-67, p53 and p16INK4a in cervical cancer, 2) to correlate the relative expression of these proteins as well as clinical parameters with the stage of disease, and 3) to determine the HPV DNA prevalence and subtype distribution. Methods Tissue Micro-Arrays (TMA) from patients with invasive cervical cancer (ICC) and controls were analyzed. HPV DNA detection was done by PCR and in situ hybridization. Ki-67, p53 and p16INK4a were analyzed by immunohistochemistry; clinical data was derived from the chart review. Results Advanced tumor stage (III and IV) was strongly associated (p<0.005) with advanced age (>55 years old), with more than four pregnancies and with the lack of formal education. HPV DNA was found in 94.3% of cases with the most prevalent types being HPV16 (67.5%), followed by HPV33 (12.0%) and HPV35 (3.6%). High expression of Ki-67 and p16 was more common in the advanced FIGO stages (p = 0.023). Women with HPV16 tended to be younger (50.9 years; SE 1.9) compared to women with other types (59.9 years; SE 2.8). Conclusion We found that Ki-67 and p16 expression were independently associated with the tumor stage. We also noted that about 1/3 of the cervical cancers in this Brazilian cohort were not associated with HPV types directly targeted by the current HPV vaccines. PMID:23505442

  8. Blood-Borne Activity-Dependent Neuroprotective Protein (ADNP) is Correlated with Premorbid Intelligence, Clinical Stage, and Alzheimer's Disease Biomarkers.

    PubMed

    Malishkevich, Anna; Marshall, Gad A; Schultz, Aaron P; Sperling, Reisa A; Aharon-Peretz, Judith; Gozes, Illana

    2016-01-01

    Biomarkers for Alzheimer's disease (AD) are vital for disease detection in the clinical setting. Discovered in our laboratory, activity-dependent neuroprotective protein (ADNP) is essential for brain formation and linked to cognitive functions. Here, we revealed that blood borne expression of ADNP and its paralog ADNP2 is correlated with premorbid intelligence, AD pathology, and clinical stage. Age adjustment showed significant associations between: 1) higher premorbid intelligence and greater serum ADNP, and 2) greater cortical amyloid and lower ADNP and ADNP2 mRNAs. Significant increases in ADNP mRNA levels were observed in patients ranging from mild cognitive impairment (MCI) to AD dementia. ADNP2 transcripts showed high correlation with ADNP transcripts, especially in AD dementia lymphocytes. ADNP plasma/serum and lymphocyte mRNA levels discriminated well between cognitively normal elderly, MCI, and AD dementia participants. Measuring ADNP blood-borne levels could bring us a step closer to effectively screening and tracking AD.

  9. Adaptation of the Ages and Stages Questionnaire for Remote Aboriginal Australia.

    PubMed

    D'Aprano, Anita; Silburn, Sven; Johnston, Vanessa; Robinson, Gary; Oberklaid, Frank; Squires, Jane

    2016-04-01

    A key challenge to providing quality developmental care in remote Aboriginal primary health care (PHC) centers has been the absence of culturally appropriate developmental screening instruments. This study focused on the cross-cultural adaptation of the Ages and Stages Questionnaires, 3rd edition (ASQ-3), with careful attention to language and culture. We aimed to adapt the ASQ-3 for use with remote dwelling Australian Aboriginal children, and to investigate the cultural appropriateness and feasibility of the adapted ASQ-3 for use in this context. We undertook a qualitative study in two remote Australian Aboriginal communities, using a six-step collaborative adaptation process. Aboriginal Health Workers (AHWs) were trained to use the adapted ASQ-3, and follow-up interviews examined participants' views of the cultural acceptability and usefulness of the adapted instrument. The adapted ASQ-3 was found to have high face validity and to be culturally acceptable and relevant to parents, AHWs, and early childhood development experts.

  10. Low Level of Microsatellite Instability Correlates with Poor Clinical Prognosis in Stage II Colorectal Cancer Patients

    PubMed Central

    Mojarad, Ehsan Nazemalhosseini; Kashfi, Seyed Mohammad Hossein; Mirtalebi, Hanieh; Taleghani, Mohammad Yaghoob; Azimzadeh, Pedram; Savabkar, Sanaz; Pourhoseingholi, Mohammad Amin; Jalaeikhoo, Hasan; Asadzadeh Aghdaei, Hamid; Kuppen, Peter J. K.; Zali, Mohammad Reza

    2016-01-01

    The influence of microsatellite instability (MSI) on the prognosis of colorectal cancer (CRC) requires more investigation. We assessed the role of MSI status in survival of individuals diagnosed with primary colorectal cancer. In this retrospective cross-sectional study the MSI status was determined in 158 formalin-fixed paraffin-embedded tumors and their matched normal tissues from patients who underwent curative surgery. Cox proportional hazard modeling was performed to assess the clinical prognostic significance. In this study we found that MSI-H tumors were predominantly located in the colon versus rectum (p = 0.03), associated with poorer differentiation (p = 0.003) and TNM stage II/III of tumors (p = 0.02). In CRC patients with stage II, MSI-L cases showed significantly poorer survival compared with patients who had MSI-H or MSS tumors (p = 0.04). This study indicates that MSI-L tumors correlate with poorer clinical outcome in patients with stage II tumors (p = 0.04) or in tumors located in the colon (p = 0.02). MSI-L characterizes a distinct subgroup of CRC patients who have a poorer outcome. This study suggests that MSI status in CRC, as a clinical prognostic marker, is dependent on other factors, such as tumor stage and location. PMID:27429617

  11. The effects of fertilization mode, embryo morphology at day 3, and female age on blastocyst formation and the clinical outcomes.

    PubMed

    Yin, Huiqun; Jiang, Hong; He, Ruibing; Wang, Cunli; Zhu, Jie; Luan, Kang

    2015-01-01

    The aim of this study was to evaluate the influence of in vitro fertilization (IVF) versus intracytoplasmic sperm injection (ICSI), fertilization mode embryonic morphology at day 3, and female age on blastocyst development, on the clinical outcomes of pregnancy after blastocyst transfer. A total of 471 cycles were retrospectively investigated. The rates of blastocyst formation and of good blastocyst morphology were higher in IVF than in ICSI cycles but there were no significant differences in the clinical pregnancies or in the miscarriage rates. The rates of formation of blastocyst and of blastocysts with good morphology were significantly higher from good-morphology embryos than from poor-morphology embryos. Nevertheless, 16.9% of the poor-morphology embryos reached the blastocyst stage. The total rates of blastocyst formation, and rates of clinical pregnancy and implantation were statistically similar in the age <35, 35-39, and >39 year groups, although tending to decrease with increasing age. When equal numbers of embryos were transferred on day 3, the rates of clinical pregnancy and implantation after blastocyst transfer were significantly higher in the <35 year age group than in the 35-39 and >39 year age groups, which were not significantly different. The miscarriage rates after embryo or blastocyst transfers were not statistically different in groups of similar age. Therefore, extended embryo culture up to the blastocyst stage could be implemented for women aged younger than 35 years to increase the pregnancy rate. For older women, transfer and vitrification of available embryos at day 3 and extended culture of morphologically poor embryos to the blastocyst stage for cryopreservation may improve the clinical outcome.

  12. Late-stage clinical development in lower urogenital targets: sexual dysfunction

    PubMed Central

    Azam, Usman

    2006-01-01

    In recent years, late-stage clinical drug development that primarily focuses on urogenital targets has centered around four areas of medical need (both unmet need and aiming to improve on existing therapies). These include male sexual dysfunction (MSD), female sexual dysfunction (FSD), prostatic pathology (neoplastic, pre-neoplasitic, and non-neoplastic), and improvement in lower urinary tract symptoms. Despite the regulatory approval of compounds to treat erectile dysfunction (ED), benign prostatic hyperplasia, a number of treatments for overactive bladder, and stress urinary incontinence, there remains a deficiency in addressing a number of conditions that arise out of pathophysiological dysfunction resulting in lower urogenital tract sexual conditions. In terms of late-stage clinical development, significant progress has most recently been made in MSD development, especially in understanding further a common and complex sexual dysfunction – that of premature ejaculation. The search also continues for compounds that improve ED in terms of better efficacy and superior safety profile compared to the currently marketed phosphodiesterase-5-inhibitors. Whilst there are no approved medications to treat the subtypes of FSD, there has been significant progress in attempting to better understand how to appropriately assess treatment benefit in clinical trial settings for this difficult to diagnose and treat condition. This review will focus on late-stage human clinical development pertaining to MSD and FSD. PMID:16465180

  13. Survival of enteric pathogens during butterhead lettuce growth: crop stage, leaf age, and irrigation.

    PubMed

    Van der Linden, Inge; Cottyn, Bart; Uyttendaele, Mieke; Vlaemynck, Geertrui; Heyndrickx, Marc; Maes, Martine

    2013-06-01

    The survival of Salmonella enterica serovar Thompson and Escherichia coli O157 was investigated on growing butterhead lettuce plants in the plant-growth chamber and greenhouse. All inoculation tests were made under conditions that approximate the greenhouse conditions for butterhead lettuce cultivation in Flanders (Belgium). The survival and proliferation of the pathogens on the leaves was determined at days 0, 4, and 8 after inoculation using standard plating techniques on selective medium. In the growth chamber, the extent to which both pathogens were able to multiply on the lettuce leaves was influenced by crop stage and leaf age. On young plants, the older leaves supported pathogen survival better. On nearly mature plants, pathogen population sizes were significantly higher on the old and young leaves compared with middle-aged leaves (p<0.001). In the greenhouse, the environmental regimen with high fluctuations in temperature and relative humidity was less conducive to the survival of E. coli O157, though its survival on nearly mature lettuce was enhanced by overhead irrigation. The moist conditions between the folded inner leaves are likely contributing to the survival of enteric pathogens in the lettuce head. Butterhead lettuce grown in greenhouses with a sprinkle irrigation system may present a potential health hazard when contaminated near harvest. Experimental design (growth chamber versus greenhouse) largely influences enteric pathogen behavior on growing lettuce plants.

  14. Neoadjuvant Chemoradiation Therapy Is Beneficial for Clinical Stage T2 N0 Esophageal Cancer Patients Due to Inaccurate Preoperative Staging

    PubMed Central

    Zhang, Jennifer Q.; Hooker, Craig M.; Brock, Malcolm V.; Shin, James; Lee, Sue; How, Remealle; Franco, Noreli; Prevas, Helen; Hulbert, Alicia; Yang, Stephen C.

    2014-01-01

    Background It remains unclear if patients with clinical stage T2 N0 (cT2 N0) esophageal cancer should be offered induction therapy vs surgical intervention alone. Methods This was a retrospective cohort study of cT2 N0 patients undergoing induction therapy, followed by surgical resection, or resection alone, at the Johns Hopkins Hospital from 1989 to 2009. Kaplan-Meier analysis was used to compare all-cause mortality in cT2 N0 patients who had resection alone vs those who had induction chemoradiation therapy, followed by resection. Results A study cohort of 69 patients was identified and divided into two groups: 55 patients (79.7%) received induction therapy and 14 (20.3%) did not. No statistically significant difference in 5-year survival rate was observed for the two groups: 49.5% for the resection-only group and 53.8% for the induction group. More than 50% of cT2 N0 patients were understaged. Conclusions For cT2 N0 esophageal cancer patients, the benefit of neoadjuvant therapy is still unclear. Induction therapy for cT2 N0 did not translate into a statistically significant improvement in survival. However, due to the significant understaging of T2 N0 patients, we recommend neoadjuvant therapy to all cT2N0 patients before operation. PMID:22269708

  15. Screening accuracy of the parent-completed Ages and Stages Questionnaires - second edition as a broadband screener for motor problems in preschoolers with autism spectrum disorders.

    PubMed

    Vanvuchelen, Marleen; Van Schuerbeeck, Lise; Braeken, Marijke Aka

    2017-01-01

    Children with autism spectrum disorders are at risk for motor problems. However, this area is often overlooked in the developmental evaluation in autism diagnostic clinics. An alternative can be to identify children who should receive intensive motor assessment by using a parent-based screener. The aim of this study was to examine whether the Ages and Stages Questionnaires - second edition may be used to identify gross and fine motor problems in children. High-functioning children with autism spectrum disorder (n = 43, 22-54 m) participated in this study. Sensitivity, specificity, predictive values and areas under the receiver operating characteristic curve were calculated by comparing the Ages and Stages Questionnaires - second edition scores to the developmental evaluation of the Peabody Developmental Motor Scale - second edition. The results revealed that both the Ages and Stages Questionnaires - second edition gross and fine motor domain may be used to identify children without motor problems. In contrast, sensitivity analyses revealed the likelihood of under screening motor problems in this population. The Ages and Stages Questionnaires - second edition met only the criteria of a fair to good accuracy to identify poor gross motor (sensitivity = 100%) and below-average fine motor development (sensitivity = 71%) in this sample. Hence, the capacity of the Ages and Stages Questionnaires - second edition to identify motor problems in preschoolers with autism spectrum disorder appears to be limited. It is recommended to include a formal standardized motor test in the diagnostic procedure for all children with autism spectrum disorder.

  16. Age matters: Developmental stage of Danio rerio larvae influences photomotor response thresholds to diazinion or diphenhydramine

    PubMed Central

    Kristofco, Lauren A.; Cruz, Luis Colon; Haddad, Samuel P.; Behra, Martine L; Chambliss, C. Kevin; Brooks, Bryan W.

    2016-01-01

    Because basic toxicological data is unavailable for the majority of industrial compounds, High Throughput Screening (HTS) assays using the embryonic and larval zebrafish provide promising approaches to define bioactivity profiles and identify potential adverse outcome pathways for previously understudied chemicals. Unfortunately, standardized approaches, including HTS experimental designs, for examining fish behavioral responses to contaminants are rarely available. In the present study, we examined movement behavior of larval zebrafish over 7 days (4–10 days post fertilization or dpf) during typical daylight workday hours to determine whether intrinsic activity differed with age and time of day. We then employed an early life stage approach using the Fish Embryo Test (FET) at multiple developmental ages to evaluate whether photomotor response (PMR) behavior differed with zebrafish age following exposure to diazinon (DZN), a well-studied orthophosphate insecticide, and diphenhydramine (DPH), an antihistamine that also targets serotonin reuptake transporters and the acetylcholine receptor. 72 h studies were conducted at 1–4, 4–7 and 7–10 dpf, followed by behavioral observations using a ViewPoint system at 4, 7 and 10 dpf. Distance traveled and swimming speeds were quantified; nominal treatment levels were analytically verified by isotope-dilution LC-MSMS. Larval zebrafish locomotion displayed significantly different (p < 0.05) activity profiles over the course of typical daylight and workday hours, and these time of day PMR activity profiles were similar across ages examined (4–10 dpf). 10 dpf zebrafish larvae were consistently more sensitive to DPH than either the 4 or 7 dpf larvae with an environmentally realistic lowest observed effect concentration of 200 ng/L. Though ELS and FET studies with zebrafish typically focus on mortality or teratogenicity in 0–4 dpf organisms, behavioral responses of slightly older fish were several orders of magnitude more

  17. Age matters: Developmental stage of Danio rerio larvae influences photomotor response thresholds to diazinion or diphenhydramine.

    PubMed

    Kristofco, Lauren A; Cruz, Luis Colon; Haddad, Samuel P; Behra, Martine L; Chambliss, C Kevin; Brooks, Bryan W

    2016-01-01

    Because basic toxicological data is unavailable for the majority of industrial compounds, High Throughput Screening (HTS) assays using the embryonic and larval zebrafish provide promising approaches to define bioactivity profiles and identify potential adverse outcome pathways for previously understudied chemicals. Unfortunately, standardized approaches, including HTS experimental designs, for examining fish behavioral responses to contaminants are rarely available. In the present study, we examined movement behavior of larval zebrafish over 7 days (4-10 days post fertilization or dpf) during typical daylight workday hours to determine whether intrinsic activity differed with age and time of day. We then employed an early life stage approach using the Fish Embryo Test (FET) at multiple developmental ages to evaluate whether photomotor response (PMR) behavior differed with zebrafish age following exposure to diazinon (DZN), a well-studied orthophosphate insecticide, and diphenhydramine (DPH), an antihistamine that also targets serotonin reuptake transporters and the acetylcholine receptor. 72h studies were conducted at 1-4, 4-7 and 7-10dpf, followed by behavioral observations using a ViewPoint system at 4, 7 and 10dpf. Distance traveled and swimming speeds were quantified; nominal treatment levels were analytically verified by isotope-dilution LC-MSMS. Larval zebrafish locomotion displayed significantly different (p<0.05) activity profiles over the course of typical daylight and workday hours, and these time of day PMR activity profiles were similar across ages examined (4-10dpf). 10dpf zebrafish larvae were consistently more sensitive to DPH than either the 4 or 7dpf larvae with an environmentally realistic lowest observed effect concentration of 200ng/L. Though ELS and FET studies with zebrafish typically focus on mortality or teratogenicity in 0-4dpf organisms, behavioral responses of slightly older fish were several orders of magnitude more sensitive to DPH. Our

  18. Early-Stage Breast Cancer in the Octogenarian: Tumor Characteristics, Treatment Choices, and Clinical Outcomes

    PubMed Central

    Mamtani, Anita; Gonzalez, Julie J.; Neo, Dayna; Slanetz, Priscilla J.; Houlihan, Mary Jane; Herold, Christina I.; Recht, Abram; Hacker, Michele R.; Sharma, Ranjna

    2016-01-01

    Background Nodal staging with sentinel node biopsy (SLNB), post-lumpectomy radiotherapy (RT), and endocrine therapy (ET) for estrogen receptor-positive (ER+) tumors is valuable in the treatment of early-stage (stages 1 or 2) breast cancer but used less often for elderly women. Methods This retrospective study investigated women referred for surgical evaluation of biopsy-proven primary early-stage invasive breast cancer from January 2001 to December 2010. Clinicopathologic features, treatment course, and outcomes for women ages 80–89 years and 50–59 years were compared. Results The study identified 178 eligible women ages 80–89 years and 169 women ages 50–59 years. The elderly women more often had grade 1 or 2 disease (p = 0.003) and ER+ tumors (p = 0.007) and less frequently had undergone adjuvant therapies (all p ≤ 0.001). Lumpectomy was performed more commonly for the elderly (92 vs. 83 %, p = 0.02), and axillary surgery was less commonly performed (46 vs. 96 %; p < 0.001). Fewer elderly women had undergone post-lumpectomy RT (42 vs. 89 %; p < 0.001) and ET for ER+ tumors (72 vs. 95 %; p < 0.001). During the median follow-up period of 56 months for the 80- to 89-year old group and 98 months for the 50- to 59-year-old group, death from breast cancer was similar (4 vs. 5 %; p = 0.5). The two groups respectively experienced 7 versus 6 locoregional recurrences and 11 versus 13 distant recurrences. Conclusions The octogenarians had disease survivorship similar to that of the younger women despite less frequent use of adjuvant therapies, likely reflecting lower-risk disease features. Whether increased use of axillary surgery, post-lumpectomy RT, and/or ET for ER+ tumors would further improve outcomes is an important area for further study, but treatment should not be deferred solely on the basis of age. PMID:27364507

  19. Does Islamic spiritual program lead to successful aging? A randomized clinical trial

    PubMed Central

    Moeini, Mahin; Sharifi, Somaye; Zandiyeh, Zahra

    2016-01-01

    Context: Successful aging is a pattern of aging that has gained much attention during recent years. One factor that has a negative impact on successful aging variables is hypertension. The phenomenon of aging when accompanied with hypertension promotes spiritual needs. The aim of this study was to examine the effect of the Islamic spiritual program on successful aging in elderly patients with hypertension who were referred to health centers of Isfahan, Iran, in 2014. Settings and Design: This study was a randomized clinical trial. Materials and Methods: The participants (52 elderly patients with hypertension) were randomly divided into experimental and control groups. While the control group received training related to health promotion, the Islamic spiritual program was implemented in the experimental group for eight sessions in two health centers of Isfahan. The data collection tools consisted of the 12-item General Health Questionnaire developed by Goldberg and the satisfaction with life scale developed by Diener. The questionnaires were completed in three steps; pretest, posttest, and follow-up (1-month). Statistical Analysis Used: Data were analyzed using SPSS statistical software version 20 and Chi-square, independent t-test, and repeated measures ANOVA. Results: Statistical tests showed that the mean score of general health and life satisfaction of the experiment group had a meaningful difference from that of the control group in the posttest stage (P < 0.001). This difference was also meaningful in the follow-up stage (P < 0.001). Conclusion: The results of the study indicated the effectiveness of an Islamic spiritual program on successful aging variables. PMID:27512694

  20. Correlation analysis of urine metabolites and clinical staging in patients with ovarian cancer

    PubMed Central

    Jiang, Ting; Lin, Yunliang; Yin, Haiqin; Wang, Shanshan; Sun, Qinglei; Zhang, Peihai; Bi, Wenxiang

    2015-01-01

    This study is to investigate the correlation between urine metabolites and clinical staging in patients with ovarian cancer. The urina sanguinis from 56 cases of primary epithelial ovarian cancer patients and 15 healthy volunteers was collected and the urine metabolites were extracted. Ultra high performance liquid chromatography/time-of-flight mass spectrometry (UPLC-Q-TOF-MS) analysis was performed. Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were used to analyze the mass spectrometry data. Database retrieval and comparison of the screened metabolites were performed and one-way ANOVA and least significant difference (LSD) t test were carried out. PCA analysis of UPLC-Q-TOF-MS results showed that the score plots of samples from healthy people and patients with ovarian cancer at different clinical stages were separated. Further PLS-DA analysis significantly improved the classification results. The R2X was 0.757, the R2Y was 0.977 and the Q2Y was 0.87, indicating that the model stability and predictability were good. Eight metabolites, including N-acetylneuraminic acid-9-phosphate, 5’-methioadenosine, uric acid-3-nucleoside, pseudouridine, L-valine, succinic acid, L-proline and β-nicotinamide mononucleotide were identified. The contents of these metabolites increased with the development of the disease. There was correlation between urine metabolites and clinical staging in patients with ovarian cancer. PMID:26770415

  1. Lymph node metastasis and pattern of recurrence in clinically early stage endometrial cancer with positive lymphovascular space invasion

    PubMed Central

    Jernigan, Amelia; Nutter, Benjamin; Michener, Chad; Rose, Peter G.

    2015-01-01

    Objective To investigate the rate, predictors of lymph node metastasis (LNM) and pattern of recurrence in clinically early stage endometrial cancer (EC) with positive lymphovascular space invasion (LVSI). Methods Women with clinically early stage EC and positive LVSI 2005 to 2012 were identified. Kaplan-Meier curves and logistic regression models were used. Results One hundred forty-eight women were identified. Of them, 25.7% had LNM (21.7% pelvic LNM, 18.5% para-aortic LNM). Among patients with LNM who had both pelvic and para-aortic lymphadenectomy, isolated pelvic, para-aortic and both LNM were noted in 51.4%, 17.1%, and 31.4% respectively. Age and depth of myometrial invasion were significant predictors of LNM in LVSI positive EC. Node positive patients had high recurrence rate (47% vs. 11.8%, p<0.05) especially distant (60.9% vs. 7.9%, p<0.001) and para-aortic (13.2% vs. 1.8%, p=0.017) recurrences compared to node negative EC. LNM was associated with lower progression-free survival (p=0.002) but not overall survival (p=0.73). Conclusion EC with positive LVSI is associated with high risk of LNM. LNM is associated with high recurrence rate especially distant and para-aortic recurrences. Adjuvant treatments should target prevention of recurrences in these areas. PMID:25686395

  2. ADAPTING A PARENT-COMPLETED, SOCIOEMOTIONAL QUESTIONNAIRE IN CHINA: THE AGES & STAGES QUESTIONNAIRES: SOCIAL-EMOTIONAL.

    PubMed

    Bian, Xiaoyan; Xie, Huichao; Squires, Jane; Chen, Chieh-Yu

    2017-03-01

    The Ages & Stages Questionnaire: Social-Emotional (ASQ:SE; Squires, Bricker, & Twombly, 2002a), developed in the United States, was translated and adapted for use in China. Lack of valid and reliable instruments for identifying social and emotional delays in young children is a worldwide issue. Professionals in China have recently focused efforts on developing methods for early identification of social, emotional, and behavioral issues in the birth-to-5 population. Following the guidelines of the International Test Commission, the ASQ:SE was translated into Simplified Chinese (ASQ:SE-C) to collect a normative sample of 2,528 children across China. Data were analyzed to evaluate the psychometric properties of the ASQ:SE-C, using both classical test theory and item response theory, including generating cutoff points appropriate for the Chinese sample. A panel of Chinese experts was surveyed to assess face validity and estimated utility of the newly adapted tool. Discussions of research findings and implications for future studies are provided.

  3. Clinical Presentation of Klinefelter's Syndrome: Differences According to Age

    PubMed Central

    Pacenza, Néstor; Pasqualini, Titania; Gottlieb, Silvia; Knoblovits, Pablo; Costanzo, Pablo R.; Stewart Usher, Jorge; Rey, Rodolfo A.; Martínez, María P.; Aszpis, Sergio

    2012-01-01

    The aim of the study was to establish the characteristics of presentation of 94 patients with Kinelfelter's syndrome (KS) referred to the endocrinologist at different ages. The diagnosis of KS was more frequent in the age group between 11 and 20 years (46.8%). Most of the patients (83.7%) showed the classic 47,XXY karyotype and 7.1% showed a 47,XXY/46,XY mosaicism. Half of the patients younger than 18 years presented mild neurodevelopmental disorders. The most frequent clinical findings were cryptorchidism in prepubertal patients, and small testes, cryptorchidism, and gynecomastia in pubertal patients. FSH, LH, AMH, and inhibin B levels were normal in prepubertal patients and became abnormal from midpuberty. Most adults were referred for small testes, infertility, and gynecomastia; 43.6% had sexual dysfunction. Testosterone levels were low in 45%. Mean stature was above the 50th percentile, and 62.5% had BMI ≥25.0 kg/m2. In conclusion, the diagnosis of Klinefelter syndrome seems to be made earlier nowadays probably because pediatricians are more aware that boys and adolescents with neuro-developmental disorders and cryptorchidism are at increased risk. The increasing use of prenatal diagnosis has also decreased the mean age at diagnosis and allowed to get insight into the evolution of previously undiagnosed cases, which probably represent the mildest forms. In adults average height and weight are slightly higher than those in the normal population. Bone mineral density is mildly affected, more at the spine than at the femoral neck level, in less than half of cases. PMID:22291701

  4. Sub-Clinical Cognitive Decline and Resting Cerebral Blood Flow in Middle Aged Men

    PubMed Central

    Henriksen, Otto Mølby; Hansen, Naja Liv; Osler, Merete; Mortensen, Erik Lykke; Hallam, Dorte Merete; Pedersen, Esben Thade; Chappell, Michael; Lauritzen, Martin Johannes; Rostrup, Egill

    2017-01-01

    Background Although dementia is associated with both global and regional cerebral blood flow (CBF) changes, little is known about cerebral perfusion in the early pre-clinical stages of cognitive decline preceding overt cognitive dysfunction. The aim of this study was to investigate the association of early sub-clinical cognitive decline with CBF. Materials and Methods The study participants were recruited from a cohort of Danish men born in 1953. Based on a regression model we selected men who performed better (Group A, n = 94) and poorer (Group B, n = 95) on cognitive testing at age 57 than expected from testing at age 20. Participants underwent supplementary cognitive testing, blood sampling and MRI including measurements of regional and global CBF. Results Regional CBF was lower in group B than in group A in the posterior cingulate gyrus and the precuneus. The associations were attenuated when corrected for global atrophy, but remained significant in regions of interest based analysis adjusting for regional gray matter volume and vascular risk factors. No influence of group on global CBF was observed. Conclusions We conclude that early sub-clinical cognitive decline is associated with reduced perfusion in the precuneus and posterior cingulate gyrus independently of regional atrophy and vascular risk factors, but cannot be statistically separated from an association with global atrophy. PMID:28095458

  5. A Multidisciplinary Sepsis Program Enabled by a Two-Stage Clinical Decision Support System: Factors That Influence Patient Outcomes.

    PubMed

    Amland, Robert C; Haley, James M; Lyons, Jason J

    2016-11-01

    Sepsis is an inflammatory response triggered by infection, with risk of in-hospital mortality fueled by disease progression. Early recognition and intervention by multidisciplinary sepsis programs may reverse the inflammatory response among at-risk patient populations, potentially improving outcomes. This retrospective study of a sepsis program enabled by a 2-stage sepsis Clinical Decision Support (CDS) system sought to evaluate the program's impact, identify early indicators that may influence outcomes, and uncover opportunities for quality improvement. Data encompassed 16 527 adult hospitalizations from 2014 and 2015. Of 2108 non-intensive care unit patients screened-in by sepsis CDS, 97% patients were stratified by 177 providers. Risk of adverse outcome improved 30% from baseline to year end, with gains materializing and stabilizing at month 7 after sepsis program go-live. Early indicators likely to influence outcomes include patient age, recent hospitalization, electrolyte abnormalities, hypovolemic shock, hypoxemia, patient location when sepsis CDS activated, and specific alert patterns.

  6. Circulation of HIV antigen in blood according to stage of infection, risk group, age and geographic origin.

    PubMed

    Goudsmit, J; Paul, D A

    1987-12-01

    Human immunodeficiency virus antigen (HIV-ag) was determined by enzyme immunoassay (EIA) in HIV-antibody (anti-HIV) positive as well as pre-anti-HIV seroconversion sera and the results analysed according to stage of infection, risk group, age and geographic origin. Eleven (19%) of 58 homosexual men tested showed HIV-ag in a serum taken 3-4 months before or one at the time of anti-HIV seroconversion. In another eight (14%) HIV-ag persisted after seroconversion and half of them developed AIDS or AIDS-related complex (ARC) in contrast to none of the other 50 anti-HIV seroconversions. Two (13%) of 16 haemophiliacs tested had HIV-ag only in the first anti-HIV seropositive sample. HIV-ag was present in 86% (30/35) of Dutch homosexual men with AIDS, in 32% (7/22) of men with ARC and in 17% (24/145) of men with persistent generalized lymphadenopathy (PGL) or without symptoms. Three percent (2/60) of sera of asymptomatic i.v. drug users from Amsterdam were HIV-ag positive. Ten percent (1 of 10) of sera from Central Africans with 'Slim Disease' were HIV-ag positive. Among infected children from the USA or Europe 89-100% (8/9 and 2/2) of AIDS cases, 67-100% (6/9 and 3/3) of children with ARC and 75% (3/4) of asymptomatic children were HIV-ag positive. The HIV-ag EIA appears to be able to identify HIV infection earlier than the available anti-HIV assays in a significant number of cases. Since persistence of HIV-ag, except possibly in African cases, is strongly associated with clinical deterioration, HIV-ag appears to be a suitable marker for, independent of their clinical status, selecting individuals for antiviral therapy and also for monitoring the efficiency of such therapy.

  7. Disability Stage Is an Independent Risk Factor for Mortality in Medicare Beneficiaries 65 Years of Age and Older

    PubMed Central

    Hennessy, Sean; Kurichi, Jibby E.; Pan, Qiang; Streim, Joel E.; Bogner, Hillary; Xie, Dawei; Stineman, Margaret G.

    2015-01-01

    Background Stages of activity limitation based on activities of daily living (ADLs) and instrumental activities of daily living (IADLs) have been found to predict mortality in those age 70 years and above but have not been examined in Medicare beneficiaries age 65 years and older using routinely collected data. Objective To examine the association between functional stages based on activities of ADLs and IADLs with three-year mortality in Medicare beneficiaries age 65 years and older, accounting for baseline sociodemographics, heath status, smoking, subjective health, and psychological well-being. Design Cohort study using the Medicare Current Beneficiary Survey (MCBS) and associated health care utilization data. Setting Community administered survey. Participants We included 9698 Medicare beneficiaries 65 years of age and older who entered the MCBS in 2005–07. Main outcome measures Death within three years of cohort entry. Results The overall mortality rate was 3.6 per 100 person years, and three-year cumulative mortality was 10.3%. Unadjusted three-year mortality was monotonically associated with both ADL stage and IADL stag. Adjusted three-year mortality was associated with ADL and IADL stages, except that in some models the hazard ratio for stage III (which includes persons with atypical activity limitation patterns) was numerically lower than that for stage II. Conclusion We found nearly monotonic relationships between ADL and IADL stage and adjusted three-year mortality. These findings could aid in the development of population health approaches and metrics for evaluating the success of alternative economic, social, or health policies on the longevity of older adults with activity limitations. PMID:26003869

  8. Diagnostic Value of Clinical T Staging Assessed by Endoscopy and Stomach Protocol Computed Tomography in Gastric Cancer: The Experience of a Low-Volume Institute

    PubMed Central

    Kim, Tae Hyeon; Kim, Jeong Jae; Kim, Seung Hyoung; Kim, Bong Soo; Song, Hyun Joo; Na, Soo Young; Boo, Sun Jin; Kim, Heung Up; Maeng, Young Hee; Hyun, Chang Lim; Kim, Kwang Sig

    2012-01-01

    Purpose Clinical staging of gastric cancer appears to be important more and more for tailored therapy. This study aimed to verify the accuracy of clinical T staging in a low-volume institute. Materials and Methods We retrospectively reviewed prospectively collected data of gastric cancer patients who underwent resection. A total of 268 patients of gastric cancer were enrolled from March 2004 to June 2012. These demographics, tumor characteristics, and clinical stages were analyzed for identification of diagnostic value of clinical T staging. Results The predictive values for pT1 of endoscopy and computed tomography were 90.0% and 89.4%, respectively. In detail, the predictive values of endoscopy for pT1a, pT1b, and pT2 or more were 87%, 58.5%, and 90.6%, respectively. The predictive values of computed tomography for pT1a, pT1b, and pT2 or more were 68.8%, 73.9%, and 84.4%, respectively. The factors leading to underestimation of pT2 or more lesions by gastroscopy were the middle third location, the size greater than 2 cm, and younger age. Those for overestimation of pT1 lesion by computed tomography were male, age more than 70 years, elevated type, and size greater than 3 cm. Conclusions Diagnostic accuracy of early gastric cancer was 90%, which is comparable to those of high volume center. In patients with early gastric cancer, limited gastrectomy or minimal invasive surgery can be safely introduced at a low volume center also. However, the surgeon of low-volume institute should consider the accuracy of clinical staging before extending the indication of limited treatment. PMID:23346494

  9. Single-stage osseointegrated implants for nasal prosthodontic rehabilitation: A clinical report.

    PubMed

    de Carvalho, Bruna M D F; Freitas-Pontes, Karina M; de Negreiros, Wagner A; Verde, Marcus A R L

    2015-08-01

    Malignant tumors in the nasal region may be treated by means of invasive surgical procedures, with large facial losses. Nasal prostheses, retained by osseointegrated facial implants, instead of plastic surgery, will, in most patients, offer good biomechanical and cosmetic results. This clinical report describes the prosthetic rehabilitation of a patient with nasal cancer who had the entire nasal vestibule removed in a single-stage surgical procedure in order to shorten the rehabilitation time. The nasal prosthesis was built on a 3-magnet bar and was made of platinum silicone with intrinsic pigmentation, thereby restoring the patient's appearance and self-esteem. The authors concluded that single-stage implants may reduce the rehabilitation time to as little as 1 month, and the correct use of materials and techniques may significantly improve the nasal prosthesis.

  10. Heterogeneity of Parkinson's disease in the early clinical stages using a data driven approach

    PubMed Central

    Lewis, S; Foltynie, T; Blackwell, A; Robbins, T; Owen, A; Barker, R

    2005-01-01

    Objective: To investigate the heterogeneity of idiopathic Parkinson's disease (PD) in a data driven manner among a cohort of patients in the early clinical stages of the disease meeting established diagnostic criteria. Methods: Data on demographic, motor, mood, and cognitive measures were collected from 120 consecutive patients in the early stages of PD (Hoehn and Yahr I–III) attending a specialist PD research clinic. Statistical cluster analysis of the data allowed the existence of the patient subgroups generated to be explored. Results: The analysis revealed four main subgroups: (a) patients with a younger disease onset; (b) a tremor dominant subgroup of patients; (c) a non-tremor dominant subgroup with significant levels of cognitive impairment and mild depression; and (d) a subgroup with rapid disease progression but no cognitive impairment. Conclusions: This study complements and extends previous research by using a data driven approach to define the clinical heterogeneity of early PD. The approach adopted in this study for the identification of subgroups of patients within Parkinson's disease has important implications for generating testable hypotheses on defining the heterogeneity of this common condition and its aetiopathological basis and thus its treatment. PMID:15716523

  11. Increased Serum Insulin Exposure Does Not Affect Age or Stage of Pancreatic Adenocarcinoma Diagnosis in Patients with Diabetes Mellitus

    PubMed Central

    Chao, David T.; Shah, Nilesh H.; Zeh, Herbert J.; Bahary, Nathan; Whitcomb, David C.; Brand, Randall E.

    2015-01-01

    Objectives In considering whether medications that increase insulin levels accelerate pancreatic adenocarcinoma (PC) development, we hypothesized that PC patients with diabetes mellitus (DM) who used exogenous insulin or insulin-stimulating medications should have an earlier age of diagnosis or present with more advanced disease. Methods Patients enrolled in our PC registry from 6/1/2003 to 5/31/2012 were stratified according to treatment solely with insulin, insulin-stimulating medications, or insulin-independent medications. Age of PC diagnosis, PC stage, and years between DM and PC diagnoses were analyzed among the cohorts. Results Of 122 DM patients (mean age: 67.4 ± 10.2 years), the mean age of PC diagnosis within the insulin-only (n=40), insulin-stimulating (n=11), insulin-independent (n=71), and non-DM (n=321) cohorts were 68.7 ± 10.5 years, 69.6 ± 10.8 years, 66.3 ± 9.7 years, and 65.5 ± 10.5 years, respectively. No significant difference among the age of PC diagnosis was observed based on duration or type of DM treatment. There was no correlation between PC stage and increased insulin exposure. Conclusions Anti-DM medications that increase exposure to insulin do not appear to accelerate PC development using outcomes of mean age of PC diagnosis, PC stage, or duration between DM and PC diagnoses. PMID:26418902

  12. Testosterone related to age and life-history stages in male baboons and geladas

    PubMed Central

    Beehner, Jacinta C.; Gesquiere, Laurence; Seyfarth, Robert M.; Cheney, Dorothy L.; Alberts, Susan C.; Altmann, Jeanne

    2013-01-01

    Despite significant advances in our knowledge of how testosterone mediates life-history trade-offs, this research has primarily focused on seasonal species. We know comparatively little about the relationship between testosterone and life-history stages for non-seasonally breeding species. Here we examine testosterone profiles across the lifespan of males from three non-seasonally breeding primates: yellow baboons (Papio cynocephalus or P. hamadryas cynocephalus), chacma baboons (Papio ursinus or P. h. ursinus), and geladas (Theropithecus gelada). First, we predict that testosterone profiles will track the reproductive profiles of each taxon across their respective breeding years. Second, we evaluate age-related changes in testosterone to determine whether several life-history transitions are associated with these changes. Subjects include males (>2.5 years) from wild populations of each taxon from whom we had fecal samples for hormone determination. Although testosterone profiles across species were broadly similar, considerable variability was found in the timing of two major changes: (1) the attainment of adult levels of testosterone, and (2) the decline in testosterone after the period of maximum production. Attainment of adult testosterone levels was delayed by one year in chacmas compared with yellows and geladas. With respect to the decline in testosterone, geladas and chacmas exhibited a significant drop after three years of maximum production, while yellows declined so gradually that no significant annual drop was ever detected. For both yellows and chacmas, increases in testosterone production preceded elevations in social dominance rank. We discuss these differences in the context of ecological and behavioral differences exhibited by these taxa. PMID:19712676

  13. Clinical outcomes of stage I endometrial carcinoma patients treated with surgery alone: Siriraj Hospital experiences

    PubMed Central

    2016-01-01

    Objective To evaluate the recurrence rates and patterns of failure in patients with stage I endometrial carcinoma after surgical staging without adjuvant therapy. Methods Medical records of 229 patients with stage I endometrial carcinoma, treated with surgery alone between 2002 and 2010 at Siriraj Hospital were retrospectively reviewed. The primary objective of this study was recurrence rates. The secondary objectives were patterns of failure, disease-free survival, overall survival, and prognostic factors related to outcomes. Results During median follow-up time of 53.3 months, 11 recurrences (4.8%) occurred with a median time to recurrence of 21.2 months (range, 7.7 to 77.8 months). Vaginal recurrence was the most common pattern of failure (8/11 patients, 72.7%). Other recurrences were pelvic, abdominal and multiple metastases. Factors that appeared to be prognostic factors on univariate analyses were age and having high intermediate risk (HIR) (Gynecologic Oncology Group [GOG] 99 criteria), none of which showed significance in multivariate analysis. The recurrence rates were higher in the patients with HIR criteria (22.2% vs. 4.1%, p=0.013) or patients with stage IB, grade 2 endometrioid carcinoma (9.4% vs. 4.3%, p=0.199). Five-year disease-free survival and 5-year overall survival were 93.9% (95% CI, 89.9 to 5.86) and 99.5% (95% CI, 97.0 to 99.9), respectively. Conclusion The patients with low risk stage I endometrial carcinoma had excellent outcomes with surgery alone. Our study showed that no single factor was demonstrated to be an independent predictor for recurrence. PMID:27329196

  14. An evaluation of a Simon 2-Stage phase II clinical trial design incorporating toxicity monitoring.

    PubMed

    Ray, H E; Rai, S N

    2011-05-01

    Phase II clinical trials are usually designed to measure efficacy but patient safety is also a very important aspect. Previous authors suggested a methodology that allows one to monitor the cumulative number of toxic events after each patient is treated, which is also known as continuous toxicity monitoring. In this work we describe how to combine the continuous toxicity monitoring methodology with the Simon 2-Stage design for response. Then we investigate through simulation the combined procedure's type I and type II error rates under various combinations of design parameters. We include the underlying relationship between toxicity and response in our examination of the error rates.

  15. Validity of the Fine Motor Area of the 12-Month Ages and Stages Questionnaire in Infants Following Major Surgery

    ERIC Educational Resources Information Center

    Smith, Cally; Wallen, Margaret; Walker, Karen; Bundy, Anita; Rolinson, Rachel; Badawi, Nadia

    2012-01-01

    The Ages and Stages Questionnaires (ASQ) are parent-report screening tools to identify infants at risk of developmental difficulties. The purpose of this study was to examine validity and internal reliability of the fine motor developmental area of the ASQ, 2nd edition (ASQ2-FM) for screening 12-month-old infants following major surgery. The…

  16. Osteonecrosis of Femoral Head Treated with Extracorporeal Shock Wave Therapy: Analysis of Short-term Clinical Outcomes of Treatment with Radiologic Staging

    PubMed Central

    Lee, Jin-Young; Kwon, Jae-Woo; Park, Jung-Seob; Han, Kyeol; Shin, Woo-jin; Lee, Jeong-Gil

    2015-01-01

    Purpose To evaluate clinical results of extracorporeal shock wave therapy (ESWT) with radiographic staging on patients with avascular necrosis of femoral head (AVNFH). Materials and Methods We evaluated 24 patients diagnosed with AVNFH (32 hip joints) who were treated with ESWT from 1993 to 2012. Average follow-up period was 27 months, and the average age of patients was 47.8 years. The Association Research Circulation Osseous (ARCO) system was used to grade radiographic stage prior to treatment. For this study patients were divided into two groups based on their ARCO stage, group 1 (ARCO stages I and II) and group 2 (ARCO stage III). Comparative analyses were done between the two groups using the visual analogue scale (VAS) score and the Harris hip score (HHS) at pre-treatment and 3, 6, 12, and 24 months after treatment. Failure was defined when radiographic stage progressed or arthroplasty surgery was needed due to clinical exacerbation. Results Both groups showed clinical improvements with VAS scoring at final follow-up (group 1: median 7 to 1.5, P<0.001; group 2: mean 7 to 4, P=0.056). Using HHS, group 1 showed a significant improvement (from 65.5 to 95 [P<0.001]), while no significance was observed for group 2 (P=0.280). At final follow-up, 3 hips from group 1 and one hip from group 2 showed radiographic improvement; however, two patients underwent total hip arthroplasty due to persistent pain and dysfunction. Conclusion ESWT can be considered as an interventional option before surgical treatment in patients with not only early stage AVNFH but also with mid stage. PMID:27536633

  17. Public funding of clinical-stage antibiotic development in the United States and European Union.

    PubMed

    Eichberg, Michael J

    2015-01-01

    The health and national security challenge of antibiotic resistance has led governments to adopt policies to stimulate new antibiotic R&D. Government programs that directly fund late-stage clinical development of antibiotics have emerged, including the Broad Spectrum Antimicrobial Program of the Biomedical Advanced Research and Development Authority in the United States, and the New Drugs for Bad Bugs program of the Innovative Medicines Initiative in the European Union. These efforts are collectively investing nearly $1 billion and are supporting nearly 20% of the global antibiotic pipeline. This article describes these programs, including the antibiotics and their targeted pathogens and clinical indications, as well as program mechanisms for project eligibility, selection, governance, funding, and IP management. Preliminary assessment of the impact of these mechanisms on the success of the programs is provided.

  18. Public Funding of Clinical-Stage Antibiotic Development in the United States and European Union

    PubMed Central

    2015-01-01

    The health and national security challenge of antibiotic resistance has led governments to adopt policies to stimulate new antibiotic R&D. Government programs that directly fund late-stage clinical development of antibiotics have emerged, including the Broad Spectrum Antimicrobial Program of the Biomedical Advanced Research and Development Authority in the United States, and the New Drugs for Bad Bugs program of the Innovative Medicines Initiative in the European Union. These efforts are collectively investing nearly $1 billion and are supporting nearly 20% of the global antibiotic pipeline. This article describes these programs, including the antibiotics and their targeted pathogens and clinical indications, as well as program mechanisms for project eligibility, selection, governance, funding, and IP management. Preliminary assessment of the impact of these mechanisms on the success of the programs is provided. PMID:26042859

  19. Learning Multiple Band-Pass Filters for Sleep Stage Estimation: Towards Care Support for Aged Persons

    NASA Astrophysics Data System (ADS)

    Takadama, Keiki; Hirose, Kazuyuki; Matsushima, Hiroyasu; Hattori, Kiyohiko; Nakajima, Nobuo

    This paper proposes the sleep stage estimation method that can provide an accurate estimation for each person without connecting any devices to human's body. In particular, our method learns the appropriate multiple band-pass filters to extract the specific wave pattern of heartbeat, which is required to estimate the sleep stage. For an accurate estimation, this paper employs Learning Classifier System (LCS) as the data-mining techniques and extends it to estimate the sleep stage. Extensive experiments on five subjects in mixed health confirm the following implications: (1) the proposed method can provide more accurate sleep stage estimation than the conventional method, and (2) the sleep stage estimation calculated by the proposed method is robust regardless of the physical condition of the subject.

  20. 47,XXY Klinefelter syndrome: clinical characteristics and age-specific recommendations for medical management.

    PubMed

    Aksglaede, Lise; Link, Katarina; Giwercman, Aleksander; Jørgensen, Niels; Skakkebaek, Niels E; Juul, Anders

    2013-02-15

    47,XXY (Klinefelter syndrome) is the most frequent sex chromosomal disorder and affects approximately one in 660 newborn boys. The syndrome is characterized by varying degrees of cognitive, social, behavioral, and learning difficulties and in adulthood additionally primary testicular failure with small testes, hypergonadotropic hypogonadism, tall stature, and eunuchoid body proportions. The phenotype is variable ranging from "near-normal" to a significantly affected individual. In addition, newborns with Klinefelter syndrome generally present with a normal male phenotype and the only consistent clinical finding in KS is small testes, that are most often not identified until after puberty. Decreased awareness of this syndrome among health professionals and a general perception that all patients with 47,XXY exhibit the classic textbook phenotype results in a highly under-diagnosed condition with up to 75% of the patients left undetected. Typically, diagnosis is delayed with the majority of patients identified during fertility workup in adulthood, and only 10% of patients diagnosed prior to puberty. Early detection of this syndrome is recommended in order to offer treatment and intervention at the appropriate ages and stages of development for the purpose of preventing osteopenia/osteoporosis, metabolic syndrome, and other medical conditions related to hypogonadism and to the XXY as well as minimizing potential learning and psychosocial problems. The aim of this review is to present the clinical aspects of XXY and the age-specific recommendations for medical management. © 2013 Wiley Periodicals, Inc.

  1. Clinical and dosimetric implications of intensity-modulated radiotherapy for early-stage glottic carcinoma

    SciTech Connect

    Ward, Matthew Christopher Pham, Yvonne D.; Kotecha, Rupesh; Zakem, Sara J.; Murray, Eric; Greskovich, John F.

    2016-04-01

    Conventional parallel-opposed radiotherapy (PORT) is the established standard technique for early-stage glottic carcinoma. However, case reports have reported the utility of intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) with or without image guidance (image-guided radiotherapy, IGRT) in select patients. The proposed advantages of IMRT/VMAT include sparing of the carotid artery, thyroid gland, and the remaining functional larynx, although these benefits remain unclear. The following case study presents a patient with multiple vascular comorbidities treated with VMAT for early-stage glottic carcinoma. A detailed explanation of the corresponding treatment details, dose-volume histogram (DVH) analysis, and a review of the relevant literature are provided. Conventional PORT remains the standard of care for early-stage glottic carcinoma. IMRT or VMAT may be beneficial for select patients, although great care is necessary to avoid a geographical miss. Clinical data supporting the benefit of CRT are lacking. Therefore, these techniques should be used with caution and only in selected patients.

  2. [The preoperative staging of rectal neoplasms: the clinical exam and diagnostic imaging].

    PubMed

    Grande, M; Danza, F M

    1999-01-01

    The management of rectal cancer remains an important clinical problem. Although there was been great progress in surgical management, the survival of patients with locally advanced disease has not improved significantly during the past decades. Preoperative staging and evaluation of the risk of recurrence may help in the choice of operation. It is difficult for clinicians to quantify reliably with digital examination the degree of fixation of the tumor, and they usually cannot distinguish nodal metastases except in advanced cases. The more frequent overstaging of small tumors within one quadrant of the rectum is a major drawback of digital examination. Computed tomography and magnetic resonance seems to underestimate the extension of rectal tumors, but both can be helpful in selecting patients with advanced tumors for whom preoperative adjuvant treatment is being considered. Endoluminal ultrasound is superior in staging tumors confined to the rectal wall, but is not the ideal tool for staging: the results are examiner dependent, the field of vision in depth is limited, and stricturing tumors cannot be passed by the ultrasound transducer. Imaging diagnostic attendibility confirms the preeminent role of intraoperative exploration in the assessment of neoplastic diffusion in order to plan a correct surgical treatment.

  3. Subsets of a Large Cognitive Battery Better Power Clinical Trials on Early Stage Alzheimer Disease

    PubMed Central

    Xiong, Chengjie; Weng, Hua; Bennett, David A.; Boyle, Patricia A.; Shah, Raj C.; Fague, Scot; Hall, Charles B.; Lipton, Richard B.; Morris, John C.

    2014-01-01

    Background/Aims Cognitive batteries routinely used by the Alzheimer disease (AD) research community may contain items uninformative for tracking disease progression to power clinical trials on early stage AD. We aim to identify subsets of the most informative items from an existing cognitive battery for better powering clinical trials on early AD. Methods Longitudinal change in item scores from the battery was associated with the onset of Mild Cognitive Impairment (MCI) in 1513 elderly individuals. Items whose longitudinal changes were correlated with the onset of MCI were selected as informative for tracking the early cognitive progression. Results 226 items in the battery were annually assessed over a follow-up of up to 13 years. Changes of item scores over time from 187 items were significantly correlated with the onset of MCI. For clinical trials on preclinical AD and on MCI, informative items permit smaller or similar sample sizes as compared to the entire battery, whereas uninformative items require much larger sample sizes. Conclusions Longitudinal changes in item scores from about 17% of items in the cognitive battery are uninformative for tracking early disease progression. Clinical trials on early AD can be better powered using informative items rather than the entire battery. PMID:25376544

  4. Defining end-stage renal disease in clinical trials: a framework for adjudication.

    PubMed

    Agarwal, Rajiv

    2016-06-01

    Unlike definition of stroke and myocardial infarction, there is no uniformly agreed upon definition to adjudicate end-stage renal disease (ESRD). ESRD remains the most unambiguous and clinically relevant end point for clinical trialists, regulators, payers and patients with chronic kidney disease. The prescription of dialysis to patients with advanced chronic kidney disease is subjective and great variations exist among physicians and countries. Given the difficulties in diagnosing ESRD, the presence of estimated GFR <15 mL/min/1.7 3m(2) itself has been suggested as an end point. However, this definition is still a surrogate since many patients may live years without being symptomatic or needing dialysis. The purpose of this report is to describe a framework to define when the kidney function ends and when ESRD can be adjudicated. Discussed in this report are (i) the importance of diagnosing symptomatic uremia or advanced asymptomatic uremia thus establishing the need for dialysis; (ii) establishing the chronicity of dialysis so as to distinguish it from acute dialysis; (iii) establishing ESRD when dialysis is unavailable, refused or considered futile and (iv) the adjudication process. Several challenges and ambiguities that emerge in clinical trials and their possible solutions are provided. The criteria proposed herein may help to standardize the definition of ESRD and reduce the variability in adjudicating the most important renal end point in clinical trials of chronic kidney disease.

  5. Conflict-Specific Aging Effects Mainly Manifest in Early Information Processing Stages-An ERP Study with Different Conflict Types.

    PubMed

    Korsch, Margarethe; Frühholz, Sascha; Herrmann, Manfred

    2016-01-01

    Aging is usually accompanied by alterations of cognitive control functions such as conflict processing. Recent research suggests that aging effects on cognitive control seem to vary with degree and source of conflict, and conflict specific aging effects on performance measures as well as neural activation patterns have been shown. However, there is sparse information whether and how aging affects different stages of conflict processing as indicated by event related potentials (ERPs) such as the P2, N2 and P3 components. In the present study, 19 young and 23 elderly adults performed a combined Flanker conflict and stimulus-response-conflict (SRC) task. Analysis of the reaction times (RTs) revealed an increased SRC related conflict effect in elderly. ERP analysis furthermore demonstrated an age-related increase of the P2 amplitude in response to the SRC task. In addition, elderly adults exhibited an increased P3 amplitude modulation induced by incongruent SRC and Flanker conflict trials.

  6. Bringing the Law to the Gerontological Stage: A Different Look at Movies and Old Age

    ERIC Educational Resources Information Center

    Doron, Israel

    2006-01-01

    Films often portray the complexities of real-life aging issues, showing how they are apparently handled outside of and around the law or legal issues. Furthermore, films considering the aged and the social issues associated with aging also reveal how the law actually functions as a framework around and within which people develop customs, habits,…

  7. Mucocutaneous Manifestations of HIV and the Correlation with WHO Clinical Staging in a Tertiary Hospital in Nigeria

    PubMed Central

    Oninla, Olumayowa Abimbola

    2014-01-01

    Skin diseases are indicators of HIV/AIDS which correlates with WHO clinical stages. In resource limited environment where CD4 count is not readily available, they can be used in assessing HIV patients. The study aims to determine the mucocutaneous manifestations in HIV positive patients and their correlation with WHO clinical stages. A prospective cross-sectional study of mucocutaneous conditions was done among 215 newly diagnosed HIV patients from June 2008 to May 2012 at adult ART clinic, Wesley Guild Hospital Unit, OAU Teaching Hospitals Complex, Ilesha, Osun State, Nigeria. There were 156 dermatoses with oral/oesophageal/vaginal candidiasis (41.1%), PPE (24.4%), dermatophytic infections (8.9%), and herpes zoster (3.8%) as the most common dermatoses. The proportions of dermatoses were 4.5%, 21.8%, 53.2%, and 20.5% in stages 1–4, respectively. A significant relationship (using Pearson's Chi square with P value <0.05) was obtained between dermatoses and WHO clinical stages. Pearson's correlation coefficient showed a positive correlation between the number of dermatoses and the WHO clinical stages. Dermatoses can therefore serve as diagnostic and prognostic markers in resource limited settings to initiate HAART in clinical stages 3 and 4. PMID:25587439

  8. Toward comprehensive management tailored to prognostic factors of patients with clinical stages I and II in Hodgkin's disease. The EORTC Lymphoma Group controlled clinical trials: 1964-1987.

    PubMed

    Tubiana, M; Henry-Amar, M; Carde, P; Burgers, J M; Hayat, M; Van der Schueren, E; Noordijk, E M; Tanguy, A; Meerwaldt, J H; Thomas, J

    1989-01-01

    From 1964 to 1987, the EORTC Lymphoma Group conducted four consecutive controlled clinical trials on clinical stages I and II Hodgkin's disease in which 1,579 patients were entered. From the onset the main aim of these trials was to identify the subsets of patients who could be treated safely by regional radiotherapy (RT). Therefore, several prognostic indicators were prospectively registered and progressively used in the trial protocols for the delineation of the favorable and unfavorable subgroups as soon as they were recognized of high predictive value. In the H2 trial (1972 to 1976), the histologic subtype was the only variable taken into account for the therapeutic strategy and the staging laparotomy findings were found to be of prognostic value only in patients with favorable prognostic indicators. In the H5 trial (1977 to 1982), patients were subdivided into two subgroups according to six prognostic indicators. Patients with favorable features were submitted to a staging laparotomy (lap); lap negative patients were randomized between mantle field RT and mantle field plus paraaortic RT. Disease free survival (DFS) and total survival (S) were similar in the two arms. Among patients with unfavorable features, DFS and S were significantly higher in the arm treated by combination of mechlorethamine, vincristine, procarbazine, prednisone (MOPP) chemotherapy (CT) and RT than in the arm treated by total nodal irradiation. Nevertheless, in patients below the age of 40, the overall survival rates were equivalent in the two arms. In the H6 trial, the delineation of the favorable subgroup was based on (a) absence of systemic symptoms and elevated ESR, (b) no more than one or two lymph node areas involved. The aim of the study was to assess the impact on survival of a therapeutic strategy including staging laparotomy. At a 4-year follow-up, no difference in survival was evidenced. In patients with unfavorable prognostic indicators, 3 MOPP-RT-3 MOPP were compared with 3

  9. Association Between Clinically Staged Node-Negative Esophageal Adenocarcinoma and Overall Survival Benefit From Neoadjuvant Chemoradiation

    PubMed Central

    Gabriel, Emmanuel; Attwood, Kristopher; Du, William; Tuttle, Rebecca; Alnaji, Raed M.; Nurkin, Steven; Malhotra, Usha; Hochwald, Steven N.; Kukar, Moshim

    2017-01-01

    Importance While neoadjuvant chemoradiation for esophageal cancer improves oncologic outcomes for a broad group of patients with locally advanced and/or node-positive tumors, it is less clear which specific subset of patients derives most benefit in terms of overall survival (OS). Objective To determine whether neoadjuvant chemoradiation based on esophageal adenocarcinoma histology has similar oncologic outcomes for patients treated with surgery alone when stratified by clinical nodal status. Design, Setting, and Participants A retrospective analysis using the American College of Surgeons National Cancer Database from 1998 to 2006. Patients with esophageal adenocarcinoma histology and clinical stage T1bN1-N3 or T2-T4aN−/+M0 were divided into 2 treatment groups: (1) neoadjuvant chemoradiation followed by surgery and (2) surgery alone. Subset analysis within each treatment group was performed for clinically node-negative patients (cN−) vs node-positive patients (cN+) in conjunction with pathological nodal status. A propensity score–adjusted analysis, which included patient demographics, comorbidity status, and clinical T stage, was also performed. Main Outcome and measures The primary outcome was 3-year OS. Secondary outcomes included margin status, postoperative length of stay, unplanned readmission rate, and 30-day mortality. Results A total of 1309 patients were identified, of whom 539 received neoadjuvant chemoradiation followed by surgery and 770 received surgery alone. Of the 1309 patients, 41.2% (n = 539) received neoadjuvant chemoradiation and 47.2% (n = 618) were cN+. Median follow-up for the entire cohort was 73.3 months (interquartile range, 64.1-93.5 months). The 3-year OS was better for neoadjuvant chemoradiation followed by surgery compared with surgery alone (49% vs 38%, respectively; P < .001). Stratifying based on clinical nodal status, the propensity score–adjusted OS was significantly better for cN+ patients who received neoadjuvant

  10. Clinical management of restless legs syndrome in end-stage renal disease patients.

    PubMed

    Sahli, Zeyad T; Jo, Jae; Mousa, Shaker A; Tarazi, Frank I

    2017-02-01

    Restless legs syndrome (RLS) is a common neurological movement disorder, characterized by restless and unpleasant sensations in the deep inside of legs. The symptoms of RLS are less noticeable during daytime, but more prevalent at night. Therefore, the disorder can induce low quality of life, insomnia, and impairment of daytime activity. RLS in end-stage renal disease (ESRD) patients is especially problematic due to premature discontinuation of dialysis and increased mortality. The prevalence of RLS among dialysis patients is much higher compared to the prevalence of the same disorder in patients with normal renal functions. Even though there are recommended treatment guidelines for the general population established by Medical Advisory Board of the RLS foundation, which include the use of dopamine agonists, levodopa, gabapentin, benzodiazepines, and opioids, limited information is available on the effects of these therapies in ESRD patients. Since the existing clinical data were extrapolated from small sample sizes in short-term clinical trials, further clinical studies are still needed to better assess the efficacy, safety, and tolerability of these medications in patients with ESRD.

  11. Variation in body condition indices of crimson finches by sex, breeding stage, age, time of day, and year

    PubMed Central

    Milenkaya, Olga; Weinstein, Nicole; Legge, Sarah; Walters, Jeffrey R.

    2013-01-01

    Body condition indices are increasingly applied in conservation to assess habitat quality, identify stressed populations before they decline, determine effects of disturbances, and understand mechanisms of declines. To employ condition indices in this manner, we need first to understand their baseline variability and sources of variation. Here, we used crimson finches (Neochmia phaeton), a tropical passerine, to describe the variation in seven commonly used condition indices by sex, age, breeding stage, time of day, and year. We found that packed cell volume, haemoglobin, total plasma protein, and scaled mass were all significantly affected by an interaction between sex and breeding stage. Furcular fat varied by sex and breeding stage and also trended by year, scaled mass showed a positive trend with age and varied by time of day, and haemoglobin additionally varied by year. Pectoral muscle scores varied and heterophil to lymphocyte ratio trended only by year. Year effects might reflect a response to annual variation in environmental conditions; therefore, those indices showing year effects may be especially worthy of further investigation of their potential for conservation applications. Pectoral muscle scores and heterophil to lymphocyte ratio may be particularly useful due to the lack of influence of other variables on them. For the other indices, the large variation that can be attributed to individual covariates, such as sex and breeding stage, suggests that one should not interpret the physiological condition of an individual as measured by these indices from their absolute value. Instead, the condition of an individual should be interpreted relative to conspecifics by sex, breeding stage, and possibly age. PMID:27293604

  12. Comparative Study of Clinical Staging of Oral Submucous Fibrosis with Qualitative Analysis of Collagen Fibers Under Polarized Microscopy

    PubMed Central

    Modak, Neha; Tamgadge, Sandhya; Tamgadge, Avinash; Bhalerao, Sudhir

    2015-01-01

    Background & Objectives: Oral submucous fibrosis (OSMF) is a condition where excessive deposition of dense collagen fibers occurred in the connective tissue of oral mucosa. An alteration of collagen necessitates an in depth understanding of collagen in oral tissues as no breakthrough studies have been reported. T herefore the aim was to correlate the clinical, functional and histopathological staging and to analyze the polarization colors and thickness of the collagen fibers in different stages of OSMF using picrosirius red stain under polarizing microscopy so as to assess the severity of disease. Methods: The study was conducted in the department of Oral Pathology and Microbiology at Padm. Dr. D. Y Patil Dental and Hospital, Navi Mumbai, India (2012-13). A sample size was of a total 40 subjects, of which 30 patients had OSMF, and 10 were in control group. Clinical, functional and histopathological staging were done depending upon definite criteria. Collagen fibers were analyzed for polarizing colors and thickness. Further clinical, functional and histopathological stages as well as qualitative parameters of collagen fibers were compared. Results: The correlation between clinical and functional staging was not significant ( P >0.05) whereas the comparison of the functional staging with histopathological staging was more reliable (P <0.01) as an indication to the severity of the disease rather than clinical staging. One-way ANOVA analysis showed highly significant correlation between functional staging and polarization colors and thickness of collagen fibers (P <0.001). Conclusion: The qualitative change in the collagen fibers of OSMF patients using polarized microscopy would help to assess its role in diagnostic evaluation, to determine the prognosis of the disease as well as to provide useful predictive treatment modalities to them. PMID:26351471

  13. Efficient estimation in two-stage randomized clinical trials using ranked sets.

    PubMed

    Hossain, Syed Shahadat; Awan, Nabil

    2016-12-14

    Clinical trials designed for survival probability estimation of different treatment policies for chronic diseases like cancer, leukemia, and schizophrenia usually need randomization of treatments in two stages. Since complete remission is rare for these diseases, initially an induction therapy is given for patient's remission. Further treatment, which is often an expensive maintenance therapy, is administered only for the patients with remission. If the maintenance therapy is so expensive that the cost of the trial inflates, only a simple random sample of patients will be treated with the expensive maintenance due to budget constraint. In this article, we have implemented a design using ranked sets instead of simple randomization in the second stage and obtained an unbiased estimator of the overall survival distribution for a particular treatment combination. Through simulation studies under different conditions, we have found that the design we developed based on ranked sets gives an unbiased estimate of the population survival probability which is more efficient than the estimate obtained by the usual design.

  14. Sham Feeding with Chewing Gum in Early Stage of Acute Pancreatitis: A Randomized Clinical Trial

    PubMed Central

    Jiang, Zongxing; Liang, Hongyin; Huang, Zhu; Tang, Jiajia; Tang, Lijun

    2017-01-01

    Background The correlation between sham feeding and acute pancreatitis (AP) has only been examined in limited studies. We aimed to investigate the efficacy and safety of sham feeding in the early stage of AP. Material/Methods A randomized controlled clinical trial was performed. Equal groups of AP patients were recruited. Patients in the sham feeding group received chewing gum 4 times a day after admission. All patients in the trial received standard treatment consistent with the guidelines for AP. The primary outcomes were mortality, length of stay (LOS), and medical expenses. Secondary outcomes were the incidence of complications and other adverse events, return of gastrointestinal function, the details of enteral nutrition and intra-abdominal pressure. Results From May 2014 to December 2015, a total of 204 patients were recruited. The LOS and hospital costs in the sham feeding group were reduced, although mortality was equivalent between groups. The return of gastrointestinal function occurred earlier in the sham feeding group, with no complications related to gum chewing. Conclusions Sham feeding with chewing gum is safe and efficacious in the early stage of AP. PMID:28154369

  15. Individualized Prediction and Clinical Staging of Bipolar Disorders using Neuroanatomical Biomarkers

    PubMed Central

    Mwangi, Benson; Wu, Mon-Ju; Cao, Bo; Passos, Ives C.; Lavagnino, Luca; Keser, Zafer; Zunta-Soares, Giovana B.; Hasan, Khader M.; Kapczinski, Flavio; Soares, Jair C.

    2016-01-01

    Background Neuroanatomical abnormalities in Bipolar disorder (BD) have previously been reported. However, the utility of these abnormalities in distinguishing individual BD patients from Healthy controls and stratify patients based on overall illness burden has not been investigated in a large cohort. Methods In this study, we examined whether structural neuroimaging scans coupled with a machine learning algorithm are able to distinguish individual BD patients from Healthy controls in a large cohort of 256 subjects. Additionally, we investigated the relationship between machine learning predicted probability scores and subjects’ clinical characteristics such as illness duration and clinical stages. Neuroimaging scans were acquired from 128 BD patients and 128 Healthy controls. Gray and white matter density maps were obtained and used to ‘train’ a relevance vector machine (RVM) learning algorithm which was used to distinguish individual patients from Healthy controls. Results The RVM algorithm distinguished patients from Healthy controls with 70.3 % accuracy (74.2 % specificity, 66.4 % sensitivity, chi-square p<0.005) using white matter density data and 64.9 % accuracy (71.1 % specificity, 58.6 % sensitivity, chi-square p<0.005) with gray matter density. Multiple brain regions – largely covering the fronto – limbic system were identified as ‘most relevant’ in distinguishing both groups. Patients identified by the algorithm with high certainty (a high probability score) – belonged to a subgroup with more than ten total lifetime manic episodes including hospitalizations (late stage). Conclusions These results indicate the presence of widespread structural brain abnormalities in BD which are associated with higher illness burden – which points to neuroprogression. PMID:27047994

  16. [Chronic lymphoid leukemia. Survival in relation to clinical stages. Statistical analysis of 95 cases (author's transl)].

    PubMed

    Rozman, C; Montserrat Costa, E; Morey, M; Aranalde, J M; Feliú, E; Grañena, A; Hernández Nieto, L; Nomdedeu, B

    1979-04-10

    The prognosis of patients with chronic lymphocytic leukemia is very difficult to evaluate. The classification system by stages, which at the present time is the most simple and useful method for the prognosis of this disease, recognizes five degrees of involvement: stage 0 (medullary and peripheral lymphocytosis); stage I (lymphocytosis + enlarged lymph nodes); stage II (lymphocyosis + hepato-and/or splenomegaly); stage III (lymphocytosis + anemia), and stage IV (lymphocytosis + thrombocytopenia). In the present report 95 controlled patients at the Farreras Valentí School of Hematology are analyzed using the classification by stages; there were 19 cases in stage 0; 16 in stage I; 30 in stage II; 21 in stage III, and 9 in stage IV. The mean survival rate in the global series was 63 months and the average 90.9 months. As in other series, it was observed that patients in stages 0 and I have a much better prognosis than those in stages III and IV. Stage II occupies an intermediate position in relation to prognosis, since the actuarial survival figure for this stage can practically be superimposed on that of the global series. The classification of chronic lymphocytic leukemia by stages permits the specification of the therapeutic indications for this condition; it also encourages the search for new modalities of treatment for stages with poor prognosis, since in these cases chronic lymphocytic leukemia behaves in the manner of an acute or subacute hemopathy.

  17. White matter integrity and reaction time intraindividual variability in healthy aging and early-stage Alzheimer disease.

    PubMed

    Jackson, Jonathan D; Balota, David A; Duchek, Janet M; Head, Denise

    2012-02-01

    Aging and early-stage Alzheimer disease (AD) have been shown to be associated with increased RT intraindividual variability (IIV, as reflected by the coefficient of variation) and an exaggeration of the slow tail of the reaction time (RT) distribution in attentional control tasks, based on ex-Gaussian analyses. The current study examined associations between white matter volume, IIV, and ex-Gaussian RT distribution parameters in cognitively normal aging and early-stage AD. Three RT attention tasks (Stroop, Simon, and a consonant-vowel odd-even switching task) in conjunction with MRI-based measures of cerebral and regional white matter volume were obtained in 133 cognitively normal and 33 early-stage AD individuals. Larger volumes were associated with less IIV and less slowing in the tail of the RT distribution, and larger cerebral and inferior parietal white matter volumes were associated with faster modal reaction time. Collectively, these results support a role of white matter integrity in IIV and distributional skewing, and are consistent with the hypothesis that IIV and RT distributional skewing are sensitive to breakdowns in executive control processes in normal and pathological aging.

  18. Plasma Ghrelin Concentrations Were Altered with Oestrous Cycle Stage and Increasing Age in Reproductively Competent Wistar Females

    PubMed Central

    Saffrey, M. Jill; Taylor, Victoria J.

    2016-01-01

    Changes in appetite occur during the ovarian cycle in female mammals. Research on appetite-regulatory gastrointestinal peptides in females is limited, because reproductive changes in steroid hormones present additional experimental factors to control for. This study aimed to explore possible changes in the orexigenic (appetite-stimulating) gastrointestinal peptide hormone ghrelin during the rodent oestrous cycle. Fed and fasted plasma and stomach tissue samples were taken from female Wistar rats (32–44 weeks of age) at each stage of the oestrous cycle for total ghrelin quantification using radioimmunoassay. Sampling occurred during the dark phase when most eating takes place in rats. Statistical analysis was by paired-samples t-test, one-way ANOVA on normally distributed data, with Tukey post-hoc tests, or Kruskal-Wallis if not. GLM univariate analysis was used to assess main effects and interactions in ghrelin concentrations in the fed or fasted state and during different stages of the ovarian cycle, with age as a covariate. No consistent fed to fasted ghrelin increases were measured in matched plasma samples from the same animals, contrary to expectations. Total ghrelin concentrations did not significantly change between cycle stages with ANOVA, in either fed or fasted plasma or in stomach tissue. This was despite significantly decreased fasted stomach contents at oestrus (P = 0.028), suggesting decreased food intake. There was however a significant interaction in ghrelin plasma concentrations between fed and fasted proestrus rats and a direct effect of age with rats over 37 weeks old having lower circulating concentrations of ghrelin in both fed and fasted states. The biological implications of altered ghrelin plasma concentrations from 37 weeks of age are as yet unknown, but warrant further investigation. Exploring peripheral ghrelin regulatory factor changes with increasing age in reproductively competent females may bring to light potential effects on

  19. Impact of Increasing Age on Cause-Specific Mortality and Morbidity in Patients With Stage I Non-Small-Cell Lung Cancer: A Competing Risks Analysis.

    PubMed

    Eguchi, Takashi; Bains, Sarina; Lee, Ming-Ching; Tan, Kay See; Hristov, Boris; Buitrago, Daniel H; Bains, Manjit S; Downey, Robert J; Huang, James; Isbell, James M; Park, Bernard J; Rusch, Valerie W; Jones, David R; Adusumilli, Prasad S

    2017-01-20

    Purpose To perform competing risks analysis and determine short- and long-term cancer- and noncancer-specific mortality and morbidity in patients who had undergone resection for stage I non-small-cell lung cancer (NSCLC). Patients and Methods Of 5,371 consecutive patients who had undergone curative-intent resection of primary lung cancer at our institution (2000 to 2011), 2,186 with pathologic stage I NSCLC were included in the analysis. All preoperative clinical variables known to affect outcomes were included in the analysis, specifically, Charlson comorbidity index, predicted postoperative (ppo) diffusing capacity of the lung for carbon monoxide, and ppo forced expiratory volume in 1 second. Cause-specific mortality analysis was performed with competing risks analysis. Results Of 2,186 patients, 1,532 (70.1%) were ≥ 65 years of age, including 638 (29.2%) ≥ 75 years of age. In patients < 65, 65 to 74, and ≥ 75 years of age, 5-year lung cancer-specific cumulative incidence of death (CID) was 7.5%, 10.7%, and 13.2%, respectively (overall, 10.4%); noncancer-specific CID was 1.8%, 4.9%, and 9.0%, respectively (overall, 5.3%). In patients ≥ 65 years of age, for up to 2.5 years after resection, noncancer-specific CID was higher than lung cancer-specific CID; the higher noncancer-specific, early-phase mortality was enhanced in patients ≥ 75 years of age than in those 65 to 74 years of age. Multivariable analysis showed that low ppo diffusing capacity of lung for carbon monoxide was an independent predictor of severe morbidity ( P < .001), 1-year mortality ( P < .001), and noncancer-specific mortality ( P < .001), whereas low ppo forced expiratory volume in 1 second was an independent predictor of lung cancer-specific mortality ( P = .002). Conclusion In patients who undergo curative-intent resection of stage I NSCLC, noncancer-specific mortality is a significant competing event, with an increasing impact as patient age increases.

  20. APPLYING TEP MEASUREMENTS TO ASSESS THE AGING STAGE OF MARAGING 250 STEEL

    SciTech Connect

    Snir, Y.; Gelbstein, Y.; Pinkas, M.; Yeheskel, O.; Landau, A.

    2008-02-28

    Thermoelectric power (TEP) measurements had been proved as an effective method for evaluating the metallurgical state of various alloys. The current work was conducted in order to evaluate the influence of the aging state of Maraging 250 steel on TEP values. Commercial Maraging 250 steel was aged at 500 deg. C for 0.5-6 hours (hrs). TEP, hardness (Rc) and ultrasonic (US) measurements, were preformed on the as received and aged specimens. XRD measurements were used to identify the formation of precipitates (mainly Ni{sub 3}(Ti,Mo)), reverted austenite and to evaluate changes in the microstrain caused by the precipitation process. A correlation was found between the TEP and the various measurements as a function of the aging time.

  1. Applying Tep Measurements to Assess the Aging Stage of Maraging 250 Steel

    NASA Astrophysics Data System (ADS)

    Snir, Y.; Pinkas, M.; Gelbstein, Y.; Yeheskel, O.; Landau, A.

    2008-02-01

    Thermoelectric power (TEP) measurements had been proved as an effective method for evaluating the metallurgical state of various alloys. The current work was conducted in order to evaluate the influence of the aging state of Maraging 250 steel on TEP values. Commercial Maraging 250 steel was aged at 500 °C for 0.5-6 hours (hrs). TEP, hardness (Rc) and ultrasonic (US) measurements, were preformed on the as received and aged specimens. XRD measurements were used to identify the formation of precipitates (mainly Ni3(Ti,Mo)), reverted austenite and to evaluate changes in the microstrain caused by the precipitation process. A correlation was found between the TEP and the various measurements as a function of the aging time.

  2. Predicting age-related differences in visual information processing using a two-stage queuing model.

    PubMed

    Ellis, R D; Goldberg, J H; Detweiler, M C

    1996-05-01

    Recent work on age-related differences in some types of visual information processing has qualitatively stated that younger adults are able to develop parallel processing capability, while older adults remain serial processors. A mathematical model based on queuing theory was used to quantitatively predict and parameterize age-related differences in the perceptual encoding and central decision-making aspects of a multiple-frame search task. Statistical results indicated main effects for frame duration, display load, age group, and session of practice. Comparison of the full model and a restricted model indicated an efficient contribution of the encoding speed parameter. The best-fitting parameter set indicated that (1) younger participants processed task information with a two-channel parallel system, while older participants were serial processors; and (2) perceptual encoding had a large impact on age-related differences in task performance. Results are discussed with implications for human factors design principles.

  3. [Morphofunctional status of gonadotropic cells of the adenohypophysis at early stages of age involution].

    PubMed

    Kozak, M V; Teplyĭ, D L

    2007-01-01

    Action of alpha-tocopherol, emoxipinum on functional status of gonadotropic cells was investigated at deficiency of sexual hormones in male and female rats of Wistar line. The alpha-tocopherol slows down aging of gonadotropic cells after gonadectomy.

  4. Dental and Chronological Ages as Determinants of Peak Growth Period and Its Relationship with Dental Calcification Stages

    PubMed Central

    Litsas, George; Lucchese, Alessandra

    2016-01-01

    Purpose: To investigate the relationship between dental, chronological, and cervical vertebral maturation growth in the peak growth period, as well as to study the association between the dental calcification phases and the skeletal maturity stages during the same growth period. Methods: Subjects were selected from orthodontic pre-treatment cohorts consisting of 420 subjects where 255 were identified and enrolled into the study, comprising 145 girls and 110 boys. The lateral cephalometric and panoramic radiographs were examined from the archives of the Department of Orthodontics, Aristotle University of Thessaloniki, Greece. Dental age was assessed according to the method of Demirjian, and skeletal maturation according to the Cervical Vertebral Maturation Method. Statistical elaboration included Spearman Brown formula, descriptive statistics, Pearson’s correlation coefficient and regression analysis, paired samples t-test, and Spearman’s rho correlation coefficient. Results: Chronological and dental age showed a high correlation for both gender(r =0.741 for boys, r = 0.770 for girls, p<0.001). The strongest correlation was for the CVM Stage IV for both males (r=0.554) and females (r=0.68). The lowest correlation was for the CVM Stage III in males (r=0.433, p<0.001) and for the CVM Stage II in females (r=0.393, p>0.001). The t-test revealed statistically significant differences between these variables (p<0.001) during the peak period. A statistically significant correlation (p<0.001) between tooth calcification and CVM stages was determined. The second molars showed the highest correlation with CVM stages (CVMS) (r= 0.65 for boys, r = 0.72 for girls). Conclusion: Dental age was more advanced than chronological for both boys and girls for all CVMS. During the peak period these differences were more pronounced. Moreover, all correlations between skeletal and dental stages were statistically significant. The second molars showed the highest correlation whereas the

  5. Clinical operations generation next… The age of technology and outsourcing.

    PubMed

    Temkar, Priya

    2015-01-01

    Huge cost pressures and the need to drive faster approvals has driven a technology transformation in the clinical trial (CT) industry. The CT industry is thus leveraging mobile data, cloud computing, social media, robotic automation, and electronic source to drive efficiencies in a big way. Outsourcing of clinical operations support services to technology companies with a clinical edge is gaining tremendous importance. This paper provides an overview of current technology trends, applicable Food and Drug Administration (FDA) guidelines, basic challenges that the pharma industry is facing in trying to implement such changes and its shift towards outsourcing these services to enable it to focus on site operations.

  6. SBRT for early-stage glottic larynx cancer—Initial clinical outcomes from a phase I clinical trial

    PubMed Central

    Schwartz, David L.; Sosa, Alan; Chun, Stephen G.; Ding, Chiuxiong; Xie, Xian-Jin; Nedzi, Lucien A.

    2017-01-01

    Purpose To confirm safety and feasibility of hypofractionated SBRT for early-stage glottic laryngeal cancer. Methods Twenty consecutive patients with cTis-T2N0M0 carcinoma of glottic larynx were enrolled. Patients entered dose-fractionation cohorts of incrementally shorter bio-equivalent schedules starting with 50 Gy in 15 fractions (fx), followed by 45 Gy/10 fx and, finally, 42.5 Gy/5 fx. Maximum combined CTV-PTV expansion was limited to 5 mm. Patients were treated on a Model G5 Cyberknife (Accuray, Sunnyvale, CA). Results Median follow-up is 13.4 months (range: 5.6–24.6 months), with 12 patients followed for at least one year. Maximum acute toxicity consisted of grade 2 hoarseness and dysphagia. Maximum chronic toxicity was seen in one patient treated with 45 Gy/10 fx who continued to smoke >1 pack/day and ultimately required protective tracheostomy. At 1-year follow-up, estimated local disease free survival for the full cohort was 82%. Overall survival is 100% at last follow-up. Conclusions We were able to reduce equipotent total fractions of SBRT from 15 to 5 without exceeding protocol-defined acute/subacute toxicity limits. With limited follow-up, disease control appears comparable to standard treatment. We continue to enroll to the 42.5 Gy/5 fx cohort and follow patients for late toxicity. Trial registration ClinicalTrials.gov NCT01984502 PMID:28253270

  7. Neoadjuvant therapy for early-stage breast cancer: the clinical utility of pertuzumab.

    PubMed

    Gollamudi, Jahnavi; Parvani, Jenny G; Schiemann, William P; Vinayak, Shaveta

    2016-01-01

    Approximately 20% of breast cancer patients harbor tumors that overexpress human epidermal growth factor receptor 2 (HER2; also known as ErbB2), a receptor tyrosine kinase that belongs to the epidermal growth factor receptor family of receptor tyrosine kinases. HER2 amplification and hyperactivation drive the growth and survival of breast cancers through the aberrant activation of proto-oncogenic signaling systems, particularly the Ras/MAP kinase and PI3K/AKT pathways. Although HER2-positive (HER2(+)) breast cancer was originally considered to be a highly aggressive form of the disease, the clinical landscape of HER2(+) breast cancers has literally been transformed by the approval of anti-HER2 agents for adjuvant and neoadjuvant settings. Indeed, pertuzumab is a novel monoclonal antibody that functions as an anti-HER2 agent by targeting the extracellular dimerization domain of the HER2 receptor; it is also the first drug to receive an accelerated approval by the US Food and Drug Administration for use in neoadjuvant settings in early-stage HER2(+) breast cancer. Here, we review the molecular and cellular factors that contribute to the pathophysiology of HER2 in breast cancer, as well as summarize the landmark preclinical and clinical findings underlying the approval and use of pertuzumab in the neoadjuvant setting. Finally, the molecular mechanisms operant in mediating resistance to anti-HER2 agents, and perhaps to pertuzumab as well, will be discussed, as will the anticipated clinical impact and future directions of pertuzumab in breast cancer patients.

  8. Neoadjuvant therapy for early-stage breast cancer: the clinical utility of pertuzumab

    PubMed Central

    Gollamudi, Jahnavi; Parvani, Jenny G; Schiemann, William P; Vinayak, Shaveta

    2016-01-01

    Approximately 20% of breast cancer patients harbor tumors that overexpress human epidermal growth factor receptor 2 (HER2; also known as ErbB2), a receptor tyrosine kinase that belongs to the epidermal growth factor receptor family of receptor tyrosine kinases. HER2 amplification and hyperactivation drive the growth and survival of breast cancers through the aberrant activation of proto-oncogenic signaling systems, particularly the Ras/MAP kinase and PI3K/AKT pathways. Although HER2-positive (HER2+) breast cancer was originally considered to be a highly aggressive form of the disease, the clinical landscape of HER2+ breast cancers has literally been transformed by the approval of anti-HER2 agents for adjuvant and neoadjuvant settings. Indeed, pertuzumab is a novel monoclonal antibody that functions as an anti-HER2 agent by targeting the extracellular dimerization domain of the HER2 receptor; it is also the first drug to receive an accelerated approval by the US Food and Drug Administration for use in neoadjuvant settings in early-stage HER2+ breast cancer. Here, we review the molecular and cellular factors that contribute to the pathophysiology of HER2 in breast cancer, as well as summarize the landmark preclinical and clinical findings underlying the approval and use of pertuzumab in the neoadjuvant setting. Finally, the molecular mechanisms operant in mediating resistance to anti-HER2 agents, and perhaps to pertuzumab as well, will be discussed, as will the anticipated clinical impact and future directions of pertuzumab in breast cancer patients. PMID:26937204

  9. Solar exposure(s) and facial clinical signs of aging in Chinese women: impacts upon age perception.

    PubMed

    Flament, Frederic; Bazin, Roland; Qiu, Huixia; Ye, Chengda; Laquieze, Sabine; Rubert, Virginie; Decroux, Aurelie; Simonpietri, Elisa; Piot, Bertrand

    2015-01-01

    A new reference clinical atlas of facial signs dedicated to photoaging was applied to 301 Chinese women of various ages through standardized photographs. Such approach aimed at better describing the facial changes induced by both real/chronological age and sun exposure and their respective impact on two subcohorts of different behavior with regard to sun exposure. A total of 28 various facial signs were individually graded according to their severity by a panel of experts, and a perceived apparent age of each subject was assessed. Results showed that the severity of major signs significantly increased rather linearly with age, with a higher rate in sun-exposed subjects as compared with subjects who regularly avoid sun exposure. The severity of facial signs, all impacted by sun exposure, better correlated with perceived apparent age than real/chronological age. The protocol used in the present work, similar to that previously applied to two cohorts of French women, assigned a greater impact of sun exposure in the facial aging signs of Asian women - all clinical signs are influenced by extrinsic factors - as compared with Caucasian women of comparable ages, likely related to much more intense ultraviolet (UV) radiation.

  10. Clinically different stages of Alzheimer's disease associated by amyloid deposition with [11C]-PIB PET imaging.

    PubMed

    Hatashita, Shizuo; Yamasaki, Hidetomo

    2010-01-01

    We investigated whether [11C]-PIB PET detects underlying amyloid deposition at clinically different stages of Alzheimer's disease (AD) and preclinical dementia. The Japanese cohort of 214 subjects underwent cognitive testing and 60-min dynamic [11C]-PIB PET. [11C]-PIB data were acquired from 35-60 min after injection. Regions of interest were defined on co-registered MRI. Distribution volume ratios (DVR) of PIB retention were determined using Logan graphical analysis. All 56 patients with AD showed a robust increase in PIB retention in cortical areas (typical PIB AD-pattern). A mean DVR value in 11 patients with moderate AD (CDR: 2.1 ± 0.4) showed significantly higher PIB retention (2.38 ± 0.42, p < 0.01) than amyloid-negative healthy control (HC) subjects. The DVR values in 23 patients with very mild AD (CDR: 0.5) and 22 patients with mild AD (CDR: 1.0) were 2.32 ± 0.45 and 2.34 ± 0.42, respectively, similar to moderate AD. In contrast, 28 (48%) of the 58 mild cognitive impairment (MCI) patients (MMSE: 27.3 ± 1.7) showed a typical AD-like pattern with a DVR value of 2.07 ± 0.34. Further, 17 (18%) of 91 HC subjects had a typical AD-like pattern with a DVR value of 2.06 ± 0.28. They did not significantly differ from very mild AD. The prevalence of AD among the 53 amyloid positive patients aged 75 years or older increased greatly to 74% whereas that of amyloid positive HC decreased by only 9% and amyloid positive MCI by 17%. Prodromal AD and AD dementia is identified, based on cognitive function and amyloid deposition by PIB PET imaging. Further, the cortical amyloid deposition could be detected at preclinical stage of AD.

  11. Another stage of development: Biological degeneracy and the study of bodily ageing.

    PubMed

    Mason, Paul H; Maleszka, Ryszard; Dominguez D, Juan F

    2016-12-21

    Ageing is a poorly understood process of human development mired by a scientific approach that struggles to piece together distributed variable factors involved in ongoing transformations of living systems. Reconfiguring existing research paradigms, we review the concept of 'degeneracy', which has divergent popular and technical definitions. The technical meaning of degeneracy refers to the structural diversity underlying functional plasticity. Degeneracy is a distributed system property that can be observed within individual brains or across different brains. For example, dementias with similar behavioural anomalies can result from a diverse range of cellular "faults", which is an example of degeneracy because the symptoms are similar in spite of different underlying mechanisms. Degeneracy is a valuable epistemological tool that can transformatively enhance scientific models of bodily ageing. We propose that movement science is one of the first areas that can productively integrate degeneracy into models of bodily ageing. We also propose model organisms such as eusocial honey bees in which degeneracy can be studied at the molecular and cellular level. Developing a vocabulary for thinking about how distributed variable factors are interlinked is important if we are to understand bodily ageing not as a single entity, but as the heterogeneous construction of changing biological, social, and environmental processes.

  12. Biological ageing and clinical consequences of modern technology.

    PubMed

    Kyriazis, Marios

    2017-02-09

    The pace of technology is steadily increasing, and this has a widespread effect on all areas of health and society. When we interact with this technological environment we are exposed to a wide variety of new stimuli and challenges, which may modulate the stress response and thus change the way we respond and adapt. In this Opinion paper I will examine certain aspects of the human-computer interaction with regards to health and ageing. There are practical, everyday effects which also include social and cultural elements. I will discuss how human evolution may be affected by this new environmental change (the hormetic immersion in a virtual/technological environment). Finally, I will also explore certain biological aspects which have direct relevance to the ageing human. By embracing new technologies and engaging with a techno-social ecosystem (which is no longer formed by several interacting species, but by just two main elements: humans and machines), we may be subjected to beneficial hormetic effects, which upregulate the stress response and modulate adaptation. This is likely to improve overall health as we age and, as I speculate here, may also result in the reduction of age-related dysfunction.

  13. Experimental ovine toxoplasmosis: influence of the gestational stage on the clinical course, lesion development and parasite distribution.

    PubMed

    Castaño, Pablo; Fuertes, Miguel; Regidor-Cerrillo, Javier; Ferre, Ignacio; Fernández, Miguel; Ferreras, M Carmen; Moreno-Gonzalo, Javier; González-Lanza, Camino; Pereira-Bueno, Juana; Katzer, Frank; Ortega-Mora, Luis Miguel; Pérez, Valentín; Benavides, Julio

    2016-03-16

    The relation between gestational age and foetal death risk in ovine toxoplasmosis is already known, but the mechanisms involved are not yet clear. In order to study how the stage of gestation influences these mechanisms, pregnant sheep of the same age and genetic background were orally dosed with 50 oocysts of Toxoplasma gondii (M4 isolate) at days 40 (G1), 90 (G2) and 120 (G3) of gestation. In each group, four animals were culled on the second, third and fourth week post infection (pi) in order to evaluate parasite load and distribution, and lesions in target organs. Ewes from G1 showed a longer period of hyperthermia than the other groups. Abortions occurred in all groups. While in G2 they were more frequent during the acute phase of the disease, in G3 they mainly occurred after day 20 pi. After challenge, parasite and lesions in the placentas and foetuses were detected from day 19 pi in G3 while in G2 or G1 they were only detected at day 26 pi. However, after initial detection at day 19 pi, parasite burden, measured through RT-PCR, in placenta or foetus of G3 did not increase significantly and, at in the third week pi it was lower than that measured in foetal liver or placenta from G1 to G3 respectively. These results show that the period of gestation clearly influences the parasite multiplication and development of lesions in the placenta and foetus and, as a consequence, the clinical course in ovine toxoplasmosis.

  14. Lymphangiogenesis in cervical cancer evaluated by expression of the VEGF-C gene in clinical stage IB-IIIB

    PubMed Central

    Franc, Magdalena; Kachel-Flis, Agata; Michalski, Bogdan; Fila-Daniłow, Anna; Mazurek, Urszula; Michalska, Anna; Kuczerawy, Ilona; Skrzypulec-Plinta, Violetta

    2015-01-01

    Introduction The aim of the present study was to evaluate the profile of VEGF-C gene expression in particular stages of cervical cancer (IB-IIIB) and to estimate the correlation between VEGF-C mRNA quantity profile and clinical stage. Material and methods Material for molecular analysis consisted of cervical cancer tissue specimens collected from 38 women (10, 15, 13 cases were classified as IB, IIB and IIIB, respectively). The control group was composed of normal cervical tissues collected from 10 women who underwent hysterectomy for non-oncological reasons. The number of VEGF-C mRNA copies in particular groups was estimated by the reverse transcription quantitative polymerase chain reaction (RT-qPCR) method. Results In the control group the average number of mRNA copies was 134 ± 36 (median: 106), in a group with stage IB it was 16 077 ± 7090 (median: 580), for stage IIB – 35 019 ± 8945 (median: 40 870). The highest number of mRNA VEGF-C copies was derived in a group of patients with cervical cancer of stage IIIB. The average quantity was 56 155 ± 12 470, whereas median 55 981. A statistically significantly higher level of VEGF-C gene expression was disclosed in cervical cancer specimens with stage IIB and IIIB than in the control group. In stage IIIB, the VEGF-C gene expression was significantly higher than in specimens derived from individuals in stage IB. Conclusions In squamous cell carcinoma of the uterine cervix of stage IB-IIIB genes involved in lymphangiogenesis, especially VEGF-C, are expressed, which expression increases as the clinical stage of cervical cancer is higher. PMID:26327898

  15. Aging and Surveillance Program MINUTEMAN II/III Stage II Program Progress.

    DTIC Science & Technology

    1985-11-01

    130 Firing Adapters Used to Fire VECP Igniters 58 132 Squib Arrangement Used in Both KR80000 Safe and Arm and FFTFs 59 133 Bladder Permeation vs Age...hydrolytic liner degradation as the primary mechanism leading ; . " to failure for the motor. Kinetic projections for service life ranged from 14 to 17...the igniter following assembly . In general, propellant in the bulk of the web is slightly harder than that measured in the fin. Propellant in the slot

  16. A study of the age attribute in a query tool for a clinical data warehouse.

    PubMed

    Scheufele, Elisabeth L; Scheufele, Elisabeth Lee; Dubey, Anil; Dubey, Anil Kumar; Murphy, Shawn N

    2008-11-06

    The RPDR, a clinical data warehouse with a user-friendly Querytool, allows researchers to perform studies on patient data. Currently, the RPDR represents age as the patient's age at the present time, which is problematic in situations where age at the time of the event is more appropriate. We will modify the Querytool to consider this by assessing the perception of age via survey, testing backend query solutions, and developing modifications based on these results.

  17. The Prognostic Impact of Molecular Subtypes and Very Young Age on Breast Conserving Surgery in Early Stage Breast Cancer

    PubMed Central

    McGuire, Kandace; Alco, Gul; Nur Pilanci, Kezban; Koksal, Ulkuhan I; Elbüken, Filiz; Erdogan, Zeynep; Agacayak, Filiz; Ilgun, Serkan; Sarsenov, Dauren; Öztürk, Alper; İğdem, Şefik; Okkan, Sait; Eralp, Yeşim; Dincer, Maktav; Ozmen, Vahit

    2016-01-01

    Background Premenopausal breast cancer with a triple-negative phenotype (TNBC) has been associated with inferior locoregional recurrence free survival (LRFS) and overall survival (OS) after breast conserving surgery (BCS). The aim of this study is to analyze the association between age, subtype, and surgical treatment on survival in young women (≤40 years) with early breast cancer in a population with a high rate of breast cancer in young women. Methods Three hundred thirty-two patients ≤40 years old with stage I-II invasive breast cancer who underwent surgery at a single institution between 1998 and 2012 were identified retrospectively. Uni- and multivariate analysis evaluated predictors of LRFS, OS, and disease free survival (DFS). Results Most patients (64.2%) underwent BCS. Mean age and follow-up time were 35 (25 ± 3.61) years, and 72 months (range, 24–252), respectively. In multivariate analysis, multicentricity/multifocality and young age (<35 years) independently predicted for poorer DFS and OS. Those aged 35–40 years had higher LRFS and DFS than those <35 in the mastectomy group (p=0.007 and p=0.039, respectively). Patients with TNBC had lower OS compared with patients with luminal A subtype (p=0.042), and those who underwent BCS had higher OS than patients after mastectomy (p=0.015). Conclusion Young age (< 35 years) is an independent predictor of poorer OS and DFS as compared with ages 35–40, even in countries with a lower average age of breast cancer presentation. In addition, TNBC in the young predicts for poorer OS. BCS can be performed in young patients with TNBC, despite their poorer overall survival. PMID:27433412

  18. Multiparametric magnetic resonance imaging for pre-treatment local staging of prostate cancer: A Cancer Care Ontario clinical practice guideline

    PubMed Central

    Salerno, Jennifer; Finelli, Antonio; Morash, Chris; Morgan, Scott C.; Power, Nicholas; Schieda, Nichola; Haider, Masoom A.

    2016-01-01

    Introduction: The utility of T2-weighted magnetic resonance imaging (MRI) in the local staging of prostate cancer is controversial. Due to the success of multiparametric MRI in cancer localization, there is renewed interested in MRI (± functional sequences) for local staging. Guidance on pre-treatment local staging of prostate cancer by MRI was developed using systematic review methodology and expert consultation. Methods: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and other databases were searched to identify studies comparing: (1) MRI staging vs. radical prostatectomy staging on diagnostic accuracy outcomes; and (2) MRI staging vs. routine clinical staging on clinical and patient outcomes. Studies meeting inclusion criteria were synthesized by outcome and sensitivity/specificity analysis by tumour location was performed. Evidence quality of included studies was assessed and considered in recommendation formulation. Results: The literature search identified 2510 citations; 62 studies were included. Analysis of MRI ≥1.5 T plus endorectal coil (ER) (± functional sequences) in the detection of extraprostatic extension or seminal vesicle invasion showed modest sensitivities (≥50%) and excellent specificities (>85%) among patients scheduled for radical prostatectomy. MRI upstaging was shown in 20/21 studies, with large variation in correctness (11–85%). Scarcity of clinical and patient outcomes among studies limited synthesis and evaluation. Quality assessment found non-trivial biases. Conclusions: Modest imaging performance was shown for MRI (1.5 T + ER and 3 T ± ER) ± functional sequences in regards to sensitivity. Limitations in study design, reporting of clinical and patient outcomes, and the heterogeneous use of MRI tempered the strength of the recommendations. PMID:27800062

  19. Translating Advances from the Basic Biology of Aging into Clinical Application

    PubMed Central

    Kirkland, James L.

    2013-01-01

    Recently, lifespan and healthspan have been extended in experimental animals using interventions that are potentially translatable into humans. A great deal of thought and work are needed beyond the usual steps in drug development to advance these findings into clinical application. Realistic pre-clinical and clinical trials paradigms need to be devised. Focusing on subjects with symptoms of age-related diseases or frailty or who are at imminent risk of developing these problems, measuring effects on short-term, clinically relevant outcomes, as opposed to long-term outcomes such as healthspan or lifespan, and developing biomarkers and outcome measures acceptable to regulatory agencies will be important. Research funding is a major roadblock, as is lack of investigators with combined expertise in the basic biology of aging, clinical geriatrics, and conducting investigational new drug clinical trials. Options are reviewed for developing a path from the bench to the bedside for interventions that target fundamental aging processes. PMID:23237984

  20. A clinical and pathologic comparison between stage-matched endometrial intraepithelial carcinoma and uterine serous carcinoma: is there a difference?

    PubMed

    Hou, June Y; McAndrew, Thomas C; Goldberg, Gary L; Whitney, Kathleen; Shahabi, Shohreh

    2014-04-01

    Endometrial intraepithelial carcinoma (EIC) is a rare pathologic variant of uterine serous carcinoma (USC). Our aim is to distinguish patterns of clinic-pathologic outcomes in patients with EIC and USC for disease limited to the endometrium (stage 1A) as well as with distant metastasis (stage 4B). Surgically staged patients were retrospectively identified and relevant variables were extracted and compared. Kaplan-Meier was used to generate the survival data. More USC (n = 29) exhibited lymphovascular invasion (stage 4, P = .01) and expressed higher levels of estrogen receptor-α than EIC (P = .0009 and .063 for stages 1 and 4, respectively). The survival is comparable, with 1 recurrence in each group for stage 1A disease. For stage 4 EIC and USC, the progression-free survival (14 vs10 months) and overall survival (19 vs 20 months) are similar to what is previously published. In conclusion, EIC, whether limited to the endometrium, or widely metastatic, imparts similar outcomes and should be treated comparably with stage-matched USC.

  1. Psychometric properties of the Brazilian-adapted version of the Ages and Stages Questionnaire in public child daycare centers.

    PubMed

    Filgueiras, Alberto; Pires, Pedro; Maissonette, Silvia; Landeira-Fernandez, J

    2013-08-01

    Well-designed screening assessment instruments that can evaluate child development in public daycare centers represent an important resource to help improve the quality of these programs, as an early detection method for early developmental delay. The Ages and Stages Questionnaire, 3rd edition (ASQ-3), comprises a series of 21 questionnaires designed to screen developmental performance in the domains of communication, gross motor skills, fine motor skills, problem solving, and personal-social ability in children aged 2 to 66 months. The purpose of the present work was to translate and adapt all of the ASQ-3 questionnaires for use in Brazilian public child daycare centers and to explore their psychometric characteristics with both Classical Test Theory and Rating Scale analyses from the Rasch model family. A total of 18 Ages & Stages Questionnaires - Brazilian translation (ASQ-BR) questionnaires administered at intervals from 6 to 60 months of age were analyzed based on primary caregiver evaluations of 45,640 children distributed in 468 public daycare centers in the city of Rio de Janeiro. The results indicated that most of the ASQ-BR questionnaires had adequate internal consistency. Exploratory factor analyses yielded a one-factor solution for each domain of all of the ASQ-BR questionnaires. The only exception was the personal-social domain in some of the questionnaires. Item Response Theory based on Rating Scale analysis (infit and outfit mean squares statistics) indicated that only 44 of 540 items showed misfit problems. In summary, the ASQ-BR questionnaires are psychometrically sound developmental screening instruments that can be easily administered by primary caregivers.

  2. Comparison of the AJCC, MSTS, and Modified Spanier Systems for Clinical and Pathologic Staging of Osteosarcoma.

    PubMed

    Cates, Justin M M

    2017-03-01

    The prognostic performance of the 2 most commonly used staging systems for skeletal sarcoma (the American Joint Committee on Cancer [AJCC] and Musculoskeletal Tumor Society [MSTS] systems) have never been compared analytically. Another staging system originally proposed by Spanier has not yet been validated. Given the recent release of the 8th edition of the AJCC Cancer Staging Manual, this study was designed to directly compare these anatomic staging systems in a series of 153 high-grade, intramedullary osteosarcomas. Kaplan-Meier curves were plotted and pairwise comparisons between each stage category were performed. Predictive accuracy of each staging system for determining 5-year disease-free survival was evaluated by comparing areas under receiver-operating characteristic curves generated from logistic regression analysis. Multiple concordance indices were calculated using bootstrapping methods (200 replications). ρk and R were estimated as measures of the variation in survival outcomes explained by the regression models. The AJCC, MSTS, and a modified version of the Spanier staging systems showed similar discriminatory abilities and no significant differences in the levels of contrast between different tumor stages across staging systems. Addition of T-category information from each staging system contributed significant prognostic information compared with a Cox proportional hazard regression model consisting only of the presence or absence of metastatic disease as a measure of disease extent. Concordance indices and predictive accuracy for 5-year disease-free survival were not significantly different among the different staging systems either. Similar findings were observed after accounting for other important prognostic variables. Additional studies are necessary to determine performance parameters of each staging system for other types of skeletal sarcoma. Prognostic performance of osteosarcoma staging systems would also be improved by incorporating

  3. Clinically Defined Type 2 Diabetes Mellitus and Prognosis in Early-Stage Breast Cancer

    PubMed Central

    Erickson, Kirsten; Patterson, Ruth E.; Flatt, Shirley W.; Natarajan, Loki; Parker, Barbara A.; Heath, Dennis D.; Laughlin, Gail A.; Saquib, Nazmus; Rock, Cheryl L.; Pierce, John P.

    2011-01-01

    Purpose Self-reported diabetes has been associated with poor breast cancer outcomes. Research is needed to investigate the relationship between biologically determined glycemic control and breast cancer prognosis. Methods Archived baseline blood samples from the Women's Healthy Eating and Living Study were used to measure hemoglobin A1C (HbA1C) among 3,003 survivors of early-stage breast cancer (age of diagnosis, 28 to 70 years) observed for a median of 7.3 years for additional breast cancer events and 10.3 years for all-cause mortality. HbA1C levels provide an accurate, precise measure of chronic glycemic levels. Cox regression analysis was performed to assess whether baseline HbA1C levels predicted disease-free and overall survival. Results Only 5.8% of women had chronic hyperglycemia (defined as HbA1C levels ≥ 6.5%). Those with HbA1C ≥ 6.5% were older and more likely to be less educated, have nonwhite ethnicity, be obese, and have more advanced breast cancer at diagnosis. HbA1C was significantly associated with overall survival (Ptrend < .001). After adjusting for confounders, risk of all-cause mortality was twice as high in women with HbA1C ≥ 7.0% compared with women with HbA1C less than 6.5% (hazard ratio [HR], 2.35; 95% CI, 1.56 to 3.54). For disease-free survival, there was a nonsignificant 30% increase in risk for HbA1C levels ≥ 7.0% (HR, 1.26; 95% CI, 0.78 to 2.02). During study follow-up, previously diagnosed rather than undiagnosed diabetes seemed to account for the increased risk. Conclusion Chronic hyperglycemia is statistically significantly associated with reduced overall survival in survivors of early-stage breast cancer. Further study of diabetes and its relationship to breast cancer outcomes is warranted. PMID:21115861

  4. Battling regional (stage III) lung cancer: bumpy road of a cancer survivor in the immunotherapy age.

    PubMed

    Hao, Zhonglin; Biddinger, Paul; Schroeder, Carsten; Tariq, Khurram

    2016-07-07

    A 58-year-old woman, a heavy smoker, was diagnosed with stage III squamous cell lung cancer. She was treated with concurrent chemotherapy and radiotherapy, with partial response. 2 months later, she had haemoptysis caused by brisk bleeding from the radiated right upper lobe. Fortunately, her bleed was self-limited. 4 months later, a rapidly enlarging renal mass was discovered and turned out to be metastatic from the lung primary. Second-line chemotherapy with docetaxel and ramucirumab did not have effects on the renal mass after 2 cycles. Despite not being eligible for a durvalumab trial because of lack of PD-L1 expression, she had a meaningful response to nivolumab. Once every 2 weeks, infusion of nivolumab resulted in rapid tumour shrinkage in multiple areas. In the next few months, she experienced a variety of side effects, some of which were potentially life-threatening. She had disease progression 9 months into treatment.

  5. Plasma 24-metabolite Panel Predicts Preclinical Transition to Clinical Stages of Alzheimer's Disease.

    PubMed

    Fiandaca, Massimo S; Zhong, Xiaogang; Cheema, Amrita K; Orquiza, Michael H; Chidambaram, Swathi; Tan, Ming T; Gresenz, Carole Roan; FitzGerald, Kevin T; Nalls, Mike A; Singleton, Andrew B; Mapstone, Mark; Federoff, Howard J

    2015-01-01

    We recently documented plasma lipid dysregulation in preclinical late-onset Alzheimer's disease (LOAD). A 10 plasma lipid panel, predicted phenoconversion and provided 90% sensitivity and 85% specificity in differentiating an at-risk group from those that would remain cognitively intact. Despite these encouraging results, low positive predictive values limit the clinical usefulness of this panel as a screening tool in subjects aged 70-80 years or younger. In this report, we re-examine our metabolomic data, analyzing baseline plasma specimens from our group of phenoconverters (n = 28) and a matched set of cognitively normal subjects (n = 73), and discover and internally validate a panel of 24 plasma metabolites. The new panel provides a classifier with receiver operating characteristic area under the curve for the discovery and internal validation cohort of 1.0 and 0.995 (95% confidence intervals of 1.0-1.0, and 0.981-1.0), respectively. Twenty-two of the 24 metabolites were significantly dysregulated lipids. While positive and negative predictive values were improved compared to our 10-lipid panel, low positive predictive values provide a reality check on the utility of such biomarkers in this age group (or younger). Through inclusion of additional significantly dysregulated analyte species, our new biomarker panel provides greater accuracy in our cohort but remains limited by predictive power. Unfortunately, the novel metabolite panel alone may not provide improvement in counseling and management of at-risk individuals but may further improve selection of subjects for LOAD secondary prevention trials. We expect that external validation will remain challenging due to our stringent study design, especially compared with more diverse subject cohorts. We do anticipate, however, external validation of reduced plasma lipid species as a predictor of phenoconversion to either prodromal or manifest LOAD.

  6. Plasma 24-metabolite Panel Predicts Preclinical Transition to Clinical Stages of Alzheimer’s Disease

    PubMed Central

    Fiandaca, Massimo S.; Zhong, Xiaogang; Cheema, Amrita K.; Orquiza, Michael H.; Chidambaram, Swathi; Tan, Ming T.; Gresenz, Carole Roan; FitzGerald, Kevin T.; Nalls, Mike A.; Singleton, Andrew B.; Mapstone, Mark; Federoff, Howard J.

    2015-01-01

    We recently documented plasma lipid dysregulation in preclinical late-onset Alzheimer’s disease (LOAD). A 10 plasma lipid panel, predicted phenoconversion and provided 90% sensitivity and 85% specificity in differentiating an at-risk group from those that would remain cognitively intact. Despite these encouraging results, low positive predictive values limit the clinical usefulness of this panel as a screening tool in subjects aged 70–80 years or younger. In this report, we re-examine our metabolomic data, analyzing baseline plasma specimens from our group of phenoconverters (n = 28) and a matched set of cognitively normal subjects (n = 73), and discover and internally validate a panel of 24 plasma metabolites. The new panel provides a classifier with receiver operating characteristic area under the curve for the discovery and internal validation cohort of 1.0 and 0.995 (95% confidence intervals of 1.0–1.0, and 0.981–1.0), respectively. Twenty-two of the 24 metabolites were significantly dysregulated lipids. While positive and negative predictive values were improved compared to our 10-lipid panel, low positive predictive values provide a reality check on the utility of such biomarkers in this age group (or younger). Through inclusion of additional significantly dysregulated analyte species, our new biomarker panel provides greater accuracy in our cohort but remains limited by predictive power. Unfortunately, the novel metabolite panel alone may not provide improvement in counseling and management of at-risk individuals but may further improve selection of subjects for LOAD secondary prevention trials. We expect that external validation will remain challenging due to our stringent study design, especially compared with more diverse subject cohorts. We do anticipate, however, external validation of reduced plasma lipid species as a predictor of phenoconversion to either prodromal or manifest LOAD. PMID:26617567

  7. Apolipoprotein D takes center stage in the stress response of the aging and degenerative brain☆

    PubMed Central

    Dassati, Sarah; Waldner, Andreas; Schweigreiter, Rüdiger

    2014-01-01

    Apolipoprotein D (ApoD) is an ancient member of the lipocalin family with a high degree of sequence conservation from insects to mammals. It is not structurally related to other major apolipoproteins and has been known as a small, soluble carrier protein of lipophilic molecules that is mostly expressed in neurons and glial cells within the central and peripheral nervous system. Recent data indicate that ApoD not only supplies cells with lipophilic molecules, but also controls the fate of these ligands by modulating their stability and oxidation status. Of particular interest is the binding of ApoD to arachidonic acid and its derivatives, which play a central role in healthy brain function. ApoD has been shown to act as a catalyst in the reduction of peroxidized eicosanoids and to attenuate lipid peroxidation in the brain. Manipulating its expression level in fruit flies and mice has demonstrated that ApoD has a favorable effect on both stress resistance and life span. The APOD gene is the gene that is upregulated the most in the aging human brain. Furthermore, ApoD levels in the nervous system are elevated in a large number of neurologic disorders including Alzheimer's disease, schizophrenia, and stroke. There is increasing evidence for a prominent neuroprotective role of ApoD because of its antioxidant and anti-inflammatory activity. ApoD emerges as an evolutionarily conserved anti-stress protein that is induced by oxidative stress and inflammation and may prove to be an effective therapeutic agent against a variety of neuropathologies, and even against aging. PMID:24612673

  8. Sedimentation processes and new age constraints on rifting stages in Lake Baikal: results of deep-water drilling

    NASA Astrophysics Data System (ADS)

    Kuzmin, M. I.; Karabanov, E. B.; Prokopenko, A. A.; Gelety, V. F.; Antipin, V. S.; Williams, D. F.; Gvozdkov, A. N.

    With this paper we present a first attempt to combine the direct results on lithology, composition and age dating in the boreholes BDP-93, BDP-96 and BDP-97 with geological and seismic data from the areas where those sections were drilled. The sedimentary environments represented by the BDP boreholes are markedly different and possess characteristic lithological features. The results of the deep drilling provide the essential means for testing numerous age models used in geological reconstructions of the Lake Baikal rifting dynamics. Neither the basin-wide unconformity interpreted from seismic data, nor the interpreted change from shallow-water to deep-water facies at the boundary of the seismic stratigraphic complexes were found in the BDP-96 boreholes on Academician Ridge. Also, lithology does not support the proposed reconstructions of intense lake level fluctuations and transgressions during the Pliocene at Academician Ridge. The continuous deep-water hemipelagic sedimentation at Academician Ridge has existed for the past 5Ma. The beginning of an intense rifting phase of the Neobaikalian sub-stage and related drastic changes in sedimentation processes were interpreted on seismic sections as the basin-wide unconformity B10. Different age estimates for this boundary ranged from Late Pliocene (3.5Ma) to Plio-Pleistocene boundary. As shown by BDP-96 borehole, B10 is associated with a lithological change from diatomaceous ooze to dense silty clay and not with an erosional contact. The new age for this boundary in BDP-96 is approximately 2.5Ma. This new age constraint suggests that the upper sedimentary strata of Northern Baikal (1.5-1.7km thick) have formed during the past 2.5Ma with average sedimentation rates of 60-70cm/ka. The BDP-93 boreholes at Buguldeika suggest that uplift in Primorsky Range took place prior to 1.07-1.31Ma, a date which exceeds the age of previous geological models.

  9. Age-stage, two-sex life table of Brontispa longissima (Gestro) (Coleoptera: Hispidae) feeding on four palm plant varieties.

    PubMed

    Jin, Tao; Lin, Yu-Ying; Jin, Qi-An; Wen, Hai-Bo; Peng, Zheng-Qiang

    2012-10-01

    The life history of Brontispa longissima (Gestro) (Coleoptera: Hispidae), reared under laboratory conditions on leaves of coconut (Cocos nucifera L.), royal palm [Roystonea regia (Kunth) O.F.Cook], bottle palm [Hyophorbe lagenicaulis (L. Bailey) H.E.Moore], and fishtail palm (Caryota ochlandra Hance) was analyzed using age-stage, two-sex life table. Means and standard errors of population growth parameters were calculated using the jackknife method. Moreover, survival rate and fecundity data were applied to project the population for revealing the different stage structure. The mean intrinsic rates of population growth when reared on each respective leaf type were 0.032, 0.031, 0.019, and 0.044. Individuals reared on C. nucifera achieved the highest net reproduction rate at 114.5 offspring per female. The mean generation times of B. longissima ranged from 93.2 d (reared on C. ochlandrai) to 161.5 d (reared on H. lagenicaulis). Projections from survival rate and fecundity data indicated that B. longissima populations can row considerably faster on C. ochlandra than on the other three host plants. The results validate the two-stage life history approach taken, providing an essential tool for developing and testing future control strategies.

  10. Age-Stage, Two-Sex Life Table Characteristics of Aedes albopictus and Aedes Aegypti in Penang Island, Malaysia.

    PubMed

    Maimusa, Hamisu A; Ahmad, Abu Hassan; Kassim, Nur Faeza A; Rahim, Junaid

    2016-03-01

    The life table developmental attributes of laboratory colonies of wild strains of Aedes albopictus and Aedes aegypti were analyzed and compared based on the age-stage, two-sex life table. Findings inclusive in this study are: adult preoviposition periods, total preoviposition period, mean intrinsic rate of increase (r), mean finite rate of increase (λ), net reproductive rates (R0), and mean generation time (T). The total preadult development time was 9.47 days for Ae. albopictus and 8.76 days for Ae. aegypti. The life expectancy was 19.01 days for Ae. albopictus and 19.94 days for Ae. aegypti. Mortality occurred mostly during the adult stage. The mean development time for each stage insignificantly correlated with temperature for Ae. albopictus (r  =  -0.208, P > 0.05) and (r  =  -0.312, P > 0.05) for Ae. aegypti. The population parameters suggest that Ae. albopictus and Ae. aegypti populations are r-strategists characterized by a high r, a large R0, and short T. This present study provides the first report to compare the life parameters of Ae. albopictus and Ae. aegypti strains from Penang island, Malaysia.

  11. [Change of clinical stomatological parameters in ageing (author's transl)].

    PubMed

    Fassauer, H; Schottke, C

    1978-01-01

    Morphological-functional changes occur in the oral cavity also in depended from the age. The morphological changes of the enamel, dentin, dental pulp, periodont, oral mucosa, salivary glands, tongue, maxillary bone and temporo-mandibular-joint change not only the functional cooperation of all parts in the orofacial system. They show effects for the whole body also. A complete gerostomatological standard does not exist for the whole gnathological system. But single indices for some partial components are known. For the judgement of the caries involvement it is possible to use the DMF-index, for which a special gerostomatological type exist. The periodontal diseases are classified adequately to the ARPA-nomenclature. For the judgement of odontolithiasis and oral hygienic conditions you can use the so called odontolith-Index (CI), the OH (oral hygienic debris) and the so called calculus-index (OHI-S). It is refered to different possibilities for classification of dentition with gaps.

  12. Clinical correlation of extensive-stage small-cell lung cancer genomics

    PubMed Central

    Dowlati, A.; Lipka, M. B.; McColl, K.; Dabir, S.; Behtaj, M.; Kresak, A.; Miron, A.; Yang, M.; Sharma, N.; Fu, P.; Wildey, G.

    2016-01-01

    Background Genomic studies in small-cell lung cancer (SCLC) lag far behind those carried out in nonsmall-cell lung cancer (NSCLC). To date, most SCLC studies have evaluated patients with surgically resectable disease. Here we sought to evaluate the genomic mutation spectrum of ‘every-day’ SCLC patient tumors with extensive stage disease (ES-SCLC) and to correlate mutations with the main clinical outcomes of response to chemotherapy, progression-free (PFS) and overall (OS) survival. Patients and methods A total of 50 SCLC patient tumors were examined in this study; targeted exome sequencing was obtained on 42 patients and whole-exome sequencing on 8 patients. Mutated genes were correlated with clinical outcomes using Kaplan–Meier methods (PFS, OS) and logistic regression (chemo-response). RB1 protein expression was detected by either western blotting of cultured cell lysates or immunohistochemistry of tumor specimens. Results In all, 39 patients had ES-SCLC; 15 patients had either primary refractory/resistant disease and 21 patients had sensitive disease. The two most frequently mutated genes were TP53 (86%) and RB1 (58%); other frequently mutated genes (>10% patients) were involved in epigenetic regulation as well as the mTOR pathway. We identified a number of low-frequency, targetable mutations, including RICTOR, FGFR1, KIT, PTCH1 and RET. Using multivariate analysis, RB1 was the only significant factor (P = 0.038) in predicting response to first-line chemotherapy, with an odds ratio of 5.58 comparing mutant RB1 with wild-type. Patients with mutant RB1 had both better OS (11.7 versus 9.1 months P = 0.04) and PFS (11.2 versus 8.6 months, P = 0.06) compared with patients with wild-type RB1. Interestingly, ∼25% of SCLC cell lines and tumor specimens expressed RB1 protein, possibly representing the subgroup with wild-type RB1. Conclusions We found that SCLC tumors harboring no mutation in RB1 had a poor response to chemotherapy. PMID:26802149

  13. A phase II trial of combined treatment of endoscopic mucosal resection and chemoradiotherapy for clinical stage I esophageal carcinoma: Japan Clinical Oncology Group Study JCOG0508.

    PubMed

    Kurokawa, Yukinori; Muto, Manabu; Minashi, Keiko; Boku, Narikazu; Fukuda, Haruhiko

    2009-10-01

    Standard treatment for clinical stage I esophageal cancer with submucosal invasion (T1b) has been surgical resection. We conducted a Phase II trial to evaluate the efficacy and the safety of combined treatment of endoscopic mucosal resection (EMR) and chemoradiotherapy for clinical stage I (T1b) esophageal cancer. Patients diagnosed as having clinical stage I (T1b) esophageal cancer which is considered to be resectable by EMR are eligible. When pathological examination of the EMR specimen confirms T1b tumor with negative or positive resection margin, the patient undergoes chemoradiotherapy. The study continues until 82 patients with T1b tumor with negative resection margin are enrolled from 20 institutions. The primary endpoint is 3-year overall survival (OS) in pT1b cases with negative resection margin. The secondary endpoints are 3-year OS and progression-free survival in all eligible cases, OS in pT1a-MM cases with margin-negative, complications of EMR and adverse events of chemoradiotherapy. The data from this trial will be expected to provide a non-surgical treatment option to the patients with clinical stage I (T1b) esophageal cancer.

  14. Neurodevelopmental delay among children under the age of three years at immunization clinics in Lagos State, Nigeria - Preliminary report.

    PubMed

    Bakare, Muideen O; Bello-Mojeed, Mashudat A; Munir, Kerim M; Ogun, Oluwayemi C; Eaton, Julian

    2016-04-29

    Late diagnosis and interventions characterize childhood neurodevelopmental disorders in Sub-Saharan Africa. This has negatively impacted on the prognosis of the children with neurodevelopmental disorders. This study examined the prevalence and pattern of neurodevelopmental delays among children under the age of 3 years attending immunization clinics in Lagos State, Nigeria and also affords opportunity of early follow-up and interventions, which had been documented to improve prognosis. The study involved two stage assessments; which consisted of first phase screening of the children for neurodevelopmental delays in immunization clinics at primary healthcare centers Lagos State, Nigeria and second phase which consists of definitive clinical evaluation and follow-up interventions for children screened positive for neurodevelopmental delays. Twenty seven (0.9%) of a total of 3,011 children under the age of 3 years were screened positive for neurodevelopmental delays and subsequently undergoing clinical evaluation and follow-up interventions. Preliminary working diagnoses among these children include cerebral palsy, autism spectrum disorder trait, nutritional deficiency, Down syndrome and Non-specific neurodevelopmental delay with co-morbid seizure disorder accounting for 33.3%, 14.8%, 18.5%, 7.4% and 25.9% respectively. This is a preliminary report that would be followed up with information on medium and long term intervention phase.

  15. Results of volume-staged fractionated Gamma Knife radiosurgery for large complex arteriovenous malformations: obliteration rates and clinical outcomes of an evolving treatment paradigm.

    PubMed

    Franzin, Alberto; Panni, Pietro; Spatola, Giorgio; Vecchio, Antonella Del; Gallotti, Alberto L; Gigliotti, Carmen R; Cavalli, Andrea; Donofrio, Carmine A; Mortini, Pietro

    2016-12-01

    OBJECTIVE There are few reported series regarding volume-staged Gamma Knife radiosurgery (GKRS) for the treatment of large, complex, cerebral arteriovenous malformations (AVMs). The object of this study was to report the results of using volume-staged Gamma Knife radiosurgery for patients affected by large and complex AVMs. METHODS Data from 20 patients with large AVMs were prospectively included in the authors' AVM database between 2004 and 2012. A staging strategy was used when treating lesion volumes larger than 10 cm(3). Hemorrhage and seizures were the presenting clinical feature for 6 (30%) and 8 (40%) patients, respectively. The median AVM volume was 15.9 cm(3) (range 10.1-34.3 cm(3)). The mean interval between stages (± standard deviation) was 15 months (± 9 months). The median margin dose for each stage was 20 Gy (range 18-25 Gy). RESULTS Obliteration was confirmed in 8 (42%) patients after a mean follow-up of 45 months (range 19-87 months). A significant reduction (> 75%) of the original nidal volume was achieved in 4 (20%) patients. Engel Class I-II seizure status was reported by 75% of patients presenting with seizures (50% Engel Class I and 25% Engel Class II) after radiosurgery. After radiosurgery, 71.5% (5/7) of patients who had presented with a worsening neurological deficit reported a complete resolution or amelioration. None of the patients who presented acutely because of hemorrhage experienced a new bleeding episode during follow-up. One (5%) patient developed radionecrosis that caused sensorimotor hemisyndrome. Two (10%) patients sustained a bleeding episode after GKRS, although only 1 (5%) was symptomatic. High nidal flow rate and a time interval between stages of less than 11.7 months were factors significantly associated with AVM obliteration (p = 0.021 and p = 0.041, respectively). Patient age younger than 44 years was significantly associated with a greater than 75% reduction in AVM volume but not with AVM obliteration (p = 0

  16. Genome-wide DNA methylation profiles reveal novel candidate genes associated with meat quality at different age stages in hens

    PubMed Central

    Zhang, Meng; Yan, Feng-Bin; Li, Fang; Jiang, Ke-Ren; Li, Dong-Hua; Han, Rui-Li; Li, Zhuan-Jan; Jiang, Rui-Rui; Liu, Xiao-Jun; Kang, Xiang-Tao; Sun, Gui-Rong

    2017-01-01

    Poultry meat quality is associated with breed, age, tissue and other factors. Many previous studies have focused on distinct breeds; however, little is known regarding the epigenetic regulatory mechanisms in different age stages, such as DNA methylation. Here, we compared the global DNA methylation profiles between juvenile (20 weeks old) and later laying-period (55 weeks old) hens and identified candidate genes related to the development and meat quality of breast muscle using whole-genome bisulfite sequencing. The results showed that the later laying-period hens, which had a higher intramuscular fat (IMF) deposition capacity and water holding capacity (WHC) and less tenderness, exhibited higher global DNA methylation levels than the juvenile hens. A total of 2,714 differentially methylated regions were identified in the present study, which corresponded to 378 differentially methylated genes, mainly affecting muscle development, lipid metabolism, and the ageing process. Hypermethylation of the promoters of the genes ABCA1, COL6A1 and GSTT1L and the resulting transcriptional down-regulation in the later laying-period hens may be the reason for the significant difference in the meat quality between the juvenile and later laying-period hens. These findings contribute to a better understanding of epigenetic regulation in the skeletal muscle development and meat quality of chicken. PMID:28378745

  17. Behavior problems of clinic children: relation to parental marital status, age and sex of child.

    PubMed

    Brady, C P; Bray, J H; Zeeb, L

    1986-07-01

    Behavior problems of 703 children seen in a clinical setting were examined for interactions between and effects of family type (i.e., parental marital status) and age and sex of child. Significant differences were found based on family type, with children of separated, divorced, and remarried parents having more problems. Expected interactions between marital status and age and sex of child were not obtained, although results support prior research with regard to the effects of age and sex.

  18. In vitro assays and clinical trials in red blood cell aging: Lost in translation.

    PubMed

    Prudent, Michel; Tissot, Jean-Daniel; Lion, Niels

    2015-06-01

    The age of erythrocyte concentrates (EC) in transfusion medicine and the adverse outcomes when transfusing long-term-stored EC are highly controversial issues. Whereas the definition of a short-term-stored EC or a long-term-stored EC is unclear in clinical trials, data based on in vitro storage assays can help defining a limit in addition of the expiration date. The present review merges together these data in order to highlight an EC age cut-off and points out potential misleading consideration. The analysis of in vitro data highlights the presence of reversible and irreversible storage lesions and demonstrates that red blood cells (RBC) exhibit two limits during storage: one around 2 weeks and another one around 4 weeks of storage. Of particular importance, the first lesions to appear, i.e. the reversible ones, are per se reversible once transfused, whereas the irreversible lesions are not. In clinical trials, the EC age cut-off for short-term storage is in general fewer than 14 days (11 ± 4 days) and more disperse for long-term-stored EC (17 ± 13 days), regardless the clinical outcomes. Taking together, EC age cut-off in clinical trials does not totally fall into line of in vitro aging data, whereas it is the key criteria in clinical studies. Long-term-stored EC considered in clinical trials are not probably old enough to answer the question: "Does transfusion of long-term-stored EC (older than 4 weeks) result in worse clinical outcomes?" Depending on ethical concerns and clinical practices, older EC than currently assayed in clinical trials should have to be considered. These two worlds trying to understand the aging of erythrocytes and the impact on patients do not seem to speak the same language.

  19. A multi-stage drop-the-losers design for multi-arm clinical trials.

    PubMed

    Wason, James; Stallard, Nigel; Bowden, Jack; Jennison, Christopher

    2017-02-01

    Multi-arm multi-stage trials can improve the efficiency of the drug development process when multiple new treatments are available for testing. A group-sequential approach can be used in order to design multi-arm multi-stage trials, using an extension to Dunnett's multiple-testing procedure. The actual sample size used in such a trial is a random variable that has high variability. This can cause problems when applying for funding as the cost will also be generally highly variable. This motivates a type of design that provides the efficiency advantages of a group-sequential multi-arm multi-stage design, but has a fixed sample size. One such design is the two-stage drop-the-losers design, in which a number of experimental treatments, and a control treatment, are assessed at a prescheduled interim analysis. The best-performing experimental treatment and the control treatment then continue to a second stage. In this paper, we discuss extending this design to have more than two stages, which is shown to considerably reduce the sample size required. We also compare the resulting sample size requirements to the sample size distribution of analogous group-sequential multi-arm multi-stage designs. The sample size required for a multi-stage drop-the-losers design is usually higher than, but close to, the median sample size of a group-sequential multi-arm multi-stage trial. In many practical scenarios, the disadvantage of a slight loss in average efficiency would be overcome by the huge advantage of a fixed sample size. We assess the impact of delay between recruitment and assessment as well as unknown variance on the drop-the-losers designs.

  20. Randomized two-stage Phase II clinical trial designs based on Barnard's exact test.

    PubMed

    Shan, Guogen; Ma, Changxing; Hutson, Alan D; Wilding, Gregory E

    2013-01-01

    In areas such as oncology, two-stage designs are often preferred as compared to one-stage designs due to the ability to stop the trial early when faced with evidence of lack of sufficient efficacy and the associated sample size savings. We present exact two-stage designs based on Barnard's exact test for differences in proportions and compare the designs to those proposed by Kepner ( 2010 ) and Jung ( 2010 ). In addition, we present tables of decision rules under a variety of assumed realities for use in trial planning. The procedure is recommended for use due to the substantial sample size savings experienced.

  1. Is Clinical Stage T2C Prostate Cancer Intermediate or High-Risk Disease?

    PubMed Central

    Klaassen, Zachary; Singh, Abhay A.; Howard, Lauren E.; Feng, Zhaoyong; Trock, Bruce; Terris, Martha K.; Aronson, William J.; Cooperberg, Matthew R.; Amling, Christopher L.; Kane, Christopher J.; Partin, Alan; Han, Misop; Freedland, Stephen J.

    2014-01-01

    Background Clinical stage T2c (cT2c) is an indeterminate factor in prostate cancer (PC) risk stratification. In D’Amico grouping and AUA guidelines, cT2c is high-risk, whereas NCCN and EAU classify cT2c as intermediate-risk. We assessed whether cT2c tumors, without other high-risk factors (cT2c not otherwise specified (cT2c-nos)), behave as intermediate or high-risk by analyzing biochemical recurrence (BCR) after radical prostatectomy. Methods We analyzed 2,759 men from SEARCH and 12,900 men from Johns Hopkins Hospital (JHH) from 1988–2011 and 1982–2012, respectively. Patients were grouped into low (PSA<10ng/mL, Gleason sum≤6, and cT1-T2a), intermediate (PSA 10–20ng/mL, Gleason sum 7, or cT2b) and high-risk PC (PSA>20ng/mL, Gleason sum 8–10, or cT3). Men with cT2c who were not otherwise high-risk (i.e. PSA<20 ng/mL and Gleason sum<8) were placed into a separate category termed cT2c -nos. Associations between cT2c-nos and intermediate-risk, and high-risk patients and BCR were tested using log-rank test and Cox proportional analyses models. Results 99 men (4%) from SEARCH and 202 (2%) from JHH were cT2c-nos. cT2c-nos patients had similar BCR risk as intermediate-risk (SEARCH p=0.27; JHH p=0.23), but significantly lower BCR vs. high-risk (SEARCH p<0.001; JHH p<0.001). When specifically compared to intermediate and high-risk patients, and after adjusting for year and center, cT2c-nos patients had outcomes comparable to intermediate-risk (SEARCH p=0.53; JHH p=0.54), but significantly better than high-risk patients (SEARCH p=0.003; JHH p<0.001). Conclusions Patients with cT2c without other high-risk features had similar outcomes as intermediate-risk and significantly better than high-risk PC. These findings suggest men with cT2c should be considered intermediate-risk. PMID:25492369

  2. Work-family conflict among members of full-time dual-earner couples: an examination of family life stage, gender, and age.

    PubMed

    Allen, Tammy D; Finkelstein, Lisa M

    2014-07-01

    Based on cross-sectional data from the 2008 National Study of the Changing Workforce, this study investigates relationships between gender, age, and work-family conflict across 6 family life stages. Participants were 690 married/partnered employees who worked 35 or more hours a week. Results indicated a small but negative relationship between age and work-family conflict. Work-family conflict was also associated with family stage, with the least amount of conflict occurring during the empty nest stage and the most occurring when the youngest child in the home was 5 years of age or younger. Gender differences were also observed. Specifically, men reported more work interference with family than did women when the youngest child in the home was a teen. Women overall reported more family interference with work than did men. Results concerning age and gender revealed a different pattern demonstrating that family stage is not simply a proxy for age. Age had a main effect on work-to-family conflict that was monotonic in nature and on family to-work conflict that was linear in nature. In conclusion, the results indicate gender, age, and family stage each uniquely relate to work-family conflict.

  3. The Effects of Comorbidity and Age on RTOG Study Enrollment in Stage III Non-Small Cell Lung Cancer Patients Who Are Eligible for RTOG Studies

    SciTech Connect

    Firat, Selim; Byhardt, Roger W.; Gore, Elizabeth

    2010-12-01

    Purpose: To determine the influence of measured comorbidity in Radiation Therapy Oncology Group (RTOG) combined modality therapy (CMT) study enrollment in Stage III non-small cell lung cancer (NSCLC). Methods and Materials: One hundred and seventy-one patients with a Karnofsky Performance Score {>=}70 and clinical Stage III NSCLC were analyzed retrospectively for comorbidity, RTOG study eligibility, and enrollment at initial consultation. Effect of comorbidity scores (Cumulative Illness Rating Scale) were tested on patient selection for CMT, RTOG enrollment, and overall survival. Results: Comorbidity (Grade 4; p < 0.005) and use of radiation only (p {<=} 0.001) were associated with inferior survival independent of other factors. Patient selection for CMT was affected by age ({>=}70, p < 0.001), comorbidity (severity index [SI]> 2, p = 0.001), and weight loss (>5%, p = 0.001). Thirty-three patients (19%) were enrolled in a CMT RTOG study (Group 1). Forty-nine patients (29%) were eligible but not enrolled (Group 2), and 57 (33%) were ineligible (Group 3). The most common ineligibility reasons were weight loss (67%) and comorbidity in the exclusion criteria of the RTOG studies (63%). Group 1 patients were the youngest (p = 0.02), with the lowest comorbidity scores (p < 0.001) and SI (p < 0.001) compared with Groups 2 and 3. Group 3 patients were the oldest with the most unfavorable comorbidity profile. Comorbidity scores (SI >2; p = 0.006) and age ({>=}70; p = 0.05) were independent factors influencing RTOG study enrollment in patients meeting study eligibility requirements (Groups 1 and 2). Conclusions: Comorbidity scales could be useful in stratification of patients in advanced lung cancer trials and interpretation of results particularly regarding the elderly population.

  4. Dental age assessment of adolescents and emerging adults in United Kingdom Caucasians using censored data for stage H of third molar roots.

    PubMed

    Boonpitaksathit, Teelana; Hunt, Nigel; Roberts, Graham J; Petrie, Aviva; Lucas, Victoria S

    2011-10-01

    The root of the third permanent molar is the only dental structure that continues development after completion of growth of the second permanent molar. It is claimed that the lack of a clearly defined end point for completion of growth of the third permanent molar means that this tooth cannot be used for dental age assessment. The aim of this study was to estimate the mean age of attainment of the four stages (E, F, G, and H) of root development of the third molar. The way in which the end point of completion of stage H can be identified is described. A total of 1223 dental panoramic tomographs (DPTs) available in the archives of the Eastman Dental Hospital, London, were used for this study. The ages of the subjects ranged from 12.6 to 24.9 years with 63 per cent of the sample being female. Demirjan's tooth development stages (TDSs), for the first and second molars, were applied to the third molars by a single examiner. For each of stages E, F, and G and for stage H censored data, the mean ages of the males and females were compared, separately within each tooth morphology type using the two sample t-test (P < 0.01). The same test was used to compare the mean ages of the upper and lower third molars on each side, separately for each gender. The mean age of attainment and the 99 per cent confidence interval (CI) for each TDS were calculated for each third molar. The final stage H data were appropriately censored to exclude data above the age of completion of root growth. The results showed that, for each gender, the age in years at which individuals attained each of the four TDSs was approximately normally distributed. The mean age for appropriately censored data was always lower than the corresponding mean age of the inappropriately censored data for stage H (male UR8 19.57, UL8 19.53, LL8 19.91, and LR8 20.02 and female UR8 20.08, UL8 20.13, LL8 20.78, and LR8 20.70). This inappropriately censored data overestimated the mean age for stage H. The appropriately

  5. Regular physical activity is associated with improved small artery distensibility in young to middle-age stage 1 hypertensives.

    PubMed

    Saladini, Francesca; Benetti, Elisabetta; Mos, Lucio; Mazzer, Adriano; Casiglia, Edoardo; Palatini, Paolo

    2014-12-01

    The aim of the present study was to investigate the association of physical activity with small artery elasticity in the early stage of hypertension. We examined 366 young-to-middle-age stage 1 hypertensives (mean blood pressure 145.6±10.3/92.5±5.8 mmHg), divided into two categories of physical activity, sedentary (n=264) and non-sedentary (n=102) subjects. The augmentation index was measured using the Specaway DAT System. Small artery compliance (C2) was measured by applanation tonometry, at the radial artery, with an HDI CR2000 device. After 6 years of follow-up, arterial distensibility assessment was repeated in 151 subjects. Heart rate was lower in active than in sedentary subjects (71.2±8.9 vs 76.6±9.7 bpm, p<0.001). After adjusting for age, sex, heart rate, smoking, and blood pressure, C2 was higher (8.0±2.6 vs 6.4±3.0 ml/mmHg × 100, p=0.008) in non-sedentary than in sedentary patients. The augmentation index was smaller in the former (8.8±20.1 vs 16.8±26.5%, p=0.044) but the difference lost statistical significance after further adjustment for blood pressure. After 6 years, C2 was still higher in the non-sedentary than sedentary subjects. In addition, an improvement in the augmentation index accompanied by a decline in total peripheral resistance was found in the former. These data show that regular physical activity is associated with improved small artery elasticity in the early phase of hypertension. This association persists over time and is independent of blood pressure and heart rate.

  6. Serum protein profiling using an aptamer array predicts clinical outcomes of stage IIA colon cancer: A leave-one-out crossvalidation

    PubMed Central

    Huh, Jung Wook; Kim, Sung Chun; Sohn, Insuk; Jung, Sin-Ho; Kim, Hee Cheol

    2016-01-01

    Background In this study, we established and validated a model for predicting prognosis of stage IIA colon cancer patients based on expression profiles of aptamers in serum. Methods Bloods samples were collected from 227 consecutive patients with pathologic T3N0M0 (stage IIA) colon cancer. We incubated 1,149 serum molecule-binding aptamer pools of clinical significance with serum from patients to obtain aptamers bound to serum molecules, which were then amplified and marked. Oligonucleotide arrays were constructed with the base sequences of the 1,149 aptamers, and the marked products identified above were reacted with one another to produce profiles of the aptamers bound to serum molecules. These profiles were organized into low- and high-risk groups of colon cancer patients based on clinical information for the serum samples. Cox proportional hazards model and leave-one-out cross-validation (LOOCV) were used to evaluate predictive performance. Results During a median follow-up period of 5 years, 29 of the 227 patients (11.9%) experienced recurrence. There were 212 patients (93.4%) in the low-risk group and 15 patients (6.6%) in the high-risk group in our aptamer prognosis model. Postoperative recurrence significantly correlated with age and aptamer risk stratification (p = 0.046 and p = 0.001, respectively). In multivariate analysis, aptamer risk stratification (p < 0.001) was an independent predictor of recurrence. Disease-free survival curves calculated according to aptamer risk level predicted through a LOOCV procedure and age showed significant differences (p < 0.001 from permutations). Conclusion Aptamer risk stratification can be a valuable prognostic factor in stage II colon cancer patients. PMID:26908450

  7. Relationships between flortaucipir PET tau binding and amyloid burden, clinical diagnosis, age and cognition

    PubMed Central

    Devous Sr, Michael D.; Navitsky, Michael; Lu, Ming; Salloway, Stephen; Schaerf, Frederick W.; Jennings, Danna; Arora, Anupa K.; McGeehan, Anne; Lim, Nathaniel C.; Xiong, Hui; Joshi, Abhinay D.; Siderowf, Andrew; Mintun, Mark A.

    2017-01-01

    Abstract The advent of tau-targeted positron emission tomography tracers such as flortaucipir (18F-AV-1451, also known as 18F-T807) have made it possible to investigate the sequence of development of tau and amyloid-β in relationship to age, and to the development of cognitive impairment due to Alzheimer’s disease. In this study, flortaucipir tau and florbetapir amyloid positron emission tomography were obtained for 217 subjects including 16 young and 58 older cognitively normal subjects, 95 subjects with mild cognitive impairment (Mini-Mental State Examination 24–30) and 48 subjects with clinically-defined possible or probable Alzheimer’s disease (Mini-Mental State Examination >10). Images were evaluated visually and quantitatively by regional and voxel-based cortical to cerebellar standard uptake value ratios. For amyloid positron emission tomography positive (Aβ+) subjects, flortaucipir neocortical standard uptake value ratio was significantly higher with more advanced clinical stage (Alzheimer’s disease > mild cognitive impairment > older cognitively normal) and was significantly elevated for Aβ+ mild cognitive impairment and Alzheimer’s disease subjects relative to the respective Aβ− subjects. In contrast, florbetapir Aβ− older cognitively normal subjects showed an increase in flortaucipir standard uptake value ratios in mesial temporal lobe regions (amygdala, hippocampus/choroid plexus region of interest) compared to younger cognitively normal subjects, but no increased standard uptake value ratios in neocortical regions. Analysis of covariance with planned contrasts showed no differences in regional or composite posterior neocortical flortaucipir standard uptake value ratio as a function of diagnostic group among Aβ− older cognitively normal or clinically diagnosed Alzheimer’s disease or mild cognitive impairment subjects. The pattern of flortaucipir distribution among Aβ+ subjects was reminiscent of the cross-sectional distribution

  8. Accuracy of the clinical diagnosis of Alzheimer disease at National Institute on Aging Alzheimer Disease Centers, 2005-2010.

    PubMed

    Beach, Thomas G; Monsell, Sarah E; Phillips, Leslie E; Kukull, Walter

    2012-04-01

    The neuropathologic examination is considered to provide the gold standard for Alzheimer disease (AD). To determine the accuracy of currently used clinical diagnostic methods, clinical and neuropathologic data from the National Alzheimer's Coordinating Center, which gathers information from the network of National Institute on Aging (NIA)-sponsored Alzheimer Disease Centers (ADCs), were collected as part of the National Alzheimer's Coordinating Center Uniform Data Set (UDS) between 2005 and 2010. A database search initially included all 1198 subjects with at least one UDS clinical assessment and who had died and been autopsied; 279 were excluded as being not demented or because critical data fields were missing. The final subject number was 919. Sensitivity and specificity were determined based on "probable" and "possible" AD levels of clinical confidence and 4 levels of neuropathologic confidence based on varying neuritic plaque densities and Braak neurofibrillary stages. Sensitivity ranged from 70.9% to 87.3%; specificity ranged from 44.3% to 70.8%. Sensitivity was generally increased with more permissive clinical criteria and specificity was increased with more restrictive criteria, whereas the opposite was true for neuropathologic criteria. When a clinical diagnosis was not confirmed by minimum levels of AD histopathology, the most frequent primary neuropathologic diagnoses were tangle-only dementia or argyrophilic grain disease, frontotemporal lobar degeneration, cerebrovascular disease, Lewy body disease and hippocampal sclerosis. When dementia was not clinically diagnosed as AD, 39% of these cases met or exceeded minimum threshold levels of AD histopathology. Neurologists of the NIA-ADCs had higher predictive accuracy when they diagnosed AD in subjects with dementia than when they diagnosed dementing diseases other than AD. The misdiagnosis rate should be considered when estimating subject numbers for AD studies, including clinical trials and epidemiologic

  9. Influence of histological degree of seminiferous tubular degeneration and stage of seminiferous cycle on the proliferation of spermatogonia in aged Syrian hamster (Mesocricetus auratus).

    PubMed

    Bernal-Mañas, C M; Cortes, S; Morales, E; Horn, R; Seco-Rovira, V; Beltran-Frutos, E; Ferrer, C; Canteras, M; Pastor, L M

    2014-08-01

    The ageing testis is associated with germ loss in the seminiferous epithelium and a decrease in spermatogonia proliferation. In this work, we study whether the stages of the seminiferous epithelium cycle and/or the degree of histological tubular degeneration resulting from ageing is related with this decrease in spermatogonia proliferation. Eleven hamsters were used, five aged 6 months and six aged 24 months. In both groups, the proliferative activity was studied by BrdU immunostaining. The number of BrdU-positive and BrdU-negative cells was measured, providing the overall proliferation index in adult and aged testes. The mean number of BrdU-positive cells was also determined for each degree of histological degeneration of seminiferous epithelium, and a spermatogonia proliferation index was obtained for each stage of the seminiferous cycle. Ageing caused an overall decrease in the BrdU-positive cell percentage and a decrease in the number of BrdU-positive cells in the tubular sections with hypospermatogenesis, the sloughing of germ cells and maturation arrest, these changes being similar in both young and old animals. The spermatogonia proliferation index was only seen to be significantly lower in ageing hamster in stages VII-VIII of the seminiferous epithelium cycle. In conclusion, the overall decrease in proliferation observed in aged seminiferous epithelium is correlated with an increase in the number of degenerated sections of the seminiferous tubules, and this decrease is a phenomenon which occurs in specific stages of the seminiferous cycle.

  10. N-acetylaspartate decrease in acute stage of ischemic stroke: a perspective from experimental and clinical studies.

    PubMed

    Igarashi, Hironaka; Suzuki, Yuji; Huber, Vincent J; Ida, Masahiro; Nakada, Tsutomu

    2015-01-01

    N-acetylaspartate (NAA) appears in a prominent peak in proton magnetic resonance spectroscopy ((1)H-MRS) of the brain. Exhibition by NAA of time-dependent attenuation that reflects energy metabolism during the acute stage of cerebral ischemia makes this metabolite a unique biomarker for assessing ischemic stroke. Although magnetic resonance (MR) imaging is a powerful technique for inspecting the pathological changes that occur during ischemic stroke, biomarkers that directly reflect the drastic metabolic changes associated with acute-stage ischemia are strongly warranted for appropriate therapeutic decision-making in daily clinical settings. In this review, we provide a brief overview of NAA metabolism and focus on the use of attenuation in NAA as a means for assessing the pathophysiological changes that occur during the acute stage of ischemic stroke.

  11. Adjuvant systemic chemotherapy for stages II and III colon cancer after complete resection: a clinical practice guideline

    PubMed Central

    Meyers, B.M.; Cosby, R.; Quereshy, F.; Jonker, D.

    2016-01-01

    Background Updated practice guidelines on adjuvant chemotherapy for completely resected colon cancer are lacking. In 2008, Cancer Care Ontario’s Program in Evidence-Based Care developed a guideline on adjuvant therapy for stages ii and iii colon cancer. With newer regimens being assessed in this patient population and older agents being either abandoned because of non-effectiveness or replaced by agents that are more efficacious, a full update of the original guideline was undertaken. Methods Literature searches (January 1987 to August 2015) of medline, embase, and the Cochrane Library were conducted; in addition, abstracts from the American Society of Clinical Oncology, the European Society for Medical Oncology, and the European Cancer Congress were reviewed (the latter for January 2007 to August 2015). A practice guideline was drafted that was then scrutinized by internal and external reviewers whose comments were incorporated into the final guideline. Results Twenty-six unique reports of eighteen randomized controlled trials and thirteen unique reports of twelve meta-analyses or pooled analyses were included in the evidence base. The 5 recommendations developed included 3 for stage ii colon cancer and 2 for stage iii colon cancer. Conclusions Patients with completely resected stage iii colon cancer should be offered adjuvant 5-fluorouracil (5fu)–based chemotherapy with or without oxaliplatin (based on definitive data for improvements in survival and disease-free survival). Patients with resected stage ii colon cancer without “high-risk” features should not receive adjuvant chemotherapy. For patients with “high-risk” features, 5fu-based chemotherapy with or without oxaliplatin should be offered, although no clinical trials have been conducted to conclusively demonstrate the same benefits seen in stage iii colon cancer. PMID:28050138

  12. Clinical trials and late-stage drug development for Alzheimer’s disease: an appraisal from 1984 to 2014

    PubMed Central

    Schneider, Lon S.; Mangialasche, Francesca; Andreasen, Niels; Feldman, Howard; Giacobini, Ezio; Jones, Roy; Mantua, Valentina; Mecocci, Patrizia; Pani, Luca; Winblad, Bengt; Kivipelto, Miia

    2014-01-01

    The modern era of drug development for Alzheimer’s disease began with the proposal of the cholinergic hypothesis of memory impairment and the 1984 research criteria for Alzheimer’s disease. Since then, despite the evaluation of numerous potential treatments in clinical trials, only four cholinesterase inhibitors and memantine have shown sufficient safety and efficacy to allow marketing approval at an international level. Although this is probably because the other drugs tested were ineffective, inadequate clinical development methods have also been blamed for the failures. Here we review the development of treatments for Alzheimer’s disease during the past 30 years, considering the drugs, potential targets, late-stage clinical trials, development methods, emerging use of biomarkers and evolution of regulatory considerations in order to summarize advances and anticipate future developments. We have considered late-stage Alzheimer’s disease drug development from 1984 to 2013, including individual clinical trials, systematic and qualitative reviews, meta-analyses, methods, commentaries, position papers and guidelines. We then review the evolution of drugs in late clinical development, methods, biomarkers and regulatory issues. Although a range of small molecules and biological products against many targets have been investigated in clinical trials, the predominant drug targets have been the cholinergic system and the amyloid cascade. Trial methods have evolved incrementally: inclusion criteria have largely remained focused on mild to moderate Alzheimer’s disease criteria, recently extending to early or prodromal Alzheimer disease or ‘mild cognitive impairment due to Alzheimer’s disease’, for drugs considered to be disease modifying. The duration of trials has remained at 6 to 12 months for drugs intended to improve symptoms; 18- to 24-month trials have been established for drugs expected to attenuate clinical course. Cognitive performance, activities

  13. Clinical trials and late-stage drug development for Alzheimer's disease: an appraisal from 1984 to 2014.

    PubMed

    Schneider, L S; Mangialasche, F; Andreasen, N; Feldman, H; Giacobini, E; Jones, R; Mantua, V; Mecocci, P; Pani, L; Winblad, B; Kivipelto, M

    2014-03-01

    The modern era of drug development for Alzheimer's disease began with the proposal of the cholinergic hypothesis of memory impairment and the 1984 research criteria for Alzheimer's disease. Since then, despite the evaluation of numerous potential treatments in clinical trials, only four cholinesterase inhibitors and memantine have shown sufficient safety and efficacy to allow marketing approval at an international level. Although this is probably because the other drugs tested were ineffective, inadequate clinical development methods have also been blamed for the failures. Here, we review the development of treatments for Alzheimer's disease during the past 30 years, considering the drugs, potential targets, late-stage clinical trials, development methods, emerging use of biomarkers and evolution of regulatory considerations in order to summarize advances and anticipate future developments. We have considered late-stage Alzheimer's disease drug development from 1984 to 2013, including individual clinical trials, systematic and qualitative reviews, meta-analyses, methods, commentaries, position papers and guidelines. We then review the evolution of drugs in late clinical development, methods, biomarkers and regulatory issues. Although a range of small molecules and biological products against many targets have been investigated in clinical trials, the predominant drug targets have been the cholinergic system and the amyloid cascade. Trial methods have evolved incrementally: inclusion criteria have largely remained focused on mild-to-moderate Alzheimer's disease criteria, recently extending to early or prodromal Alzheimer disease or 'mild cognitive impairment due to Alzheimer's disease', for drugs considered to be disease modifying. The duration of trials has remained at 6-12 months for drugs intended to improve symptoms; 18- to 24-month trials have been established for drugs expected to attenuate clinical course. Cognitive performance, activities of daily living

  14. Palynology, geochemistry and Re-Os age of the Lower-Middle Pennsylvanian stage boundary, central Appalachian basin, USA

    NASA Astrophysics Data System (ADS)

    Geboy, N.; Tripathy, G. R.; Ruppert, L. F.; Eble, C. F.; Blake, B. M.; Hannah, J. L.; Stein, H. J.

    2014-12-01

    Wales and Germany and therefore has implications across the Carboniferous Euramerican Belt. Further, the Betsie has been interpreted to represent the Lower-Middle Pennsylvanian stage boundary in North America, making this directly measured age an important marker not only within the CAB but also for refinement of the Carboniferous timescale.

  15. Clinical outcomes of advanced-stage glassy cell carcinoma of the uterine cervix: a need for reappraisal

    PubMed Central

    Yoon, Nara; Kim, Ji-Ye; Kim, Hyun-Soo

    2016-01-01

    We performed a retrospective analysis of the clinical features and patient outcomes for advanced-stage glassy cell carcinoma of the uterine cervix. The study was restricted to cases in which the glassy cell features constituted at least 95% of the biopsied specimen. During the study period, 675 patients were diagnosed with primary cervical carcinoma. Five (0.7%) of the 675 patients had cervical glassy cell carcinoma; of these, three were premenopausal, and two were postmenopausal. Abnormal vaginal bleeding was the most frequent presenting symptom. Glassy cell carcinoma presented as a fungating, exophytic, or infiltrative mass. The greatest tumor dimension ranged from 3 to 9 cm. All patients had parametrial extension. Four patients had stage IIB tumors, and one had a stage IIIB tumor. All patients received concurrent chemoradiation therapy. The patient with a stage IIIB tumor died of hypovolemic shock caused by upper gastrointestinal bleeding during radiation therapy. Three patients with stage IIB tumors survived for more than 8 years without tumor recurrence or metastasis. One of these three patients died of pelvic recurrence 10 years after the initial diagnosis. Cervical glassy cell carcinoma has traditionally been considered an aggressive, highly malignant tumor with poor prognosis, but our data suggest that patient survival is not significantly decreased compared with other histological types of cervical carcinoma. It will be necessary to analyze patient outcomes using a larger number of cervical glassy cell carcinoma cases to confirm our findings. PMID:27793022

  16. Parenting clinically anxious versus healthy control children aged 4-12 years.

    PubMed

    van der Sluis, C M; van Steensel, F J A; Bögels, S M

    2015-05-01

    This study investigated whether parenting behaviors differed between parents of 68 clinically anxious children and 106 healthy control children aged 4-12 years. The effects of parent gender, child gender and child age on parenting were explored. Mothers and fathers completed a questionnaire to assess parenting behaviors in for children hypothetically anxious situations. Results showed that parents of clinically anxious children reported more anxiety-enhancing parenting (reinforcement of dependency and punishment) as well as more positive parenting (positive reinforcement). For the clinical sample, fathers reported using more modeling/reassurance than mothers, and parents reported using more force with their 4-7-year-olds than with their 8-12-year-olds. No interaction effects were found for child gender with child anxiety status on parenting. Results indicate that for intervention, it is important to measure parenting behaviors, and to take into account father and mother differences and the age of the child.

  17. Population Analysis of Adverse Events in Different Age Groups Using Big Clinical Trials Data

    PubMed Central

    Eldredge, Christina; Cho, Chi C; Cisler, Ron A

    2016-01-01

    Background Understanding adverse event patterns in clinical studies across populations is important for patient safety and protection in clinical trials as well as for developing appropriate drug therapies, procedures, and treatment plans. Objectives The objective of our study was to conduct a data-driven population-based analysis to estimate the incidence, diversity, and association patterns of adverse events by age of the clinical trials patients and participants. Methods Two aspects of adverse event patterns were measured: (1) the adverse event incidence rate in each of the patient age groups and (2) the diversity of adverse events defined as distinct types of adverse events categorized by organ system. Statistical analysis was done on the summarized clinical trial data. The incident rate and diversity level in each of the age groups were compared with the lowest group (reference group) using t tests. Cohort data was obtained from ClinicalTrials.gov, and 186,339 clinical studies were analyzed; data were extracted from the 17,853 clinical trials that reported clinical outcomes. The total number of clinical trial participants was 6,808,619, and total number of participants affected by adverse events in these trials was 1,840,432. The trial participants were divided into eight different age groups to support cross-age group comparison. Results In general, children and older patients are more susceptible to adverse events in clinical trial studies. Using the lowest incidence age group as the reference group (20-29 years), the incidence rate of the 0-9 years-old group was 31.41%, approximately 1.51 times higher (P=.04) than the young adult group (20-29 years) at 20.76%. The second-highest group is the 50-59 years-old group with an incidence rate of 30.09%, significantly higher (P<.001) when compared with the lowest incidence in the 20-29 years-old group. The adverse event diversity also increased with increase in patient age. Clinical studies that recruited older

  18. Clinical and Immunological Features of HIV-Infection in Children Aged 3-5 and 6-14 Years.

    PubMed

    Sizyakina, Ludmila P.; Denisenko, V. B.; Simovanyan, E. N.

    1998-04-01

    Ninety-five HIV-infected children aged 3-5 and 6-14 years were examined. Clinical picture matched primary symptoms of stage IIV (phase of generalized lymphadenopathy by Pokrovsky V.I. classification, 1989) and included basic symptoms associated with HIV cytopathogenic action. Local opportunistic infections, either without damage of vital organs (phase IIIA of the secondary stage), or with damage of these organs (phase IIIB) were observed in patients with pre-AIDS. Generalized opportunistic infections and malignant tumors developed in patients with AIDS (phase IIIB and terminal stage IV). High frequency of bacterial infections, bacterial sepsis, splenomegaly, respiratory, gastrointestinal, cerebral, cardiac, common-infections syndromes, and rapid progression characterized the disease in young children. Local and generalized viral, fungal and protozoal infections were more frequently revealed in older children. Immunological alterations (T cell immunodeficiency, polyclonal activation of B lymphocytes, abnormalities of neutrophil metabolism) were diognosed in all children with phase IIV and were the most pronounced in young children. Progressive B lymphocyte polyclonal activation in young children, T cell immunodeficiency in older children and activation of neutrophil metabolism in those with pre-AIDS were observed. T cell immunodeficiency, B lymphocyte polyclonal activation, decreased neutrophil metabolism progressed steadily in all the patients with AIDS.

  19. Clinical stage 1 non-Hodgkin's lymphoma: long-term follow-up of patients treated by the British National Lymphoma Investigation with radiotherapy alone as initial therapy.

    PubMed Central

    Vaughan Hudson, B.; Vaughan Hudson, G.; MacLennan, K. A.; Anderson, L.; Linch, D. C.

    1994-01-01

    A retrospective analysis was performed of 451 adult patients with clinical stage 1/1E non-Hodgkin's lymphoma treated initially with radiotherapy alone. Histopathologically 208 patients had low-grade disease and 243 patients high-grade disease. The complete remission (CR) rate was higher in patients with low-grade disease (98%) than in those with high-grade disease (84%) (P < 0.0001). The relapse rate was similar in both histological categories, and relapse usually occurred within 5 years. The resulting overall actuarial percentage of patients achieving CR and remaining disease free (at 10 years) was 47% in patients with low-grade disease and 45% for those with high-grade disease. Salvage therapy was frequently successful in younger patients, and the overall cause-specific survival at 10 years was 71% for low-grade disease and 67% for high-grade disease. In those patients under 60 years of age at diagnosis, the overall cause-specific survival at 10 years was 84% and 80% for those with low-grade and high-grade disease respectively. These long-term results in young patients with clinical stage 1 disease are encouraging, and it will be difficult to demonstrate improved survival with initial chemotherapy either with or without radiotherapy, until new prognostic factors are found to identify poor-risk patients. PMID:8198975

  20. An International Multi-Institutional Validation of Age 55 Years as a Cutoff for Risk Stratification in the AJCC/UICC Staging System for Well-Differentiated Thyroid Cancer

    PubMed Central

    Nixon, Iain J.; Wang, Laura Y.; Migliacci, Jocelyn C.; Eskander, Antoine; Campbell, Michael J.; Aniss, Ahmad; Morris, Lilah; Vaisman, Fernanda; Corbo, Rossana; Momesso, Denise; Vaisman, Mario; Carvalho, Andre; Learoyd, Diana; Leslie, William D.; Nason, Richard W.; Kuk, Deborah; Wreesmann, Volkert; Morris, Luc; Palmer, Frank L.; Ganly, Ian; Patel, Snehal G.; Singh, Bhuvanesh; Tuttle, R. Michael; Shaha, Ashok R.; Gönen, Mithat; Pathak, K. Alok; Shen, Wen T.; Sywak, Mark; Kowalski, Luis; Freeman, Jeremy; Perrier, Nancy; Shah, Jatin P.

    2016-01-01

    Background: Age is a critical factor in outcome for patients with well-differentiated thyroid cancer. Currently, age 45 years is used as a cutoff in staging, although there is increasing evidence to suggest this may be too low. The aim of this study was to assess the potential for changing the cut point for the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) staging system from 45 years to 55 years based on a combined international patient cohort supplied by individual institutions. Methods: A total of 9484 patients were included from 10 institutions. Tumor (T), nodes (N), and metastasis (M) data and age were provided for each patient. The group was stratified by AJCC/UICC stage using age 45 years and age 55 years as cutoffs. The Kaplan–Meier method was used to calculate outcomes for disease-specific survival (DSS). Concordance probability estimates (CPE) were calculated to compare the degree of concordance for each model. Results: Using age 45 years as a cutoff, 10-year DSS rates for stage I–IV were 99.7%, 97.3%, 96.6%, and 76.3%, respectively. Using age 55 years as a cutoff, 10-year DSS rates for stage I–IV were 99.5%, 94.7%, 94.1%, and 67.6%, respectively. The change resulted in 12% of patients being downstaged, and the downstaged group had a 10-year DSS of 97.6%. The change resulted in an increase in CPE from 0.90 to 0.92. Conclusions: A change in the cutoff age in the current AJCC/UICC staging system from 45 years to 55 years would lead to a downstaging of 12% of patients, and would improve the statistical validity of the model. Such a change would be clinically relevant for thousands of patients worldwide by preventing overstaging of patients with low-risk disease while providing a more realistic estimate of prognosis for those who remain high risk. PMID:26914539

  1. Critical action research applied in clinical placement development in aged care facilities.

    PubMed

    Xiao, Lily D; Kelton, Moira; Paterson, Jan

    2012-12-01

    The aim of this study was to develop quality clinical placements in residential aged care facilities for undergraduate nursing students undertaking their nursing practicum topics. The proportion of people aged over 65 years is expected to increase steadily from 13% in 2006 to 26% of the total population in Australia in 2051. However, when demand is increasing for a nursing workforce competent in the care of older people, studies have shown that nursing students generally lack interest in working with older people. The lack of exposure of nursing students to quality clinical placements is one of the key factors contributing to this situation. Critical action research built on a partnership between an Australian university and five aged care organisations was utilised. A theoretical framework informed by Habermas' communicative action theory was utilised to guide the action research. Multiple research activities were used to support collaborative critical reflection and inform actions throughout the action research. Clinical placements in eight residential aged care facilities were developed to support 179 nursing students across three year-levels to complete their practicum topics. Findings were presented in three categories described as structures developed to govern clinical placement, learning and teaching in residential aged care facilities.

  2. Multi-stage uplift of the Rocky Mountains: new age constraints on the Telluride Conglomerate and regional compilation of apatite fission track ages

    NASA Astrophysics Data System (ADS)

    Donahue, M. S.; Karlstrom, K. E.; Gonzales, D. A.; Pecha, M.; McKeon, R. E.

    2011-12-01

    The Telluride Conglomerate, exposed on the western flanks of Oligocene caldera complexes of the San Juan Mountains of Colorado, has historically been considered an Eocene alluvial deposit overlying the "Rocky Mountain erosion surface" and pre-dating Oligocene volcanism. Measured sections show that the Telluride preserves an unroofing sequence with basal units dominated by Paleozoic sedimentary clasts transitioning into upper units dominated by locally derived Proterozoic basement mixed with previously unrecognized andesitic Oligocene volcanics. Paleoflow directions and thicknesses of the preserved unit indicate the Telluride Conglomerate was deposited by a large, high-energy WNW- flowing braided river system. Detrital zircon analysis indicates minimum ages for individual grains within the Telluride Conglomerate of 28.0 to 31.5 Ma. This, plus the entrained volcanic clasts, redefines the unit as being of Oligocene age and indicates that conglomeratic deposition overlapped with regional San Juan volcanism and just predated major caldera eruptions at 28.4 Ma (San Juan and Uncompahgre) and 27.6 Ma (Silverton). We interpret the deposition of the Telluride Conglomerate to be the depositional response to regional uplift and erosion related to early stages of San Juan magmatism. These units have undergone significant post-depositional tectonism: the Telluride Conglomerate is found at ~9,000ft elevation near Telluride, CO, but is at ~13,000' at its westernmost exposure at Mt. Wilson. We attribute this differential uplift to be associated with faulting, pluton emplacement, and additional mantle driven uplift associated with the emplacement and cooling of the Wilson Stock in the last 20-22 Ma as documented by Miocene cooling seen in apatite helium (AHe) ages. This cooling fits into our regional compilation of published apatite fission track (AFT) and AHe data showing temporally and spatially partitioned Cenozoic cooling indicative of multistage uplift of the Rocky Mountain

  3. Assessment of Choroidal Microstructure and Subfoveal Thickness Change in Eyes With Different Stages of Age-Related Macular Degeneration

    PubMed Central

    Lu, Linna; Xu, Shiqiong; He, Fangling; Liu, Yan; Zhang, Yidan; Wang, Jing; Wang, Zhiliang; Fan, Xianqun

    2016-01-01

    Abstract Age-related macular degeneration (AMD) is a major cause of irreversible blindness. Choroidal structural changes seem to be inevitable in AMD pathogenesis. Our study revealed associated choroidal microstructural changes in AMD eyes. The aim of the study was to compare choroidal microstructural changes in eyes with AMD of different stages. The study was a retrospective, cross-sectional case series. The participants comprised of 32 age-matched normal eyes as controls, and 26 fellow uninvolved eyes of intermediate/late AMD, 29 of early AMD, 28 of intermediate AMD, and 39 of late AMD. All subjects underwent comprehensive ophthalmologic examination. The choroid images, including subfoveal choroidal thickness, percentage of Sattler layer area, and en face images of the choroid, were obtained using spectral-domain optical coherence tomography. The main outcome measures were subfoveal choroidal thickness changes, percentage of Sattler layer area changes, and en face images of the choroid in AMD eyes. One hundred fifty-four eyes of 96 individuals with mean age of 67.1±9.2 years were included. The mean subfoveal choroidal thickness was 295.4 ± 56.8 μm in age-matched normal eyes, 306.7 ± 68.4 μm in fellow uninvolved eyes with AMD, 293.8 ± 80.4 μm in early AMD, 215.6 ± 80.4 μm in intermediate AMD, and 200.4 ± 66.6 μm in late AMD (F = 14.2, all P < 0.001). Choroidal thickness was greater in early AMD eyes than in intermediate/late AMD eyes (P < 0.001). Mean percentage of Sattler layer area in each group showed a similar tendency. Microstructure of the choroid showed reduced vascular density of Sattler layer areas in late AMD eyes compared with normal eyes. Decreasing subfoveal choroidal thickness and percentage of Sattler layer area were demonstrated in the progression of AMD. The choroidal change was related to atrophy of the microstructural changes of underlying capillaries and medium-sized vessels. PMID:26962799

  4. Relation between clinical findings and progression of cerebral cortical pathology in MM1-type sporadic Creutzfeldt-Jakob disease: proposed staging of cerebral cortical pathology.

    PubMed

    Iwasaki, Yasushi; Tatsumi, Shinsui; Mimuro, Maya; Kitamoto, Tetsuyuki; Hashizume, Yoshio; Yoshida, Mari

    2014-06-15

    In our pathologic observation of the cerebral cortex including the neocortex, hippocampus, and limbic cortex in 43 Japanese patients with MM1-type sporadic Creutzfeldt-Jakob disease, the earliest pathologic finding was spongiform change and next was gliosis. Subsequently, neuropil rarefaction appeared, followed by neuron loss. On the basis of these observations, we propose the following cortical pathologic staging: Stage I, spongiform change; Stage II, hypertrophic astrocytosis; Stage III, neuropil rarefaction; Stage IV, neuron loss; Stage V, status spongiosus; and Stage VI, large cavity formation. We also suggest a more simple staging classification: Stages I and II, mild; Stages III and IV, moderate; and Stages V and VI, severe involvement. Based on statistical analysis of the cases, strong correlation coefficients were obtained between the neocortical and limbic pathologic stage and both total disease duration and brain weight. We estimated that the first observation times of cortical hyperintensity on diffusion-weighted images of magnetic resonance imaging, myoclonus, and periodic sharp wave complexes on the electroencephalogram approximately correspond to the early phase of Stage II of the neocortex. The time to reach the akinetic mutism state approximately corresponds to the middle phase of Stage II of the neocortex. Therefore, we think that approximate clinical manifestations at death, total disease duration, and brain weight can be estimated according to the pathologic stage of the neocortex or limbic cortex. Panencephalopathic-type pathology appeared approximately 12 months after disease onset, and this time approximately corresponds to the middle phase of Stage III of the neocortex.

  5. Frameworks for Proof-of-Concept Clinical Trials of Interventions That Target Fundamental Aging Processes.

    PubMed

    Justice, Jamie; Miller, Jordan D; Newman, John C; Hashmi, Shahrukh K; Halter, Jeffrey; Austad, Steve N; Barzilai, Nir; Kirkland, James L

    2016-11-01

    Therapies targeted at fundamental processes of aging may hold great promise for enhancing the health of a wide population by delaying or preventing a range of age-related diseases and conditions-a concept dubbed the "geroscience hypothesis." Early, proof-of-concept clinical trials will be a key step in the translation of therapies emerging from model organism and preclinical studies into clinical practice. This article summarizes the outcomes of an international meeting partly funded through the NIH R24 Geroscience Network, whose purpose was to generate concepts and frameworks for early, proof-of-concept clinical trials for therapeutic interventions that target fundamental processes of aging. The goals of proof-of-concept trials include generating preliminary signals of efficacy in an aging-related disease or outcome that will reduce the risk of conducting larger trials, contributing data and biological samples to support larger-scale research by strategic networks, and furthering a dialogue with regulatory agencies on appropriate registration indications. We describe three frameworks for proof-of-concept trials that target age-related chronic diseases, geriatric syndromes, or resilience to stressors. We propose strategic infrastructure and shared resources that could accelerate development of therapies that target fundamental aging processes.

  6. Frameworks for Proof-of-Concept Clinical Trials of Interventions That Target Fundamental Aging Processes

    PubMed Central

    Justice, Jamie; Miller, Jordan D.; Newman, John C.; Hashmi, Shahrukh K.; Halter, Jeffrey; Austad, Steve N.; Barzilai, Nir

    2016-01-01

    Therapies targeted at fundamental processes of aging may hold great promise for enhancing the health of a wide population by delaying or preventing a range of age-related diseases and conditions—a concept dubbed the “geroscience hypothesis.” Early, proof-of-concept clinical trials will be a key step in the translation of therapies emerging from model organism and preclinical studies into clinical practice. This article summarizes the outcomes of an international meeting partly funded through the NIH R24 Geroscience Network, whose purpose was to generate concepts and frameworks for early, proof-of-concept clinical trials for therapeutic interventions that target fundamental processes of aging. The goals of proof-of-concept trials include generating preliminary signals of efficacy in an aging-related disease or outcome that will reduce the risk of conducting larger trials, contributing data and biological samples to support larger-scale research by strategic networks, and furthering a dialogue with regulatory agencies on appropriate registration indications. We describe three frameworks for proof-of-concept trials that target age-related chronic diseases, geriatric syndromes, or resilience to stressors. We propose strategic infrastructure and shared resources that could accelerate development of therapies that target fundamental aging processes. PMID:27535966

  7. Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline

    PubMed Central

    Harris, Lyndsay N.; McShane, Lisa M.; Andre, Fabrice; Collyar, Deborah E.; Gonzalez-Angulo, Ana M.; Hammond, Elizabeth H.; Kuderer, Nicole M.; Liu, Minetta C.; Mennel, Robert G.; Van Poznak, Catherine; Bast, Robert C.; Hayes, Daniel F.

    2016-01-01

    Purpose To provide recommendations on appropriate use of breast tumor biomarker assay results to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer. Methods A literature search and prospectively defined study selection sought systematic reviews, meta-analyses, randomized controlled trials, prospective-retrospective studies, and prospective comparative observational studies published from 2006 through 2014. Outcomes of interest included overall survival and disease-free or recurrence-free survival. Expert panel members used informal consensus to develop evidence-based guideline recommendations. Results The literature search identified 50 relevant studies. One randomized clinical trial and 18 prospective-retrospective studies were found to have evaluated the clinical utility, as defined by the guideline, of specific biomarkers for guiding decisions on the need for adjuvant systemic therapy. No studies that met guideline criteria for clinical utility were found to guide choice of specific treatments or regimens. Recommendations In addition to estrogen and progesterone receptors and human epidermal growth factor receptor 2, the panel found sufficient evidence of clinical utility for the biomarker assays Oncotype DX, EndoPredict, PAM50, Breast Cancer Index, and urokinase plasminogen activator and plasminogen activator inhibitor type 1 in specific subgroups of breast cancer. No biomarker except for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 was found to guide choices of specific treatment regimens. Treatment decisions should also consider disease stage, comorbidities, and patient preferences. PMID:26858339

  8. Repairing the Aged Parkinsonian Striatum: Lessons from the Lab and Clinic

    PubMed Central

    Mercado, Natosha M; Collier, Timothy J; Freeman, Thomas; Steece-Collier, Kathy

    2016-01-01

    The primary risk factor associated with Parkinson's disease (PD) is advanced age. While there are symptomatic therapies for PD, efficacy of these eventually wane and/or side-effects develop over time. An alternative experimental therapy that has received a great deal of attention over the past several decades has been neural transplantation aimed at replacing nigral dopamine (DA) neurons that degenerate in PD. However, in PD patients and parkinsonian rats, advanced age is associated with inferior benefit following intrastriatal grafting of embryonic DA neurons. Traditionally it has been thought that decreased therapeutic benefit results from the decreased survival of grafted DA neurons and the accompanying poor reinnervation observed in the aged host. However, recent clinical and preclinical data suggest that factors inherent to the aged striatum per se limit successful brain repair. In this short communication, we focus discussion on the implications of our recent grafting study in aged parkinsonian rats, with additional emphasis on a recent clinical report of the outcome of cell therapy in an aged PD patient with long-term (24 years) survival of DA neuron grafts. To address aging as a limiting factor in successful brain repair, we use the example of cell transplantation as a means to interrogate the environment of the aged striatum and identify factors that may, or may not, respond to interventions aimed at improving the prospects for adequate repair of the aged brain. We offer discussion of how these recent reports, in the context of other historical grafting studies, might provide new insight into specific risk factors that have potential to negatively impact all DA cell or terminal replacement strategies for clinical use in PD. PMID:28111608

  9. The experiences of close persons caring for people with chronic kidney disease stage 5 on conservative kidney management: Contested discourses of ageing

    PubMed Central

    Myers, Jason; Smith, Glenn; Higgs, Paul; Burns, Aine; Hopkins, Katherine; Jones, Louise

    2014-01-01

    Chronic kidney disease stage 5 is a global health challenge in the context of population ageing across the world. The range of treatment options available to patients at all ages has increased and includes transplantation and dialysis. However, these options are often seen as inappropriate for older frailer patients who are now offered the option of conservative kidney management, which is presented as a non-invasive alternative to dialysis, involving symptom management and addressing psychosocial needs. In this study, we conducted qualitative interviews with 26 close persons caring for someone with chronic kidney disease stage 5 in the United Kingdom to investigate how conservative kidney management interacted with implicit ideas of ageing, in both the experience of conservative kidney management and the understanding of the prognosis and future care of the kidney disease. Our findings highlighted participant confusion about the nature of conservative kidney management, which stems from an initial lack of clarity about how conservative kidney management differed from conventional treatments for chronic kidney disease stage 5. In particular, some respondents were not aware of the implicit palliative nature of the intervention or indeed the inevitable end-of-life issues. Although these findings can be situated within the context of communication failure, we would further argue that they also bring to the surface tensions in the discourses surrounding ageing and old age, drawing on the use of a ‘natural’ and a ‘normal’ paradigm of ageing. In the context of chronic kidney disease stage 5, more patients are being dialysed at older ages, but conservative kidney management is being advanced as a better option than dialysis in terms of quality of life and experience. However, in doing so, conservative kidney management implicitly draws on a notion of older age that echoes natural ageing rather than advocate a more interventionist approach. The role of discourses

  10. The experiences of close persons caring for people with chronic kidney disease stage 5 on conservative kidney management: contested discourses of ageing.

    PubMed

    Low, Joe; Myers, Jason; Smith, Glenn; Higgs, Paul; Burns, Aine; Hopkins, Katherine; Jones, Louise

    2014-11-01

    Chronic kidney disease stage 5 is a global health challenge in the context of population ageing across the world. The range of treatment options available to patients at all ages has increased and includes transplantation and dialysis. However, these options are often seen as inappropriate for older frailer patients who are now offered the option of conservative kidney management, which is presented as a non-invasive alternative to dialysis, involving symptom management and addressing psychosocial needs. In this study, we conducted qualitative interviews with 26 close persons caring for someone with chronic kidney disease stage 5 in the United Kingdom to investigate how conservative kidney management interacted with implicit ideas of ageing, in both the experience of conservative kidney management and the understanding of the prognosis and future care of the kidney disease. Our findings highlighted participant confusion about the nature of conservative kidney management, which stems from an initial lack of clarity about how conservative kidney management differed from conventional treatments for chronic kidney disease stage 5. In particular, some respondents were not aware of the implicit palliative nature of the intervention or indeed the inevitable end-of-life issues. Although these findings can be situated within the context of communication failure, we would further argue that they also bring to the surface tensions in the discourses surrounding ageing and old age, drawing on the use of a 'natural' and a 'normal' paradigm of ageing. In the context of chronic kidney disease stage 5, more patients are being dialysed at older ages, but conservative kidney management is being advanced as a better option than dialysis in terms of quality of life and experience. However, in doing so, conservative kidney management implicitly draws on a notion of older age that echoes natural ageing rather than advocate a more interventionist approach. The role of discourses of ageing

  11. Developmental screening in a Canadian First Nation (Mohawk): psychometric properties and adaptations of ages & stages questionnaires (2nd edition)

    PubMed Central

    2014-01-01

    Background The need for early intervention tools adapted to the First Nation culture is well documented. However, standards derived from First Nation communities are absent from the literature. This study examines the psychometric properties of an adaptation of a caregiver-completed screening tool, the Ages & Stages Questionnaires (ASQ), for the Mohawk population. Methods Participants who completed the questionnaires include 17 teachers, along with the parents of 282 children (130 girls and 152 boys) between the ages of 9 and 66 months who attend the Child and Family Center Mohawk Territory, Quebec. Results For the internal consistency of the four questionnaires (36-, 42-, 48- and 54-month intervals), Cronbach’s alphas varied between .61 and .84. Five results were below 0.60: “gross motor” (Q36 and Q42), “problem solving” (Q36) and “personal-social” (Q36 and Q42). A comparison of the results shows that parents and teachers agreed in 85% of the cases concerning the referral of the child for further evaluation. Moreover, the group discussion with the parents revealed that the use of the questionnaire was appreciated and was deemed appropriate for use within the community. Conclusion The results show that the ASQ is a screening test that may be appropriate for use with children from communities that are seemingly very different in terms of geographic, climatic and cultural backgrounds. This preliminary study with the Child and Family Center appears to support further study and the use of the ASQ with the Mohawk population. PMID:24467769

  12. Comparing adult hippocampal neurogenesis in mammalian species and orders: influence of chronological age and life history stage.

    PubMed

    Amrein, Irmgard; Isler, Karin; Lipp, Hans-Peter

    2011-09-01

    Adult hippocampal neurogenesis is a prominent event in rodents. In species with longer life expectancies, newly born cells in the adult dentate gyrus of the hippocampal formation are less abundant or can be completely absent. Several lines of evidence indicate that the regulatory mechanisms of adult neurogenesis differ between short- and long-lived mammals. After a critical appraisal of the factors and problems associated with comparing different species, we provide a quantitative comparison derived from seven laboratory strains of mice (BALB, C57BL/6, CD1, outbred) and rats (F344, Sprague-Dawley, Wistar), six other rodent species of which four are wild-derived (wood mouse, vole, spiny mouse and guinea pig), three non-human primate species (marmoset and two macaque species) and one carnivore (red fox). Normalizing the number of proliferating cells to total granule cell number, we observe an overall exponential decline in proliferation that is chronologically equal between species and orders and independent of early developmental processes and life span. Long- and short-lived mammals differ with regard to major life history stages; at the time points of weaning, age at first reproduction and average life expectancy, long-lived primates and foxes have significantly fewer proliferating cells than rodents. Although the database for neuronal differentiation is limited, we find indications that the extent of neuronal differentiation is subject to species-specific selective adaptations. We conclude that absolute age is the critical factor regulating cell genesis in the adult hippocampus of mammals. Ontogenetic and ecological factors primarily influence the regulation of neuronal differentiation rather than the rate of cell proliferation.

  13. [Clinical and pathogenetical peculiarities and treatment policy in ischemic stroke of elderly and old age].

    PubMed

    Gafurov, B G; Alikulova, N A

    2004-01-01

    The data on randomized study of 2 groups of patients with ischemic brain hemisphere stroke of elderly and old (over 70 years) as well as middle (under 60 years) age are presented. In elderly and old age, stroke develops on the basis of common affection of major vessels, with a great role of the "steal syndrome" in its pathogenesis. In authors' opinion, in treatment of ischemic stroke of elderly and old age attention should be paid to metabolic therapy, in particular to using high dosages of Cerebrolysin. Basing on clinical and paraclinical study, efficacy of this medication is revealed.

  14. Association mining of mutated cancer genes in different clinical stages across 11 cancer types

    PubMed Central

    Wang, Tingzhang; Zheng, Shu

    2016-01-01

    Many studies have demonstrated that some genes (e.g. APC, BRAF, KRAS, PTEN, TP53) are frequently mutated in cancer, however, underlying mechanism that contributes to their high mutation frequency remains unclear. Here we used Apriori algorithm to find the frequent mutational gene sets (FMGSs) from 4,904 tumors across 11 cancer types as part of the TCGA Pan-Cancer effort and then mined the hidden association rules (ARs) within these FMGSs. Intriguingly, we found that well-known cancer driver genes such as BRAF, KRAS, PTEN, and TP53 were often co-occurred with other driver genes and FMGSs size peaked at an itemset size of 3∼4 genes. Besides, the number and constitution of FMGS and ARs differed greatly among different cancers and stages. In addition, FMGS and ARs were rare in endocrine-related cancers such as breast carcinoma, ovarian cystadenocarcinoma, and thyroid carcinoma, but abundant in cancers contact directly with external environments such as skin melanoma and stomach adenocarcinoma. Furthermore, we observed more rules in stage IV than in other stages, indicating that distant metastasis needed more sophisticated gene regulatory network. PMID:27556693

  15. Association mining of mutated cancer genes in different clinical stages across 11 cancer types.

    PubMed

    Hu, Wangxiong; Li, Xiaofen; Wang, Tingzhang; Zheng, Shu

    2016-10-18

    Many studies have demonstrated that some genes (e.g. APC, BRAF, KRAS, PTEN, TP53) are frequently mutated in cancer, however, underlying mechanism that contributes to their high mutation frequency remains unclear. Here we used Apriori algorithm to find the frequent mutational gene sets (FMGSs) from 4,904 tumors across 11 cancer types as part of the TCGA Pan-Cancer effort and then mined the hidden association rules (ARs) within these FMGSs. Intriguingly, we found that well-known cancer driver genes such as BRAF, KRAS, PTEN, and TP53 were often co-occurred with other driver genes and FMGSs size peaked at an itemset size of 3~4 genes. Besides, the number and constitution of FMGS and ARs differed greatly among different cancers and stages. In addition, FMGS and ARs were rare in endocrine-related cancers such as breast carcinoma, ovarian cystadenocarcinoma, and thyroid carcinoma, but abundant in cancers contact directly with external environments such as skin melanoma and stomach adenocarcinoma. Furthermore, we observed more rules in stage IV than in other stages, indicating that distant metastasis needed more sophisticated gene regulatory network.

  16. A robust two-stage design identifying the optimal biological dose for phase I/II clinical trials.

    PubMed

    Zang, Yong; Lee, J Jack

    2017-01-15

    We propose a robust two-stage design to identify the optimal biological dose for phase I/II clinical trials evaluating both toxicity and efficacy outcomes. In the first stage of dose finding, we use the Bayesian model averaging continual reassessment method to monitor the toxicity outcomes and adopt an isotonic regression method based on the efficacy outcomes to guide dose escalation. When the first stage ends, we use the Dirichlet-multinomial distribution to jointly model the toxicity and efficacy outcomes and pick the candidate doses based on a three-dimensional volume ratio. The selected candidate doses are then seamlessly advanced to the second stage for dose validation. Both toxicity and efficacy outcomes are continuously monitored so that any overly toxic and/or less efficacious dose can be dropped from the study as the trial continues. When the phase I/II trial ends, we select the optimal biological dose as the dose obtaining the minimal value of the volume ratio within the candidate set. An advantage of the proposed design is that it does not impose a monotonically increasing assumption on the shape of the dose-efficacy curve. We conduct extensive simulation studies to examine the operating characteristics of the proposed design. The simulation results show that the proposed design has desirable operating characteristics across different shapes of the underlying true dose-toxicity and dose-efficacy curves. The software to implement the proposed design is available upon request. Copyright © 2016 John Wiley & Sons, Ltd.

  17. Clinical Characteristics and Outcomes of Gastric Cancer Patients Aged over 80 Years: A Retrospective Case-Control Study

    PubMed Central

    Jung, Hwoon-Yong; Lee, Jeong Hoon; Jung, Kee Wook; Kim, Do Hoon; Choi, Kee Don; Song, Ho June; Lee, Gin Hyug; Kim, Jin-Ho; Han, Seungbong

    2016-01-01

    Background and Aims The average human life expectancy is increasing worldwide, thus the proportion of elderly gastric cancer patients is also increasing. In this case-control study, we investigated the clinical and oncologic outcomes of gastric cancer in patients over 80 years old. Methods From January 2004 to December 2010, 291 patients aged over 80 years old (case group) were diagnosed and treated with gastric cancer at Asan Medical Center, Seoul, Korea. From the same period, 291 patients aged 18 to 80 years old were selected as the control group. The clinical findings and clinical outcomes of gastric cancer were retrospectively reviewed and compared between the two groups. Results There were significant differences in the overall 5-year survival rate between the case and control groups (30.9% vs. 73.8%, respectively; P<0.001). In patients who received the curative treatment, overall 3- and 5-year survival rates showed 74.3% and 57.9% in case group and 91.6% and 86.5% in the control group. When analysis was confined to resectable elderly patients with a favorable performance, the curative resection group showed significantly better overall 3- and 5-year survival rates than the conservative treatment group (73.7% and 58.8% vs. 29.8% and 0%, respectively). Conclusions Although elderly gastric cancer patients show an advanced stage at diagnosis and poor prognosis compared with non-elderly patients, elderly patients with good performance could benefit from curative resection. Thus, the clinical decision whether to undergo curative resection or conservative management should be made on an individualized basis. PMID:27942044

  18. Evaluation of Nontraditional Age Learners' Experiences in Internet-Based Clinical Social Work Courses

    ERIC Educational Resources Information Center

    Swanke, Jayme; Zeman, Laura Dreuth

    2015-01-01

    This study involves an evaluation of online learners' experiences with two Internet-based clinical social work courses. The evaluation sought to discover whether there were differences in learning between traditional (under 25 years old) and nontraditional age learners (25 years and over) who completed the asynchronous online course. The study…

  19. Differential Profiles of Risk of Self-Harm among Clinically Referred Primary School Aged Children

    ERIC Educational Resources Information Center

    Angelkovska, Anne; Houghton, Stephen; Hopkins, Sarah

    2012-01-01

    Risk of self-harm among clinic referred children aged 6- to 12-years-old was investigated using the recently developed Self-Harm Risk Assessment for Children (SHRAC) instrument which comprises six factors: Affect traits; verbalizing of self-harm; socialization; dissociation; self-directing; and self-appraisal. The SHRAC was completed by the…

  20. Aggressive Conduct Disorder: The Influence of Social Class, Sex and Age on the Clinical Picture.

    ERIC Educational Resources Information Center

    Behar, D.; Stewart, M.A.

    1984-01-01

    Investigates how socioeconomic status, sex, and age of admission to a child psychiatry ward influenced the clinical picture of aggressive conduct disorder among 58 affected children. As little evidence of variation in any of the three variables was found, results reinforced the idea that the disorder is a valid psychiatric syndrome. (RH)

  1. Age-related differences in the clinical presentation of food-induced anaphylaxis

    PubMed Central

    Rudders, Susan A.; Banerji, Aleena; Clark, Sunday; Camargo, Carlos A.

    2010-01-01

    Food-induced anaphylaxis may be more difficult to recognize in younger children. We describe age-related patterns in the clinical presentation of children with anaphylaxis, which may facilitate the early recognition and treatment of this potentially life-threatening condition. PMID:21094954

  2. Relationship of Clinical and Pathologic Nodal Staging in Locally Advanced Breast Cancer: Current Controversies in Daily Practice?

    PubMed Central

    De Felice, Francesca; Musio, Daniela; Bulzonetti, Nadia; Raffetto, Nicola; Tombolini, Vincenzo

    2014-01-01

    Systemic neo-adjuvant therapy plays a primary role in the management of locally advanced breast cancer. Without having any negative effect in overall survival, induction chemotherapy potentially assures a surgery approach in unresectable disease or a conservative treatment in technically resectable disease and acts on a well-vascularized tumor bed, without the modifications induced by surgery. A specific issue has a central function in the neo-adjuvant setting: lymph nodes status. It still represents one of the strongest predictors of long-term prognosis in breast cancer. The discussion of regional radiation therapy should be a matter of debate, especially in a pathological complete response. Currently, the indication for radiotherapy is based on the clinical stage before the surgery, even for the irradiation of the loco-regional lymph nodes. Regardless of pathological down-staging, radiation therapy is accepted as standard adjuvant treatment in locally advanced breast cancer. PMID:25247013

  3. Microscopic Haematuria and Clinical Outcomes in Patients With Stage 3-5 Nondiabetic Chronic Kidney Disease.

    PubMed

    You-Hsien Lin, Hugo; Yen, Chun-Yu; Lim, Lee-Moay; Hwang, Daw-Yang; Tsai, Jer-Chia; Hwang, Shang-Jyh; Hung, Chi-Chih; Chen, Hung-Chun

    2015-10-16

    Microscopic haematuria is proposed as a prognostic factor for renal outcomes in patients with glomerulonephritis. However, the role of haematuria in patients with advanced chronic kidney disease (CKD) or heavy proteinuria has not been investigated. We divided 1799 patients with stage 3-5 nondiabetic CKD into 3 groups according to the results from 3 urinalyses: no haematuria (0-2 red blood cells [RBCs]/hpf ≥2 times), mild haematuria (2-5 RBCs/hpf ≥2 times) and moderate haematuria (≥5-10 RBCs/hpf ≥2 times). The estimated glomerular filtration rate was 25.4 mL/min/1.73 m(2), with a urine protein-to-creatinine ratio (UPCR) of 881 mg/g. The hazard ratios (HRs) of mild and moderate haematuria for end-stage renal disease (ESRD) were 1.28 (95% confidence interval [CI]: 1.05-1.56, P = 0.024) and 1.34 (95% CI: 1.03-1.74, P = 0.030), respectively. The HR of moderate haematuria for mortality was 1.56 (95% CI: 1.11-2.20, P = 0.011). According to subgroup analysis, the HR of moderate haematuria for ESRD in patients with a UPCR of <500 mg/g was more prominent than that in patients with a UPCR of ≥500 mg/g. Microscopic haematuria in patients with stage 3-5 nondiabetic CKD is associated with increased risks of ESRD and mortality.

  4. Patient Perspectives on Deep Brain Stimulation Clinical Research in Early Stage Parkinson's Disease.

    PubMed

    Heusinkveld, Lauren; Hacker, Mallory; Turchan, Maxim; Bollig, Madelyn; Tamargo, Christina; Fisher, William; McLaughlin, Lauren; Martig, Adria; Charles, David

    2017-01-01

    The FDA has approved a multicenter, double-blind, Phase III, pivotal trial testing deep brain stimulation (DBS) in 280 people with very early stage Parkinson's disease (PD; IDE#G050016). In partnership with The Michael J. Fox Foundation for Parkinson's Research, we conducted a survey to investigate motivating factors, barriers, and gender differences among potentially eligible patients for participation in a trial testing DBS in early PD compared to standard medical treatment. The majority of survey respondents (72%) indicated they would consider learning more about participating. Early PD patients are therefore likely to consider enrolling in trials of invasive therapies that may slow symptom progression and help future patients.

  5. The geriatric clinic: dry and limp: aging queers, zombies, and sexual reanimation.

    PubMed

    McGlotten, Shaka; Moore, Lisa Jean

    2013-06-01

    This essay looks to the omission of aging queer bodies from new medical technologies of sex. We extend the Foucauldian space of the clinic to the mediascape, a space not only of representations but where the imagination is conditioned and different worlds dreamed into being. We specifically examine the relationship between aging queers and the marketing of technologies of sexual function. We highlight the ways queers are excluded from the spaces of the clinic, specifically the heternormative sexual scripts that organize biomedical care. Finally, using recent zombie theory, we gesture toward both the constraints and possibilities of queer inclusion within the discourses and practices that aim to reanimate sexual function. We suggest that zombies usefully frame extant articulations of aging queers with sex and the dangerous lure of medical treatments that promise revitalized, but normative, sexual function at the cost of other, perhaps queerer intimacies.

  6. Art Therapy for an Individual with Late Stage Dementia: A Clinical Case Description

    ERIC Educational Resources Information Center

    Tucknott-Cohen, Tisah; Ehresman, Crystal

    2016-01-01

    This article describes the healing benefits of art therapy for an individual with dementia of the Alzheimer's type. In this clinical case description, a woman diagnosed with Alzheimer's disease received individual art therapy for 17 weeks. The treatment concerns that arose, altered view of reality, agitation, and retrogenesis provide insight on…

  7. Natural History of Clinically Staged Low- and Intermediate-Risk Prostate Cancer Treated With Monotherapeutic Permanent Interstitial Brachytherapy

    SciTech Connect

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

    2010-02-01

    Purpose: To evaluate the natural history of clinically staged low- and intermediate-risk prostate cancer treated with permanent interstitial seed implants as monotherapy. Methods and Materials: Between April 1995 and May 2005, 463 patients with clinically localized prostate cancer underwent brachytherapy as the sole definitive treatment. Men who received supplemental external beam radiotherapy or androgen deprivation therapy were excluded. Dosimetric implant quality was determined based on the minimum dose that covered 90% of the target volume and the volume of the prostate gland receiving 100% of the prescribed dose. Multiple parameters were evaluated as predictors of treatment outcomes. Results: The 12-year biochemical progression-free survival (bPFS), cause-specific survival, and overall survival rates for the entire cohort were 97.1%, 99.7%, and 75.4%, respectively. Only pretreatment prostate-specific antigen level, percent positive biopsy cores, and minimum dose that covered 90% of the target volume were significant predictors of biochemical recurrence. The bPFS, cause-specific survival, and overall survival rates were 97.4%, 99.6%, and 76.2%, respectively, for low-risk patients and 96.4%, 100%, and 74.0%, respectively, for intermediate-risk patients. The bPFS rate was 98.8% for low-risk patients with high-quality implants versus 92.1% for those with less adequate implants (p < 0.01), and it was 98.3% for intermediate-risk patients with high-quality implants versus 86.4% for those with less adequate implants (p < 0.01). Conclusions: High-quality brachytherapy implants as monotherapy can provide excellent outcomes for men with clinically staged low- and intermediate-risk prostate cancer. For these men, a high-quality implant can achieve results comparable to high-quality surgery in the most favorable pathologically staged patient subgroups.

  8. Lumbar extracavitary corpectomy with a single stage circumferential arthrodesis: surgical technique and clinical series.

    PubMed

    Singh, Kern; Park, Daniel K

    2012-07-01

    Circumferential arthrodesis and reconstruction is necessary after a lumbar corpectomy in the setting of malignancy and infection. The advent of expandable cage technology now allows for safe anterior column reconstruction via a posterior approach with no transection and minimal retraction of the lumbar spinal nerve roots. Fifteen patients underwent a single-stage, circumferential corpectomy and anterior spinal reconstruction with an expandable cage via a midline, posterior, lateral lumbar extracavitary approach. Posterior segmental pedicle screw fixation and iliac crest bone graft was used in all cases. Fifteen lumbar extracavitary corpectomy nerve root-sparing procedures have been performed to date, with at least 1-year follow-up (12 tumors/3 infections). No patient suffered any neurological complications. One patient suffered from a postoperative myocardial infarction 10 days after the procedure. Two patients had medical complications that were treated without sequelae. We present a technical description and case series of patients undergoing a single-stage, circumferential corpectomy and anterior spinal reconstruction with an expandable cage via a midline, posterior, lateral lumbar extracavitary approach with at least 1-year follow-up. The technique is safe, technically feasible, and obviates an anterior approach in this oftentimes critically ill patient population.

  9. Increased susceptibility of aging gastric mucosa to injury: the mechanisms and clinical implications.

    PubMed

    Tarnawski, Andrzej S; Ahluwalia, Amrita; Jones, Michael K

    2014-04-28

    This review updates the current views on aging gastric mucosa and the mechanisms of its increased susceptibility to injury. Experimental and clinical studies indicate that gastric mucosa of aging individuals-"aging gastropathy"-has prominent structural and functional abnormalities vs young gastric mucosa. Some of these abnormalities include a partial atrophy of gastric glands, impaired mucosal defense (reduced bicarbonate and prostaglandin generation, decreased sensory innervation), increased susceptibility to injury by a variety of damaging agents such as ethanol, aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs), impaired healing of injury and reduced therapeutic efficacy of ulcer-healing drugs. Detailed analysis of the above changes indicates that the following events occur in aging gastric mucosa: reduced mucosal blood flow and impaired oxygen delivery cause hypoxia, which leads to activation of the early growth response-1 (egr-1) transcription factor. Activation of egr-1, in turn, upregulates the dual specificity phosphatase, phosphatase and tensin homologue deleted on chromosome ten (PTEN) resulting in activation of pro-apoptotic caspase-3 and caspase-9 and reduced expression of the anti-apoptosis protein, survivin. The imbalance between pro- and anti-apoptosis mediators results in increased apoptosis and increased susceptibility to injury. This paradigm has human relevance since increased expression of PTEN and reduced expression of survivin were demonstrated in gastric mucosa of aging individuals. Other potential mechanisms operating in aging gastric mucosa include reduced telomerase activity, increase in replicative cellular senescence, and reduced expression of vascular endothelial growth factor and importin-α-a nuclear transport protein essential for transport of transcription factors to nucleus. Aging gastropathy is an important and clinically relevant issue because of: (1) an aging world population due to prolonged life span; (2) older

  10. Operating characteristics of a Simon two-stage phase II clinical trial design incorporating continuous toxicity monitoring.

    PubMed

    Ray, H E; Rai, S N

    2012-01-01

    Phase II clinical trials are usually designed to measure efficacy, but safety is also an important end point. Previous authors recommended a method to monitor toxic events after each patient is enrolled, which is also known as continuously monitoring the toxicity. In this work, we investigate combining the usual Simon two-stage design to monitor response with the continuous toxicity monitoring methodology. Theoretical justification is given for the nominal size, probability of early termination, and average sample size under the null hypothesis of the combined testing procedure. A series of simulations are performed to investigate the performance of the combined procedure.

  11. Function, Role, and Clinical Application of MicroRNAs in Vascular Aging

    PubMed Central

    Zhan, Jun-Kun; Wang, Yan-Jiao; Tan, Pan; Chen, Yi-Yin; Deng, Hui-Qian

    2016-01-01

    Vascular aging, a specific type of organic aging, is related to age-dependent changes in the vasculature, including atherosclerotic plaques, arterial stiffness, fibrosis, and increased intimal thickening. Vascular aging could influence the threshold, process, and severity of various cardiovascular diseases, thus making it one of the most important risk factors in the high mortality of cardiovascular diseases. As endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) are the main cell biological basis of these pathology changes of the vasculature, the structure and function of ECs and VSMCs play a key role in vascular aging. MicroRNAs (miRNAs), small noncoding RNAs, have been shown to regulate the expression of multiple messenger RNAs (mRNAs) posttranscriptionally, contributing to many crucial aspects of cell biology. Recently, miRNAs with functions associated with aging or aging-related diseases have been studied. In this review, we will summarize the reported role of miRNAs in the process of vascular aging with special emphasis on EC and VSMC functions. In addition, the potential application of miRNAs to clinical practice for the diagnosis and treatment of cardiovascular diseases will also be discussed. PMID:28097140

  12. Aging and Multimorbidity: New Tasks, Priorities, and Frontiers for Integrated Gerontological and Clinical Research

    PubMed Central

    Fabbri, Elisa; Zoli, Marco; Gonzalez-Freire, Marta; Salive, Marcel E.; Studenski, Stephanie A.; Ferrucci, Luigi

    2016-01-01

    Aging is characterized by rising susceptibility to development of multiple chronic diseases and, therefore, represents the major risk factor for multimorbidity. From a gerontological perspective, the progressive accumulation of multiple diseases, which significantly accelerates at older ages, is a milestone for progressive loss of resilience and age-related multisystem homeostatic dysregulation. Because it is most likely that the same mechanisms that drive aging also drive multiple age-related chronic diseases, addressing those mechanisms may reduce the development of multimorbidity. According to this vision, studying multimorbidity may help to understand the biology of aging and, at the same time, understanding the underpinnings of aging may help to develop strategies to prevent or delay the burden of multimorbidity. As a consequence, we believe that it is time to build connections and dialogue between the clinical experience of general practitioners and geriatricians and the scientists who study aging, so as to stimulate innovative research projects to improve the management and the treatment of older patients with multiple morbidities. PMID:25958334

  13. Clinical presentation of Attenuated Psychosis Syndrome in children and adolescents: Is there an age effect?

    PubMed

    Ribolsi, Michele; Lin, Ashleigh; Wardenaar, Klaas J; Pontillo, Maria; Mazzone, Luigi; Vicari, Stefano; Armando, Marco

    2017-03-01

    There is limited research on clinical features related to age of presentation of the Attenuated Psychosis Syndrome in children and adolescents (CAD). Based on findings in CAD with psychosis, we hypothesized that an older age at presentation of Attenuated Psychosis Syndrome would be associated with less severe symptoms and better psychosocial functioning than presentation in childhood or younger adolescence. Ninety-four CAD (age 9-18) meeting Attenuated Psychosis Syndrome criteria participated in the study. The sample was divided and compared according to the age of presentation of Attenuated Psychosis Syndrome (9-14 vs 15-18 years). The predictive value of age of Attenuated Psychosis Syndrome presentation was investigated using receiver operating characteristic (ROC)-curve calculations. The two Attenuated Psychosis Syndrome groups were homogeneous in terms of gender distribution, IQ scores and comorbid diagnoses. Older Attenuated Psychosis Syndrome patients showed better functioning and lower depressive scores. ROC curves revealed that severity of functional impairment was best predicted using an age of presentation cut-off of 14.9 years for social functioning and 15.9 years for role functioning. This study partially confirmed our hypothesis; older age at presentation of Attenuated Psychosis Syndrome was associated with less functional impairment, but age was not associated with psychotic symptoms.

  14. Accuracy of MRI in Prediction of Tumour Thickness and Nodal Stage in Oral Tongue and Gingivobuccal Cancer With Clinical Correlation and Staging

    PubMed Central

    Parihar, Pratap Singh; Parihar, Akhilesh; Goel, Ashok Kumar; Waghwani, Kapil; Gupta, Richa; Bhutekar, Umesh

    2016-01-01

    Introduction Squamous cell carcinoma of lower gingivo-buccal complex and tongue are the most common cancer in the Indian sub-continent. The value of imaging in the staging of Oral Squamous Cell Carcinoma (OSCC) is in judging operability, assessment of the prognostic characteristics and dimensions of the primary tumour, depth of tumour invasion, the presence of cervical metastasis and detection of bone infiltration. Aim This study evaluated squamous cell carcinomas of the oral cavity (tongue and gingivo-buccal complex) on the basis of their appearance, soft tissue extent, depth of tumour invasion and staging. Further, this study assessed the accuracy of MRI in the detection of cervical lymph nodal metastasis on the basis of ADC values on diffusion weighted MR sequence. Materials and Methods T1- and T2-weighted MR, diffusion-weighted sequences and post contrast T1W sequences were performed in various planes on biopsy proven squamous cell carcinomas (61 cases) involving tongue and/or gingivo-buccal region. Depth of tumour invasion was calculated on axial images of post contrast T1W images. The Apparent Diffusion Coefficient (ADC) was measured by using two b factors (500 and 1000 s/mm2). MRI findings were compared clinically and histopathologically. Results Average depth of invasion calculated on MRI was 8.47mm and by histopathology was 6.85mm. Pearson’s correlation coefficient was 0.988. Shrinkage factor was 0.8. A 71% of patients with depth of invasion greater than 9mm showed evidence of cervical lymph nodal metastasis at one or another levels. Cut-off value to discriminate between malignant and benign lymph nodes was 1.038 x10-3 mm2/s in the present study. Conclusion Depth of tumour invasion in oral malignancies can be measured reliably on MRI which helps in predicting cervical lymph node metastasis. Benign or malignant cervical lymph nodes can be differentiated on diffusion-weighted imaging of MRI on the basis of their ADC values. PMID:27504375

  15. Stages in the implementation of innovative clinical programs in complex organizations.

    PubMed

    Rosenheck, R

    2001-12-01

    Organizational processes can have an important impact on the introduction of innovative treatments into practice. Conceptual frameworks from organization theory and experiences implementing several hundred specialized mental health programs in the Department of Veterans Affairs (VA) over the past 15 years are used to illustrate stages and processes in the implementation of new treatment models. Four phases in the implementation of new treatments in complex organizational settings are described: a) the decision to implement, b) initial implementation, c) sustained implementation, and d) termination or transformation. Key strategies for moving research into practice include constructing decision-making coalitions, linking new initiatives to legitimate goals and values, quantitative monitoring of implementation and performance, and the development of self-sustaining communities of practice as well as learning organizations. Effective dissemination of new treatment methods requires different organizational strategies at different phases of implementation.

  16. Imaging tests in staging and surveillance of non-metastatic breast cancer: changes in routine clinical practice and cost implications

    PubMed Central

    De Placido, S; De Angelis, C; Giuliano, M; Pizzi, C; Ruocco, R; Perrone, V; Bruzzese, D; Tommasielli, G; De Laurentiis, M; Cammarota, S; Arpino, G; Arpino, G

    2017-01-01

    Background: Although guidelines do not recommend computerised tomography (CT), positron emission tomography (PET) or magnetic resonance imaging (MRI) for the staging or follow-up of asymptomatic patients with non-metastatic breast cancer, they are often requested in routine clinical practice. The aim of this study was to determine the staging and follow-up patterns, and relative costs in a large population of breast cancer patients living and treated in a Southern Italian region. Methods: We analysed the clinical computerised information recorded by 567 primary-care physicians assisting about 650 000 inhabitants in the Campania region. Patients with non-metastatic breast cancer were identified and divided into calendar years from 2001 to 2010. The number of diagnostic tests prescribed per 100 patients (N/Pts) and the mean cost per patient was determined 3 months before diagnosis and up to 1 year after diagnosis. Costs are expressed in constant 2011 euros. Results: We identified 4680 newly diagnosed cases of asymptomatic non-metastatic breast cancer. N/Pts increased significantly (P<0.0001) from 2001 to 2010. The mean number of prescribed mammograms, bone scans, abdominal ultrasound and chest X-rays (‘routine tests'), and costs was unchanged. However, the number of CT, PET scans and MRI (‘new tests')prescriptions almost quadrupled and the mean cost per patient related to these procedures significantly increased from €357 in 2001 to €830 in 2010 (P<0.0001). Conclusions: New test prescriptions and relative costs significantly and steadily increased throughout the study period. At present there is no evidence that the delivery of new tests to asymptomatic patients improves breast cancer outcome. Well-designed clinical trials are urgently needed to shed light on the impact of these tests on clinical outcome and overall survival. PMID:28170371

  17. Clinical and Biomechanical Evaluations of Staged Bilateral Total Knee Arthroplasty Patients with Two Different Implant Designs

    PubMed Central

    Renaud, Alexandre; Fuentes, Alexandre; Hagemeister, Nicola; Lavigne, Martin; Vendittoli, Pascal-André

    2016-01-01

    Background: Various implants of total knee arthroplasty (TKA) are used in clinical practice and each presents specific design characteristics. No implant managed this day to reproduce perfectly the biomechanics of the natural knee during gait. Objectives: We therefore asked whether (1) differences in tridimensional (3D) kinematic data during gait could be observed in two different designs of TKA on the same patients, (2) if those gait kinematic data are comparable with those of asymptomatic knees and (3) if difference in clinical subjective scores can be observed between the two TKA designs on the same patient. Methods: We performed knee kinematic analysis on 15 patients (30 TKAs) with two different TKA implant designs (Nexgen, Zimmer and Triathlon, Stryker) on each knee and on 25 asymptomatic subjects (35 knees). Clinical evaluation included range of motion, weight bearing radiographs, questionnaire of joint perception, KOOS, WOMAC and SF-12. Results: Comparison between TKAs and asymptomatic knees revealed that asymptomatic knees had significantly less knee flexion at initial contact (p < 0.04) and more flexion for most of the swing phase (p between 0.004 and 0.04). Asymptomatic knees also had less varus at loading response, during stance phase and during most of the swing phase (p between 0.001 - 0.05). Transverse plane analysis showed a tendency for asymptomatic knees to be more in internal rotation during stance phase (p 0.02 - 0.04). Comparing both TKA designs, NexgenTM implant had significantly more flexion at the end of swing phase (p = 0.04) compared to knees with the TriathlonTM implant. In frontal plane, from initial contact to maximum mid stance angle and between the mean mid stance angle and initial contact NexgenTM TKA had significantly more adduction (varus, p =0.02 – 0.03). Clinical scores of both TKAs did not have significant difference. Conclusions: TKA with the tested implants did not reproduce natural knee kinematics during gait. In our cohort

  18. Sustained expression of a neuron-specific isoform of the Taf1 gene in development stages and aging in mice

    SciTech Connect

    Jambaldorj, Jamiyansuren; Makino, Satoshi; Munkhbat, Batmunkh; Tamiya, Gen

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer We identified the mouse homologue of neuron-specific TAF1 (N-Taf1). Black-Right-Pointing-Pointer Taf1 mRNA was expressed in most tissues and cell lines. Black-Right-Pointing-Pointer N-Taf1 mRNA was expressed in the brain and Neuroblastoma N2a cell lines. Black-Right-Pointing-Pointer Taf1 and N-Taf1 showed different expression profile in development stage and aging. -- Abstract: TATA-box binding protein associated factor 1 (TAF1) protein is the largest and the essential component of the TFIID complex in the pathway of RNA polymerase II-mediated gene transcription, and it regulates transcription of a large number of genes related to cell division. The neuron-specific isoform of the TAF1 gene (N-TAF1), which we reported previously, may have an essential role in neurons through transcriptional regulation of many neuron-specific genes. In the present study, we cloned the full-length cDNA that encodes the mouse homologue of N-TAF1 (N-Taf1) protein. By carrying out of real time RT-PCR, we investigated the expression analysis of the N-Taf1 mRNA in mouse tissues and cell lines. As well as the human N-TAF1, the N-Taf1 showed limited expression in the brain and neuroblastoma, whereas Taf1 expressed elsewhere. Furthermore, in mouse embryo head or mouse brain, mRNA expression of TAF1 changes dramatically during development but N-Taf1 showed sustained expression. Our result suggests that the N-Taf1 gene has an important role in non-dividing neuronal cell rather than in cell division and proliferation during neurogenesis.

  19. The rates of change of the stochastic trajectories of acceleration variability are a good predictor of normal aging and of the stage of Parkinson's disease

    PubMed Central

    Torres, Elizabeth B.

    2013-01-01

    The accelerometer data from mobile smart phones provide stochastic trajectories that change over time. This rate of change is unique to each person and can be well-characterized by the continuous two-parameter family of Gamma probability distributions. Accordingly, on the Gamma plane each participant can be uniquely localized by the shape and the scale parameters of the Gamma probability distribution. The scatter of such points contains information that can unambiguously separate the normal controls (NC) from those patients with Parkinson's disease (PD) that are at a later stage of the disease. In general normal aging seems conducive of more predictable patterns of variation in the accelerometer data. Yet this trend breaks down in PD where the statistical signatures seem to be a more relevant predictor of the stage of the disease. Those patients at a later stage of the disease have more random and noisier patterns than those in the earlier stages, whose statistics resemble those of the older NC. Overall the peak rates of change of the stochastic trajectories of the accelerometer are a good predictor of the stage of PD and of the age of a “normally” aging individual. PMID:23882193

  20. On Simon's two-stage design for single-arm phase IIA cancer clinical trials under beta-binomial distribution.

    PubMed

    Liu, Junfeng; Lin, Yong; Shih, Weichung Joe

    2010-05-10

    Simon (Control. Clin. Trials 1989; 10:1-10)'s two-stage design has been broadly applied to single-arm phase IIA cancer clinical trials in order to minimize either the expected or the maximum sample size under the null hypothesis of drug inefficacy, i.e. when the pre-specified amount of improvement in response rate (RR) is not expected to be observed. This paper studies a realistic scenario where the standard and experimental treatment RRs follow two continuous distributions (e.g. beta distribution) rather than two single values. The binomial probabilities in Simon's (Control. Clin. Trials 1989; 10:1-10) design are replaced by prior predictive Beta-binomial probabilities that are the ratios of two beta functions and domain-restricted RRs involve incomplete beta functions to induce the null hypothesis acceptance probability. We illustrate that Beta-binomial mixture model based two-stage design retains certain desirable properties for hypothesis testing purpose. However, numerical results show that such designs may not exist under certain hypothesis and error rate (type I and II) setups within maximal sample size approximately 130. Furthermore, we give theoretical conditions for asymptotic two-stage design non-existence (sample size goes to infinity) in order to improve the efficiency of design search and to avoid needless searching.

  1. Pretreatment Modified Glasgow Prognostic Score Predicts Clinical Outcomes After Stereotactic Body Radiation Therapy for Early-Stage Non-Small Cell Lung Cancer

    SciTech Connect

    Kishi, Takahiro; Matsuo, Yukinori Ueki, Nami; Iizuka, Yusuke; Nakamura, Akira; Sakanaka, Katsuyuki; Mizowaki, Takashi; Hiraoka, Masahiro

    2015-07-01

    Purpose: This study aimed to evaluate the prognostic significance of the modified Glasgow Prognostic Score (mGPS) in patients with non-small cell lung cancer (NSCLC) who received stereotactic body radiation therapy (SBRT). Methods and Materials: Data from 165 patients who underwent SBRT for stage I NSCLC with histologic confirmation from January 1999 to September 2010 were collected retrospectively. Factors, including age, performance status, histology, Charlson comorbidity index, mGPS, and recursive partitioning analysis (RPA) class based on sex and T stage, were evaluated with regard to overall survival (OS) using the Cox proportional hazards model. The impact of the mGPS on cause of death and failure patterns was also analyzed. Results: The 3-year OS was 57.9%, with a median follow-up time of 3.5 years. A higher mGPS correlated significantly with poor OS (P<.001). The 3-year OS of lower mGPS patients was 66.4%, whereas that of higher mGPS patients was 44.5%. On multivariate analysis, mGPS and RPA class were significant factors for OS. A higher mGPS correlated significantly with lung cancer death (P=.019) and distant metastasis (P=.013). Conclusions: The mGPS was a significant predictor of clinical outcomes for SBRT in NSCLC patients.

  2. Generation Changes over the Period of 1986-2006 in the Physical Fitness of Boys Aged 7-19 from Eastern Poland at Particular Stages of Education

    ERIC Educational Resources Information Center

    Saczuk, Jerzy; Wasiluk, Agnieszka; Zalech, Miroslaw

    2012-01-01

    Study aim: To assess the size of secular trends in the physical fitness of boys from eastern Poland taking into consideration stages of education. Material and methods: The physical fitness results of boys aged 7-19 years living in eastern regions of Poland were analyzed: 3188 students were examined in 1986 while in 2006 the research included 10…

  3. Glycoprotein 130 is associated with adverse postoperative clinical outcomes of patients with late-stage non-metastatic gastric cancer

    PubMed Central

    Cao, Yifan; Zhang, Heng; Liu, Hao; Lin, Chao; Li, Ruochen; Wu, Songyang; He, Hongyong; Li, He; Xu, Jiejie

    2016-01-01

    The interaction of glycoprotein 130 (gp130) with the cytokines of Interleukin-6 (IL-6) family has proved to play a crucial part in several cancers. Our current study is designed to discover the clinical prognostic significance of gp130 in non-metastatic gastric cancer. We examined intratumoral gp130 expression in retrospectively enrolled 370 gastric cancer patients who underwent radical gastrectomy with standard D2 lymphadenectomy at Zhongshan Hospital of Fudan University during 2007 and 2008 by immunohistochemical staining. The expression of gp130 was significantly correlated with T classification, N classification and TNM stage (P = 0.003, P < 0.001 and P < 0.001, respectively; T, N, TNM refers to Tumor Invasion, Regional lymph node metastasis and Tumor Node Metastasis, respectively). Elevated intratumoral gp130 expression implied unfavourable overall survival (OS) (P < 0.001) and disease-free survival (DFS) (P < 0.001), respectively. Furthermore, among TNM II and III gp130-high patients, those who were treated with 5-fluorouracil (5-FU) based adjuvant chemotherapy had better OS (P < 0.001). The generated nomogram performed well in predicting the 3- and 5-year OS of gastric cancer patients. The incorporation of gp130 into contemporary TNM staging system would be of great significance to improve the current individual risk stratification. These findings contribute to better clinical management for those patients who would benefit from adjuvant chemotherapy. PMID:27917904

  4. The predictive value of transcranial sonography in clinically diagnosed patients with early stage Parkinson's disease: comparison with DAT PET scans.

    PubMed

    Liu, Ping; Li, Xin; Li, Fang-Fei; Ou-Yang, Qiao-Hong; Zhang, Hong-Xia; Feng, Tao

    2014-10-17

    Early and correct diagnosis of Parkinson's disease (PD) is critical for patient counseling and therapeutic management. The diagnostic accuracy of transcranial sonography of substantia nigra (SN-TCS) for early stage PD patients remains controversial. Dopamine transporter (DAT) imaging is sensitive to detect presynaptic dopamine neuronal dysfunction, and has been studied as a diagnostic tool for degenerative Parkinsonism. To investigate the predictive value of SN-TCS for the DAT PET scans in clinically diagnosed early stage PD patients, we performed the SN-TCS and DAT Positron Emission Computed Tomography (PET) imaging examinations on 53 patients. Using the DAT PET results as clinical gold standard, the sensitivity and specificity of TCS was 68.75% and 40% respectively. The positive predictive value (PPV) of an abnormal TCS for an abnormal PET scan was 91.67%. However, the negative predictive value (NPV) for a normal PET scan was only 11.76%. The false negative rate was 31.25%. In 35 patients, the result of the SN-TCD was in accordance with the result of the DAT PET scan (Kappa=0.042, P>0.05). The consistency between SN-TCS and PET scans was poor. We conclude that SN-TCS would not be used as a diagnostic tool for early stage PD patients. Negative result of TCS could not exclude the diagnosis of PD. Further tests like DAT-PET is needed for validation. On the other hand, positive SN-TCS will reduce the added diagnostic value of a presynaptic neuronimaging scan.

  5. Multi-stage uplift of the Colorado Plateau and the age of Grand Canyon and precursor canyons

    NASA Astrophysics Data System (ADS)

    Karlstrom, K. E.; Lee, J. P.; Kelley, S. A.; Crow, R.

    2012-12-01

    Debates about the age of Grand Canyon link to debates about the timing of surface uplift(s) of the Colorado Plateau- Rocky Mountain (CP-RM) region. One "old Grand Canyon" model proposes that a paleocanyon of almost the same depth and location as today's Grand Canyon was carved by a NE-flowing "California" paleoriver 80-70 Ma, then was re-used at ~55 Ma by a SW-flowing "Arizona" paleoriver. This model postulates the CP-RM region was uplifted to near modern elevations during the Laramide orogeny. A second model postulates a 17 Ma Grand Canyon; this time corresponds to Basin and Range extension and postulated mantle-driven surface uplift. The "young Grand Canyon" model postulates that >2/3 of modern Grand Canyon was carved by W-flowing Colorado River that became integrated to the Gulf of California at 5-6 Ma during Neogene mantle-driven uplift of the CP/RM region. Thermochronologic data are poised to substantially resolve these debates. Our thermochronology dataset combines published and new apatite fission-track and helium analyses, and joint thermal history modeling using both systems. This dataset reveals three major cooling episodes: 1) a multi-stage Sevier-Laramide contraction episode from about 90 Ma to 50 Ma with structural relief on upwarps on the order 0.5-1 km, compatible with a similar magnitude of surface uplift; 2) 30-20 Ma cooling that was associated with denudation and northward cliff retreat of most of the Mesozoic section from Grand Canyon region; 3) <10 Ma cooling that is best documented in eastern Grand Canyon as part of a general pattern of decreasing age of cooling/denudation to the NE. Combined geologic and thermochronologic data define the age and 3-D geometry of Cenozoic paleotopography that led to Grand Canyon carving. Combined AHe and AFT data indicate 2-4 km of sedimentary rocks covered the Grand Canyon region until about 40 Ma, negating the California River model. These strata were not removed from the Marble Canyon area until after about

  6. The incidence of cervical spondylosis decreases with aging in the elderly, and increases with aging in the young and adult population: a hospital-based clinical analysis

    PubMed Central

    Wang, Chuanling; Tian, Fuming; Zhou, Yingjun; He, Wenbo; Cai, Zhiyou

    2016-01-01

    Background and purpose Cervical spondylosis is well accepted as a common degenerative change in the cervical spine. Compelling evidence has shown that the incidence of cervical spondylosis increases with age. However, the relationship between age and the incidence of cervical spondylosis remains obscure. It is essential to note the relationship between age and the incidence of cervical spondylosis through more and more clinical data. Methods In the case-controlled study reported here, retrospective clinical analysis of 1,276 cases of cervical spondylosis has been conducted. We analyzed the general clinical data, the relationship between age and the incidence of cervical spondylosis, and the relationship between age-related risk factors and the incidence of cervical spondylosis. A chi-square test was used to analyze the associations between different variables. Statistical significance was defined as a P-value of less than 0.05. Results The imaging examination demonstrated the most prominent characteristic features of cervical spondylosis: bulge or herniation at C3-C4, C4-C5, and C5-C6. The incidence of cervical spondylosis increased with aging before age 50 years and decreased with aging after age 50 years, especially in the elderly after 60 years old. The occurrence rate of bulge or herniation at C3-C4, C4-C5, C5-C6, and C6-C7 increased with aging before age 50 years and decreased with aging after age 50 years, especially after 60 years. Moreover, the incidence of hyperosteogeny and spinal stenosis increased with aging before age 60 years and decreased with aging after age 60 years, although there was no obvious change in calcification. The age-related risk factors, such as hypertension, hyperlipidemia, diabetes, cerebral infarct, cardiovascular diseases, smoking, and drinking, have no relationship with the incidence of cervical spondylosis. Conclusion A decreasing proportion of cervical spondylosis with aging occurs in the elderly, while the proportion of

  7. Clinically Relevant Cognitive Impairment in Middle-Aged Adults With Childhood-Onset Type 1 Diabetes

    PubMed Central

    Nunley, Karen A.; Ryan, Christopher M.; Jennings, J. Richard; Aizenstein, Howard J.; Zgibor, Janice C.; Costacou, Tina; Boudreau, Robert M.; Miller, Rachel; Orchard, Trevor J.; Saxton, Judith A.

    2015-01-01

    OBJECTIVE The aim of this study was to investigate the presence and correlates of clinically relevant cognitive impairment in middle-aged adults with childhood-onset type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS During 2010–2013, 97 adults diagnosed with T1D and aged <18 years (age and duration 49 ± 7 and 41 ± 6 years, respectively; 51% female) and 138 similarly aged adults without T1D (age 49 ± 7 years; 55% female) completed extensive neuropsychological testing. Biomedical data on participants with T1D were collected periodically since 1986–1988. Cognitive impairment status was based on the number of test scores ≥1.5 SD worse than demographically appropriate published norms: none, mild (only one test), or clinically relevant (two or more tests). RESULTS The prevalence of clinically relevant cognitive impairment was five times higher among participants with than without T1D (28% vs. 5%; P < 0.0001), independent of education, age, or blood pressure. Effect sizes were large (Cohen d 0.6–0.9; P < 0.0001) for psychomotor speed and visuoconstruction tasks and were modest (d 0.3–0.6; P < 0.05) for measures of executive function. Among participants with T1D, prevalent cognitive impairment was related to 14-year average A1c >7.5% (58 mmol/mol) (odds ratio [OR] 3.0; P = 0.009), proliferative retinopathy (OR 2.8; P = 0.01), and distal symmetric polyneuropathy (OR 2.6; P = 0.03) measured 5 years earlier; higher BMI (OR 1.1; P = 0.03); and ankle-brachial index ≥1.3 (OR 4.2; P = 0.01) measured 20 years earlier, independent of education. CONCLUSIONS Clinically relevant cognitive impairment is highly prevalent among these middle-aged adults with childhood-onset T1D. In this aging cohort, chronic hyperglycemia and prevalent microvascular disease were associated with cognitive impairment, relationships shown previously in younger populations with T1D. Two additional potentially modifiable risk factors for T1D-related cognitive impairment, vascular health and BMI

  8. Behavioral deficits during early stages of aging in Caenorhabditis elegans result from locomotory deficits possibly linked to muscle frailty.

    PubMed

    Glenn, Charles F; Chow, David K; David, Lawrence; Cooke, Carol A; Gami, Minaxi S; Iser, Wendy B; Hanselman, Keaton B; Goldberg, Ilya G; Wolkow, Catherine A

    2004-12-01

    Many behavioral responses require the coordination of sensory inputs with motor outputs. Aging is associated with progressive declines in both motor function and muscle structure. However, the consequences of age-related motor deficits on behavior have not been clearly defined. Here, we examined the effects of aging on behavior in the nematode, Caenorhabditis elegans. As animals aged, mild locomotory deficits appeared that were sufficient to impair behavioral responses to sensory cues. In contrast, sensory ability appeared well maintained during aging. Age-related behavioral declines were delayed in animals with mutations in the daf-2/insulin-like pathway governing longevity. A decline in muscle tissue integrity was correlated with the onset of age-related behavioral deficits, although significant muscle deterioration was not. Treatment with a muscarinic agonist significantly improved locomotory behavior in aged animals, indicating that improved neuromuscular signaling may be one strategy for reducing the severity of age-related behavioral impairments.

  9. Breast Cancer/Stromal Cells Coculture on Polyelectrolyte Films Emulates Tumor Stages and miRNA Profiles of Clinical Samples.

    PubMed

    Daverey, Amita; Brown, Karleen M; Kidambi, Srivatsan

    2015-09-15

    In this study, we demonstrate a method for controlling breast cancer cells adhesion on polyelectrolyte multilayer (PEM) films without the aid of adhesive proteins/ligands to study the role of tumor and stromal cell interaction on cancer biology. Numerous studies have explored engineering coculture of tumor and stromal cells predominantly using transwell coculture of stromal cells cultured onto coverslips that were subsequently added to tumor cell cultures. However, these systems imposed an artificial boundary that precluded cell-cell interactions. To our knowledge, this is the first demonstration of patterned coculture of tumor cells and stromal cells that captures the temporal changes in the miRNA signature as the breast tumor develops through various stages. In our study we used synthetic polymers, namely poly(diallyldimethylammonium chloride) (PDAC) and sulfonated poly(styrene) (SPS), as the polycation and polyanion, respectively, to build PEMs. Breast cancer cells attached and spread preferentially on SPS surfaces while stromal cells attached to both SPS and PDAC surfaces. SPS patterns were formed on PEM surfaces, by either capillary force lithography (CFL) of SPS onto PDAC surfaces or vice versa, to obtain patterns of breast cancer cells and patterned cocultures of breast cancer and stromal cells. In this study, we utilized cancer cells derived from two different tumor stages and two different stromal cells to effectively model a heterogeneous tumor microenvironment and emulate various tumor stages. The coculture model mimics the proliferative index (Ki67 expression) and tumor aggressiveness (HER-2 expression) akin to those observed in clinical tumor samples. We also demonstrated that our patterned coculture model captures the temporal changes in the miRNA-21 and miRNA-34 signature as the breast tumor develops through various stages. The engineered coculture platform lays groundwork toward precision medicine wherein patient-derived tumor cells can be

  10. The earliest stage of cognitive impairment in transition from normal aging to Alzheimer disease is marked by prominent RNA oxidation in vulnerable neurons.

    PubMed

    Nunomura, Akihiko; Tamaoki, Toshio; Motohashi, Nobutaka; Nakamura, Masao; McKeel, Daniel W; Tabaton, Massimo; Lee, Hyoung-Gon; Smith, Mark A; Perry, George; Zhu, Xiongwei

    2012-03-01

    Although neuronal RNA oxidation is a prominent and established feature in age-associated neurodegenerative disorders such as Alzheimer disease (AD), oxidative damage to neuronal RNA in aging and in the transitional stages from normal elderly to the onset of AD has not been fully examined. In this study, we used an in situ approachto identify an oxidized RNA nucleoside 8-hydroxyguanosine (8OHG) in the cerebral cortex of 65 individuals without dementia ranging in age from 0.3 to 86 years. We also examined brain samples from 20 elderly who were evaluated for their premortem clinicaldementia rating score and postmortem brain pathologic diagnoses to investigate preclinical AD and mild cognitive impairment. Relative density measurements of 8OHG-immunoreactivity revealed a statistically significant increase in neuronal RNA oxidation during aging in the hippocampus and the temporal neocortex. In subjects with mild cognitive impairment but not preclinical AD, neurons of the temporal cortex showed a higher burden of oxidized RNA compared to age-matched controls. These results indicate that, although neuronal RNA oxidation fundamentally occurs as an age-associated phenomenon, more prominent RNA damage than in normal aging correlates with the onset of cognitive impairment in the prodromal stage of AD.

  11. Clinical and economic aspects of sevelamer therapy in end-stage renal disease patients.

    PubMed

    Ossareh, Shahrzad

    2014-01-01

    Phosphate control is still a great challenge in chronic kidney disease (CKD), and in spite of the great improvements in dialysis techniques, achievement of the goals for mineral metabolism control is still far from ideal. Aluminum hydroxide has been largely abandoned due to the high risk of aluminum toxicity, while the use of calcium-based phosphate binders may cause hypercalcemia, overzealous parathyroid suppression, and extraskeletal calcification. Sevelamer hydrochloride has been introduced as an efficient medication for phosphate control, with a lower risk of hypercalcemia and parathyroid suppression. Various clinical trials have compared the risk of vascular calcification between sevelamer and calcium salts with inconsistent results. In spite of these inconsistencies, the Kidney Disease Outcomes Quality Initiative (KDOQI) suggests non-calcium phosphate binders as the preferred phosphate binder in dialysis patients with severe vascular and/or other soft-tissue calcifications and in those with hypercalcemia or parathyroid hormone (PTH) <150 mg/dL. The Kidney Disease Improving Global Outcome (KDIGO) limits the use of non-calcium phosphate binders to patients with hypercalcemia. Regarding the effect on mortality, the results of clinical trials are again inconsistent. The other important aspect of using sevelamer is the issue of price, which is substantially higher than calcium-based phosphate binders. Reviewing the studies on economic aspects shows that sevelamer increases quality-adjusted life-years (QALY) and possibly life years, with a higher cost compared to calcium-based phosphate binders. In conclusion, sevelamer is a very useful drug for phosphate control, reduction of hypercalcemia, and lessening the risk of adynamic bone disease, with probable reduction in vascular calcification and possible reduction in mortality rate. It has a higher economic burden on health care systems compared to calcium-based phosphate binders. This may affect its extensive use

  12. Clinical Diagnoses before Age 75 and Men's Survival to Their 85th Birthday: The Manitoba Follow-Up Study

    ERIC Educational Resources Information Center

    Tate, Robert B.; Michaels, Leon; Cuddy, T. Edward; Bayomi, Dennis J.

    2013-01-01

    Purpose: Of all Canadian and American men who live to age 75 years, about half can expect to live to age 85. Our objective is to examine how clinical diagnoses made before age 75 relate to a man's survival to age 85 years. Design and Methods: Since 1948, a cohort of 3,983 young men (mean age of 31 years at entry) has been followed with routine…

  13. Mastectomy With Immediate Expander-Implant Reconstruction, Adjuvant Chemotherapy, and Radiation for Stage II-III Breast Cancer: Treatment Intervals and Clinical Outcomes

    SciTech Connect

    Wright, Jean L.; Cordeiro, Peter G.; Ben-Porat, Leah; Van Zee, Kimberly J.; Hudis, Clifford; Beal, Kathryn; McCormick, Beryl

    2008-01-01

    Purpose: To determine intervals between surgery and adjuvant chemotherapy and radiation in patients treated with mastectomy with immediate expander-implant reconstruction, and to evaluate locoregional and distant control and overall survival in these patients. Methods and Materials: Between May 1996 and March 2004, 104 patients with Stage II-III breast cancer were routinely treated at our institution under the following algorithm: (1) definitive mastectomy with axillary lymph node dissection and immediate tissue expander placement, (2) tissue expansion during chemotherapy, (3) exchange of tissue expander for permanent implant, (4) radiation. Patient, disease, and treatment characteristics and clinical outcomes were retrospectively evaluated. Results: Median age was 45 years. Twenty-six percent of patients were Stage II and 74% Stage III. All received adjuvant chemotherapy. Estrogen receptor staining was positive in 77%, and 78% received hormone therapy. Radiation was delivered to the chest wall with daily 0.5-cm bolus and to the supraclavicular fossa. Median dose was 5040 cGy. Median interval from surgery to chemotherapy was 5 weeks, from completion of chemotherapy to exchange 4 weeks, and from exchange to radiation 4 weeks. Median interval from completion of chemotherapy to start of radiation was 8 weeks. Median follow-up was 64 months from date of mastectomy. The 5-year rate for locoregional disease control was 100%, for distant metastasis-free survival 90%, and for overall survival 96%. Conclusions: Mastectomy with immediate expander-implant reconstruction, adjuvant chemotherapy, and radiation results in a median interval of 8 weeks from completion of chemotherapy to initiation of radiation and seems to be associated with acceptable 5-year locoregional control, distant metastasis-free survival, and overall survival.

  14. Dopamine transporter availability in clinically normal aging is associated with individual differences in white matter integrity.

    PubMed

    Rieckmann, Anna; Hedden, Trey; Younger, Alayna P; Sperling, Reisa A; Johnson, Keith A; Buckner, Randy L

    2016-02-01

    Aging-related differences in white matter integrity, the presence of amyloid plaques, and density of biomarkers indicative of dopamine functions can be detected and quantified with in vivo human imaging. The primary aim of the present study was to investigate whether these imaging-based measures constitute independent imaging biomarkers in older adults, which would speak to the hypothesis that the aging brain is characterized by multiple independent neurobiological cascades. We assessed MRI-based markers of white matter integrity and PET-based marker of dopamine transporter density and amyloid deposition in the same set of 53 clinically normal individuals (age 65-87). A multiple regression analysis demonstrated that dopamine transporter availability is predicted by white matter integrity, which was detectable even after controlling for chronological age. Further post-hoc exploration revealed that dopamine transporter availability was further associated with systolic blood pressure, mirroring the established association between cardiovascular health and white matter integrity. Dopamine transporter availability was not associated with the presence of amyloid burden. Neurobiological correlates of dopamine transporter measures in aging are therefore likely unrelated to Alzheimer's disease but are aligned with white matter integrity and cardiovascular risk. More generally, these results suggest that two common imaging markers of the aging brain that are typically investigated separately do not reflect independent neurobiological processes. Hum Brain Mapp 37:621-631, 2016. © 2015 Wiley Periodicals, Inc.

  15. BLOOD-BORNE ACTIVITY-DEPENDENT NEUROPROTECTIVE PROTEIN (ADNP) IS CORRELATED WITH PREMORBID INTELLIGENCE, CLINICAL STAGE AND ALZHEIMER’S DISEASE BIOMARKERS

    PubMed Central

    Malishkevich, Anna; Marshall, Gad A.; Schultz, Aaron P.; Sperling, Reisa A.; Aharon-Peretz, Judith; Gozes, Illana

    2015-01-01

    Biomarkers for Alzheimer’s disease (AD) are vital for disease detection in the clinical setting. Discovered in our laboratory, activity-dependent neuroprotective protein (ADNP) is essential for brain formation and linked to cognitive functions. Here, we revealed that blood borne expression of ADNP and its paralog ADNP2 is correlated with premorbid intelligence, AD pathology, and clinical stage. Age adjustment showed significant associations between: 1] higher premorbid intelligence and greater serum ADNP, and 2] greater cortical amyloid and lower ADNP and ADNP2 mRNAs. Significant increases in ADNP mRNA levels were observed in patients ranging from mild cognitive impairment (MCI) to AD dementia. ADNP2 transcripts showed high correlation with ADNP transcripts, especially in AD dementia lymphocytes. ADNP plasma/serum and lymphocyte mRNA levels discriminated well between cognitively normal elderly, MCI, and AD dementia participants. Measuring ADNP blood-borne levels could bring us a step closer to effectively screening and tracking AD. PMID:26639975

  16. Sentinel lymph node dissection in stage I/II melanoma patients: surgical management and clinical follow-up study.

    PubMed

    Macripò, Giuseppe; Quaglino, Pietro; Caliendo, Virginia; Ronco, Anna Maria; Soltani, Shoreh; Giacone, Elena; Pau, Stefano; Fierro, Maria Teresa; Bernengo, Maria Grazia

    2004-04-01

    Selective sentinel lymph node (SLN) dissection is widely used in the management of cutaneous melanoma patients without clinical evidence of nodal metastases. A series of 274 consecutive melanoma patients who underwent melanoma primary excision and SLN mapping at our institutions since 1998, and were thereafter followed up and eventually treated, is reported in this prospective study. The aim was to analyse the parameters associated with a higher risk of occult nodal metastases, to evaluate the clinical outcome of melanoma patients who underwent SLN procedure, and to identify by means of multivariate analysis the prognostic parameters with independent predictive value on disease-free survival (DFS) in node-positive and negative patients. The SLN was tumour-negative in 228 patients (83.2%). A disease progression occurred in 25 (10.9%); among them, 10 patients in whom the initially identified SLN had been negative, developed a clinically and histologically evident positive lymph node in the same basin during follow-up. Five-year DFS and overall survival were 75% and 82%, respectively. In 46 patients (16.8%), the SLN proved to be tumour positive. The percentage of SLN-positive patients varied according to the primary thickness, from 11.8% in patients with Breslow of 2 mm or lower, to 34.7% in patients with Breslow from 2 to 4 mm, up to 55.9% in patients with Breslow greater than 4 mm (P<0.001). Only two patients with Breslow thickness lower than 1 mm had positive SLN biopsy. Five-year DFS and overall survival (OS) were 42 and 69%, respectively, significantly lower than those of negative SLN-patients (P<0.001). Multivariate analyses showed that the parameters with prognostic independent value on DFS were SLN status (micrometastases or macrometastases; P=0.0001), and to a lesser extent, Breslow thickness (P=0.04). In conclusion, our data support the clinical usefulness of SLN dissection as a reliable and accurate staging method in patients with cutaneous melanoma. SLN

  17. Tuberculosis in ageing: high rates, complex diagnosis and poor clinical outcomes

    PubMed Central

    Cruz-Hervert, Luis Pablo; García-García, Lourdes; Ferreyra-Reyes, Leticia; Bobadilla-del-Valle, Miriam; Cano-Arellano, Bulmaro; Canizales-Quintero, Sergio; Ferreira-Guerrero, Elizabeth; Báez-Saldaña, Renata; Téllez-Vázquez, Norma; Nava-Mercado, Ariadna; Juárez-Sandino, Luis; Delgado-Sánchez, Guadalupe; Fuentes-Leyra, César Alejandro; Montero-Campos, Rogelio; Martínez-Gamboa, Rosa Areli; Small, Peter M.; Sifuentes-Osornio, José; Ponce-de-León, Alfredo

    2012-01-01

    Background: worldwide, the frequency of tuberculosis among older people almost triples that observed among young adults. Objective: to describe clinical and epidemiological consequences of pulmonary tuberculosis among older people. Methods: we screened persons with a cough lasting more than 2 weeks in Southern Mexico from March 1995 to February 2007. We collected clinical and mycobacteriological information (isolation, identification, drug-susceptibility testing and IS6110-based genotyping and spoligotyping) from individuals with bacteriologically confirmed pulmonary tuberculosis. Patients were treated in accordance with official norms and followed to ascertain treatment outcomes, retreatment, and vital status. Results: eight hundred ninety-three tuberculosis patients were older than 15 years of age; of these, 147 (16.5%) were 65 years of age or older. Individuals ≥65 years had significantly higher rates of recently transmitted and reactivated tuberculosis. Older age was associated with treatment failure (OR = 5.37; 95% CI: 1.06–27.23; P = 0.042), and death due to tuberculosis (HR = 3.52; 95% CI: 1.78–6.96; P < 0.001) adjusting for sociodemographic and clinical variables. Conclusions: community-dwelling older individuals participate in chains of transmission indicating that tuberculosis is not solely due to the reactivation of latent disease. Untimely and difficult diagnosis and a higher risk of poor outcomes even after treatment completion emphasise the need for specific strategies for this vulnerable group. PMID:22431155

  18. Effects of laser immunotherapy on late-stage, metastatic breast cancer patients in a Phase II clinical trial

    NASA Astrophysics Data System (ADS)

    Ferrel, Gabriela L.; Zhou, Feifan; Li, Xiaosong; Hode, Tomas; Nordquist, Robert E.; Alleruzzo, Luciano; Chen, Wei R.

    2014-03-01

    Laser immunotherapy (LIT), a novel technique with a local intervention to induce systemic antitumor effects, was developed to treat metastatic cancers. The pre-clinical studies of LIT have shown its unique characteristics in generating a specific antitumor immunity in treating metastatic tumors in rats and mice. For late-stage, metastatic breast cancer patients, who were considered to be out of other available treatment options, we conducted a small Phase II clinical trial using LIT starting in 2009 in Lima, Peru. This Phase II study was closed in December of 2012, as acknowldged by the Ministry of Health (MOH) of Peur letter 438-2014-OGITT/INS dated March 5th, 2014. Ten patients were enrolled and received LIT in one or multiple 4-week treatment cycles. At the study closing date, four patients were alive and two of them remained cancer free. Here, following the successful conclusion of our Phase II study, we report the clinical effects of LIT on metastatic breast cancer patients. Specifically, we present the overall status of all the patients three years after the treatment and also the outcomes of two long-term surviving patients.

  19. Clustering of Subgingival Microbiota Reveals Microbial Disease Ecotypes Associated with Clinical Stages of Periodontitis in a Cross-Sectional Study.

    PubMed

    Boutin, Sébastien; Hagenfeld, Daniel; Zimmermann, Heiko; El Sayed, Nihad; Höpker, Tanja; Greiser, Halina K; Becher, Heiko; Kim, Ti-Sun; Dalpke, Alexander H

    2017-01-01

    Periodontitis is characterized by chronic inflammation associated with alteration of the oral microbiota. In contrast to previous microbiome studies focusing a priori on comparison between extreme phenotypes, our study analyzed a random sample of 85 people. The aim of this study was to link microbial differences to disease's prevalence and severity. Using next generation sequencing of 16S rRNA amplicons and cluster analysis, we observed that the population can be divided into two major ecotypes: One mainly contained periodontal healthy/mild periodontitis individuals whereas the second ecotype showed a heterogeneous microbial distribution and clustered into three distinct sub-ecotypes. Those sub-ecotypes differed with respect to the frequency of diseased patients and displayed a gradual change in distinct subgingival microbiota that goes along with clinical disease symptoms. In ecotype 2, the subgroup with no clinical signs of disease was linked to an increase of F. nucleatum vincentii but also several other species, while only in "end-stage" dysbiosis classical red complex bacteria gained overweight. Therefore, the microbial disease ecotypes observed in our population can lead to an establishment of an early microbial risk profile for clinically healthy patients.

  20. [The role of clinical-electrophysiological indices in therapy for late-stage residual stroke by dynamic correction of proprioception].

    PubMed

    Veĭn, A M; Shvarkov, S B; Khaspekova, N B; Vendrova, M I; Davydov, O S; Bobrovskaia, A N

    2001-01-01

    The new method dynamic proprioceptive correction using a medical loading costume was included into complex therapy in patients with late-stage residual stroke. Application of the costume promoted normalization of complex locomotor acts of walking by correcting proprioceptive pulsation resulted from the system of elastic draughts. Thus, a new motor stereotype was forced upon the patients. Clinical observation, computer analysis of the motor potential, spectrum of heart rhythm variabilities before and after therapy, and psychological testing were performed in 120 patients with motor disorders (pareses, paralyses) resulted from acute cerebral circulatory disorders. A steady-state clinical effect (p < 0.05) was found in 71.9% of the patients after 15 sessions of therapy. The patients became to walk independently, a possibility to self-attendance appeared, their speech became better. Lateralization of a damage and preservation of both the most significant homeostatic vasomotor mechanisms and the cerebral mechanisms of preparation of a movement with the minimal manifestations of emotional-affective disorders were shown to have impact on the patients' rehabilitation and on the early clinical features of pyramidal defect.

  1. Fertility sparing surgery for stage IA type I and G2 endometrial cancer in reproductive-aged patients: evidence-based approach and future perspectives.

    PubMed

    Vitale, Salvatore Giovanni; Rossetti, Diego; Tropea, Alessandro; Biondi, Antonio; Laganà, Antonio Simone

    2017-02-10

    Fertility-sparing surgery (FSS) in reproductive-age patients affected by endometrial cancer (EC) gained growing attention in the last decade, although the first reports were already published in 1990-2000s. Nevertheless, only few patients undergoing FSS for stage I, type I EC had been reported in each case series, without a robust multicenter study. In the available literature there are even fewer reported cases of conservative treatment of Stage IA and G2 EC. Considering these important gaps in our current knowledge, the purpose of this review was to summarize the available evidence about conservative treatments for stage IA type I and G2 EC, to improve the pretreatment counseling for reproductive-age patients. According to our overview, women who have low-risk disease (G1 or G2, endometrioid histotype confined to the endometrium) are candidates for progestin therapy. In addition, FSS could be considered a valid option for reproductive-aged patients with stage IA type I and G2 EC. Nevertheless, we solicit new trials to clarify the medium- and long-term outcomes in this kind of patients.

  2. Impact of Age, Race and Socio-economic Status on Temporal Trends in Late-Stage Prostate Cancer Diagnosis in Florida

    PubMed Central

    Goovaerts, Pierre; Xiao, Hong; Gwede, Clement K.; Tan, Fei; Huang, Youjie; Adunlin, Georges; Ali, Askal

    2015-01-01

    Individual-level data from the Florida Cancer Data System (1981–2007) were analysed to explore temporal trends of prostate cancer late-stage diagnosis, and how they vary based on race, income and age. Annual census-tract rates were computed for two races (white and black) and two age categories (40–65, >65) before being aggregated according to census tract median household incomes. Joinpoint regression and a new disparity statistic were applied to model temporal trends and detect potential racial and socio-economic differences. Multi-dimensional scaling was used as an innovative way to visualize similarities among temporal trends in a 2-D space. Analysis of time-series indicated that late-stage diagnosis was generally more prevalent among blacks, for age category 40–64 compared to older patients covered by Medicare, and among classes of lower socio-economic status. Joinpoint regression also showed that the rate of decline in late-stage diagnosis was similar among older patients. For younger patients, the decline occurred at a faster pace for blacks with rates becoming similar to whites in the late 90s, in particular for higher incomes. Both races displayed distinct spatial patterns with higher rates of late-stage diagnosis in the Florida Panhandle for whites whereas high rates clustered in South-eastern Florida for blacks. PMID:26644992

  3. Impact of Age, Race and Socio-economic Status on Temporal Trends in Late-Stage Prostate Cancer Diagnosis in Florida.

    PubMed

    Goovaerts, Pierre; Xiao, Hong; Gwede, Clement K; Tan, Fei; Huang, Youjie; Adunlin, Georges; Ali, Askal

    2015-11-01

    Individual-level data from the Florida Cancer Data System (1981-2007) were analysed to explore temporal trends of prostate cancer late-stage diagnosis, and how they vary based on race, income and age. Annual census-tract rates were computed for two races (white and black) and two age categories (40-65, >65) before being aggregated according to census tract median household incomes. Joinpoint regression and a new disparity statistic were applied to model temporal trends and detect potential racial and socio-economic differences. Multi-dimensional scaling was used as an innovative way to visualize similarities among temporal trends in a 2-D space. Analysis of time-series indicated that late-stage diagnosis was generally more prevalent among blacks, for age category 40-64 compared to older patients covered by Medicare, and among classes of lower socio-economic status. Joinpoint regression also showed that the rate of decline in late-stage diagnosis was similar among older patients. For younger patients, the decline occurred at a faster pace for blacks with rates becoming similar to whites in the late 90s, in particular for higher incomes. Both races displayed distinct spatial patterns with higher rates of late-stage diagnosis in the Florida Panhandle for whites whereas high rates clustered in South-eastern Florida for blacks.

  4. Plasma viscosity: a potential predictor of both medical treatment response and clinical stage of ulcerative colitis.

    PubMed

    Tolga, Yakar; Mansur, Cosar Arif; Savas, Gokturk Hu Seyin; Gulhan, Unler Kanat Ayse; Alper, Parlakgumus; Ilknur, Kozanoglu; Ender, Serin

    2016-01-01

    La colite ulcerosa (UC) è una delle maggiori forme di colonpatia infiammatoria cronica recidivante. La capacità di identificare tipo, gravità e sensibilità alla terapia su parametri di laboratorio è da tempo oggetto di ricerca degli studi clinici. Lo scopo di questo studio è quello di accertare la relazione tra la viscosità del plasma (PV), l’attività della malattia e la risposta al trattamento medico. Lo studio si è svolto su 105 pazienti con UC e 42 volontari sani. I prelievi di sangue sono stati utilizzati per valutare la viscosità del plasma (PV), la velocità di eritrosedimentazione (ESR), la proteina C-reattiva ultrasensibile (hs-CRP), il D-dimero e il fibrinogeno. I pazienti con UC sono stati raggruppati in relazione al grado di attività flogistica (cioè 59 attivi e 46 in remissione). La PV è risultata più elevata in quelli con UC attiva rispetto a quella dei soggetti in remissione o nei soggetti sani. È risultata significativamente più elevata sia nei casi di UC refrattaria al trattamento steroideo rispetto a quelli sensibili (p< 0.001), e nelle UC rafrattarie alla ciclosrporina rispetto a quelli sensibili (p= 0.003). Con l’aumento della PV nei pazienti affetti da UC sono risultati significativamente associati il punteggio del SCCAI (Increased Simple Clinical Colitis Activity Index), dell’EGS (Endoscopic Grading Scale) e del HAD (Histological Disease Activity (HAD). Si conclude che la PV è un marker utile per la previsione di sensibilità al trattamento sterorideo e con ciclosporina nei pazienti con UC attiva. Potrebbe essere rimpiazzata dalla ESR e dalla hs-CRP come misura della risposta in fase acuta in quanto sufficientemente sensibile. Questi risultati possono essere utili per l’identificazione dei pazienti con UC attiva da destinare alla colectomia.

  5. Amyloid PET Screening for Enrichment of Early-Stage Alzheimer Disease Clinical Trials: Experience in a Phase 1b Clinical Trial.

    PubMed

    Sevigny, Jeff; Suhy, Joyce; Chiao, Ping; Chen, Tianle; Klein, Gregory; Purcell, Derk; Oh, Joonmi; Verma, Ajay; Sampat, Mehul; Barakos, Jerome

    2016-01-01

    Amyloid positron emission tomography (PET) imaging is being investigated as a screening tool to identify amyloid-positive patients as an enrichment strategy for Alzheimer disease (AD) clinical trial enrollment. In a multicenter, phase 1b trial, patients meeting clinical criteria for prodromal or mild AD underwent florbetapir PET scanning at screening. PET, magnetic resonance imaging, and coregistered PET/magnetic resonance imaging scans were reviewed by 2 independent readers and binary visual readings tabulated. Semiquantitative values of cortical to whole cerebellar standard uptake value ratios were computed (threshold 1.10). Of 278 patients with an evaluable PET scan, 170 (61%) and 185 (67%) were amyloid-positive by visual reading and quantitative analysis, respectively; 39% were excluded from the study due to an amyloid-negative scan based on visual readings. More ApoE ε4 carriers than noncarriers were amyloid-positive (80% vs. 43%). Comparison of visual readings with quantitative results identified 21 discordant cases (92% agreement). Interreader and intrareader agreements from visual readings were 98% and 100%, respectively. Amyloid PET imaging is an effective and feasible screening tool for enrollment of amyloid-positive patients with early stages of AD into clinical trials.

  6. Stages of Adolescence

    MedlinePlus

    ... Español Text Size Email Print Share Stages of Adolescence Page Content Article Body Adolescence, these years from puberty to adulthood, may be roughly divided into three stages: early adolescence, generally ages eleven to fourteen; middle adolescence, ages ...

  7. Global estimate of the incidence of clinical pneumonia among children under five years of age.

    PubMed Central

    Rudan, Igor; Tomaskovic, Lana; Boschi-Pinto, Cynthia; Campbell, Harry

    2004-01-01

    OBJECTIVE: Clinical pneumonia (defined as respiratory infections associated with clinical signs of pneumonia, principally pneumonia and bronchiolitis) in children under five years of age is still the leading cause of childhood mortality in the world. In this paper we aim to estimate the worldwide incidence of clinical pneumonia in young children. METHODS: Our estimate for the developing world is based on an analysis of published data on the incidence of clinical pneumonia from community based longitudinal studies. Among more than 2000 studies published since 1961, we identified 46 studies that reported the incidence of clinical pneumonia, and 28 of these met pre-defined quality criteria. FINDINGS: The estimate of the median incidence from those studies was 0.28 episodes per child-year (e/cy). The 25-75% interquartile range was 0.21-0.71. We assessed the plausibility of this estimate using estimates of global mortality from acute respiratory infections and reported case fatality rates for all episodes of clinical pneumonia reported in community-based studies or the case-fatality rate reported only for severe cases and estimates of the proportion of severe cases occurring in a defined population or community. CONCLUSION: The overlap between the ranges of the estimates implies that a plausible incidence estimate of clinical pneumonia for developing countries is 0.29 e/cy. This equates to an annual incidence of 150.7 million new cases, 11-20 million (7-13%) of which are severe enough to require hospital admission. In the developed world no comparable data are available. However, large population-based studies report that the incidence of community-acquired pneumonia among children less than five years old is approximately 0.026 e/cy, suggesting that more than 95% of all episodes of clinical pneumonia in young children worldwide occur in developing countries. PMID:15654403

  8. Phase I-II clinical trial of Californium-252. Treatment of stage IB carcinoma of the cervix.

    PubMed

    Maruyama, Y; VanNagell, J R; Yoneda, J; Donaldson, E; Gallion, H; Rowley, K; Kryscio, R; Beach, J L

    1987-04-15

    Intracavitary Californium-252 combined with whole-pelvis photon radiotherapy was tested as the sole form of treatment for 22 patients with Stage IB carcinoma of the cervix. Californium-252 (Cf) is a fast neutron-emitting radioisotope currently being tested in trials of neutron brachytherapy (NT). The outcomes of the treated group of patients were traced for local tumor control, survival, patterns of failure, and complications. The Cf intracavitary therapy combined with whole-pelvis photon radiotherapy resulted in 95% 2-year and 91% 5-year actuarial survival. There were 9% Grade II-III complications by the Stockholm scale and 4% local failures. These results were obtained in an early clinical trial with a group of largely poor-risk patients with tumors of mean diameter of 4.3 cm.

  9. Phase I-II clinical trial of Californium-252. Treatment of stage IB carcinoma of the cervix

    SciTech Connect

    Maruyama, Y.; VanNagell, J.R.; Yoneda, J.; Donaldson, E.; Gallion, H.; Rowley, K.; Kryscio, R.; Beach, J.L.

    1987-04-15

    Intracavitary Californium-252 combined with whole-pelvis photon radiotherapy was tested as the sole form of treatment for 22 patients with Stage IB carcinoma of the cervix. Californium-252 (Cf) is a fast neutron-emitting radioisotope currently being tested in trials of neutron brachytherapy (NT). The outcomes of the treated group of patients were traced for local tumor control, survival, patterns of failure, and complications. The Cf intracavitary therapy combined with whole-pelvis photon radiotherapy resulted in 95% 2-year and 91% 5-year actuarial survival. There were 9% Grade II-III complications by the Stockholm scale and 4% local failures. These results were obtained in an early clinical trial with a group of largely poor-risk patients with tumors of mean diameter of 4.3 cm.

  10. Clinical profile of patients with advanced age and inflammatoric dilated cardiomyopathy on endomyocardial biopsy

    PubMed Central

    Ohlow, Marc-Alexander; Chen, Ting-Hui; Schmidt, Andreas; Saenger, Joerg; Lauer, Bernward

    2015-01-01

    Background Endomyocardial biopsy (EMB) is an important tool when patients with inflammatoric cardiomyopathy (DCMi) are evaluated. We aimed to assess the clinical profile of elderly patients with DCMi on EMB. Methods Retrospective study of all consecutive patients hospitalized from January 2007 to December 2011 with clinical suspicion of DCMi undergoing EMB. Patients with evidence of DCMi on EMB (Group 1 ≥ 70 years, n = 85; Group 3 < 70 years; n = 418) were compared to patients of the same age group without evidence of DCMi on EMB (Group 2 ≥ 70 years, n = 45; Group 4 < 70 years; n = 147). Results Among 24,275 patients treated at our institution during the study period, 695 had clinical suspicion of DCMi and underwent EMB; 503 (2.1%) patients had DCMi on EMB. There were more male patients in Group 1, mean age was 74 ± 2.8 years, mean ejection fraction was 38% ± 14%. On presentation, signs of hemodynamic compromise (NYHA functional class III/IV, low cardiac output/index, and low cardiac power index) were more frequent in Group 1. EMB revealed viral genome in 78% of the patients, parvovirus B19 (PVB) was frequently encountered in both age groups (Group 1: 69.4% vs. Group 2: 59.6%); detection of more than one viral genome was more frequent in Group 1 (21.2% vs. 11.2%; P = 0.02) whereas the extent of immune response was significantly lower in individuals with advanced age. Conclusions In patients ≥ 70 years with DCMi on EMB signs of hemodynamic compromise, detection of multiple viral genomes together with an overall lower extent of immune response were more frequently observed. PMID:26788036

  11. Report of a consultation on the optimization of clinical challenge trials for evaluation of candidate blood stage malaria vaccines, 18-19 March 2009, Bethesda, MD, USA.

    PubMed

    Moorthy, V S; Diggs, C; Ferro, S; Good, M F; Herrera, S; Hill, A V; Imoukhuede, E B; Kumar, S; Loucq, C; Marsh, K; Ockenhouse, C F; Richie, T L; Sauerwein, R W

    2009-09-25

    Development and optimization of first generation malaria vaccine candidates has been facilitated by the existence of a well-established Plasmodium falciparum clinical challenge model in which infectious sporozoites are administered to human subjects via mosquito bite. While ideal for testing pre-erythrocytic stage vaccines, some researchers believe that the sporozoite challenge model is less appropriate for testing blood stage vaccines. Here we report a consultation, co-sponsored by PATH MVI, USAID, EMVI and WHO, where scientists from all institutions globally that have conducted such clinical challenges in recent years and representatives from regulatory agencies and funding agencies met to discuss clinical malaria challenge models. Participants discussed strengthening and harmonizing the sporozoite challenge model and considered the pros and cons of further developing a blood stage challenge possibly better suited for evaluating the efficacy of blood stage vaccines. This report summarizes major findings and recommendations, including an update on the Plasmodium vivax clinical challenge model, the prospects for performing experimental challenge trials in malaria endemic countries and an update on clinical safety data. While the focus of the meeting was on the optimization of clinical challenge models for evaluation of blood stage candidate malaria vaccines, many of the considerations are relevant for the application of challenge trials to other purposes.

  12. Age-dependent vitreous separation from the macula in a clinic population

    PubMed Central

    Syed, Zahid; Stewart, Michael W

    2016-01-01

    Background Vitreous degeneration begins soon after birth and accelerates throughout life. Vitreous liquefaction with a slowly progressive separation of the posterior hyaloid from the peripheral macula usually leads to complete posterior vitreous detachment. The purpose of this study is to measure the age-related prevalence of partial vitreous separation and the length of residual vitreous adhesion in an ophthalmology clinic population. Methods Patients examined by the senior author (MWS) during a 6-month period were included in a retrospective chart review. Demographic data and spectral domain optical coherence tomography scan results were gathered. Data analysis with descriptive statistics focused on the prevalence and extent of partial vitreous separation. Results The mean age of the study patients was 69.9 years, and 62% were phakic. The highest prevalence of partial posterior hyaloid separation from the internal limiting membrane (71.2%) was seen in the 50- to 54-year age group. This prevalence rate steadily decreased to 5.6% in the 95- to 99-year age group. The prevalence of complete vitreous detachment as determined by slit-lamp biomicroscopy increased from 1.7% in the <50-year age group to a maximum of 29.2% in the 75- to 79-year group. The length of vitreomacular adhesion averaged 4.6 mm in the 50- to 54-year age group and steadily decreased to 2.1 mm in the 90- to 95-year group. Conclusion Vitreomacular separation affects the majority of eyes in the sixth decade of life. The prevalence of partial vitreous separation decreases with advancing age, probably because an increasing number of these patients progress to complete posterior vitreous detachment. PMID:27462138

  13. Comparison of Clinical and Pathological Differences of Breast Cancer Patients under 35 and above 55 Years of Age

    PubMed Central

    Emiroğlu, Mustafa; Karaali, Cem; Sert, İsmail; Salimoğlu, Semra; Uğurlu, Levent; Aksoy, Süleyman; Aydın, Cengiz

    2015-01-01

    Objective In this study, we aimed to evaluate the clinical, pathologic and management differences between breast cancer patients under 35 years of age and postmenopausal patients above 55 years of age. Materials and Methods Patients who were operated on for breast cancer between November 2003 and March 2013 in our hospital were retrospectively analyzed. Patients were separated into two Groups according their age; Group 1 (<35 years) and Group 2 (>55 years). Results 94 patients with breast cancer, 45 patients in Group 1 and 49 patients in Group 2, were included in the study. The mean follow-up was 51 (19–121) months and 50 (19–120) months in Groups 1 and 2, respectively. Stages of breast cancer at the time of diagnosis were similar between the two groups. The groups were similar in terms of rates of re-excision (p=0.42), local recurrence (p=0.34) and solid organ metastases (p=0.182). The number of oncoplastic and reconstructive procedures were higher in Group 1 (p=0.04). Regarding pathological results, the rate of grade 3 tumors, those with Ki-67>12 and triple negative breast cancer were found to be higher in Group 1. In addition, the number of patients receiving chemotherapy was significantly higher in Group 1 (p=0.03). Conclusion Oncologic results were similar between young patients and postmenopausal patients. Nevertheless, tumor biology was found to be worse in young patients. In addition, oncoplastic and reconstructive approaches were significantly higher in young patients.

  14. COGNITIVE-HD study: protocol of an observational study of neurocognitive functioning and association with clinical outcomes in adults with end-stage kidney disease treated with haemodialysis

    PubMed Central

    Palmer, Suetonia C; Ruospo, Marinella; Barulli, Maria Rosaria; Iurillo, Annalisa; Saglimbene, Valeria; Natale, Patrizia; Gargano, Letizia; Murgo, Angelo M; Loy, Clement; van Zwieten, Anita; Wong, Germaine; Tortelli, Rosanna; Craig, Jonathan C; Johnson, David W; Tonelli, Marcello; Hegbrant, Jörgen; Wollheim, Charlotta; Logroscino, Giancarlo; Strippoli, G F M

    2015-01-01

    Introduction The prevalence of cognitive impairment may be increased in adults with end-stage kidney disease compared with the general population. However, the specific patterns of cognitive impairment and association of cognitive dysfunction with activities of daily living and clinical outcomes (including withdrawal from treatment) among haemodialysis patients remain incompletely understood. The COGNITIVE impairment in adults with end-stage kidney disease treated with HemoDialysis (COGNITIVE-HD) study aims to characterise the age-adjusted and education-adjusted patterns of cognitive impairment (using comprehensive testing for executive function, perceptual-motor function, language, learning and memory, and complex attention) in patients on haemodialysis and association with clinical outcomes. Methods and analysis A prospective, longitudinal, cohort study of 750 adults with end-stage kidney disease treated with long-term haemodialysis has been recruited within haemodialysis centres in Italy (July 2013 to April 2014). Testing for neurocognitive function was carried out by a trained psychologist at baseline to assess cognitive functioning. The primary study factor is cognitive impairment and secondary study factors will be specific domains of cognitive function. The primary outcome will be total mortality. Secondary outcomes will be cause-specific mortality, major cardiovascular events, fatal and non-fatal myocardial infarction and stroke, institutionalisation, and withdrawal from treatment at 12 months. Ethics and dissemination This protocol was approved before study conduct by the following responsible ethics committees: Catania (approval reference 186/BE; 26/09/2013), Agrigento (protocol numbers 61–62; 28/6/2013), USL Roma C (CE 39217; 24/6/2013), USL Roma F (protocol number 0041708; 23/7/2013), USL Latina (protocol number 20090/A001/2011; 12/7/2013), Trapani (protocol number 3413; 16/7/2013) and Brindisi (protocol number 40259; 6/6/2013). All participants

  15. [From classification medicine to clinical medicine (the end of the XVIII century--1870s). Communication 2. The first stage of clinical medicine development: introduction of the method of clinico-anatomic correlations].

    PubMed

    2011-01-01

    The first stage of clinical medicine development is analysed which covers the period from early 1800s to middle 1870s. Considered are basic research achievements associated with introduction of the method of clinico-anatomic correlations into practical medicine.

  16. Rotator Cuff Repair in Patients over 75 Years of Age: Clinical Outcome and Repair Integrity

    PubMed Central

    Park, Jung Gwan; Cho, Nam Su; Song, Jong Hoon; Baek, Jong Hun; Jeong, Ho Yeon

    2016-01-01

    Background Some studies have shown significant functional improvement after rotator cuff (RC) repair in elderly patients. However, few studies have reported the healing potential of RC tears in elderly patients. Methods Twenty-five patients aged ≥ 75 years who underwent RC repair were enrolled. The mean age at the time of surgery was 78.3 years (range, 75 to 88 years) while the mean follow-up was 36.3 months (range, 18 to 114 months). We evaluated clinical and structural outcomes after RC repair in the retear and healed groups. Results Of 25 patients, 16 (64%) had healed RC lesions and 9 (36%) had retorn cuff lesions. The retear rate increased significantly with increasing initial tear size (small to medium, 13%; large, 60%; massive, 80%; p = 0.024) but not with increasing age (p = 0.072). The mean visual analog scale (VAS), University of California Los Angeles (UCLA), and Constant scores significantly improved from 5.2, 15.8, and 49.3 preoperatively to 1.4, 31.1, and 71.9 in the healed group and from 6.0, 14.4, and 39.5 preoperatively to 2.4, 28.3, and 63.6 in the retear group at the final follow-up (p < 0.05, respectively). There were no significant differences in clinical outcomes between the 2 groups at the final follow-up. Retear was significantly correlated with initial tear size (p = 0.001; odds ratio [OR], 2.771; 95% confidence interval [CI], 1.394 to 5.509 for large to massive tears) (p = 0.001; OR, 0.183; 95% CI, 0.048 to 0.692 for small to medium tears). Conclusions There were significant improvements in clinical outcomes after RC repair in patients ≥ 75 years. Structural integrity after cuff repair did not affect the final clinical outcome. Even in elderly patients aged ≥ 75 years, healing of repaired RC can be expected in cases of small to medium tears. Although the retear rate was relatively high for large to massive tears, clinical outcomes still showed significant improvement. PMID:27904725

  17. Repeat retail clinic visits: impact of insurance coverage and age of patient.

    PubMed

    Angstman, Kurt B; Bernard, Matthew E; Rohrer, James E; Garrison, Gregory M; Maclaughlin, Kathy L

    2012-12-01

    As retail clinics provide a less costly alternative for health care, it would be reasonable to expect an increase in multiple (repeat) retail visits by those patients who may have expenses for receiving primary care. If costs were not a significant factor, then repeat visits should not be significantly different between these patients and those with coverage for primary care visits. The hypothesis for this study was that patients with the potential for out-of-pocket expenses would have a higher frequency of repeat retail clinic visits within 180 days compared to those with primary care coverage. A retrospective chart review was conducted of 5703 patients utilizing a retail clinic in Rochester, Minnesota from January 1, 2009 through June 30, 2009. The first visit to the retail clinic was considered the index visit and the chart was reviewed for repeat retail clinic visits within the next 180 days. Using a multiple logistic regression model, the odds of a pediatric patient (N=2344) having a repeat retail visit within 180 days of the index visit were not significantly impacted by insurance coverage (P=0.4209). Of the 3359 adult patients, those with unknown coverage had a 25.6% higher odds ratio of repeat retail clinic visits than those with insurance coverage (odds ratio 1.2557, confidence interval 1.0421-1.5131). This study suggested that when cost is an issue, the adult patient may favor retail clinics for episodic, low-acuity health care. In contrast, the pediatric population did not, suggesting that other factors, such as convenience, may play more of a role in the choice of episodic health care for this age group.

  18. Clinical Implications of Obstructed Hemivagina and Ipsilateral Renal Anomaly (OHVIRA) Syndrome in the Prepubertal Age Group

    PubMed Central

    Han, Jang Hee; Lee, Yong Seung; Im, Young Jae; Kim, Sang Woon; Lee, Mi-Jung; Han, Sang Won

    2016-01-01

    Purpose Obstructed hemivagina and ipsilateral renal anomaly (OHVIRA) syndrome is a rare syndrome characterized by Müllerian duct and renal anomalies. It is usually regarded as a disease of adolescence; however, due to a number of possible problems, the management of patients before puberty should not be overlooked. We assessed the clinical course of prepubertal patients to propose appropriate management. Materials and Methods We retrospectively assessed 43 prepubertal OHVIRA syndrome patients who were diagnosed and followed up at our institution from July 2004 to June 2015. We reviewed medical records, focusing on presentation, radiologic findings, surgical management, and the overall clinical course. Results Median age at diagnosis was 1.3 months and median follow-up period was 25.5 months. The most common accompanying ipsilateral urologic anomalies were ectopic ureter and ureterocele, while the most common contralateral anomaly was vesicoureteral reflux. During the follow-up period, six patients (14.0%) required surgery at a median age of 31.2 months due to recurrent urinary tract infection, uncontrolled vaginal distention compressing adjacent organs, urinary incontinence, or intractable abdominal pain. Conclusions While OHVIRA syndrome is known as a postpubertal disease, about 13% of prepubertal patients in our study required surgery. When ectopic ureter insertion into the vagina is present, further treatment may be needed to address the complications caused by continuous urine production. Patients should be monitored for complications arising from either obstructed hemivagina or renal anomalies with regular follow-up, especially before the age of five years. PMID:27861623

  19. Limbal Stem Cells from Aged Donors Are a Suitable Source for Clinical Application

    PubMed Central

    Martínez-Conesa, Eva M.

    2016-01-01

    Limbal stem cells (LSC) are the progenitor cells that maintain the transparency of the cornea. Limbal stem cell deficiency (LSCD) leads to corneal opacity, inflammation, scarring, and blindness. A clinical approach to treat this condition consists in LSC transplantation (LSCT) after ex vivo expansion of LSC. In unilateral LSCD, an autologous transplant is possible, but cases of bilateral LSCD require allogenic LSCT. Cadaveric donors represent the most important source of LSC allografts for treatment of bilateral LSCD when living relative donors are not available. To evaluate the suitability of aged cadaveric donors for LSCT, we compared three pools of LSC from donors of different ages (<60 years, 60–75 years, and >75 years). We evaluated graft quality in terms of percent of p63-positive (p63+) cells by immunofluorescence, colony forming efficiency, and mRNA and protein expression of p63, PAX6, Wnt7a, E-cadherin, and cytokeratin (CK) 12, CK3, and CK19. The results showed that LSC cultures from aged donors can express ≥3% of p63+ cells—considered as the minimum value for predicting favorable clinical outcomes after LSCT—suggesting that these cells could be a suitable source of LSC for transplantation. Our results also indicate the need to evaluate LSC graft quality criteria for each donor. PMID:28042298

  20. Effects of leaf age within growth stages of pepper and sorghum plants on leaf thickness, water, chlorophyll, and light reflectance. [in spectral vegetation discrimination

    NASA Technical Reports Server (NTRS)

    Gausman, H. W.; Cardenas, R.; Berumen, A.

    1974-01-01

    Pepper and sorghum plants (characterized by porous and compact leaf mesophylls, respectively) were used to study the influence of leaf age on light reflectance. Measurements were limited to the upper five nodal positions within each growth stage, since upper leaves make up most of the reflectance surfaces remotely sensed. The increase in leaf thickness and water content with increasing leaf age was taken into consideration, since each of these factors affects the reflectance as well as the selection of spectral wavelength intervals for optimum discrimination of vegetation.

  1. AGING AND LIFE-STAGE SUSCEPTIBILITY: TOLUENE EFFECTS ON BRAIN OXIDATIVE STRESS PARAMETERS IN BROWN NORWAY RATS.

    EPA Science Inventory

    The influence of aging on susceptibility to environmental contaminants is poorly understood. The objectives of this study were to test whether oxidative stress (OS) is a potential toxicity pathway following toluene exposure and to determine if these effects are age-dependent. We ...

  2. Update on Clinical Trials in Dry Age-related Macular Degeneration.

    PubMed

    Taskintuna, Ibrahim; Elsayed, M E A Abdalla; Schatz, Patrik

    2016-01-01

    This review article summarizes the most recent clinical trials for dry age-related macular degeneration (AMD), the most common cause of vision loss in the elderly in developed countries. A literature search through websites https://www.pubmed.org and https://www.clinicaltrials.gov/, both accessed no later than November 04, 2015, was performed. We identified three Phase III clinical trials that were completed over the recent 5 years Age-Related Eye Disease Study 2 (AREDS2), implantable miniature telescope and tandospirone, and several other trials targeting a variety of mechanisms including, oxidative stress, complement inhibition, visual cycle inhibition, retinal and choroidal blood flow, stem cells, gene therapy, and visual rehabilitation. To date, none of the biologically oriented therapies have resulted in improved vision. Vision improvement was reported with an implantable mini telescope. Stem cells therapy holds a potential for vision improvement. The AREDS2 formulas did not add any further reduced risk of progression to advanced AMD, compared to the original AREDS formula. Several recently discovered pathogenetic mechanisms in dry AMD have enabled development of new treatment strategies, and several of these have been tested in recent clinical trials and are currently being tested in ongoing trials. The rapid development and understanding of pathogenesis holds promise for the future.

  3. Update on Clinical Trials in Dry Age-related Macular Degeneration

    PubMed Central

    Taskintuna, Ibrahim; Elsayed, M. E. A. Abdalla; Schatz, Patrik

    2016-01-01

    This review article summarizes the most recent clinical trials for dry age-related macular degeneration (AMD), the most common cause of vision loss in the elderly in developed countries. A literature search through websites https://www.pubmed.org and https://www.clinicaltrials.gov/, both accessed no later than November 04, 2015, was performed. We identified three Phase III clinical trials that were completed over the recent 5 years Age-Related Eye Disease Study 2 (AREDS2), implantable miniature telescope and tandospirone, and several other trials targeting a variety of mechanisms including, oxidative stress, complement inhibition, visual cycle inhibition, retinal and choroidal blood flow, stem cells, gene therapy, and visual rehabilitation. To date, none of the biologically oriented therapies have resulted in improved vision. Vision improvement was reported with an implantable mini telescope. Stem cells therapy holds a potential for vision improvement. The AREDS2 formulas did not add any further reduced risk of progression to advanced AMD, compared to the original AREDS formula. Several recently discovered pathogenetic mechanisms in dry AMD have enabled development of new treatment strategies, and several of these have been tested in recent clinical trials and are currently being tested in ongoing trials. The rapid development and understanding of pathogenesis holds promise for the future. PMID:26957835

  4. Performance of the CogState computerized battery in the Mayo Clinic Study on Aging

    PubMed Central

    Mielke, Michelle M.; Machulda, Mary M.; Hagen, Clinton E.; Edwards, Kelly K.; Roberts, Rosebud O.; Pankratz, V. Shane; Knopman, David S.; Jack, Clifford R.; Petersen, Ronald C.

    2015-01-01

    Background The feasibility and validity of brief computerized cognitive batteries at the population-level are unknown. Methods Non-demented participants (n = 1660, age 50–97) in the Mayo Clinic Study on Aging completed the computerized CogState battery and standard neuropsychological battery. The correlation between tests was examined and comparisons between CogState performance on the personal computer (PC) and iPad (n = 331), and in the Clinic vs. at home (n = 194), were assessed. Results We obtained valid data on >97% of participants on each test. Correlations between the CogState and neuropsychological tests ranged from −0.462 to 0.531. While absolute differences between the PC and iPad were small and participants preferred the iPad, performance on the PC was faster. Participants performed faster on Detection, One Card Learning, and One Back at home compared to the Clinic. Conclusions The computerized CogState battery, especially the iPad, was feasible, acceptable, and valid in the population. PMID:25858683

  5. Spontaneous Pushing in Lateral Position versus Valsalva Maneuver During Second Stage of Labor on Maternal and Fetal Outcomes: A Randomized Clinical Trial

    PubMed Central

    Vaziri, Farideh; Arzhe, Amene; Asadi, Nasrin; Pourahmad, Saeedeh; Moshfeghy, Zeinab

    2016-01-01

    Background There are concerns about the harmful effects of the Valsalva maneuver during the second stage of labor. Objectives Comparing the effects of spontaneous pushing in the lateral position with the Valsalva maneuver during the second stage of labor on maternal and fetal outcomes. Methods Inclusion criteria in this randomized clinical trial conducted in Iran were as follows: nulliparous mothers, live fetus with vertex presentation, gestational age of 37 - 40 weeks, spontaneous labor, and no complications. The intervention group pushed spontaneously while they were in the lateral position, whereas the control group pushed using Valsalva method while in the supine position at the onset of the second stage of labor. Maternal outcomes such as pain and fatigue severity and fetal outcomes such as pH and pO2 of the umbilical cord blood were measured. Results Data pertaining to 69 patients, divided into the intervention group (35 subjects) and control group (34 subjects), were analyzed statistically. The mean pain (7.80 ± 1.21 versus 9.05 ± 1.11) and fatigue scores (46.59 ± 21 versus 123.36 ± 43.20) of the two groups showed a statistically significant difference (P < 0.001). Moreover, the mean duration of the second stage in the intervention group was significantly higher than that in the control group (76.32 ± 8.26 minutes versus 64.56 ± 15.24 minutes, P = 0.001). The umbilical cord blood pO2 levels of both groups showed a statistically significant difference (28.29 ± 11.76 versus 18.83 ± 9.86, P < 0.001), whereas their pH levels were not significantly different (P = 0.10). Conclusions Spontaneous pushing in the lateral position reduced fatigue and pain severity of the mothers. Also, it did not worsen fetal outcomes. Thus, it can be used as an alternative method for the Valsalva maneuver. PMID:28180019

  6. Impact of early personal-history characteristics on the Pace of Aging: implications for clinical trials of therapies to slow aging and extend healthspan.

    PubMed

    Belsky, Daniel W; Caspi, Avshalom; Cohen, Harvey J; Kraus, William E; Ramrakha, Sandhya; Poulton, Richie; Moffitt, Terrie E

    2017-04-12

    Therapies to extend healthspan are poised to move from laboratory animal models to human clinical trials. Translation from mouse to human will entail challenges, among them the multifactorial heterogeneity of human aging. To inform clinical trials about this heterogeneity, we report how humans' pace of biological aging relates to personal-history characteristics. Because geroprotective therapies must be delivered by midlife to prevent age-related disease onset, we studied young-adult members of the Dunedin Study 1972-73 birth cohort (n = 954). Cohort members' Pace of Aging was measured as coordinated decline in the integrity of multiple organ systems, by quantifying rate of decline across repeated measurements of 18 biomarkers assayed when cohort members were ages 26, 32, and 38 years. The childhood personal-history characteristics studied were known predictors of age-related disease and mortality, and were measured prospectively during childhood. Personal-history characteristics of familial longevity, childhood social class, adverse childhood experiences, and childhood health, intelligence, and self-control all predicted differences in cohort members' adulthood Pace of Aging. Accumulation of more personal-history risks predicted faster Pace of Aging. Because trials of anti-aging therapies will need to ascertain personal histories retrospectively, we replicated results using cohort members' retrospective personal-history reports made in adulthood. Because many trials recruit participants from clinical settings, we replicated results in the cohort subset who had recent health system contact according to electronic medical records. Quick, inexpensive measures of trial participants' early personal histories can enable clinical trials to study who volunteers for trials, who adheres to treatment, and who responds to anti-aging therapies.

  7. Prediction of Small for Gestational Age Infants in Healthy Nulliparous Women Using Clinical and Ultrasound Risk Factors Combined with Early Pregnancy Biomarkers

    PubMed Central

    McCowan, Lesley M. E.; Thompson, John M. D.; Taylor, Rennae S.; Baker, Philip N.; North, Robyn A.; Poston, Lucilla; Roberts, Claire T.; Simpson, Nigel A. B.; Walker, James J.; Myers, Jenny; Kenny, Louise C.

    2017-01-01

    for gestational age, which combine biomarkers, clinical and ultrasound data from a cohort of low-risk nulliparous women achieved modest performance. Incorporation of biomarkers into the models resulted in no improvement in performance of prediction of All-SGA and Normotensive-SGA but a small improvement in prediction of Hypertensive-SGA. Our models currently have insufficient reliability for application in clinical practice however, they have potential utility in two-staged screening tests which include third trimester biomarkers and or fetal biometry. PMID:28068394

  8. Early stages of salmon calcitonin aggregation: effect induced by ageing and oxidation processes in water and in the presence of model membranes.

    PubMed

    Gaudiano, Maria Cristina; Colone, Marisa; Bombelli, Cecilia; Chistolini, Pietro; Valvo, Luisa; Diociaiuti, Marco

    2005-06-30

    The natural ageing- and hydrogen peroxide-induced aggregation of salmon calcitonin were studied in water and in the presence of dipalmitoylphosphatidylcholine (DPPC) liposomes. The early stages of the aggregation process at low protein concentration were investigated by means of Circular Dichroism spectroscopy (CD) and conventional and immunogold labelling Transmission Electron Microscopy (TEM). In buffered water solution, salmon calcitonin showed a two-stage conformational variation related to fibril formation and phase-separation of larger aggregates. A first stage, characterised by small conformational changes but a decrease in dichroic band intensity, was followed by a second stage, 6 days after, leading to higher conformational variations and aggregations. Salmon calcitonin showed a distinct modification in the secondary structure and aggregate morphology in the presence of hydrogen peroxide with respect to natural ageing, indicating that the two aggregation processes (natural and chemical-induced) followed a distinct mechanism. The oxidised forms of the peptide were separated by liquid chromatography. The same study was performed in the presence of DPPC liposomes. The results obtained by conventional and immunogold labelling TEM evidenced that salmon calcitonin in buffered water solution essentially does not enter the liposomes but forms around them a fibril network characterised by the same conformational changes after 6 days. The oxidised sample in the presence of liposomes showed a "fibrils hank", separated from liposomes. The presence of liposomes did not affect either the aggregation or the conformational modifications yet observed by TEM and CD in water solution.

  9. New K-Ar ages and the geologic evidence against rejuvenated-stage volcanism at Haleakalā, East Maui, a postshield-stage volcano of the Hawaiian island chain

    USGS Publications Warehouse

    Sherrod, David R.; Nishimitsu, Yoshitomo; Tagami, Takahiro

    2003-01-01

    The age of the Kula/Hāna boundary is ca. 0.15–0.12 Ma; thus, volcanic quiescence of only ∼0.03 m.y. separates the two formations, much shorter than the previously known limit of 0.25–0.30 m.y. The brevity of this hiatus, coupled with coincident vent loci and broadly similar geochemical characteristics for the Hāna and the upper part of the Kula Volcanics, indicates that the Hāna Volcanics unit comprises deposits of postshield-stage volcanism that has waned substantially since ca. 0.4–0.3 Ma. Haleakalā has not yet begun a classically defined rejuvenated stage. Our findings support recent numerical modeling of plume-lithosphere interactions that predict that Haleakalā is near the end of its postshield growth.

  10. Clinical efficacy and safety of tripterygium glycosides in treatment of stage IV diabetic nephropathy: A meta-analysis

    PubMed Central

    Hong, Yan; Gui, Zhihong; Cai, Xiaoping

    2016-01-01

    Abstract The aim of this meta-analysis was to evaluate the clinical efficacy and safety of tripterygium glycosides in treatment of stage IV diabetic nephropathy. Methods Through searching the PubMed and CNKI databases, the open published clinically controlled trials related to efficacy and safety of tripterygium glycosides in the treatment of stage IV diabetic nephropathy were collected. The pooled total efficacy, 24h urinary protein, serum creatinine and tripterygium glycosides related toxicity were calculated using Stata 11.0 software. Results Fourteen publications including 992 subjects (512 in the experimental group and 480 in the control group) were included in this study. Eight studies reported the total clinical efficacy comparing the experiment and control groups. No significant statistical heterogeneity was found in total efficacy (I2=24.9%, p>0.05). Thus, the combined odds ratio (OR) was pooled by fixed effect model. The pooled OR=4.16 with its 95% CI 2.71~6.37 (p<0.05), which indicated the total efficacy in the experiment group, was significant higher than that of control group (p<0.05); Thirteen studies reported the post-treatment 24h urinary protein value. Statistical heterogeneity analysis indicated significant heterogeneity across studies (I2=91.1%, p<0.05); that data was pooled by a random effects model. The combined standardized mean difference (SMD) was -1.55 with its 95% I -2.06~1.03, (p<0.05). The results indicated that post-treatment 24h urinary protein in the experiment group was significant lower than that in control group (p<0.05); Ten studies reported the post-treatment serum creatinine. Significant heterogeneity existed across those studies (I2=82.3%, p<0.05). Thereafter, the data was pooled by a random effect model. The combined standardized mean difference (SMD) was −0.24 with its 95%CI −0.40~0.09, (p<0.05). The results indicated that the post-treatment serum creatinine in experiment group was significant lower than that of control

  11. DNA damage response (DDR) and senescence: shuttled inflamma-miRNAs on the stage of inflamm-aging.

    PubMed

    Olivieri, Fabiola; Albertini, Maria Cristina; Orciani, Monia; Ceka, Artan; Cricca, Monica; Procopio, Antonio Domenico; Bonafè, Massimiliano

    2015-11-03

    A major issue in aging research is how cellular phenomena affect aging at the systemic level. Emerging evidence suggests that DNA damage response (DDR) signaling is a key mechanism linking DNA damage accumulation, cell senescence, and organism aging. DDR activation in senescent cells promotes acquisition of a proinflammatory secretory phenotype (SASP), which in turn elicits DDR and SASP activation in neighboring cells, thereby creating a proinflammatory environment extending at the local and eventually the systemic level. DDR activation is triggered by genomic lesions as well as emerging bacterial and viral metagenomes. Therefore, the buildup of cells with an activated DDR probably fuels inflamm-aging and predisposes to the development of the major age-related diseases (ARDs). Micro (mi)-RNAs - non-coding RNAs involved in gene expression modulation - are released locally and systemically by a variety of shuttles (exosomes, lipoproteins, proteins) that likely affect the efficiency of their biological effects. Here we suggest that some miRNAs, previously found to be associated with inflammation and senescence - miR-146, miR-155, and miR-21 - play a central role in the interplay among DDR, cell senescence and inflamm-aging. The identification of the functions of shuttled senescence-associated miRNAs is expected to shed light on the aging process and on how to delay ARD development.

  12. A Method for Utilizing Bivariate Efficacy Outcome Measures to Screen Regimens for Activity in 2-Stage Phase II Clinical Trials

    PubMed Central

    Rubinstein, Larry; Litwin, Samuel; Yothers, Greg

    2012-01-01

    Background Most phase II clinical trials utilize a single primary endpoint to determine the promise of a regimen for future study. However, many disorders manifest themselves in complex ways. For example, migraine headaches can cause pain, auras, photophobia, and emesis. Investigators may believe a drug is effective at reducing migraine pain and the severity of emesis during an attack. Nevertheless, they could still be interested in proceeding with development of the drug if it is effective against only one of these symptoms. Such a study would be a candidate for a clinical trial with co-primary endpoints. Purpose The purpose of the article is to provide a method for designing a 2-stage clinical trial with dichotomous co-primary endpoints of efficacy that has the ability to detect activity on either response measure with high probability when the drug is active on one or both measures, while at the same time rejecting the drug with high probability when there is little activity on both dimensions. The design enables early closure for futility and is flexible with regard to attained accrual. Methods The design is proposed in the context of cancer clinical trials where tumor response is used to assess a drug's ability to kill tumor cells and progression-free survival (PFS) status after a certain period is used to evaluate the drug's ability to stabilize tumor growth. Both endpoints are assumed to be distributed as binomial random variables, and uninteresting probabilities of success are determined from historical controls. Given the necessity of accrual flexibility, exhaustive searching algorithms to find optimum designs do not seem feasible at this time. Instead, critical values are determined for realized sample sizes using specific procedures. Then accrual windows are found to achieve a design's desired level of significance, probability of early termination (PET), and power. Results The design is illustrated with a clinical trial that examined bevacizumab in

  13. Clinical and radiological outcome of the cemented Contemporary acetabular component in patients < 50 years of age.

    PubMed

    Schmitz, M W J L; Timmer, C; Rijnen, W H C; Gardeniers, J W M; Schreurs, B W

    2013-12-01

    Despite the worldwide usage of the cemented Contemporary acetabular component (Stryker), no published data are available regarding its use in patients aged < 50 years. We undertook a mid- to long-term follow-up study, including all consecutive patients aged < 50 years who underwent a primary total hip replacement using the Contemporary acetabular component with the Exeter cemented stem between January 1999 and January 2006. There were 152 hips in 126 patients, 61 men and 65 women, mean age at surgery 37.6 years (16 to 49 yrs). One patient was lost to follow-up. Mean clinical follow-up of all implants was 7.6 years (0.9 to 12.0). All clinical questionnaire scores, including Harris hip score, Oxford hip score and several visual analogue scales, were found to have improved. The eight year survivorship of all acetabular components for the endpoints revision for any reason or revision for aseptic loosening was 94.4% (95% confidence interval (CI) 89.2 to 97.2) and 96.4% (95% CI 91.6 to 98.5), respectively. Radiological follow-up was complete for 146 implants. The eight year survival for the endpoint radiological loosening was 93.1% (95% CI 86.2 to 96.6). Three surviving implants were considered radiologically loose but were asymptomatic. The presence of acetabular osteolysis (n = 17, 11.8%) and radiolucent lines (n = 20, 13.9%) in the 144 surviving cups indicates a need for continued observation in the second decade of follow-up in order to observe their influence on long-term survival. The clinical and radiological data resulting in a ten-year survival rate > 90% in young patients support the use of the Contemporary acetabular component in this specific patient group.

  14. Age of onset influences on clinical and laboratory profile of patients with systemic lupus erythematosus.

    PubMed

    Sassi, Rafael Hennemann; Hendler, Jordana Vaz; Piccoli, Giovana Fagundes; Gasparin, Andrese Aline; da Silva Chakr, Rafael Mendonça; Brenol, João Carlos Tavares; Monticielo, Odirlei André

    2017-01-01

    The present study aims to evaluate differences in clinical and laboratory manifestations and medication use in the different ages of disease onset in patients with systemic lupus erythematosus (SLE). This cross-sectional study consisted of 598 SLE patients (550 female and 48 male), who attended the Rheumatology Clinic of the Hospital de Clínicas de Porto Alegre between 2003 and 2015. Demographic, clinical and laboratory data were collected. The patients were classified into three groups according to their ages at disease diagnosis. Mean age of diagnosis was 33.6 ± 14.3 years, and the median (25th-75th percentile) disease duration was 13 (7-20) years. Among the patients studied, 419 (70%) were adult-onset (aSLE), 90 (14.8%) were late-onset (lSLE) and 89 (14.8%) were childhood-onset (cSLE). The female to male ratio was higher in aSLE (18:1) compared to the other groups (p = 0.001). Arthritis was predominantly found in aSLE (78.5%) when compared with lSLE (57.7%) (p < 0.001). Nephritis was more common in cSLE (60.6%) than in lSLE (26.6%) (p < 0.001). Median (25th-75th percentile) of SLE disease activity index (SLEDAI) was higher in the cSLE group [2 (0-5)] when compared to the lSLE group [0 (0-4)] (p = 0.045). Childhood-onset SLE showed a more severe disease due to the higher incidence of nephritis and needed a more aggressive treatment with immunosuppressive drugs.

  15. [Clinical and epidemiological characteristics of ocular trauma in children under 14 years of age].

    PubMed

    Quezada-Del Cid, Nancy C; Zimmermann-Paiz, Martin A; Ordoñez-Rivas, Ana M

    2015-10-01

    Pediatric ocular trauma is common and the leading cause of non congenital unilateral blindness. The information in developing countries is scarce. The objective of this case series is to describe clinical and epidemiological characteristics of ocular trauma in children under 14 years of age who visited Hospital Dr. Rodolfo Robles Valverde in Guatemala City in 2010. In this study 119 patients were included. School-aged (7-9 years) male gender was the most affected. Closed globe injury was the commonest. The most frequent objects causing the lesions were: wooden objects, toys and chemicals. Trauma occurred most frequently at home. Twenty one of the patients were surgically intervened. Education and prevention programs for pediatric ocular trauma are necessary.

  16. Cortical Thickness and Anxiety Symptoms Among Cognitively Normal Elderly Persons: The Mayo Clinic Study of Aging.

    PubMed

    Pink, Anna; Przybelski, Scott A; Krell-Roesch, Janina; Stokin, Gorazd B; Roberts, Rosebud O; Mielke, Michelle M; Spangehl, Kathleen A; Knopman, David S; Jack, Clifford R; Petersen, Ronald C; Geda, Yonas E

    2017-01-01

    The authors conducted a cross-sectional study to investigate the association between anxiety symptoms and cortical thickness, as well as amygdalar volume. A total of 1,505 cognitively normal participants, aged ≥70 years, were recruited from the Mayo Clinic Study of Aging in Olmsted County, Minnesota, on whom Beck Anxiety Inventory and 3T brain MRI data were available. Even though the effect sizes were small in this community-dwelling group of participants, anxiety symptoms were associated with reduced global cortical thickness and reduced thickness within the frontal and temporal cortex. However, after additionally adjusting for comorbid depressive symptoms, only the association between anxiety symptoms and reduced insular thickness remained significant.

  17. Age-related macular degeneration-clinical review and genetics update.

    PubMed

    Ratnapriya, R; Chew, E Y

    2013-08-01

    Age-related macular degeneration (AMD) is the leading cause of central vision impairment in persons over the age of 50 years in developed countries. Both genetic and non-genetic (environmental) factors play major roles in AMD etiology, and multiple gene variants and lifestyle factors such as smoking have been associated with the disease. While dissecting the basic etiology of the disease remains a major challenge, current genetic knowledge has provided opportunities for improved risk assessment, molecular diagnosis and clinical testing of genetic variants in AMD treatment and management. This review addresses the potential of translating the wealth of genetic findings for improved risk prediction and therapeutic intervention in AMD patients. Finally, we discuss the recent advancement in genetics and genomics and the future prospective of personalized medicine in AMD patients.

  18. Axis II comorbidity in borderline personality disorder is influenced by sex, age, and clinical severity.

    PubMed

    Barrachina, Judith; Pascual, Juan C; Ferrer, Marc; Soler, Joaquim; Rufat, M Jesús; Andión, Oscar; Tiana, Thais; Martín-Blanco, Ana; Casas, Miquel; Pérez, Víctor

    2011-01-01

    Borderline personality disorder (BPD) is a severe psychiatric disorder that has a high clinical heterogeneity and frequent co-occurrence with other personality disorders (PDs). Although several studies have been performed to assess axis II comorbidity in BPD, more research is needed to clarify associated factors. The aim of this study was to determine the prevalence of co-occurrent axis II disorders in a large sample of patients with BPD and to investigate the influence of sex, age, and severity on this comorbidity. Data were collected from 484 patients with BPD through 2 semistructured interviews. We analyzed the frequency of axis II comorbidity and assessed differences regarding sex, age, and severity of BPD. About 74% of patients with BPD had at least 1 co-occurrent axis II disorder. The most common were paranoid, passive-aggressive, avoidant, and dependent PDs. Significant sex differences were found. Women presented more comorbidity with dependent PD, whereas men showed higher rates of comorbidity with antisocial PD. We also observed a significant positive correlation between age and the number of co-occurrent axis II disorders in women with BPD. Another finding was the positive correlation between BPD severity and the number of co-occurrent axis II disorders. These findings suggest that comorbidity with other axis II disorders and sex, age, and severity should be taken into account when developing treatment strategies and determining the prognosis of BPD.

  19. Clinical manifestations and etiology of renal stones in children less than 14 years age.

    PubMed

    Sepahi, Mohsen Akhavan; Heidari, Akram; Shajari, Ahmad

    2010-01-01

    Urolithiasis is one of the commonest problems in pediatric nephrology. Prevalence of urolithiasis in pediatric patients is increasing. The purpose was to properly diagnose and treat with the special attention to the risk factors. This study is case-series and was performed on 100 pediatric patients for evaluation of clinical manifestation and etiology of renal stone in Qom. Hundred Children, fewer than 14 years old with mean age of 3.32 years, were included (54% male). Etiology of urolithiasis in 5% was unclear. Metabolic disorders found in patients were mainly: Hypocitraturia in 54, hyperoxaluria in 14, hyperuricosuria in 25, cystinuria in 6, hypercalciuria in 28 and phosphaturia in 8 patients. The main clinical presentation was fever, pain, irritability, dysuria and hematuria. Family history of urolithiasis was found in 23% of patients and 54% presented with urinary tract infection (UTI). We conclude that majority of patients were symptomatic and hypocitraturia was the commenest risk factor among others.

  20. The National Anesthesia Clinical Outcomes Registry: A Sustainable Model for the Information Age?

    PubMed Central

    Dutton, Richard P.

    2014-01-01

    Anesthesiologists care for patients of all ages, with all conceivable comorbidities, in every kind of health care facility. This leads to a significant challenge in the collection of data to describe the specialty, and in the development of evidence-based performance measures for anesthesiologists. Whereas narrowly defined medical specialties have developed registries based on manual abstraction of clinical data from the medical record (e.g., cardiac surgery), this approach would be prohibitively expensive for anesthesiology, and is unlikely to generate statistically useful data when major adverse outcomes occur a handful of times in tens of thousands of cases. The American Society of Anesthesiologists (ASA) addressed this challenge in 2008 by funding a related organization, the Anesthesia Quality Institute (AQI), to develop the National Anesthesia Clinical Outcomes Registry (NACOR). The technical development of this registry and the approach taken to define the specialty of anesthesiology and the performance of anesthesiologists may serve as a model for other specialty society efforts. PMID:25848607

  1. Dry age-related macular degeneration: A currently unmet clinical need.

    PubMed

    Girmens, Jean-François; Sahel, José-Alain; Marazova, Katia

    2012-08-01

    Age-related macular degeneration (AMD) is a leading cause of severe visual impairment and disability in older people worldwide. Although considerable advances in the management of the neovascular form of AMD have been made in the last decade, no therapy is yet available for the advanced dry form of AMD (geographic atrophy). This review focuses on current trends in the development of new therapies targeting specific pathophysiological pathways of dry AMD. Increased understanding of the complex mechanisms that underlie dry AMD will help to address this largely unmet clinical need.

  2. Mesenchymal Stem Cells from Adipose Tissue in Clinical Applications for Dermatological Indications and Skin Aging

    PubMed Central

    Gaur, Meenakshi; Dobke, Marek; Lunyak, Victoria V.

    2017-01-01

    Operating at multiple levels of control, mesenchymal stem cells from adipose tissue (ADSCs) communicate with organ systems to adjust immune response, provide signals for differentiation, migration, enzymatic reactions, and to equilibrate the regenerative demands of balanced tissue homeostasis. The identification of the mechanisms by which ADSCs accomplish these functions for dermatological rejuvenation and wound healing has great potential to identify novel targets for the treatment of disorders and combat aging. Herein, we review new insights into the role of adipose-derived stem cells in the maintenance of dermal and epidermal homeostasis, and recent advances in clinical applications of ADSCs related to dermatology. PMID:28117680

  3. Dry age-related macular degeneration: A currently unmet clinical need

    PubMed Central

    Girmens, Jean-François; Sahel, José-Alain; Marazova, Katia

    2012-01-01

    Summary Age-related macular degeneration (AMD) is a leading cause of severe visual impairment and disability in older people worldwide. Although considerable advances in the management of the neovascular form of AMD have been made in the last decade, no therapy is yet available for the advanced dry form of AMD (geographic atrophy). This review focuses on current trends in the development of new therapies targeting specific pathophysiological pathways of dry AMD. Increased understanding of the complex mechanisms that underlie dry AMD will help to address this largely unmet clinical need. PMID:25343081

  4. Mesenchymal Stem Cells from Adipose Tissue in Clinical Applications for Dermatological Indications and Skin Aging.

    PubMed

    Gaur, Meenakshi; Dobke, Marek; Lunyak, Victoria V

    2017-01-20

    Operating at multiple levels of control, mesenchymal stem cells from adipose tissue (ADSCs) communicate with organ systems to adjust immune response, provide signals for differentiation, migration, enzymatic reactions, and to equilibrate the regenerative demands of balanced tissue homeostasis. The identification of the mechanisms by which ADSCs accomplish these functions for dermatological rejuvenation and wound healing has great potential to identify novel targets for the treatment of disorders and combat aging. Herein, we review new insights into the role of adipose-derived stem cells in the maintenance of dermal and epidermal homeostasis, and recent advances in clinical applications of ADSCs related to dermatology.

  5. Long-term (60-month) results for the implantable miniature telescope: efficacy and safety outcomes stratified by age in patients with end-stage age-related macular degeneration

    PubMed Central

    Boyer, David; Freund, K Bailey; Regillo, Carl; Levy, Marc H; Garg, Sumit

    2015-01-01

    Background The purpose of this study was to evaluate the long-term results of an implantable miniature telescope (IMT) in patients with bilateral, end-stage, age-related macular degeneration (AMD). Methods A prospective, open-label, multicenter clinical trial with fellow eye controls enrolled 217 patients (mean age 76 years) with AMD and moderate-to-profound bilateral central visual acuity loss (20/80–20/800) resulting from untreatable geographic atrophy, disciform scars, or both. A subgroup analysis was performed with stratification for age (patient age 65 to <75 years [group 1; n=70] and patient age ≥75 years [group 2; n=127]), with a comparative evaluation of change in best-corrected distance visual acuity (BCDVA), quality of life, ocular complications from surgery, adverse events, and endothelial cell density (ECD). Follow-up in an extension study was 60 months. Results Data were available for 22, 38, and 31 patients in group 1 and 42, 46, and 32 patients in group 2 at 36, 48, and 60 months, respectively. Mean BCDVA improvement from baseline to 60 months was 2.41±2.69 lines in all patients (n=76), with 2.64±2.55 lines in group 1 and 2.09±2.88 lines in group 2. Quality of life scores were significantly higher in group 1. The most common significant surgery-related ocular complications in group 1 were iritis >30 days after surgery (7/70; 10%) and persistent corneal edema (3/70; 4.3%); and in group 2 were a decrease in BCDVA in the implanted eye or IMT removal (10/127 each; 7.9%), corneal edema >30 days after surgery (9/127; 7.1%), and persistent corneal edema (6/127; 4.7%). Significant adverse events included four corneal transplants, comprising two (2.9%) in group 1 and two (1.6%) in group 2. At 60 months, one patient in group 1 (3.2%) and three patients in group 2 (9.4%) had lost ≥2 lines of vision. The IMT was removed in one (1.4%) and ten (7.9%) patients in group 1 and group 2, respectively. Mean ECD loss was 20% at 3 months. Chronic loss was 3% per

  6. Clinical outcomes and mechanism of action for rheopheresis treatment of age-related macular degeneration (AMD).

    PubMed

    Pulido, Jose; Sanders, Donald; Winters, Jeffrey L; Klingel, Reinhard

    2005-10-01

    The primary goals are to provide a comprehensive explanation of the potential role of therapeutic apheresis in the treatment of Age-Related Macular Degeneration (AMD). Initial clinical results with this technique and a summary of current literature that addresses the mechanism of action for the Rheopheresis approach are presented. Rheopheresis has been found to be a safe and effective application of double filtration plasmapheresis (DFPP) for extracorporeal hemorheotherapy. In this report, it is proposed that Rheopheresis results in an immediate decrease in the proportion of high molecular weight proteins that could combine with the TIMP-3 fibulin complex allowing for the barely functioning retinal pigment epithelial (RPE) cells to function better and diminish the release of vascular endothelial growth factor (VEGF). Interim results from the randomized, double-masked MIRA-1 clinical trial include (1) improved vision restoration; 28.0% of Treated Primary Eyes increased by > or = 2 lines of best corrected visual acuity (BCVA) compared to 18.2% of Placebo Eyes; (2) a decline in progressive vision loss; 0.0% of treated eyes progressing to worse than 20/200 vision over the 12-month study compared to 18.2% of Placebo Eyes; (3) 57.9% of Treatment Eyes obtained improvement in their BCVA to 20/40 or better (driver's license qualification), compared to only 14.3% of Placebo Eyes 12-month post-treatment. Rheopheresis treatment shows strong promise as a viable clinical option for patients suffering from the dry form of AMD in terms of minimizing vision loss, vision restoration, and overall quality of life factors. Expanded clinical outcomes from the ongoing MIRA-1 clinical study will be valuable in the assessment of this new clinical tool for ophthalmic applications.

  7. An Alternative to Farmer Age as an Indicator of Life-Cycle Stage: The Case for a Farm Family Age Index

    ERIC Educational Resources Information Center

    Burton, Rob J. F.

    2006-01-01

    In studies of farming, the age of the principal decision-maker (PDM) has been associated with numerous farm structural and managerial features and has been widely accepted as a good indicator of the influence of life-cycle factors on decision-making. As such, it has become an important aspect of many quantitative studies of agricultural change.…

  8. Hepatic resection versus transarterial chemoembolization for patients with Barcelona Clinic Liver Cancer intermediate stage Child-Pugh A hepatocellular carcinoma

    PubMed Central

    Zhao, Yin-Nong; Zhang, Yong-Quan; Ye, Jia-Zhou; Liu, Xing; Yang, Hong-Zhi; Cong, Feng-Yun; Xiang, Bang-De; Wu, Fei-Xiang; Ma, Liang; Li, Le-Qun; Ye, Hai-Hong

    2016-01-01

    The present study aimed to compare the overall and recurrence-free survival rates following hepatic resection (HR) and transcatheter arterial chemoembolization (TACE) in patients with Barcelona Clinic Liver Cancer (BCLC) classified intermediate-stage Child-Pugh A hepatocellular carcinoma (HCC). A total of 443 patients were examined, among whom 274 underwent HR, whereas 169 received TACE. The overall survival, recurrence-free survival between groups and subgroups, and risk factors with respect to mortality and recurrence, were analyzed. The 1-, 3- and 5-year overall and recurrence-free survival rates were 70, 46 and 37% and 73, 52, and 37%, respectively after HR, compared with 38, 15, and 12% and 44, 25 and 16%, respectively after TACE. Overall and recurrence-free survival rates were significantly increased following HR compared with TACE. Subgroup analysis in the multi-nodule group showed that the 1-, 3- and 5-year overall survival rates were 68, 38 and 30% after HR, compared with 36, 10 and 0% following TACE. In the solitary tumor group, 1-, 3- and 5-year overall survival rates were 71, 50 and 38% after HR, and 41, 22 and 15% after TACE. The overall survival rate after HR was significantly increased compared with that after TACE in the solitary tumor and multi-nodule groups. The risk factors for mortality include solitary tumor diameter >10 cm, multi-nodules, serum albumin level ≥35 g/l, prothrombin time >13 sec, alphafetoprotein levels >400 ng/ml, and patients with hepatitis B virus. Solitary tumor diameter >10 cm, multi-nodules, and hepatitis B virus (P<0.001) were found to be associated with higher recurrence of HCC. Overall and recurrence-free survival rates were improved after HR compared with those after TACE in BCLC stage B, Child-Pugh A, HCC patients. PMID:28105115

  9. Comparison of myocardial damage among dogs at different stages of clinical leishmaniasis and dogs with idiopathic chronic kidney disease.

    PubMed

    Martínez-Hernández, L; Casamian-Sorrosal, D; Barrera-Chacón, R; Cuesta-Gerveno, J M; Belinchón-Lorenzo, S; Gómez Nieto, L C; Duque-Carrasco, F J

    2017-03-01

    Canine leishmaniasis (CanL) is a systemic disease caused by the protozoan parasite Leishmania infantum. Myocarditis in CanL has been described previously in CanL by histopathological analysis of post-mortem specimens and by evaluation of cardiac troponin I (cTnI) levels. However, the degree of myocardial damage at different stages of CanL and the role that concurrent azotaemia plays in this myocardial injury are unknown. The aim of this study was to prospectively evaluate and compare the presence of myocardial injury in dogs at different stages of clinical CanL and in dogs with severe idiopathic chronic kidney disease (CKD) by measuring cTnI. Forty-eight dogs were included in the study, divided into four groups: (1) group A (10 healthy dogs); (2) group B (17 dogs with CanL without renal azotaemia, classified as mild to severe in the LeishVet scheme); (3) group C (11 dogs with CanL and renal azotaemia, classified as very severe in the LeishVet scheme); and (4) group D (10 dogs with idiopathic CKD). Dogs in group C had significantly higher cTnI than dogs in groups B and D, although cTnI was also elevated in these groups. Dogs in group A had normal cTnI values. Dogs in groups D and C had similar renal IRIS classification scorers. Severe lymphoplasmocytic myocarditis and a positive real time PCR of L. infantum DNA were observed in all dogs in group C. Dogs with very severe CanL exhibit more myocardial injury than dogs with milder CanL or dogs with idiopathic CKD.

  10. Aging

    PubMed Central

    Park, Dong Choon

    2013-01-01

    Aging is initiated based on genetic and environmental factors that operate from the time of birth of organisms. Aging induces physiological phenomena such as reduction of cell counts, deterioration of tissue proteins, tissue atrophy, a decrease of the metabolic rate, reduction of body fluids, and calcium metabolism abnormalities, with final progression onto pathological aging. Despite the efforts from many researchers, the progression and the mechanisms of aging are not clearly understood yet. Therefore, the authors would like to introduce several theories which have gained attentions among the published theories up to date; genetic program theory, wear-and-tear theory, telomere theory, endocrine theory, DNA damage hypothesis, error catastrophe theory, the rate of living theory, mitochondrial theory, and free radical theory. Although there have been many studies that have tried to prevent aging and prolong life, here we introduce a couple of theories which have been proven more or less; food, exercise, and diet restriction. PMID:24653904

  11. Basic and Clinical Research Against Advanced Glycation End Products (AGEs): New Compounds to Tackle Cardiovascular Disease and Diabetic Complications.

    PubMed

    Nenna, Antonio; Spadaccio, Cristiano; Lusini, Mario; Ulianich, Luca; Chello, Massimo; Nappi, Francesco

    2015-01-01

    Diabetes is a major risk factor for cardiovascular disease, and recent advances in research indicate that a detailed understanding of the pathophysiology of its effects is mandatory to reduce diabetes-related mortality and morbidity. Advanced Glycation End Products (AGEs) play a central role in the genesis and progression of complications of both type 1 and type 2 diabetes mellitus, and have been found to be important even in non-diabetic patients as a marker of cardiovascular disease. AGEs have a profound impact on patient's prognosis regardless of the glycemic control, and therefore pharmacologic approaches against AGEs accumulation have been proposed over the years to treat cardiovascular diseases, parallel to a more detailed understanding of AGEs pathophysiology. Compounds with anti-AGEs effects are currently under investigation in both pre-clinical and clinical scenarios, and many of the drugs previously used to treat specific diseases have been found to have AGE-inhibitory effects. Some products are still in "bench evaluation", whereas others have been already investigated in clinical trials with conflicting evidences. This review aims at summarizing the mechanisms of AGEs formation and accumulation, and the most relevant issues in pre-clinical and clinical experiences in anti-AGEs treatment in cardiovascular research.

  12. Clinical and neuroimaging differences between posterior cortical atrophy and typical amnestic Alzheimer’s disease patients at an early disease stage

    PubMed Central

    Peng, Guoping; Wang, Jianqin; Feng, Zhan; Liu, Ping; Zhang, Yafei; He, Fangping; Chen, Zhongqin; Zhao, Kui; Luo, Benyan

    2016-01-01

    To identify clinical and neuroimaging characteristics between posterior cortical atrophy (PCA) and typical amnestic Alzheimer’s disease (tAD) patients at an early disease stage, 16 PCA and 13 age-matched tAD patients were enrolled. Compared with tAD patients, PCA patients showed higher mean recognition and recall test scores, and lower mean calculation, spatial attention, shape discrimination, and writing test scores. Mean right hippocampal volume was larger in PCA patients compared with tAD patients, while cortical gray matter (GM) volume of bilateral parietal and occipital lobes was smaller in PCA patients. Further, when compared with tAD patients, significant hypometabolism was observed in bilateral parietal and occipital lobes, particularly the right occipitotemporal junction in PCA patients. Additionally, there were significant positive correlations in recognition and recall scores with hippocampal volumes. In PCA patients, calculation and visuospatial ability scores are positively associated with GM volume of parietal and occipital lobes. And only spatial attention and shape discrimination scores are positively associated with regional glucose metabolism of parietal and occipital lobes. Therefore, PCA patients display better recognition and recall scores, which are associated with larger hippocampal volumes and poorer performance in visual spatial tasks because of marked GM atrophy and hypometabolism of parietal and occipital lobes. PMID:27377199

  13. [Comorbidity of opioid addiction and alcoholism in patients of young age: clinical variants of the double diagnosis].

    PubMed

    Bokhan, N A; Blagov, L N; Kurgak, D I

    2012-01-01

    A study included 115 male patients with opioid addiction, aged from 17 to 27 years. Comorbidity of opioid addiction and alcoholism in patients of young age was represented by two main variants distinguishing between primary dependence on opioid or alcohol. In the first variant, additional variants of vicarious alcoholization and replacement of addiction form were singled out. In the second case, alcoholism preceded opioid addiction that developed as a form of polyaddiction and the formation of preliminary (primary) alcoholism was considered as a protracted stage of searching narcotism with the transition from alcoholism to opioid addiction. Stages and differential criteria of the variants of double disorders are described.

  14. Ambulatory BP monitoring and clinic BP in predicting small-for-gestational-age infants during pregnancy.

    PubMed

    Eguchi, K; Ohmaru, T; Ohkuchi, A; Hirashima, C; Takahashi, K; Suzuki, H; Kario, K; Matsubara, S; Suzuki, Mitsuaki

    2016-01-01

    The significance of ambulatory blood pressure (ABP) monitoring during pregnancy has not been established. We performed a prospective study to elucidate whether ABP measures are associated with small-for-gestational-age birth weight (SGA). We studied 146 pregnant women who were seen for maternal medical checkups or suspected hypertension. ABP monitoring was performed for further assessment of hypertension. The outcome measure was SGA. The subjects were classified by their medical history and ABP as having preeclampsia or gestational hypertension (n=68 cases), chronic hypertension (n=48) or white-coat hypertension (n=30). There were 50 (34.2%) cases of SGA by the fetal growth reference standard. In multivariable logistic regression analyses adjusting for age, body mass index, the presence of prior pregnancy, current smoking habit and the use of antihypertensive medications, 24-h SBP (per 10 mm Hg (odds ratio (OR): 1.74; 95% confidence interval (CI): 1.28-2.38; P<0.001)) was more closely associated with SGA than clinic BP (OR: 1.40; 95% CI: 0.92-2.13; P=0.11). The results were essentially the same if 24-h BP was replaced by awake or sleep SBP. Ambulatory diastolic BP showed the same tendency. However, abnormal circadian rhythm was not associated with the outcome. In conclusion, ambulatory BP monitoring measures performed during pregnancy were more closely associated with SGA than clinic BP.

  15. Patterns of Sociodemographic and Clinicopathologic Characteristics of Stages II and III Colorectal Cancer Patients by Age: Examining Potential Mechanisms of Young-Onset Disease

    PubMed Central

    Sanoff, Hanna K.; Stitzenberg, Karyn B.; Baron, John A.; Lund, Jennifer L.; Sandler, Robert S.

    2017-01-01

    Background and Aims. As a first step toward understanding the increasing incidence of colorectal cancer (CRC) in younger (age < 50) populations, we examined demographic, clinicopathologic, and socioeconomic characteristics and treatment receipt in a population-based sample of patients newly diagnosed with stages II and III CRC. Methods. Patients were sampled from the National Cancer Institute's Patterns of Care studies in 1990/91, 1995, 2000, 2005, and 2010 (n = 6, 862). Tumor characteristics and treatment data were obtained through medical record review and physician verification. We compared sociodemographic and clinicopathologic characteristics and treatment patterns of younger (age < 50) and older (age 50–69, age ≥ 70) CRC patients. Results. Younger patients were more likely to be black (13%) and Hispanic (15%) than patients aged 50–69 years (11% and 10%, resp.) and ≥70 years (7% each). A larger proportion of young white (41%) and Hispanic (33%) patients had rectal tumors, whereas tumors in the right colon were the most common in young black patients (39%). The majority of younger patients received chemotherapy and radiation therapy, although receipt of microsatellite instability testing was suboptimal (27%). Conclusion. Characteristics of patients diagnosed with young-onset CRC differ considerably by race/ethnicity, with a higher proportion of black and Hispanic patients diagnosed at the age of < 50 years. PMID:28239395

  16. The Role of Postmastectomy Radiation Therapy After Neoadjuvant Chemotherapy in Clinical Stage II-III Breast Cancer Patients With pN0: A Multicenter, Retrospective Study (KROG 12-05)

    SciTech Connect

    Shim, Su Jung; Park, Won; Huh, Seung Jae; Choi, Doo Ho; Shin, Kyung Hwan; Lee, Nam Kwon; Suh, Chang-Ok; Keum, Ki Chang; Kim, Yong Bae; Ahn, Seung Do; Kim, Su Ssan; Ha, Sung W.; Chie, Eui Kyu; Kim, Kyubo; Shin, Hyun Soo; Kim, Jin Hee; Lee, Hyung-Sik

    2014-01-01

    Purpose: The purpose of this study was to investigate the role of postmastectomy radiation therapy (PMRT) after neoadjuvant chemotherapy (NAC) in clinical stage II-III breast cancer patients with pN0. Methods and Materials: We retrospectively identified 417 clinical stage II-III breast cancer patients who achieved an ypN0 at surgery after receiving NAC between 1998 and 2009. Of these, 151 patients underwent mastectomy after NAC. The effect of PMRT on disease-free survival (DFS), locoregional recurrence-free survival (LRRFS), and overall survival (OS) was evaluated by multivariate analysis including known prognostic factors using the Kaplan-Meier method and compared using the log–rank test and Cox proportional regression analysis. Results: Of the 151 patients who underwent mastectomy, 105 (69.5%) received PMRT and 46 patients (30.5%) did not. At a median follow-up of 59 months, 5 patients (3.3%) developed LRR (8 sites of recurrence) and 14 patients (9.3%) developed distant metastasis. The 5-year DFS, LRRFS, and OS rates were 91.2, 98.1, and 93.3% with PMRT and 83.0%, 92.3%, and 89.9% without PMRT, respectively (all P values not significant). By univariate analysis, only age (≤40 vs >40 years) was significantly associated with decreased DFS (P=.027). By multivariate analysis, age (≤40 vs >40 years) and pathologic T stage (0-is vs 1 vs 2-4) were significant prognostic factors affecting DFS (hazard ratio [HR] 0.353, 95% confidence interval [CI] 0.135-0.928, P=.035; HR 2.223, 95% CI 1.074-4.604, P=.031, respectively). PMRT showed no correlation with a difference in DFS, LRRFS, or OS by multivariate analysis. Conclusions: PMRT might not be necessary for pN0 patients after NAC, regardless of clinical stage. Prospective randomized clinical trial data are needed to assess whether PMRT can be safely omitted in pN0 patients after NAC and mastectomy for clinical stage II-III breast cancer.

  17. The impact of sleep on age-related sarcopenia: Possible connections and clinical implications.

    PubMed

    Piovezan, Ronaldo D; Abucham, Julio; Dos Santos, Ronaldo Vagner Thomatieli; Mello, Marco Tulio; Tufik, Sergio; Poyares, Dalva

    2015-09-01

    Sarcopenia is a geriatric condition that comprises declined skeletal muscle mass, strength and function, leading to the risk of multiple adverse outcomes, including death. Its pathophysiology involves neuroendocrine and inflammatory factors, unfavorable nutritional habits and low physical activity. Sleep may play a role in muscle protein metabolism, although this hypothesis has not been studied extensively. Reductions in duration and quality of sleep and increases in prevalence of circadian rhythm and sleep disorders with age favor proteolysis, modify body composition and increase the risk of insulin resistance, all of which have been associated with sarcopenia. Data on the effects of age-related slow-wave sleep decline, circadian rhythm disruptions and obstructive sleep apnea (OSA) on hypothalamic-pituitary-adrenal (HPA), hypothalamic-pituitary-gonadal (HPG), somatotropic axes, and glucose metabolism indicate that sleep disorder interventions may affect muscle loss. Recent research associating OSA with the risk of conditions closely related to the sarcopenia process, such as frailty and sleep quality impairment, indirectly suggest that sleep can influence skeletal muscle decline in the elderly. Several protein synthesis and degradation pathways are mediated by growth hormone (GH), insulin-like growth factor-1 (IGF-1), testosterone, cortisol and insulin, which act on the cellular and molecular levels to increase or reestablish muscle fiber, strength and function. Age-related sleep problems potentially interfere intracellularly by inhibiting anabolic hormone cascades and enhancing catabolic pathways in the skeletal muscle. Specific physical exercises combined or not with nutritional recommendations are the current treatment options for sarcopenia. Clinical studies testing exogenous administration of anabolic hormones have not yielded adequate safety profiles. Therapeutic approaches targeting sleep disturbances to normalize circadian rhythms and sleep homeostasis may

  18. Recruitment strategies for an acupuncture randomized clinical trial of reproductive age women

    PubMed Central

    Pastore, Lisa M.; Dalal, Parchayi

    2009-01-01

    Summary Objectives To assess the most effective recruitment strategies for an acupuncture clinical trial of reproductive age women. Design The underlying study is an acupuncture randomized clinical trial for an ovulatory disorder that affects approximately 6.5% of reproductive age women (Polycystic Ovary Syndrome). Study participation involved 2 months of intervention and 3 months of follow-up with US$170 compensation. Success of each recruitment method used during the first 37 study months was analyzed. Setting Clinical trial in the Dept. of OB/GYN at the University of Virginia, US. The original geographic residency target was an 80 mile radius around a college town in Virginia (population 155,000), and was expanded to the state capital (population 850,000) in recruitment year 2. Main outcome measures Number of study inquiries (phone calls or emails) over time and by recruitment source. Results In the first 37 months of recruitment (Jan 2006 – Jan 2009), there were 800 study inquiries (582 by phone, 218 by email), of which 749 were screened via telephone questionnaire. The most successful recruitment methods were flyers (28% of inquiries and 26 % of participants) and direct mailing to targeted zip codes (26% and 27%, respectively). The direct mailing cost US$110/inquiry, while the flyers cost less than US$300 in total. Study inquiries were least likely in May and November. Almost all prospective participants (94%) were acupuncture-naïve. Conclusions Posters/flyers and direct mailings proved to be the most successful recruitment methods for this CAM study. Active recruitment with multiple methods was needed for continual enrollment. PMID:19632551

  19. Aetiology and clinical features of dysentery in children aged <5 years in rural Bangladesh.

    PubMed

    Ferdous, F; Ahmed, S; DAS, S K; Farzana, F D; Latham, J R; Chisti, M J; Faruque, A S G

    2014-01-01

    The study identified the common aetiological agents and prominent clinical features of dysentery cases in children aged <5 years and compared this to non-dysentery diarrhoeal cases from the same population. From January 2010 to December 2011, 2324 children aged <5 years received treatment at Kumudini Hospital, of which 682 (29%) presented with dysentery. Of the dysenteric children, aetiology could not be determined for over half (61%). Shigella spp. accounted for 32% of dysentery cases. Significant associations were found between presence of blood in stool and: child age (24-59 months) [odds ratio (OR) 2.21, 95% confidence interval (CI) 1.49-3.27], no treatment of drinking water at home (OR 2.00, 95% CI 1.09-3.67), vomiting (OR 0.19, 95% CI 0.14-0.25), abdominal pain (OR 4.68, 95% CI 3.24-6.77), straining (OR 16.45, 95% CI 11.92-22.69), wasting (OR 1.66, 95% CI 1.15-2.41), and presence of Shigella in stool (OR 6.25, 95% CI 4.20-9.29) after controlling for confounders. This study makes it clear that appropriate public health strategies are needed to reduce the burden of dysentery in Bangladesh.

  20. Age, Stigma, Adherence and Clinical Indicators in HIV-Infected Women

    PubMed Central

    McCoy, Katryna; Higgins, Melinda; Zuñiga, Julie Ann; Holstad, Marcia McDonnell

    2016-01-01

    Stigma has become a gendered phenomenon that affects increasing numbers of HIV-infected women worldwide. This study examined the role of age as a possible moderator of the relationship between stigma and antiretroviral therapy adherence, CD4% and viral load among 120 HIV-infected women. A secondary analysis was conducted using data from the Keeping Healthy and Active with Risk Reduction and Medication Adherence (KHARMA) Project, an National Institutes of Health (NIH) funded randomized controlled trial to improve Antiretroviral treatment (ART) adherence and reduce risky behaviors in HIV-infected women at five clinical sites in a South-eastern city from 2005 to 2008. Stigma was measured using the Perceived Personal Stigma of Human Immunodeficiency Virus and Acquired Immune Deficiency Syndrome (HIV/AIDS) scale. Among participants <50 years old (n=90), age was significantly associated with viral load (rho=−.24, p=.02) and stigma was negatively associated with CD4% (r =−.26, p=.02). For the 30 participants >50 years old, age was not significantly associated with viral load, stigma or CD4%, and there was no significant association between stigma and CD4% (r=.07, p=.70). These findings indicate the need for further study regarding this potential moderating effect and possible interventions to address the susceptibility of younger women to the harmful effects of stigma. PMID:27200416

  1. Incidence of WHO Stage 3 and 4 Events, Tuberculosis, and Mortality in Untreated, HIV-Infected Children Enrolling in Care Before 1 Year of Age: An Iedea (International Epidemiologic Databases To Evaluate AIDS) East Africa Regional Analysis

    PubMed Central

    Ciaranello, Andrea; Lu, Zhigang; Ayaya, Samuel; Losina, Elena; Musick, Beverly; Vreeman, Rachel; Freedberg, Kenneth A.; Abrams, Elaine J.; Dillabaugh, Lisa; Doherty, Katie; Ssali, John; Yiannoutsos, Constantin T.; Wools-Kaloustian, Kara

    2014-01-01

    Background Few studies have reported CD4%- and age-stratified rates of WHO Stage 3 (WHO3) events, WHO Stage 4 (WHO4) events, tuberculosis (TB), and mortality in HIV-infected infants before initiation of antiretroviral therapy (ART). Methods HIV-infected children enrolled before 1 year of age in the International Epidemiologic Databases to Evaluate AIDS (IeDEA) East Africa region (10/01/2002-11/30/2008) were included. We estimated incidence rates of earliest clinical event (WHO3, WHO4, and TB), prior to ART initiation per local guidelines, stratified by current age (< or ≥6 months) and current CD4% (<15%, 15–24%, ≥25%). CD4%-stratified mortality rates were estimated separately for children who did not experience a clinical event (“background” mortality) and for children who experienced an event, including “acute” mortality (≤30 days post-event) and “later” mortality (>30 days post-event). Results Among 847 children (median enrollment age: 4.8 months; median pre-ART follow-up: 10.8 months; 603 (71%) with ≥1 CD4% recorded), event rates were comparable for those aged <6 and ≥6 months. Current CD4% was associated with risk of WHO4 events for children <6 months old, and with all evaluated events for children ≥6 months old (p<0.05). “Background” mortality was 3.7–8.4/100py. “Acute” mortality (≤30 days post-event) was 33.8/100py (after TB) and 41.1/100py (after WHO3 or WHO4). “Later” mortality (>30 days post-event) ranged by CD4% from 4.7–29.1/100py. Conclusions In treatment-naïve, HIV-infected infants, WHO3, WHO4, and TB events were common before and after 6 months of age and led to substantial increases in mortality. Early infant HIV diagnosis and treatment are critically important, regardless of CD4%. PMID:24378935

  2. Clinical staging of acute limb ischemia as the basis for choice of revascularization method: when and how to intervene.

    PubMed

    Rutherford, Robert B

    2009-03-01

    In acute lower limb ischemia, there are basically three management options: (1) clot removal by catheter-directed thrombolysis with or without percutaneous mechanical thrombectomy, (2) surgical thromboembolectomy followed by correction of underlying arterial lesions, and (3) anticoagulation with continued observation. Arterial embolic occlusion presents more abruptly and with more severe ischemia than arterial thrombosis, which occurs in narrowed arterial segments that have generally developed some degree of collateral circulation. The appropriate choice of treatment for acute limb ischemia depends to a great extent on the severity of the ischemia. Level of ischemia is readily determined by examining for sensory loss or motor deficit and interrogating the distal arteries and veins for audible flow signals with a handheld Doppler velocity detector. After clot removal, appropriate management of the responsible underlying lesion depends on its characteristics, best determined by vascular imaging. Staging the severity of ischemia according to clinical classification levels in the current reporting standards for lower extremity ischemia continues to serve as the basis for logical management decisions. This approach is outlined in algorithmic form and alternative pathways are discussed in this article.

  3. Clinical correlates of obsessive-compulsive symptom dimensions in at-risk mental states and psychotic disorders at early stages.

    PubMed

    Mariné, Rosa; Creus, Marta; Solé, Montse; Cabezas, Ángel; Algora, Maria José; Moreno, Irene; Izquierdo, Eduard; Stojanovic-Pérez, Alexander; Labad, Javier

    2015-08-30

    We studied the clinical correlates of obsessive-compulsive symptom dimensions in 109 individuals with early psychosis (31 At-Risk Mental States [ARMS], 78 psychotic disorders with <3 years of illness) and 59 healthy subjects. Obsessive-compulsive symptoms were assessed by the Obsessive-Compulsive Inventory - Revised. We also assessed the severity of psychotic symptoms, depressive symptoms and functioning. ARMS and psychotic disorder patients reported more obsessive-compulsive symptoms than did healthy subjects. The ARMS individuals also reported more overall and checking obsessive-compulsive symptoms compared with the PD patients. Different types of obsessive-compulsive symptoms were related with depressive symptoms in both diagnostic groups. However, a different pattern was observed in the relationship between obsessive-compulsive dimensions and functioning by diagnosis (better functioning in ARMS; poorer functioning in psychotic disorders). Our study suggests that obsessive-compulsive symptoms are present in the early stages of psychotic illness, as well as in individuals at risk for psychosis. Future prospective studies are needed to elucidate how obsessive-compulsive symptoms in ARMS may influence the prognosis in terms of global functioning and the risk of psychosis transition.

  4. Outcomes of Positron Emission Tomography-Staged Clinical N3 Breast Cancer Treated With Neoadjuvant Chemotherapy, Surgery, and Radiotherapy

    SciTech Connect

    Park, Hae Jin; Shin, Kyung Hwan; Cho, Kwan Ho; Park, In Hae; Lee, Keun Seok; Ro, Jungsil; Jung, So-Youn; Lee, Seeyoun; Kim, Seok Won; Kang, Han-Sung; Chie, Eui Kyu; Ha, Sung Whan

    2011-12-01

    Purpose: To evaluate the treatment outcome and efficacy of regional lymph node irradiation after neoadjuvant chemotherapy (NCT) and surgery in positron emission tomography (PET)-positive clinical N3 (cN3) breast cancer patients. Methods and Materials: A total of 55 patients with ipsilateral infraclavicular (ICL), internal mammary (IMN), or supraclavicular (SCL) lymph node involvement in the absence of distant metastases, as revealed by an initial PET scan, were retrospectively analyzed. The clinical nodal stage at diagnosis (2002 AJCC) was cN3a in 14 patients (26%), cN3b in 12 patients (22%), and cN3c in 29 patients (53%). All patients were treated with NCT, followed by mastectomy or breast-conserving surgery and subsequent radiotherapy (RT) with curative intent. Results: At the median follow-up of 38 months (range, 9-80 months), 20 patients (36%) had developed treatment failures, including distant metastases either alone or combined with locoregional recurrences that included one ipsilateral breast recurrence (IBR), six regional failures (RF), and one case of combined IBR and RF. Only 3 patients (5.5%) exhibited treatment failure at the initial PET-positive clinical N3 lymph node. The 5-year locoregional relapse-free survival, disease-free survival (DFS), and overall survival rates were 80%, 60%, and 79%, respectively. RT delivered to PET-positive IMN regions in cN3b patients and at higher doses ({>=}55 Gy) to SCL regions in cN3c patients was not associated with improved 5-year IMN/SCL relapse-free survival or DFS. Conclusion: NCT followed by surgery and RT, including the regional lymph nodes, resulted in excellent locoregional control for patients with PET-positive cN3 breast cancer. The primary treatment failure in this group was due to distant metastasis rather than RF. Neither higher-dose RT directed at PET-positive SCL nodes nor coverage of PET-positive IMN nodes was associated with additional gains in locoregional control or DFS.

  5. Phase II clinical trials with time-to-event endpoints: optimal two-stage designs with one-sample log-rank test.

    PubMed

    Kwak, Minjung; Jung, Sin-Ho

    2014-05-30

    Phase II clinical trials are often conducted to determine whether a new treatment is sufficiently promising to warrant a major controlled clinical evaluation against a standard therapy. We consider single-arm phase II clinical trials with right censored survival time responses where the ordinary one-sample logrank test is commonly used for testing the treatment efficacy. For planning such clinical trials, this paper presents two-stage designs that are optimal in the sense that the expected sample size is minimized if the new regimen has low efficacy subject to constraints of the type I and type II errors. Two-stage designs, which minimize the maximal sample size, are also determined. Optimal and minimax designs for a range of design parameters are tabulated along with examples.

  6. Evaluation of the appropriateness of the preclinical phase (stage A and stage B) of heart failure Management in Outpatient clinics in Italy rationale and design of the 'VASTISSIMO' study.

    PubMed

    Mureddu, Gian F; Nistri, Stefano; Faggiano, Pompilio; Fimiani, Biagio; Misuraca, Gianfranco; Maggi, Antonio; Gori, Anna M; Uguccioni, Massimo; Tavazzi, Luigi; Zito, Giovanni B

    2016-07-01

    Early detection of heart failure, when still preclinical, is fundamental. Therefore, it is important to assess whether preclinical heart failure management by cardiologists is adequate. The VASTISSIMO study ('EValuation of the AppropriateneSs of The preclInical phase (Stage A and Stage B) of heart failure Management in Outpatient clinics in Italy') is a prospective nationwide study aimed to evaluate the appropriateness of diagnosis and management of preclinical heart failure (stages A and B) by cardiologists working in outpatient clinics in Italy. Secondary goals are to verify if an online educational course for cardiologists can improve management of preclinical heart failure, and evaluate how well cardiologists are aware of patients' adherence to medications. The study involves 80 outpatient cardiology clinics distributed throughout Italy, affiliated either to the Hospital Cardiologists Association or to the Regional Association of Outpatient Cardiologists, and is designed with two phases of consecutive outpatient enrolment each lasting 1 month. In phase 1, physicians' awareness of the risk of heart failure and their decision-making process are recorded. Subsequently, half of the cardiologists are randomized to undergo an online educational course aimed to improve preclinical heart failure management through implementation of guideline recommendations. At the end of the course, all cardiologists are evaluated (phase 2) to see whether changes in clinical management have occurred in those who underwent the educational program versus those who did not. Patients' adherence to prescribed medications will be assessed through the Morisky Self-report Questionnaire. This study should provide valuable information about cardiologists' awareness of preclinical heart failure and the appropriateness of clinical practice in outpatient cardiology clinics in Italy.

  7. A Severity-Based Clinical Staging Model for the Psychosis Prodrome: Longitudinal Findings From the New York Recognition and Prevention Program.

    PubMed

    Carrión, Ricardo E; Correll, Christoph U; Auther, Andrea M; Cornblatt, Barbara A

    2017-01-01

    Clinical staging improved the possibility of intervening during the psychosis prodrome to limit progression of illness. The current study aimed to validate a novel 4-stage severity-based model with a focus on clinical change over time and risk for conversion to psychosis. One hundred seventy-one individuals at clinical high risk (CHR) for psychosis were followed prospectively (3 ± 1.6 y) as part of the Recognition and Prevention (RAP) program and divided into 4 diagnostic stages according to absence/presence and severity of attenuated positive symptoms. Twenty-two percent of the combined sample recovered (no prodromal symptoms) by study outcome. The negative symptoms only subgroup had the highest symptom stability (70%), but the lowest conversion rate at 5.9%. The subgroup with more severe baseline attenuated positive symptom levels had a higher conversion rate (28%) and a more rapid onset when compared to the moderate attenuated positive symptom subgroup (11%). Finally, the Schizophrenia-Like Psychosis (SLP) subgroup showed low stability (3%), with 49% developing a specific psychotic disorder. The proposed stage model provides a more finely grained classification system than the standard diagnostic approach for prodromal individuals. All 4 stages are in need of early intervention because of low recovery rates. The negative symptom only stage is possibly a separate clinical syndrome, with an increased risk of functional disability. Both subgroups with attenuated positive symptoms are appropriate for studying the mechanisms of psychosis risk, however, individuals with more severe baseline positive symptoms appear better suited to clinical trials. Finally, the SLP category represents an intermediate outcome group appropriate for preventative intervention research but questionable for inclusion in prodromal studies of mechanisms.

  8. Age-Related Differences in Collagen-Induced Arthritis: Clinical and Imaging Correlations

    PubMed Central

    Wilson-Gerwing, Tracy D; Pratt, Isaac V; Cooper, David M L; Silver, Tawni I; Rosenberg, Alan M

    2013-01-01

    Arthritis is among the most common chronic diseases in both children and adults. Although intraarticular inflammation is the feature common among all patients with chronic arthritis there are, in addition to age at onset, clinical characteristics that further distinguish the disease in pediatric and adult populations. In this study, we aimed to demonstrate the utility of microCT (µCT) and ultrasonography in characterizing pathologic age-related differences in a collagen-induced arthritis (CIA) rat model. Juvenile (35 d old) and young adult (91 d old) male Wistar rats were immunized with bovine type II collagen and incomplete Freund adjuvant to induce polyarthritis. Naïve male Wistar rats served as controls. All paws were scored on a scale of 0 (normal paw) to 4 (disuse of paw). Rats were euthanized at 14 d after the onset of arthritis and the hindpaws imaged by µCT and ultrasonography. Young adult rats had more severe signs of arthritis than did their juvenile counterparts. Imaging demonstrated that young adult CIA rats exhibited more widespread and severe skeletal lesions of the phalanges, metatarsals, and tarsal bones, whereas juvenile CIA rats had more localized and less proliferative and osteolytic damage that was confined predominantly to the phalanges and metatarsals. This report demonstrates the utility of imaging modalities to compare juvenile and young adult rats with CIA and provides evidence that disease characteristics and progression differ between the 2 age groups. Our observations indicate that the CIA model could help discern age-related pathologic processes in inflammatory joint diseases. PMID:24326225

  9. Comparison of DSM-IV Symptoms in Elementary School-Age Children with PDD versus Clinic and Community Samples

    ERIC Educational Resources Information Center

    Gadow, Kenneth D.; Devincent, Carla J.; Pomeroy, John; Azizian, Allen

    2005-01-01

    This study compares DSM-IV symptoms in children (ages 6 to 12 years) with pervasive developmental disorder (PDD), clinic controls, and community-based samples. Parents/teachers completed the Child Symptom Inventory-4 for four samples: PDD (N= 284/284) and non-PDD psychiatric clinic referrals (N= 189/181) and pupils in regular (N= 385/404) and…

  10. Advanced maternal age and the risk of Down syndrome characterized by the meiotic stage of the chromosomal error: A population-based study

    SciTech Connect

    Yoon, P.W.; Khoury, M.J.; Freeman, S.B.

    1996-03-01

    The identification of DNA polymorphisms makes it possible to classify trisomy 21 according to the parental origin and stage (meiosis I [MI], meiosis II [MII], or postzygotic mitotic) of the chromosomal error. Studying the effect of parental age on these subgroups could shed light on parental exposures and their timing. From 1989 through 1993, 170 infants with trisomy 21 and 267 randomly selected control infants were ascertained in a population-based, case-control study in metropolitan Atlanta. Blood samples for genetic studies were obtained from case infants and their parents. Using logistic regression, we independently examined the association between maternal and paternal age and subgroups of trisomy 21 defined by parental origin and meiotic stage. The distribution of trisomy 21 by origin was 86% maternal (75% MI and 25% MII), 9% paternal (50% MI and 50% MII), and 5% mitotic. Compared with women <25 years of age, women {>=}40 years old had an odds ratio of 5.2 (95% confidence interval, 1.0-27.4) for maternal MI (MMI) errors and 51.4 (95% confidence interval, 2.3-999.0) for maternal MII (MMII) errors. Birth-prevalence rates for women {>=}40 years old were 4.2/1,000 births for MMI errors and 1.9/1,000 births for MMII errors. These results support an association between advanced maternal age and both MMI and MMII errors. The association with MI does not pinpoint the timing of the error; however, the association with MII implies that there is at least one maternal age-related mechanism acting around the time of conception. 16 refs., 1 fig., 2 tabs.

  11. Predicting the risk of mild cognitive impairment in the Mayo Clinic Study of Aging

    PubMed Central

    Pankratz, V. Shane; Roberts, Rosebud O.; Mielke, Michelle M.; Knopman, David S.; Jack, Clifford R.; Geda, Yonas E.; Rocca, Walter A.

    2015-01-01

    Objective: We sought to develop risk scores for the progression from cognitively normal (CN) to mild cognitive impairment (MCI). Methods: We recruited into a longitudinal cohort study a randomly selected, population-based sample of Olmsted County, MN, residents, aged 70 to 89 years on October 1, 2004. At baseline and subsequent visits, participants were evaluated for demographic, clinical, and neuropsychological measures, and were classified as CN, MCI, or dementia. Using baseline demographic and clinical variables in proportional hazards models, we derived scores that predicted the risk of progressing from CN to MCI. We evaluated the ability of these risk scores to classify participants for MCI risk. Results: Of 1,449 CN participants, 401 (27.7%) developed MCI. A basic model had a C statistic of 0.60 (0.58 for women, 0.62 for men); an augmented model resulted in a C statistic of 0.70 (0.69 for women, 0.71 for men). Both men and women in the highest vs lowest sex-specific quartiles of the augmented model's risk scores had an approximately 7-fold higher risk of developing MCI. Adding APOE ε4 carrier status improved the model (p = 0.002). Conclusions: We have developed MCI risk scores using variables easily assessable in the clinical setting and that may be useful in routine patient care. Because of variability among populations, validation in independent samples is required. These models may be useful in identifying patients who might benefit from more expensive or invasive diagnostic testing, and can inform clinical trial design. Inclusion of biomarkers or other risk factors may further enhance the models. PMID:25788555

  12. Clinical characteristics and outcome of patients with stage III esophageal carcinoma: a single-center experience from Turkey.

    PubMed

    Ugur, Vahide I; Kara, Sakire P; Kucukplakci, Bulent; Demirkasimoglu, Taciser; Misirlioglu, Cem; Ozgen, Aytul; Elgin, Yesim; Sanri, Ergun; Altundag, Kadri; Ozdamar, Nadi

    2008-01-01

    Esophageal carcinoma is an extremely deadly disease, and prognosis is poor. We retrospectively evaluated stage III esophageal carcinoma patients in our center. Median age of the patients was 52. Men to women ratio were 3/1. Epidermoid carcinoma was the major histology. Incidence of esophageal carcinoma was higher in the distal and middle third of the esophagus. In 19 patients tumor size was more than 5 cm. In total of 17 of the patients were operated. About 58 patients were irradiated. About 45 of the patients were irradiated with curative intent, 31 of them were primarily irradiated and 14 of them were irradiated postoperatively. Only 13 of the patients received concurrent chemoradiotherapy. Overall 1, 2, 3, and 4 year survival rates were 38.9%, 11.1%, 5.6%, and %1.9, respectively and median survival was 12 months. Median survival for tumors located in cervical esophageal, middle esophagus, and distal esophagus were 23, 8, and 14 months, respectively. One, 2, 3, 4 year survival rates of operated patients were 58.8%, 29.4%, 17.6%, 5.9%, respectively and median survival was 23 months. For inoperable patients 1 and 2 year survival rates were 29.7% and 2.7% and median survival was 8 months. Differences between operable and inoperable patients were statistically significant (P: 0.0003). One, 2, 3, 4 years survival results of patients treated with surgery and postoperative radiotherapy was 62.5%, 25%, 12.5%, 12.5% and median survival was 21 months, 1, 2, 3, 4 years survival results of patients treated with surgery and concurrent chemoradiotherapy was 55.6%, 33.3%, 22.2%, and 0% and median survival was 27 months. There was no statistically significant difference between groups (P: 0.5390). During the therapy, disphagia was the major side effect observed in seven patients. Fatigue, pain, and mild weight loss were the other side effects. Three patients could not tolerate the treatment and left the therapy. We demonstrated that stage III esophageal carcinoma is an extremely

  13. [Wolff-Parkinson-White syndrome after 50 yars of age. Clinical and electrophysiological data].

    PubMed

    Lévy, S; Borde, C; Dupon, J; Bémurat, M; Gérard, R; Bricaud, H

    1980-07-01

    The Wolff-Parkinson-White syndrome is usually observed in young people and is much rarer in patients over 50 years old. This fact may be explained by the demise of a certain number of patients before the age of 50 and/or a change in the clinical features of the syndrome with age and/or of the electrophysiological properties of the normal and accessory conduction pathways. To test the latter hypothesis, the clinical and electrophysiological data of 15 patients over 50 years old with the Wolff-Parkinson-White syndrome (Group I) were compared with that of 10 patients under 30 years old with the same syndrome (Group II). The same protocol of electrophysiological investigation was used in both groups of patients. The results showed a significant difference (p < 0.001) between the two groups in the incidence of associated cardiac disease. This was more common in Group I (1 4 out of 15 patients) than in Group II (2 out of 10 patients). The cardiothoracic ratio was significantly higher in Group I (p < 0.01). The two groups also differed in the age at which tachycardia first occured. 9 out of 11 patients in Group I only had symptoms after thirty years. On the other hand, there was no significant difference in the types of tachycardia and the frequency of attacks. There was no significant difference in QRS, PR, AH, HV intervals, in the ventriculo-atrial conduction time and the effective refractory periods of the atrium, right ventricle or atrio-ventricular node. There was no significant difference in the anterograde and retrograde refractory periods of the accessory pathways between the two groups. Reciprocating tachycardia, initiated by electrical stimulation in 7 patients in Group I and 6 patients in Group II, was conducted anterogradely to the ventricles through the normal pathway and retrogradely to the atria through the the accessory pathway. This study suggest that age-related changes in the electrophysiological properties of the accessory are not an important

  14. Utility of CT after sonography for suspected appendicitis in children: integration of a clinical scoring system with a staged imaging protocol.

    PubMed

    Srinivasan, Abhay; Servaes, Sabah; Peña, Andrès; Darge, Kassa

    2015-02-01

    To improve diagnosis of pediatric appendicitis, many institutions have implemented a staged imaging protocol utilizing ultrasonography (US) first and then computed tomography (CT). A substantial number of children with suspected appendicitis undergo CT after US, and the efficient and accurate diagnosis of pediatric appendicitis continues to be challenging. The objective of the study is to characterize the utility of CT following US for diagnosis of pediatric appendicitis, in conjunction with a clinical appendicitis score (AS). Imaging studies of children with suspected appendicitis who underwent CT after US in an imaging protocol were retrospectively reviewed by three radiologists in consensus. Chart review derived the AS (range 0-10) and obtained the patient diagnosis and disposition, and an AS was applied to each patient. Clinical and radiologic data were analyzed to assess the yield of CT after US. Studies of 211 children (mean age 11.3 years) were included. The positive threshold for AS was determined to be 6 out of 10. When AS and US were concordant (N = 140), the sensitivity and specificity of US were similar to CT. When AS and US were discordant (N = 71) and also when AS ≥ 6 (N = 84), subsequent CT showed superior sensitivity and specificity to US alone. In the subset where US showed neither the appendix nor inflammatory change in the right lower quadrant (126/211, 60 % of scans), when AS < 6 (N = 83), the negative predictive value (NPV) of US was 0.98. However, when AS ≥ 6 (N = 43), NPV of US was 0.58, and the positive predictive value of subsequent CT was 1. There was a significant decrease in depiction of the appendix on US with patient weight-to-age ratio of >6 (kg/year, P < 0.001) and after-hours (1700 -0730 hours) performance of US (P < 0.001). Results suggest that the appendicitis score has utility in guiding an imaging protocol and support the contention that non-visualization of the appendix on US is not

  15. Metering Self-Reported Adherence to Clinical Outcomes in Malaysian Patients with Hypertension: Applying the Stages of Change Model to Healthful Behaviors in the CORFIS Study

    ERIC Educational Resources Information Center

    Karupaiah, Tilakavati; Wong, Kimberly; Chinna, Karuthan; Arasu, Kanimolli; Chee, Winnie Siew Swee

    2015-01-01

    The CORFIS ("Community-Based Cardiovascular Risk Factors Intervention Strategies") program was piloted in community clinics in Malaysia to address the lack of health education in chronic disease management. The stages of change model was applied in a multicenter quasi-experimental design to evaluate adherence to advocated behaviors in…

  16. FGFR4 Gly388Arg polymorphism may affect the clinical stage of patients with lung cancer by modulating the transcriptional profile of normal lung.

    PubMed

    Falvella, Felicia S; Frullanti, Elisa; Galvan, Antonella; Spinola, Monica; Noci, Sara; De Cecco, Loris; Nosotti, Mario; Santambrogio, Luigi; Incarbone, Matteo; Alloisio, Marco; Calabrò, Elisa; Pastorino, Ugo; Skaug, Vidar; Haugen, Aage; Taioli, Emanuela; Dragani, Tommaso A

    2009-06-15

    The association of the fibroblast growth factor receptor 4 (FGFR4) Gly388Arg polymorphism with clinical stage and overall survival in a series of 541 Italian lung adenocarcinoma (ADCA) patients indicated a significantly decreased survival in patients carrying the rare Arg388 allele as compared to that in Gly/Gly homozygous patients [hazard ratio (HR) = 1.5; 95% confidence interval (CI) 1.1-1.9], with the decrease related to the association of the same polymorphism with clinical stage (HR = 1.8, 95% CI 1.3-2.6). By contrast, no significant association was detected in small series of either Norwegian lung ADCA patients or Italian lung squamous cell carcinoma (SQCC) patients. Single nucleotide polymorphisms of known FGFR4 ligands expressed in lung (FGF9, FGF18 and FGF19) were not associated with clinical stage or survival and showed no interaction with FGFR4. Analysis of gene expression profile in normal lungs according to FGFR4 genotype indicated a specific transcript pattern associated with the allele carrier status, suggesting a functional role for the FGFR4 polymorphism already detectable in normal lung. These findings confirm the significant association of the FGFR4 Gly388Arg polymorphism with clinical stage and overall survival in an Italian lung ADCA population and demonstrate a FGFR4 genotype-dependent transcriptional profile present in normal lung tissue.

  17. Clinically derived early postoperative pain trajectories differ by age, sex, and type of surgery.

    PubMed

    Tighe, Patrick J; Le-Wendling, Linda T; Patel, Ameet; Zou, Baiming; Fillingim, Roger B

    2015-04-01

    The objective of this study was to determine the effects of age, sex, and type of surgery on postoperative pain trajectories derived in a clinical setting from pain assessments in the first 24 hours after surgery. This study is a retrospective cohort study using a large electronic medical records system to collect and analyze surgical case data. The sample population included adult patients undergoing nonambulatory nonobstetric surgery in a single institution over a 1-year period. Analyses of postoperative pain trajectories were performed using a linear mixed-effects model. Pain score observations (91,708) from 7293 patients were included in the statistical analysis. On average, the pain score decreased about 0.042 (95% confidence interval [CI]: -0.044 to -0.040) points on the numerical rating scale (NRS) per hour after surgery for the first 24 postoperative hours. The pain score reported by male patients was approximately 0.27 (95% CI: -0.380 to -0.168) NRS points lower than that reported by females. Pain scores significantly decreased over time in all age groups, with a slightly more rapid decrease for younger patients. Pain trajectories differed by anatomic location of surgery, ranging from -0.054 (95% CI: -0.062 to -0.046) NRS units per hour for integumentary and nervous surgery to -0.104 (95% CI: -0.110 to -0.098) NRS units per hour for digestive surgery, and a positive trajectory (0.02 [95% CI: 0.016 to 0.024] NRS units per hour) for musculoskeletal surgery. Our data support the important role of time after surgery in considering the influence of biopsychosocial and clinical factors on acute postoperative pain.

  18. A Model Predicting Lymph Node Status for Patients with Clinical Stage T1aN0-2M0 Nonsmall Cell Lung Cancer

    PubMed Central

    Zang, Ruo-Chuan; Qiu, Bin; Gao, Shu-Geng; He, Jie

    2017-01-01

    Background: Lymph node status of patients with early-stage nonsmall cell lung cancer has an influence on the choice of surgery. To assess the lymph node status more correspondingly and accurately, we evaluated the relationship between the preoperative clinical variables and lymph node status and developed one model for predicting lymph node involvement. Methods: We collected clinical and dissected lymph node information of 474 patients with clinical stage T1aN0-2M0 nonsmall cell lung cancer (NSCLC). Logistic regression analysis of clinical characteristics was used to estimate independent predictors of lymph node metastasis. The prediction model was validated by another group. Results: Eighty-two patients were diagnosed with positive lymph nodes (17.3%), and four independent predictors of lymph node disease were identified: larger consolidation size (odds ratio [OR] = 2.356, 95% confidence interval [CI]: 1.517–3.658, P < 0.001,), central tumor location (OR = 2.810, 95% CI: 1.545–5.109, P = 0.001), abnormal status of tumor marker (OR = 3.190, 95% CI: 1.797–5.661, P < 0.001), and clinical N1–N2 stage (OR = 6.518, 95% CI: 3.242–11.697, P < 0.001). The model showed good calibration (Hosmer–Lemeshow goodness-of-fit, P < 0.766) with an area under the receiver operating characteristics curve (AUC) of 0.842 (95% [CI]: 0.797–0.886). For the validation group, the AUC was 0.810 (95% CI: 0.731–0.889). Conclusions: The model can assess the lymph node status of patients with clinical stage T1aN0-2M0 NSCLC, enable surgeons perform an individualized prediction preoperatively, and assist the clinical decision-making procedure. PMID:28218211

  19. Clinical Trial Participation and Time to Treatment Among Adolescents and Young Adults With Cancer: Does Age at Diagnosis or Insurance Make a Difference?

    PubMed Central

    Parsons, Helen M.; Harlan, Linda C.; Seibel, Nita L.; Stevens, Jennifer L.; Keegan, Theresa H.M.

    2011-01-01

    Purpose Because adolescent and young adult (AYA) patients with cancer have experienced variable improvement in survival over the past two decades, enhancing the quality and timeliness of cancer care in this population has emerged as a priority area. To identify current trends in AYA care, we examined patterns of clinical trial participation, time to treatment, and provider characteristics in a population-based sample of AYA patients with cancer. Methods Using the National Cancer Institute Patterns of Care Study, we used multivariate logistic regression to evaluate demographic and provider characteristics associated with clinical trial enrollment and time to treatment among 1,358 AYA patients with cancer (age 15 to 39 years) identified through the Surveillance, Epidemiology, and End Results Program. Results In our study, 14% of patients age 15 to 39 years had enrolled onto a clinical trial; participation varied by type of cancer, with the highest participation in those diagnosed with acute lymphoblastic leukemia (37%) and sarcoma (32%). Multivariate analyses demonstrated that uninsured, older patients and those treated by nonpediatric oncologists were less likely to enroll onto clinical trials. Median time from pathologic confirmation to first treatment was 3 days, but this varied by race/ethnicity and cancer site. In multivariate analyses, advanced cancer stage and outpatient treatment alone were associated with longer time from pathologic confirmation to treatment. Conclusion Our study identified factors associated with low clinical trial participation in AYA patients with cancer. These findings support the continued need to improve access to clinical trials and innovative treatments for this population, which may ultimately translate into improved survival. PMID:21931022

  20. Preclinical and Pilot Clinical Studies of Docetaxel Chemoradiation for Stage III Non-Small-Cell Lung Cancer

    SciTech Connect

    Chen Yuhchyau; Pandya, Kishan J.; Hyrien, Ollivier; Keng, Peter C.; Smudzin, Therese; Anderson, Joy; Qazi, Raman; Smith, Brian; Watson, Thomas J.; Feins, Richard H.; Johnstone, David W.

    2011-08-01

    Purpose: Local and distant failure rates remain high despite aggressive chemoradiation (CRT) treatment for Stage III non-small-cell lung cancer. We conducted preclinical studies of docetaxel's cytotoxic and radiosensitizing effects on lung cancer cell lines and designed a pilot study to target distant micrometastasis upfront with one-cycle induction chemotherapy, followed by low-dose radiosensitizing docetaxel CRT. Methods and Materials: A preclinical study was conducted in human lung cancer cell lines NCI 520 and A549. Cells were treated with two concentrations of docetaxel for 3 h and then irradiated immediately or after a 24-h delay. A clonogenic survival assay was conducted and analyzed for cytotoxic effects vs. radiosensitizing effects of docetaxel. A pilot clinical study was designed based on preclinical study findings. Twenty-two patients were enrolled with a median follow-up of 4 years. Induction chemotherapy consisted of 75 mg/m{sup 2} of docetaxel and 75 mg/m{sup 2} of cisplatin on Day 1 and 150 mg/m{sup 2} of recombinant human granulocyte colony-stimulating factor on Days 2 through 10. Concurrent CRT was started 3 to 6 weeks later with twice-weekly docetaxel at 10 to 12 mg/m{sup 2} and daily delayed radiation in 1.8-Gy fractions to 64.5 Gy for gross disease. Results: The preclinical study showed potent cytotoxic effects of docetaxel and subadditive radiosensitizing effects. Delaying radiation resulted in more cancer cell death. The pilot clinical study resulted in a median survival of 32.6 months for the entire cohort, with 3- and 5-year survival rates of 50% and 19%, respectively, and a distant metastasis-free survival rate of 61% for both 3 and 5 years. A pattern-of-failure analysis showed 75% chest failures and 36% all-distant failures. Therapy was well tolerated with Grade 3 esophagitis observed in 23% of patients. Conclusions: One-cycle full-dose docetaxel/cisplatin induction chemotherapy with recombinant human granulocyte colony-stimulating factor

  1. An analysis of meiotic stage of nondisjunction and clinical characteristics in 27 children with Down syndrome and leukemia

    SciTech Connect

    Shugar, A.; Soukup, S.

    1994-09-01

    The observation that children with Down syndrome experience a significantly increased risk for leukemia was made in the 1950`s. Recent research has revealed that two specific forms of leukemia, acute non-lymphoblastic leukemia (specifically the subtype M7) and transient leukemia (TL) are preferentially associated with trisomy 21. The specific association of these leukemias with trisomy 21 has suggested to others that there may be a gene on chromosome 21 which predisposes to TL and M7 leukemia. If a recessive gene for susceptibility existed, then trisomies arising as a duplication of one parental centromere through a mitotic or meiosis II error would be expected to have a higher frequency of TL and M7 leukemia. The purpose of this study was (i) To test the models which propose that disomic homozygosity is preponderant in cases of TL and M7 leukemia in a Down syndrome population (ii) To further characterize the clinical characteristics of leukemia in the Down syndrome population. We utilized a combination of cytogenetic and DNA polymorphism analyses to determine stage of non-disjunction and parental orgin of the extra chromosome in 18 children with Down syndrome and leukemia. The DNA analyses are reported elsewhere. Among 27 cases of Down Syndrome leukemics, meiosis II or mitotic errors were seen in 4 out of 5 informative TL and M7 cases and in only 1 out of 5 cases of other leukemias. Clinical analysis revealed that the frequency of M7 leukemia is significantly higher in DS-leukemics compared to non-Down syndrome-leukemics. A case of Down syndrome TL with subsequent development of M7 leukemia was anecdotal evidence that TL and M7 leukemia may be of common clonal origin. The fact that fewer than 100% of TL and M7 leukemia cases demonstrated meiosis II or mitotic errors indicates that disomic homozygosity is not necessary for the development of these leukemias, however it may be an important factor which predisposes to TL and M7 leukemia in Down syndrome.

  2. Perioperative outcomes and long-term survival in clinically early-stage thymic malignancies: video-assisted thoracoscopic thymectomy versus open approaches

    PubMed Central

    Wang, Hao; Gu, Zhitao; Tan, Lijie; Fu, Jianhua; Shen, Yi; Wei, Yucheng; Zhang, Peng; Han, Yongtao; Chen, Chun; Zhang, Renquan; Li, Yin; Chen, Keneng; Chen, Hezhong; Liu, Yongyu; Cui, Youbing; Wang, Yun; Pang, Liewen; Yu, Zhentao; Zhou, Xinming; Liu, Yangchun; Liu, Yuan

    2016-01-01

    Background Video-assisted thoracoscopic surgery (VATS) theoretically offers advantages over open thymectomy for clinically early-stage (Masaoka-Koga stage I and II) thymic malignancies. However, long-term outcomes have not been well studied. We compared the postoperative outcomes and survival from a cohort study based on the database of the Chinese Alliance for Research in Thymomas (ChART). Methods Between 1994 and 2012, data of 1,117 patients having surgery for clinically early-stage (Masaoka-Koga stage I and II) tumors were enrolled for the study. Among them, 241 cases underwent VATS thymectomy (VATS group), while 876 cases underwent open thymectomy (Open group). Univariate analyses were used to compare the clinical character and perioperative outcomes between the two groups. And multivariate analysis was performed to determine the independent predictive factors for long-term survival. Results Compared with the Open group, the VATS group had higher percentage of total thymectomy (80.5% vs. 73.9%, P=0.028), resection rate (98.8% vs. 88.7%, P=0.000) and less recurrence (2.9% vs. 16.0%, P=0.000). Five-year overall survival was 92% after VATS and 92% after open thymectomy, with no significant difference between the two groups (P=0.15). However, 5-year disease free survival were 92% in VATS group and 83% in Open group (P=0.011). Cox proportional hazards model revealed that WHO classification, Masaoka-Koga stage and adjuvant therapy were independent predictive factors for overall survival, while surgical approach had no significant impact on long-term outcome. Conclusions This study suggests that VATS thymectomy is an effective approach for clinically early-stage thymic malignancies. And it may offer better perioperative outcomes, as well as equal oncological survival. PMID:27114834

  3. 5-azacitidine efficacy and safety in patients aged >65 years with myelodysplastic syndromes outside clinical trials.

    PubMed

    Breccia, Massimo; Loglisci, Giuseppina; Salaroli, Adriano; Serrao, Alessandra; Petrucci, Luigi; Mancini, Marco; Alimena, Giuliana

    2012-08-01

    The efficacy and safety of azacitidine in elderly patients (aged >65 years) with myelodysplastic syndromes (MDS) treated outside clinical trials are reported. Thirty-eight patients with MDS received azacitidine (75 mg/m(2), schedule 5+2 +2): seven patients were classified as having refractory cytopenia with multilineage dysplasia (RCMD), nine patients with refractory anemia with excess of blasts (RAEB) type 1, 18 patients with RAEB type 2 and four patients with chronic myelomonocytic leukemia type 2 (CMML-2). According to International Working Group (IWG) 2006 criteria, after the first four cycles we detected complete remission in seven patients (CR, 18%), improvement of bone marrow dysplasia and reduction of blast percentage in seven patients (partial response, 18%), stable disease in 20 patients (53%) and progression to acute leukemia in four patients (10%). Median overall survival for all patients treated was 16.4 months. Only mild non-hematologic toxicity was detected (grade 1-2 nausea and pruritus), whereas 55% of patients experienced hematologic side effects (25% grade 3-4 thrombocytopenia and 30% grade 3-4 neutropenia). Our results suggest that advanced age should not preclude effective treatment with azacitidine in non-selected elderly patients wih MDS.

  4. A clinic-based study of refractive errors, strabismus, and amblyopia in pediatric age-group

    PubMed Central

    Al-Tamimi, Elham R.; Shakeel, Ayisha; Yassin, Sanaa A.; Ali, Syed I.; Khan, Umar A.

    2015-01-01

    Purpose: The purpose of this cross-sectional observational study was to determine the distribution and patterns of refractive errors, strabismus, and amblyopia in children seen at a pediatric eye care. Materials and Methods: The study was conducted in a Private Hospital in Dammam, Kingdom of Saudi Arabia, from March to July 2013. During this period, a total of 1350 children, aged 1–15 years were seen at this Center's Pediatric Ophthalmology Unit. All the children underwent complete ophthalmic examination with cycloplegic refraction. Results: Refractive errors accounted for 44.4% of the cases, the predominant refractive error being hypermetropia which represented 83%. Strabismus and amblyopia were present in 38% and 9.1% of children, respectively. Conclusions: In this clinic-based study, the focus was on the frequency of refractive errors, strabismus, and amblyopia which were considerably high. Hypermetropia was the predominant refractive error in contrast to other studies in which myopia was more common. This could be attributed to the criteria for sample selection since it was clinic-based rather than a population-based study. However, it is important to promote public education on the significance of early detection of refractive errors, and have periodic screening in schools. PMID:26392796

  5. Improving function in age-related macular degeneration: design and methods of a randomized clinical trial.

    PubMed

    Rovner, Barry W; Casten, Robin J; Hegel, Mark T; Massof, Robert W; Leiby, Benjamin E; Tasman, William S

    2011-03-01

    Age-Related Macular Degeneration (AMD) is the leading cause of severe vision loss in older adults and impairs the ability to read, drive, and live independently and increases the risk for depression, falls, and earlier mortality. Although new medical treatments have improved AMD's prognosis, vision-related disability remains a major public health problem. Improving Function in AMD (IF-AMD) is a two-group randomized, parallel design, controlled clinical trial that compares the efficacy of Problem-Solving Therapy (PST) with Supportive Therapy (ST) (an attention control treatment) to improve vision function in 240 patients with AMD. PST and ST therapists deliver 6 one-hour respective treatment sessions to subjects in their homes over 2 months. Outcomes are assessed masked to treatment assignment at 3 months (main trial endpoint) and 6 months (maintenance effects). The primary outcome is targeted vision function (TVF), which refers to specific vision-dependent functional goals that subjects highly value but find difficult to achieve. TVF is an innovative outcome measure in that it is targeted and tailored to individual subjects yet is measured in a standardized way. This paper describes the research methods, theoretical and clinical aspects of the study treatments, and the measures used to evaluate functional and psychiatric outcomes in this population.

  6. Improving Function in Age-Related Macular Degeneration: Design and Methods of a Randomized Clinical Trial

    PubMed Central

    Rovner, Barry W.; Casten, Robin J.; Hegel, Mark T.; Massof, Robert W.; Leiby, Benjamin E.; Tasman, William S.

    2010-01-01

    Age-Related Macular Degeneration (AMD) is the leading cause of severe vision loss in older adults and impairs the ability to read, drive, and live independently and increases the risk for depression, falls, and earlier mortality. Although new medical treatments have improved AMD’s prognosis, vision-related disability remains a major public health problem. Improving Function in AMD (IF-AMD) is a two-group randomized, parallel design, controlled clinical trial that compares the efficacy of Problem-Solving Therapy (PST) with Supportive Therapy (ST) (an attention control treatment) to improve vision function in 240 patients with AMD. PST and ST therapists deliver 6 one-hour respective treatment sessions to subjects in their homes over 2 months. Outcomes are assessed masked to treatment assignment at 3 months (main trial endpoint) and 6 months (maintenance effects). The primary outcome is targeted vision function (TVF), which refers to specific vision-dependent functional goals that subjects highly value but find difficult to achieve. TVF is an innovative outcome measure in that it is targeted and tailored to individual subjects yet is measured in a standardized way. This paper describes the research methods, theoretical and clinical aspects of the study treatments, and the measures used to evaluate functional and psychiatric outcomes in this population. PMID:20974293

  7. [Advanced curriculum for clinical assessment and skill in new age pharmacist education].

    PubMed

    Kiuchi, Yuji; Masuda, Yutaka; Kamei, Daisuke; Kogo, Mari; Nakamura, Akihiro

    2013-01-01

    In Showa University School of pharmacy, 7 competencies for outcome-based education were set up in 2011. We are now creating sequential curriculum in order to achieve these competencies. As a member of team medical treatment, pharmacist must share a patient's information with other members, assess each patient's condition, propose the best medication with evidence, and also check the effect of medication. Therefore, many active practices in a hospital and community and problem-based learning (PBL) tutorials are carried out in curriculum in School of Pharmacy. As a training for the future pharmacists who positively perform primary care with responsibility in community pharmacy, students study the method of clinical assessment (assessment of condition of disease from the patient's complain, and choice of appropriate proposal). Furthermore, the exercise and training of parenteral medication, physical assessment, and first aid, etc. are also taken in the curriculums as new clinical skill. The systematic and gradual interprofessional education curriculum for the team medical education has been carried out aiming at training of active members in medical team in a hospital and community. At this symposium, I will introduce these systematic advanced curriculums for the pharmacist of a new age, and to show the usefulness and learning effect.

  8. Improving quality of life in patients with end-stage age-related macular degeneration: focus on miniature ocular implants

    PubMed Central

    Singer, Michael A; Amir, Nancy; Herro, Angela; Porbandarwalla, Salman S; Pollard, Joseph

    2012-01-01

    Low vision devices in the past have been mainly extraocular. There are now four new devices in different stages of development and implementation that are currently available. Three of them, the Implantable Miniature Telescope (IMT, VisionCare Ophthalmic Technologies, Saratoga, CA), Intraocular Lens for Visually Impaired People (IOL-VIP, IOL-VIP System, Soleko, Pontecorvo, Italy), and Lipschitz Mirror Implant (LMI, Optolight Vision Technology, Herzlia, Israel) are implanted into the anterior segment while the Argus II (Second Sight Medical Products, Sylmar, CA) is implanted into the posterior segment. The goal of these devices is to increase the patient quality of life which has been measured by Visual Functioning Questionnaire (VFQ) scales. The IMT is the only device that has been shown to increase the VFQ score by seven points at 6 months compared to baseline. It is the only FDA-approved device in the US while the Argus has been approved in Europe. Each of these prosthetics has potential benefits for patients. PMID:22259233

  9. Improving quality of life in patients with end-stage age-related macular degeneration: focus on miniature ocular implants.

    PubMed

    Singer, Michael A; Amir, Nancy; Herro, Angela; Porbandarwalla, Salman S; Pollard, Joseph

    2012-01-01

    Low vision devices in the past have been mainly extraocular. There are now four new devices in different stages of development and implementation that are currently available. Three of them, the Implantable Miniature Telescope (IMT, VisionCare Ophthalmic Technologies, Saratoga, CA), Intraocular Lens for Visually Impaired People (IOL-VIP, IOL-VIP System, Soleko, Pontecorvo, Italy), and Lipschitz Mirror Implant (LMI, Optolight Vision Technology, Herzlia, Israel) are implanted into the anterior segment while the Argus II (Second Sight Medical Products, Sylmar, CA) is implanted into the posterior segment. The goal of these devices is to increase the patient quality of life which has been measured by Visual Functioning Questionnaire (VFQ) scales. The IMT is the only device that has been shown to increase the VFQ score by seven points at 6 months compared to baseline. It is the only FDA-approved device in the US while the Argus has been approved in Europe. Each of these prosthetics has potential benefits for patients.

  10. Nature and Age of Neighbours Matter: Interspecific Associations among Tree Species Exist and Vary across Life Stages in Tropical Forests

    PubMed Central

    Ledo, Alicia

    2015-01-01

    Detailed information about interspecific spatial associations among tropical tree species is scarce, and hence the ecological importance of those associations may have been underestimated. However, they can play a role in community assembly and species diversity maintenance. This study investigated the spatial dependence between pairs of species. First, the spatial associations (spatial attraction and spatial repulsion) that arose between species were examined. Second, different sizes of trees were considered in order to evaluate whether the spatial relationships between species are constant or vary during the lifetime of individuals. Third, the consistency of those spatial associations with the species-habitat associations found in previous studies was assessed. Two different tropical ecosystems were investigated: a montane cloud forest and a lowland moist forest. The results showed that spatial associations among species exist, and these vary among life stages and species. The rarity of negative spatial interactions suggested that exclusive competition was not common in the studied forests. On the other hand, positive interactions were common, and the results of this study strongly suggested that habitat associations were not the only cause of spatial attraction among species. If this is true, habitat associations and density dependence are not the only mechanisms that explain species distribution and diversity; other ecological interactions, such as facilitation among species, may also play a role. These spatial associations could be important in the assembly of tropical tree communities and forest succession, and should be taken into account in future studies. PMID:26581110

  11. Psychosocial impact of illness intrusiveness moderated by self-concept and age in end-stage renal disease.

    PubMed

    Devins, G M; Beanlands, H; Mandin, H; Paul, L C

    1997-11-01

    This study assesses whether a person's self-concept as a "chronic kidney patient" differentially moderates the psychosocial impact of illness intrusiveness--illness-induced lifestyle disruptions--across the life span. Renal transplant (n = 52) and maintenance dialysis patients (n = 49) completed the illness Intrusiveness Ratings Scale, a semantic-differential self-concept measure, and structured interviews measuring psychosocial well-being and emotional distress. Across ages, distress rose with increasing illness intrusiveness when self-concept was similar, but not dissimilar, to the chronic kidney patient stereotype. The relation between illness intrusiveness and psychosocial well-being differed significantly between younger and older respondents depending on whether they construed themselves as similar versus dissimilar to the chronic kidney patient. Although self-definition moderates the psychosocial impact of chronic disease, this varies across the life span and across affect states.

  12. [Neuromuscular status of children of different gestational age on the stage of transition from intrauterine immersion to the earth's gravity].

    PubMed

    2012-01-01

    The work was aimed at describing the neuromuscular status of premature baby in the context of the ontogenetic and zero gravity model using the results of superficial interference electromyography (IEMG). Throughout six postnatal weeks, IEMG of premature babies is similar to EMG of full-term child on the first days of extrauterine life; IEMG is characterized by a "simplified" temporal structure, low amplitude and frequency, IEMG dynamics of fullterm child is slow in contrast to premature baby; the reason seems to be maximum long intrauterine life during which the motor system gets better prepared and maturates. On the other hand, complexity and high amplitude of premature baby IEMG as compared with full-term child of the same postconceptual age are associated with the inevitable sensory stimulation after birth. Abilitation procedures provided to premature baby could be adapted to the purposes of post-flight rehabilitation of cosmonauts.

  13. Quantitative pteridine fluorescence analysis: A possible age-grading technique for the adult stages of the blow fly Calliphora vicina (Diptera: Calliphoridae).

    PubMed

    Bernhardt, Victoria; Hannig, Laura; Kinast, Ronja; Verhoff, Marcel A; Rothweiler, Florian; Zehner, Richard; Amendt, Jens

    2017-03-04

    Age estimation of adult flies could extend the possible window of time for calculating the minimal postmortem interval (PMImin) by means of entomological methods. Currently, this is done by estimating the time required by necrophagous Diptera to reach certain juvenile developmental landmarks, and the method only works until the end of metamorphosis and emergence of the adult fly. Particularly at indoor crime scenes, being able to estimate the age of trapped adult flies would be an important tool with which to extend the calculable PMI beyond the developmental period. Recently, several promising age-dependent morphological and physiological characteristics of adult insects have been investigated in medical and forensic entomology, but the results are still preliminary and restricted to a few species. We examined adults of the forensically relevant blow fly species Calliphora vicina and investigated the fluorescence levels of pteridine, a group of metabolites that accumulates in the eyes during aging. From Day 1 to Day 25 post-emergence, flies were kept at three different temperature regimes (20°C, 25°C, and fluctuating temperatures in the context of a field study) and 12:12 L:D. From Day 1 until Day 7, the fluorescence of pteridine was determined on a daily basis, and thereafter, every three days. The achieved fly age was multiplied with the relevant temperature and converted into accumulated degree-days (ADD). The fluorescence level of pteridine increased linear with increasing ADD (females: R(2)=0.777; males: R(2)=0.802). The difference between sexes was significant (p<0.001). Neither head weight nor temperature had an effect on pteridine fluorescence. Because the variation in pteridine fluorescence increased with increasing ADD, it seems favorable to combine several aging methods for more precise results. In context, we emphasize that different body parts of the same specimen can be used to analyze cuticular hydrocarbons (legs), pteridine fluorescence (head

  14. Simulation of multi-stage nonlinear bone remodeling induced by fixed partial dentures of different configurations: a comparative clinical and numerical study.

    PubMed

    Liao, Zhipeng; Yoda, Nobuhiro; Chen, Junning; Zheng, Keke; Sasaki, Keiichi; Swain, Michael V; Li, Qing

    2017-04-01

    This paper aimed to develop a clinically validated bone remodeling algorithm by integrating bone's dynamic properties in a multi-stage fashion based on a four-year clinical follow-up of implant treatment. The configurational effects of fixed partial dentures (FPDs) were explored using a multi-stage remodeling rule. Three-dimensional real-time occlusal loads during maximum voluntary clenching were measured with a piezoelectric force transducer and were incorporated into a computerized tomography-based finite element mandibular model. Virtual X-ray images were generated based on simulation and statistically correlated with clinical data using linear regressions. The strain energy density-driven remodeling parameters were regulated over the time frame considered. A linear single-stage bone remodeling algorithm, with a single set of constant remodeling parameters, was found to poorly fit with clinical data through linear regression (low [Formula: see text] and R), whereas a time-dependent multi-stage algorithm better simulated the remodeling process (high [Formula: see text] and R) against the clinical results. The three-implant-supported and distally cantilevered FPDs presented noticeable and continuous bone apposition, mainly adjacent to the cervical and apical regions. The bridged and mesially cantilevered FPDs showed bone resorption or no visible bone formation in some areas. Time-dependent variation of bone remodeling parameters is recommended to better correlate remodeling simulation with clinical follow-up. The position of FPD pontics plays a critical role in mechanobiological functionality and bone remodeling. Caution should be exercised when selecting the cantilever FPD due to the risk of overloading bone resorption.

  15. Novel leukemic lymphoma with probable derivation from immature stage of natural killer (NK) lineage in an aged patient.

    PubMed

    Kawano, S; Tatsumi, E; Yoneda, N; Yamaguchi, N; Goji, J; Ito, H; Nagai, T; Nishikori, M; Okamura, A; Koiwai, O

    1995-01-01

    A 66-year-old male patient was admitted with dyspnea; physical examination revealed petechiae and systemic lymphadenopathy. Laboratory findings showed leukemia. The blasts in the peripheral blood were negative for cytochemical myeloperoxidase, and had condensed nuclear chromatin with a nucleolus. The histological diagnosis of the biopsied neck lymph node was lymphoblastic lymphoma. The leukemia cells expressed CD2, CD6, CD7, CD13low, CD56, beta chain of IL-2 receptorlow (IL-2R beta), and HLA-DR antigens, but not other pan-T (CD5, CD3, CD4, and CD8); pan-B (CD10, CD19, CD20, and CD24); natural killer (NK) (CD16, CD57); or myeloid (CD33) antigens. Electronmicroscopy revealed convoluted nuclei with conspicuous nucleoli and peripherally condensed heterochromatin. Membrane-bound granules containing an electron dense matrix were observed in the cytoplasm, indicating the NK cell nature of the neoplastic cells. While terminal deoxynucleotidyl transferase (TdT) and cytoplasmic CD3 were not detected by immunofluorescence on fixed smears, Northern blot analysis revealed the gene expression of CD3 epsilon, CD3 zeta, and TdT. Gene rearrangement analysis revealed that the beta, gamma, and delta chains of T-cell receptor (TCR) and immunoglobulin heavy chain (IgH) were of germline genotype. While the overall interpretation of the phenotype and genotype was difficult, the derivation of an immature stage of NK lineage was strongly suggested, based predominantly on the electronmicroscopic features. Despite initially successful chemotherapy, the patient died 14 months after initial presentation.

  16. Causal Therapy of Breast Cancer Irrelevant of Age, Tumor Stage and 
ER-Status: Stimulation of Estrogen Signaling Coupled With Breast 
Conserving Surgery

    PubMed Central

    Suba, Zsuzsanna

    2016-01-01

    Abstract: Background Results of long-term studies justify that the rate of breast cancer recurrence and tumor-related mortality remains quite unpredictable, regardless of the use of any current therapeutic measures. Objective Since the application of standard therapies, such as surgery, radiation, chemotherapy and antiestrogen administration does not work as might be expected; our therapeutic practice requires thorough rethinking. Method Published long-term therapeutic results on breast cancer cases were analyzed in correlation with stage at diagnosis, ER-status of tumors and patients’ age. The effectiveness of current therapeutic measures was also compared by estimating the rate of tumor-free survival, breast cancer recurrence and breast cancer-specific mortality. Results Diagnosis and treatment of breast cancer at an early stage cannot improve the rate of tumor-free survival. Poor differentiation of tumors, ER-negativity in particular, defines poor prognosis even after applying aggressive therapies. In patients treated with in situ breast cancer, the recurrence-rate of invasive tumor increased directly with ageing irrespective of tumor size or ER-status at diagnosis. Women who underwent lumpectomy without adjuvant radiation or chemotherapy exhibited significantly better overall and breast cancer specific survival rates than those receiving mastectomy, regardless of stage and ER-status of tumors. Antiestrogen treatment exhibited unforeseeable effectiveness even on targeted ER-positive tumors. Recent patents propose the detection of ESR1-gene amplification or restoration of ER-alpha expression for prediction of effective antiestrogen treatment, suggesting a crucial inhibitory role of estrogen-signaling against tumor-growth. Conclusion Estradiol-induced upregulation of estrogen signaling coupled with sparing of the estrogen-rich mammary fatpad are the most effective strategies against breast cancer. PMID:27087654

  17. Concomitant boost IMRT-based neoadjuvant chemoradiotherapy for clinical stage II/III rectal adenocarcinoma: results of a phase II study

    PubMed Central

    2014-01-01

    Aim This study was designed to evaluate the efficacy and toxicities of concomitant boost intensity-modulated radiation therapy (IMRT) along with capecitabine and oxaliplatin, followed by a cycle of Xelox, in neoadjuvant course for locally advanced rectal cancer. Materials and methods Patients with histologically confirmed, newly diagnosed, locally advanced rectal adenocarcinoma (cT3-T4 and/or cN+) located within 12 cm of the anal verge were included in this study. Patients received IMRT to the pelvis of 50 Gy and a concomitant boost of 5 Gy to the primary tumor in 25 fractions, and concurrent with oxaliplatin (50 mg/m2 d1 weekly) and capecitabine (625 mg/m2 bid d1–5 weekly). One cycle of Xelox (oxaliplatin 130 mg/m2 on d1 and capecitabine 1000 mg/m2 twice daily d1–14) was given two weeks after the completion of chemoradiation, and radical surgery was scheduled eight weeks after chemoradiation. Tumor response was evaluated by tumor regression grade (TRG) system and acute toxicities were evaluated by NCI-CTC 3.0 criteria. Survival curves were estimated using the Kaplan-Meier method and compared with Log-rank test. Results A total of 78 patients were included between March 2009 and May 2011 (median age 54 years; 62 male). Seventy-six patients underwent surgical resection. Twenty-eight patients underwent sphincter-sparing lower anterior resection and 18 patients (23.7%) were evaluated as pathological complete response (pCR). The incidences of grade 3 hematologic toxicity, diarrhea, and radiation dermatitis were 3.8%, 10.3%, and 17.9%, respectively. The three-year LR (local recurrence), DFS (disease-free survival) and OS (overall survival) rates were 14.6%, 63.8% and 77.4%, respectively. Initial clinical T stage and tumor regression were independent prognostic factors to DFS. Conclusion An intensified regimen of concomitant boost radiotherapy plus concurrent capecitabine and oxaliplatin, followed by one cycle of Xelox, can be safely administered in patients

  18. Regarding the real diversity of Glyptodontidae (Mammalia, Xenarthra) in the late Pliocene (Chapadmalalan Age/Stage) of Argentina.

    PubMed

    Zurita, Alfredo E; Taglioretti, Matías; DE Los Reyes, Martín; Cuadrelli, Francisco; Poire, Daniel

    2016-06-07

    A large diversity of Glyptodontidae has been proposed as characterizing the Chapadmalalan Age (Pliocene). Most of these taxa were recognized on the basis of partial dorsal carapaces and/or caudal tubes, whereas the main diagnostic characteristic is a particular morphology of the exposed surface of the osteoderms. From a biostratigraphic point of view some species are biostratigraphically important. The Upper Chapadmalalan is based on the Paraglyptodon chapadmalensis biozone. Both the re-evaluation of the type and referred materials and new significant findings from the Chapadmalal and El Polvorín Formations indicate that the diversity of Pliocene Glyptodontidae is more limited than previously supposed. The particular morphology of the exposed surface of the osteoderms that characterizes some of the species actually corresponds to a taphonomic alteration, which results in a non-real ornamentation pattern. Thus, the Glyptodontinae P. chapadmalensis must be replaced as a fossil guide because neither this species nor the species included in the genera Urotherium, Trachycalyptus and Lomaphorus are well characterized. Taking into account the diversity of Glyptodontidae for this lapse, the Glyptodontinae are very scarce (a situation that contrasts with its records in the Pleistocene), whereas Eosclerocalyptus, "Plohophorini" (Plohophorus) and Doedicurinae (cf. Eleutherocercus antiquus) are among the most recorded taxa.

  19. Highly retentive core domains in K-feldspar preserve argon ages from high temperature stages of granite exhumation

    NASA Astrophysics Data System (ADS)

    Forster, Marnie; Lister, Gordon

    2016-04-01

    Retentive core domains are characterized by diffusion parameters that imply K-feldspar should be able to retain argon even at temperatures near or above the granite solidus. In this case it should be possible to date granite emplacement using argon geochronology, and the same answer should be obtained as by using other methods. We present one case study where this is the case, from the elevated Capoas granite stock on Palawan, in the Philippines, and another where it is not, from the South Cyclades Shear Zone, on Ios, Greece. We attempt to determine the factors such as the role of fluid ingress in triggering the in situ recrystallization that can eliminate and/or modify the core domains, leading to relatively youthful ages. Thermochronology is still possible, because less retentive diffusion domains exist, but different methods need to be applied to interpret the data. The work also demonstrates that K-feldspar can be sufficiently retentive as to allow direct dating of processes that reduce the dimensions of diffusion domains, e.g., cataclased and/or recrystallized K-feldspar in fault rock and/or mylonite. These are important developments in the methodology of 40Ar/39Ar geochronology, but to further advance we need to clarify the nature of these highly retentive core domains. In particular, we need better understand how they are modified by microstructural processes during deformation and metamorphism. We need also to assess the role of any crystal structural changes during step-heating in vacuo.

  20. Immune-related Adverse Events of Dendritic Cell Vaccination Correlate With Immunologic and Clinical Outcome in Stage III and IV Melanoma Patients

    PubMed Central

    Boudewijns, Steve; Westdorp, Harm; Koornstra, Rutger H.T.; Aarntzen, Erik H.J.G.; Schreibelt, Gerty; Creemers, Jeroen H.A.; Punt, Cornelis J.A.; Figdor, Carl G.; Gerritsen, Winald R.; Bol, Kalijn F.

    2016-01-01

    The purpose of this study was to determine the toxicity profile of dendritic cell (DC) vaccination in stage III and IV melanoma patients, and to evaluate whether there is a correlation between side effects and immunologic and clinical outcome. This is a retrospective analysis of 82 stage III and 137 stage IV melanoma patients, vaccinated with monocyte-derived or naturally circulating autologous DCs loaded with tumor-associated antigens gp100 and tyrosinase. Median follow-up time was 54.3 months in stage III patients and 12.9 months in stage IV patients. Treatment-related adverse events occurred in 84% of patients; grade 3 toxicity was present in 3% of patients. Most common adverse events were flu-like symptoms (67%) and injection site reactions (50%), and both correlated with the presence of tetramer-positive CD8+ T cells (both P<0.001). In stage III melanoma patients experiencing flu-like symptoms, median overall survival (OS) was not reached versus 32.3 months in patients without flu-like symptoms (P=0.009); median OS in patients with an injection site reaction was not reached versus 53.7 months in patients without an injection site reaction (P<0.05). In stage IV melanoma patients (primary uveal and mucosal melanomas excluded), median OS in patients with or without flu-like symptoms was 13.1 versus 8.9 months, respectively (P=0.03); median OS in patients with an injection site reaction was 15.7 months versus 9.8 months in patients without an injection site reaction (P=0.003). In conclusion, DC vaccination is safe and tolerable and the occurrence of the immune-related side effects, such as flu-like symptoms and injection site reactions, correlates with immunologic and clinical outcome. PMID:27227325

  1. Competence for Regeneration during Tobacco Internodal Development (Involvement of Plant Age, Cell Elongation Stage, and Degree of Polysomaty).

    PubMed Central

    Gilissen, LJW.; Van Staveren, M. J.; Hakkert, J. C.; Smulders, MJM.

    1996-01-01

    This study deals with internodal development in vegetative plants of Nicotiana tabacum cv Samsun NN and its reflection in changes of the cellular competence for regeneration. During elongation of the internodes, the cells of the epidermis, subepidermis, and cortex exclusively expanded and increased their DNA content cell type specifically, generally from 2C to 4C. Cells with the 8C DNA content were found mainly among the cortex cells of mature internodes. The frequency of shoot regeneration (directly from subepidermal and epidermal cells together) on thin cell layer explants increased to an optimum along with elongation of the internodes and decreased in mature internodes along with aging. The frequencies of diploid shoots among the regenerants from elongating and mature internodes were high (88 and 75% on the average, respectively), indicating that most cells that had achieved the 4C DNA content generally retained the G2 phase of the diploid cell cycle. Shoots regenerated from explants of young plant material mainly had a vitrified appearance. The occurrence of this type of malformed growth was already determined by the physiological state of the cells in the internode and did not interfere with their acquisition of competence. Vitrification was unrelated to the degree of polysomaty of the internodal tissue. Using the occurrence of tetraploid root regenerants (from intermediate cortex-derived callus), up to a frequency of 50%, we show that the position in the plant where a majority of the 4C cortex cells switched to the G1 phase of the tetraploid cell cycle was at the transition from the elongation phase to the mature phase. PMID:12226359

  2. Bevacizumab for neovascular age-related macular degeneration in Chinese patients in a clinical setting

    PubMed Central

    Ng, Danny Siu-Chun; Kwok, Alvin Kwan-Ho; Tong, Justin Man-Kit; Chan, Clement Wai-Nang; Li, Walton Wai-Tat

    2016-01-01

    AIM To determine the outcome of non-investigational treatment with intravitreal bevacizumab (IVB) in neovascular age-related macular degeneration (AMD) patients. METHODS Retrospective chart review of 81 eyes with neovascular AMD followed-up for at least 12mo and received 3-monthly loading IVB injections. Re-treat was based upon the individual clinician's judgment. Best-corrected visual acuity (BCVA) and optical coherence tomography measurements of central foveal thickness outcomes were evaluated at 12, 24mo. RESULTS Eighty-one eyes (of 75 patients) completed 12mo of follow-up and 44 eyes (of 41 patients) completed 24mo of follow-up. The mean baseline logMAR BCVA significantly improved from 0.94±0.69 to 0.85±0.68 at 12mo (P<0.001) and from 0.91±0.65 to 0.85±0.60 (P=0.004) at 24mo. The proportion of eyes that lost <15 logMAR letters at 12mo was 90.1% and at 24mo was 81.8%. IVB was effective in improving visual acuity in both treatment naïve and previous photodynamic therapy (PDT)-treated subgroups. Treatment naive patients required significantly fewer injections than patients with prior PDT. Multiple regression analysis identified that poorer baseline visual acuity was associated with greater improvement in visual acuity (P=0.015). CONCLUSION Fewer injections in clinical practice may result in suboptimal visual outcomes compared with clinical trials of IVB in neovascular AMD patients. Poor baseline visual acuity and prior PDT treatment may also improve vision after IVB. The safety and durability of effect was maintained at 24mo. PMID:27158614

  3. Natural growth and diet of known-age pallid sturgeon (Scaphirhynchus albus) early life stages in the upper Missouri River basin, Montana and North Dakota

    USGS Publications Warehouse

    Braaten, P.J.; Fuller, D.B.; Lott, R.D.; Haddix, T.M.; Holte, L.D.; Wilson, R.H.; Bartron, M.L.; Kalie, J.A.; DeHaan, P.W.; Ardren, W.R.; Holm, R.J.; Jaeger, M.E.

    2012-01-01

    Prior to anthropogenic modifications, the historic Missouri River provided ecological conditions suitable for reproduction, growth, and survival of pallid sturgeon Scaphirhynchus albus. However, little information is available to discern whether altered conditions in the contemporary Missouri River are suitable for feeding, growth and survival of endangered pallid sturgeon during the early life stages. In 2004 and 2007, nearly 600 000 pallid sturgeon free embryos and larvae were released in the upper Missouri River and survivors from these releases were collected during 2004–2010 to quantify natural growth rates and diet composition. Based on genetic analysis and known-age at release (1–17 days post-hatch, dph), age at capture (dph, years) could be determined for each survivor. Totals of 23 and 28 survivors from the 2004 and 2007 releases, respectively, were sampled. Growth of pallid sturgeon was rapid (1.91 mm day-1) during the initial 13–48 dph, then slowed as fish approached maximum length (120–140 mm) towards the end of the first growing season. The diet of young-of-year pallid sturgeon was comprised of Diptera larvae, Diptera pupae, and Ephemeroptera nymphs. Growth of pallid sturgeon from ages 1–6 years was about 48.0 mm year-1. This study provides the first assessment of natural growth and diet of young pallid sturgeon in the wild. Results depict pallid sturgeon growth trajectories that may be expected for naturally produced wild stocks under contemporary habitat conditions in the Missouri River and Yellowstone River.

  4. Correlation and discriminant analysis between clinical, endoscopic, thoracic X-ray and bronchoalveolar lavage fluid cytology scores, for staging horses with recurrent airway obstruction (RAO).

    PubMed

    Tilley, P; Sales Luis, J P; Branco Ferreira, M

    2012-10-01

    As recurrent airway obstruction (RAO) is progressive and as medical history is frequently unknown by owners, it's important to suggest a score model to characterize RAO stages for a more accurate diagnosis and treatment. The authors correlated clinical (CS), endoscopic (ES), thoracic X-ray (XRS) and bronchoalveolar lavage fluid (BALFS) scores in horses with RAO, in an attempt to establish relevance of each factor's contribution for the characterization of RAO stages and to suggest a staging method. Thirty horses with RAO and ten healthy controls were studied. Pearson correlation coefficients were determined between CS, ES, XRS and BALFS. Only significant correlation coefficients (>0.60) were considered. One way variance analyses were used to compare the two groups. A discriminant analysis model was adjusted on the RAO staging method suggested. There was a significant correlation coefficient between the CS cough, nostril flare and abdominal lift, all the mucus ES (0.61-0.84), the XRS interstitial pattern, bronchial radiopacity and thickening and tracheal thickening (0.67-0.78) and the BALFS neutrophil percentages (0.63-0.84). These variables (e.g., cough) which presented a significant correlation coefficient were considered relevant and chosen for a score model to characterize RAO stages. The ten healthy controls were attributed stage 0 and the 30 RAO horses were attributed stages 1 (4 horses), 2 (7 horses), 3 (10 horses) and 4 (9 horses). There was also a significant correlation coefficient between all the relevant variables and the RAO stage (0.61-0.89). Furthermore, discriminant analysis of the RAO staging method showed 92.5% of original grouped cases and 85.0% of cross-validated grouped cases correctly classified, having confirmed major contribution of the same variables that had significant correlation coefficients. Even though further confirmation by lung functional testing is desirable, the significant correlation between relevant variables and RAO stage and

  5. Women's age and embryo developmental speed accurately predict clinical pregnancy after single vitrified-warmed blastocyst transfer.

    PubMed

    Kato, Keiichi; Ueno, Satoshi; Yabuuchi, Akiko; Uchiyama, Kazuo; Okuno, Takashi; Kobayashi, Tamotsu; Segawa, Tomoya; Teramoto, Shokichi

    2014-10-01

    The aim of this study was to establish a simple, objective blastocyst grading system using women's age and embryo developmental speed to predict clinical pregnancy after single vitrified-warmed blastocyst transfer. A 6-year retrospective cohort study was conducted in a private infertility centre. A total of 7341 single vitrified-armed blastocyst transfer cycles were included, divided into those carried out between 2006 and 2011 (6046 cycles) and 2012 (1295 cycles). Clinical pregnancy rate, ongoing pregnancy rate and delivery rates were stratified by women's age (<35, 35-37, 38-39, 40-41, 42-45 years) and time to blastocyst expansion (<120, 120-129, 130-139, 140-149, >149 h) as embryo developmental speed. In all the age groups, clinical pregnancy rate, ongoing pregnancy rate and delivery rates decreased as the embryo developmental speed decreased (P < 0.0001). A simple five-grade score based on women's age and embryo developmental speed was determined by actual clinical pregnancy rates observed in the 2006-2011 cohort. Subsequently, the novel grading score was validated in the 2012 cohort (1295 cycles), finding an excellent association. In conclusion, we established a novel blastocyst grading system using women's age and embryo developmental speed as objective parameters.

  6. Late-Stage HIMU-Type Volcanism on the Walvis Ridge: Not just Part of an Age-Progressive Tristan-Gough Hotspot Track

    NASA Astrophysics Data System (ADS)

    Homrighausen, S.; Hoernle, K.; Hauff, F.; Portnyagin, M.; Werner, R.; Geldmacher, J.; Garbe-Schoenberg, C. D.

    2015-12-01

    The Walvis Ridge forms the NE portion of the Tristan-Gough hotspot track. It links the Etendeka large igneous province (LIP) in Africa, initially connected to the Parana LIP in South America, to the Guyot Province, that ends at the active volcanic islands of Tristan da Cunha and Gough. After the plume head stage, the hotspot changed from a ridge-centered plume tail, forming the Walvis Ridge and Rio Grande Rise (130-60 Ma), to an intraplate setting resulting in the geochemical distinct Tristan and Gough subtracks (Rohde et al. 2013; Geology 41). New major and trace element and radiogenic isotope data have been generated from 36 new dredge locations on the Walvis Ridge during R/V Sonne cruises SO233 and SO234. Based on the bathymetric data, we have identified tectonic structures and subsidence rates which indicate a complex geodynamic interplay of the Walvis Ridge formation and westward migration of the Mid Atlantic Ridge and the Rio Grande Rise. Our new results confirm that the age-progressive basement of the Walvis Ridge reflects only the enriched Gough component with no evidence of the Tristan component being present (Hoernle et al., 2015; Nat. Comm.). Superimposed large seamounts (including ridge- and guyot-like structures), especially in the SE portion of the Walvis Ridge, belong to a later-stage of alkalic volcanism with distinct HIMU incompatible element and Sr-Nd-Pb-Hf isotopic composition. The HIMU late-stage volcanism (206Pb/204Pb up to 20.8) is similar in composition to St. Helena and a late-stage (Eocene) sample from the Rio Grande Rise (Rohde et al., 2013; Tectonophysics 604). The new geochemical, bathymetric and existing age data indicate a magmatic reactivation c. 20-40 Ma after the formation of the Walvis Ridge basement, which may be related to passage of the Walvis Ridge over a batch of upwelling St. Helena type plume material. Our new results indicate a more complex formation of the Walvis Ridge than previously thought, which included two major

  7. Postoperative chemoradiotherapy improves survival in patients with stage II–III esophageal squamous cell carcinoma: An analysis of clinical outcomes

    PubMed Central

    Zou, Bingwen; Pang, Jing; Liu, Yongmei; Xu, Yong; Li, Lu; Zhou, Lin; Zhu, Jiang; Huang, Meijuan; Wang, Jin; Ren, Li; Gong, Youlin; Lu, You; Chen, Longqi

    2016-01-01

    Background We compared the efficacy of postoperative chemoradiation (POCRT) and surgery alone (SA) in patients with stage II–III esophageal squamous cell carcinoma (ESCC). Methods We analyzed the records of 265 patients with stage II–III ESCC who had undergone transthoracic esophagectomy and lymphadenectomy; 105 patients received POCRT, while 160 had SA. Results The median disease‐free survival (DFS) of the whole cohort was 22 months (95% confidence interval [CI], 19.2–24.8), while the median overall survival (OS) was 29 months (95% CI 25.5–32.5). The median DFS of the SA group was 21 months (95% CI 17.9–24.0), while that of the POCRT group was 29 months (95% CI 18.8–31.2; P = 0.048). Consistently, patients in the POCRT group had significantly longer median OS than patients in the SA group (34 vs. 26 months, respectively). Subgroup analysis showed that in patients with positive lymph nodes, pathological stage III, T3–4 stage, and poorly differentiated carcinoma, POCRT was apparently more effective than SA at improving OS and decreasing the rates of local recurrence and distant metastasis. Multivariate analysis demonstrated that lymph node involvement and treatment with POCRT were independent prognostic factors. Conclusion Compared with SA, POCRT may be more effective in improving OS and decreasing the rates of local recurrence and distant metastasis, particularly in stage III or positive lymph node stage II–III ESCC patients. PMID:27766781

  8. A new T staging system for nasopharyngeal carcinoma based on intensity-modulated radiation therapy: results from a prospective multicentric clinical study

    PubMed Central

    Kang, Min; Zhou, Pingting; Wei, Tingting; Zhao, Tingting; Long, Jianxiong; Li, Guisheng; Yan, Haolin; Feng, Guosheng; Liu, Meilian; Zhu, Jinxian; Wang, Rensheng

    2017-01-01

    Purpose: This prospective multicentric study aimed to establish a new clinical T staging standard for nasopharyngeal carcinoma (NPC) based on intensity-modulated radiotherapy (IMRT). Methods and materials: Between January 2006 and December 2009, four hundred and ninety-two NPC patients undergoing IMRT were staged according to the seventh edition of the UICC/AJCC staging system. The Kaplan-Meier method was used to calculate survival rates, and the log-rank test was used to compare survival differences. Results: The 5-year overall survival (OS), disease-free survival (DFS), recurrence-free survival (RFS), and distant metastasis-free survival (DMSF) rates were 80.5%, 78.6%, 94.1%, and 84.3%, respectively. Univariate and multivariate analyses showed that the invasion of the nasal cavity, parapharyngeal space, oropharynx, skull base, internal pterygoid muscle, external pterygoid muscle, paranasal sinus, infratemporal fossa, orbit, cranial nerves, cavernous sinus, and intracalvarium were independent prognostic factors (P<0.05). According to the results of risk variety and survival curves, we suggest that the new T staging system for NPC based on magnetic resonance imaging and intensity modulated radiation therapy can be classified as T1 (nasopharynx, nasal cavity, parapharyngeal space, oropharynx, skull base and internal pterygoid muscle) and T2 (external pterygoid muscle, paranasal sinus, infratemporal fossa, orbit, cranial nerves, cavernous sinus and intracalvarium). Compared to the seventh edition of UICC/AJCC staging system, our new recommended staging system performs better in risk difference and distribution balance. Furthermore, the differences between the substages of 5-year curves of LRFS, DMFS and OS were all statistically significant in our new recommended staging system. Conclusions: Our new recommended staging system is more adaptable to IMRT and can predict the prognosis of NPC patient in a more objective and accurate manner.

  9. Advanced glycation end-products (AGEs) and heart failure: pathophysiology and clinical implications.

    PubMed

    Hartog, Jasper W L; Voors, Adriaan A; Bakker, Stephan J L; Smit, Andries J; van Veldhuisen, Dirk J

    2007-12-01

    Advanced glycation end-products (AGEs) are molecules formed during a non-enzymatic reaction between proteins and sugar residues, called the Maillard reaction. AGEs accumulate in the human body with age, and accumulation is accelerated in the presence of diabetes mellitus. In patients with diabetes, AGE accumulation is associated with the development of cardiac dysfunction. Enhanced AGE accumulation is not restricted to patients with diabetes, but can also occur in renal failure, enhanced states of oxidative stress, and by an increased intake of AGEs. Several lines of evidence suggest that AGEs are related to the development and progression of heart failure in non-diabetic patients as well. Preliminary small intervention studies with AGE cross-link breakers in heart failure patients have shown promising results. In this review, the role of AGEs in the development of heart failure and the role of AGE intervention as a possible treatment for heart failure are discussed.

  10. [From classificational medicine to clinical medicine (the end of the XVIII century to 1870s). Communication 3. The second stage of clinical medicine development: introduction of methods of laboratory experiment and chemical analysis].

    PubMed

    Stochik, A M; Zatravkin, S N

    2011-01-01

    The article concerns the end stage of clinical medicine establishment covering the period from early 1840s to the middle 1870s of the XIX century. Basic scientific achievements related to introduction into practical medicine of the methods of laboratory experiment and chemical analysis are reviewed.

  11. Dante and cardiology: Physiopathology and clinical features of cardiovascular diseases in the Middle Ages.

    PubMed

    Riva, M A; Cambioli, L; Castagna, F; Cianci, N; Varrenti, M; Giannattasio, C; Cesana, G

    2015-02-15

    Ancient non-medical texts can unexpectedly provide useful information on the development of knowledge about the heart and its diseases throughout history. The 750th anniversary of the birth of the Italian poet Dante Alighieri (1265-1321) provides a timely opportunity to analyze medical references in his works, in particular, focusing on literary descriptions that may be attributed to cardiovascular disorders. Dante's high level of medical knowledge, probably derived from his academic studies, is testified by his affiliation to the Florentine Guild of physicians and pharmacists. In all his works, the poet shows a deep interest for the heart. However, his anatomical and physiological knowledge of the circulatory system appears to be poor, probably due to it being based on theories and concepts brought forth by Aristotle and Galen, which were taught in medieval universities. Despite this, accurate descriptions of some symptoms (emotional syncope, orthopnea, dyspnea on exertion) and signs (ascites, paleness), which may be attributed to cardiovascular disorders, can be easily found in Dante's works, particularly in his masterpiece, the Divine Comedy. The literary and historical analysis of cardiovascular signs and symptoms allows us to assume that clinical features due to alterations of heart function were probably known by medieval physicians, but their etiology and pathophysiological mechanisms were not completely understood in that period. Historians of cardiology and clinicians should consider analysis of non-medical texts (including poetry) as an opportunity to better investigate the evolution of their discipline throughout the ages.

  12. Differentiating Early Stage Cystic Keratoacanthoma, Nodular Basal Cell Carcinoma, and Excoriated Acne Vulgaris by Clinical Exam, Dermoscopy, and Optical Coherence Tomography: A Report of 3 Cases.

    PubMed

    Markowitz, Orit; Utz, Sarah

    2015-04-01

    Making accurate diagnoses when certain lesions are in a relatively young stage can prove challenging, as their "textbook descriptions" are often not fully apparent, and may in fact be markedly different. The authors present three interesting cases of early lesions that were clinically difficult to differentiate from one another: a cystic variation of a keratoacanthoma squamous cell carcinoma, a basal cell carcinoma, and an excoriated facial acne vulgaris. The subtle clinical nuances found in each of these cases demonstrated the importance of a careful clinical evaluation; however, this was not sufficient for adequate assessment of whether or not to biopsy. With early lesions such as these, the use of the noninvasive imaging modalities of dermoscopy and optical coherence tomography becomes critical in order to avoid unnecessary biopsy. The discussion of the clinically and dermoscopically challenging features is both instructive and enlightening. Oftentimes, "textbook descriptions" of lesions focus on the description of an already mature stage of growth, despite the fact that we continue to strive toward earlier detection of potential malignancies. With this in mind, the features found with optical coherence tomography proved essential to the elucidation of these difficult lesions. These three interesting cases illustrated the challenges encountered when dealing with early lesions specifically. The authors bring to light features in each of these cases that are often not thought of as being the "typical" presentation in each lesion category and demonstrate the clinical utility of noninvasive devices in difficult-to-diagnose cases such as these.

  13. Differentiating Early Stage Cystic Keratoacanthoma, Nodular Basal Cell Carcinoma, and Excoriated Acne Vulgaris by Clinical Exam, Dermoscopy, and Optical Coherence Tomography: A Report of 3 Cases

    PubMed Central

    Utz, Sarah

    2015-01-01

    Making accurate diagnoses when certain lesions are in a relatively young stage can prove challenging, as their “textbook descriptions” are often not fully apparent, and may in fact be markedly different. The authors present three interesting cases of early lesions that were clinically difficult to differentiate from one another: a cystic variation of a keratoacanthoma squamous cell carcinoma, a basal cell carcinoma, and an excoriated facial acne vulgaris. The subtle clinical nuances found in each of these cases demonstrated the importance of a careful clinical evaluation; however, this was not sufficient for adequate assessment of whether or not to biopsy. With early lesions such as these, the use of the noninvasive imaging modalities of dermoscopy and optical coherence tomography becomes critical in order to avoid unnecessary biopsy. The discussion of the clinically and dermoscopically challenging features is both instructive and enlightening. Oftentimes, “textbook descriptions” of lesions focus on the description of an already mature stage of growth, despite the fact that we continue to strive toward earlier detection of potential malignancies. With this in mind, the features found with optical coherence tomography proved essential to the elucidation of these difficult lesions. These three interesting cases illustrated the challenges encountered when dealing with early lesions specifically. The authors bring to light features in each of these cases that are often not thought of as being the “typical” presentation in each lesion category and demonstrate the clinical utility of noninvasive devices in difficult-to-diagnose cases such as these. PMID:26060518

  14. Validation of Transient Elastography and Comparison with Spleen Length Measurement for Staging of Fibrosis and Clinical Prognosis in Primary Sclerosing Cholangitis

    PubMed Central

    Ehlken, Hanno; Wroblewski, Raluca; Corpechot, Christophe; Arrivé, Lionel; Rieger, Tim; Hartl, Johannes; Lezius, Susanne; Hübener, Peter; Schulze, Kornelius; Zenouzi, Roman; Sebode, Marcial; Peiseler, Moritz; Denzer, Ulrike W.; Quaas, Alexander; Weiler-Normann, Christina; Lohse, Ansgar W.; Chazouilleres, Olivier; Schramm, Christoph

    2016-01-01

    Background Patients with primary sclerosing cholangitis (PSC) develop progressive liver fibrosis and end-stage liver disease. Non-invasive and widely available parameters are urgently needed to assess disease stage and the risk of clinical progression. Transient elastography (TE) has been reported to predict fibrosis stage and disease progression. However, these results have not been confirmed in an independent cohort and comparison of TE measurement to other non-invasive means is missing. Methods In a retrospective study we collected data from consecutive PSC patients receiving TE measurements from 2006 to 2014 (n = 139). Data from 62 patients who also underwent a liver biopsy were used to assess the performance of TE and spleen length (SL) measurement for the staging of liver fibrosis. Follow-up data from this cohort (n = 130, Hamburg) and another independent cohort (n = 80, Paris) was used to compare TE and SL as predictors of clinical outcome applying Harrel’s C calculations. Results TE measurement had a very good performance for the diagnosis and exclusion of higher fibrosis stages (≥F3: AUROC 0.95) and an excellent performance for the diagnosis and exclusion of cirrhosis (F4 vs. < F4: AUROC 0.98). Single-point TE measurement had very similar predictive power for patient outcome as previously published. In a combined cohort of PSC patients (n = 210), SL measurements had a similar performance as TE for the prediction of patient outcome (5 x cross-validated Harrel’s C 0.76 and 0.72 for SL and TE, respectively). Conclusions Baseline TE measurement has an excellent performance to diagnose higher fibrosis stages in PSC. Baseline measurements of SL and TE have similar usefulness as predictive markers for disease progression in patients with PSC. PMID:27723798

  15. The Articular Morphology of the First Carpometacarpal Joint Does Not Differ between Men and Women, but Changes with Aging and Early Stage Osteoarthritis

    PubMed Central

    Halilaj, Eni; Moore, Douglas C.; Laidlaw, David H.; Got, Christopher J.; Weiss, Arnold-Peter C.; Ladd, Amy L.; Crisco, Joseph J.

    2014-01-01

    The increased prevalence of thumb carpometacarpal (CMC) joint osteoarthritis (OA) in women has been previously linked to the articular morphology of the trapezium. However, studies report conflicting results on how the articular shapes of male and female trapezia compare to one another, mainly because their findings are based on data from older cadaver specimens. The purpose of this in vivo study was to dissociate the effect of sex from that of aging and early OA by using cohorts of healthy young and healthy older subjects, as well as patients with early stage OA. Computed tomography scans from 68 healthy subjects and 87 arthritic subjects were used to obtain 3-D bone models. The trapezial and metacarpal articular surfaces were manually delineated on scaled bone models, to remove the effect of size, and then were compared between sex, age, and health groups by using polar histograms of curvature and average curvature values. We found no sex differences, but significant age-group and health-group differences, in the articular surfaces of both bones. The older healthy subjects had higher curvature in the concave and lower curvature in the convex directions of both the trapezial and metacarpal saddles than the healthy young subjects. Subjects with early OA had significantly different metacarpal and trapezial articular shapes from healthy subjects. These findings suggest that aging and OA affect the articular shape of the CMC joint, but that, in contrast to previously held beliefs, inherent sex differences are not responsible for the higher incidence of CMC OA in women. PMID:24909332

  16. Modeling the Effects of Constant and Variable Temperatures on the Vital Rates of an Age-, Stage-, and Sex-Structured Population by Means of the SANDY Approach.

    PubMed

    Nachman, G; Gotoh, T

    2015-06-01

    We present a general and flexible mathematical model (called SANDY) that can be used to describe many biological phenomena, including the phenology of arthropods. In this paper, we demonstrate how the model can be fitted to vital rates (i.e., rates associated with development, survival, hatching, and oviposition) of the two-spotted spider mite (Tetranychus urticae (Koch)) exposed to different constant temperatures ranging from 15°C to 37.5°C. SANDY was incorporated into an age-, stage- and sex-structured dynamic model, which was fitted to cohort life-tables of T. urticae conducted at five constant temperatures (15, 20, 25, 30, and 35°C). Age- and temperature-dependent vital rates for the three main stages (eggs, immatures, and adults) constituting the life-cycle of mites were adequately described by the SANDY model. The modeling approach allows for simulating the growth of a population in a variable environment. We compared the predicted net reproductive rate (R0) and intrinsic rate of natural increase (rm) at fluctuating temperatures with empirical values obtained from life-table experiments conducted at temperatures that changed with a daily amplitude (±0, ±3, ±6, ±9, and ±12°C) around an average of 22°C. Results show that R0 decreases with increasing amplitude, while rm is more robust to variable temperatures. An advantage of SANDY is that the same simple mathematical expression can be applied to describe all the vital rates. Besides, the approach is not confined to modeling the influence of a single factor on population growth but allows for incorporating the combined effect of several limiting factors, provided that the combined effect of the factors is multiplicative.

  17. Radiotherapy for Early-Stage Hodgkin's Lymphoma: A 21st Century Perspective and Review of Multiple Randomized Clinical Trials

    SciTech Connect

    Bar Ad, Voichita Paltiel, Ora; Glatstein, Eli

    2008-12-01

    The treatment of Hodgkin's lymphoma has improved dramatically over the past decades. Over the last half century, Hodgkin's lymphoma has become one of the most curable cancers of adulthood. More than 90% of the patients with localized stages of the disease can be cured with modern treatment strategies. Long-term toxicities are now the major concern for survivors of early-stage disease. Contemporary therapeutic approaches for Hodgkin's lymphoma attempt to preserve the high cure rate achieved, while reducing treatment-related acute and late toxicities. The aim of this review is to re-examine the historical and the current role of radiotherapy for early-stage Hodgkin's lymphoma, given the latest evidence of an increasing role of chemotherapy for the treatment of this malignancy. The literature search was performed in PubMed Plus. Studies on children were excluded.

  18. The Mayo Clinic cohort study of personality and aging: design and sampling, reliability and validity of instruments, and baseline description.

    PubMed

    Rocca, Walter A; Grossardt, Brandon R; Peterson, Brett J; Bower, James H; Trenerry, Max R; Ahlskog, J Eric; Sanft, Kevin R; de Andrade, Mariza; Maraganore, Demetrius M

    2006-01-01

    We established a historical cohort of 7,216 subjects who completed the Minnesota Multiphasic Personality Inventory (MMPI) at the Mayo Clinic from 1962 through 1965 for research (not clinical indication), and who resided within a 120-mile radius centered in Rochester, Minnesota. We describe here the overall cohort design and sampling, we report results concerning reliability and validity, and we describe age and sex patterns at baseline for four MMPI scores of primary interest (depression, anxiety, social introversion, and negativity). Subjects excluded from the cohort because of missing data had MMPI scores similar to subjects included (after appropriate rescaling). A cut-off specific for age and sex at the 75th percentile of the distribution of raw scores was valid compared with the traditional clinical cut-off (T scores plus one standard deviation). Baseline scores for all four scales were higher in women than in men at all ages (all p < 0.0001). Depression and social introversion scores showed an increasing trend with age in both sexes (Spearman rank correlation, rho = 0.05 and 0.08, respectively, p < 0.0001 for both). Baseline scores on the anxiety scale showed a decreasing trend with age in both sexes (rho = -0.06, p < 0.0001). Negativity scores remained relatively stable with age in both sexes (rho = 0.03, p = 0.01). We found a high correlation between the anxiety score and the negativity score (rho = 0.90, p < 0.0001) even after the exclusion of overlapping items (rho = 0.68, p < 0.0001). This newly established historical cohort study provides opportunities to test hypotheses regarding the link between personality and aging, aging-related diseases, and overall mortality.

  19. Effect of {sup 18}F-FDG PET/CT Imaging in Patients With Clinical Stage II and III Breast Cancer

    SciTech Connect

    Groheux, David Moretti, Jean-Luc; Baillet, Georges; Espie, Marc; Giacchetti, Sylvie; Hindie, Elif; Hennequin, Christophe; Vilcoq, Jacques-Robert; Cuvier, Caroline; Toubert, Marie-Elisabeth; Filmont, Jean-Emmanuel; Sarandi, Farid; Misset, Jean-Louis

    2008-07-01

    Purpose: To investigate the potential effect of using {sup 18}F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) in the initial assessment of patients with clinical Stage II or III breast cancer. Methods and Materials: During 14 consecutive months, 39 patients (40 tumors) who presented with Stage II or III breast cancer on the basis of a routine extension assessment were prospectively included in this study. PET/CT was performed in addition to the initial assessment. Results: In 3 cases, PET/CT showed extra-axillary lymph node involvement that had not been demonstrated with conventional techniques. Two of these patients had hypermetabolic lymph nodes in the subpectoral and infraclavicular regions, and the third had a hypermetabolic internal mammary node. PET/CT showed distant uptake in 4 women. Of these 4 women, 1 had pleural involvement and 3 had bone metastasis. Overall, of the 39 women, the PET/CT results modified the initial stage in 7 (18%). The modified staging altered the treatment plan for 5 patients (13%). It led to radiotherapy in 4 patients (bone metastasis, pleural lesion, subpectoral lymph nodes, and internal mammary nodes) and excision of, and radiotherapy to, the infraclavicular lymph nodes in 1 patient. Conclusions: PET/CT can provide information on extra-axillary lymph node involvement and can uncover occult distant metastases in a significant percentage of patients. Therefore, initial PET/CT could enable better treatment planning for patients with Stage II and III breast cancer.

  20. Internal Consistency and Associated Characteristics of Informant Discrepancies in Clinic Referred Youths Age 11 to 17 Years

    ERIC Educational Resources Information Center

    De Los Reyes, Andres; Youngstrom, Eric A.; Pabon, Shairy C.; Youngstrom, Jennifer K.; Feeny, Norah C.; Findling, Robert L.

    2011-01-01

    In this study, we examined the internal consistency of informant discrepancies in reports of youth behavior and emotional problems and their unique relations with youth, caregiver, and family characteristics. In a heterogeneous multisite clinic sample of 420 youths (ages 11-17 years), high internal consistency estimates were observed across…

  1. Serum Adiponectin Levels, Neuroimaging, and Cognition in the Mayo Clinic Study of Aging

    PubMed Central

    Wennberg, Alexandra M. V.; Gustafson, Deborah; Hagen, Clinton E.; Roberts, Rosebud O.; Knopman, David; Jack, Clifford; Petersen, Ronald C.; Mielke, Michelle M.

    2016-01-01

    BACKGROUND Adiponectin, a protein involved in inflammatory pathways, may impact the development and progression of Alzheimer’s disease (AD). Adiponectin levels have been associated with mild cognitive impairment (MCI) and AD; however, its association with Alzheimer-associated neuroimaging and cognitive outcomes is unknown. OBJECTIVE Determine the cross-sectional association between plasma adiponectin and neuroimaging and cognitive outcomes in an older population-based sample. METHODS Multivariable adjusted regression models were used to investigate the association between plasma adiponectin and hippocampal volume (HVa), PiB-PET, FDG PET, cortical thickness, MCI diagnosis, and neuropsychological test performance. Analyses included 535 non-demented participants aged 70 and older enrolled in the Mayo Clinic Study of Aging. RESULTS Women had higher adiponectin than men (12,631 ng/mL vs. 8,908 ng/mL, P < .001). Among women, higher adiponectin was associated with smaller HVa (B=−0.595; 95% CI −1.19, −0.005), poorer performance in language (B−0.676; 95% CI −1.23, −0.121) and global cognition (B=−0.459; 95% CI −0.915, −0.002), and greater odds of a MCI diagnosis (OR=6.23; 95% CI 1.20, 32.43). In analyses stratified by sex and elevated amyloid (PiB-PET SUVR>1.4), among women with elevated amyloid, higher adiponectin was associated with smaller HVa (B=−0.723; 95% CI −1.43, −0.014), poorer performance in memory (B=−1.02; 95% CI −1.73, −0.312), language (B=−0.896; 95% CI −1.58, −0.212), and global (B=−0.650; 95% CI −1.18, −0.116) cognition, and greater odds of MCI (OR=19.34; 95% CI 2.72, 137.34). CONCLUSION Higher plasma adiponectin was associated with neuroimaging and cognitive outcomes among women. Longitudinal analyses are necessary to determine whether higher adiponectin predicts neurodegeneration and cognitive decline. PMID:27163809

  2. Quality of care and health-related quality of life of climacteric stage women cared for in family medicine clinics in Mexico

    PubMed Central

    2010-01-01

    Objectives 1) To design and validate indicators to measure the quality of the process of care that climacteric stage women receive in family medicine clinics (FMC). 2) To assess the quality of care that climacteric stage women receive in FMC. 3) To determine the association between quality of care and health-related quality of life (HR-QoL) among climacteric stage women. Methods The study had two phases: I. Design and validation of indicators to measure the quality of care process by using the RAND/UCLA Appropriateness Method. II. Evaluation of the quality of care and its association with HR-QoL through a cross-sectional study conducted in two FMC located in Mexico City that included 410 climacteric stage women. The quality of care was measured by estimating the percentage of recommended care received (PRCR) by climacteric stage women in three process components: health promotion, screening, and treatment. The HR-QoL was measured using the Cervantes scale (0-155). The association between quality of care and HR-QoL was estimated through multiple linear regression analysis. Results The lowest mean of PRCR was for the health promotion component (24.1%) and the highest for the treatment component (86.6%). The mean of HR-QoL was 50.1 points. The regression analysis showed that in the treatment component, for every 10 additional points of the PRCR, the global HR-QoL improved 2.8 points on the Cervantes scale (coefficient -0.28, P < 0.0001). Conclusion The indicators to measure quality of care for climacteric stage women are applicable and feasible in family medicine settings. There is a positive association between the quality of the treatment component and HR-QoL; this would encourage interventions to improve quality of care for climacteric stage women. PMID:20144238

  3. Improving Function in Age-Related Macular Degeneration: A Randomized Clinical Trial

    PubMed Central

    Rovner, Barry W.; Casten, Robin J.; Hegel, Mark T.; Massof, Robert W.; Leiby, Benjamin E.; Ho, Allen C.; Tasman, William S.

    2013-01-01

    Purpose To compare the efficacy of Problem-Solving Therapy (PST) with Supportive Therapy (ST) to improve Targeted Vision Function in Age-Related Macular Degeneration (AMD). Design Single-masked, attention controlled randomized clinical trial with outcome assessments at 3 months (main trial endpoint) and 6 months (maintenance effects). Participants Patients with AMD (N = 241) attending retina practices. Interventions PST uses a structured problem-solving approach to reduce vision-related task difficulty. ST is a standardized attention control treatment. Main Outcome Measures Targeted Vision Function (TVF); National Eye Institute Vision Function Questionnaire - 25 plus Supplement (NEI VFQ); Activities Inventory (AI); and Vision-Related Quality of Life. Results There were no significant between-group differences in TVF scores at 3 months (p = 0.47) or 6 months (p = 0.62). For PST subjects, mean [standard deviation (SD)] TVF scores improved from 2.71 (0.52) at baseline to 2.18 (0.88) at 3 months (p = 0.001) and were 2.18 (0.95) at 6 months (change from 3 to 6 months, p = .74). For ST subjects, TVF scores improved from 2.73 (0.52) at baseline to 2.14 (0.96) at 3 months (p = 0.001) and were 2.15 (0.96) at 6 months (change from 3 to 6 months, p = .85). Similar proportions of PST and ST subjects had less difficulty performing a TVF goal at 3 months (77.4% vs. 78.6%, respectively; p = 0.83) and 6 months (76.2% vs. 79.1%, respectively; p = 0.61). There were no significant changes in the NEI VFQ or AI. Vision-related quality-of-life improved for PST relative to ST subjects at 3 months [F (4,192) = 2.46; p = 0.05] and 6 months [F (4,178) = 2.55; p = 0.05)]. PST subjects also developed more adaptive coping strategies than ST subjects. Conclusions We found that PST was not superior to ST at improving vision function in patients with AMD but PST improved their vision-related quality of life. Despite the benefits of anti-vascular endothelial growth factor (anti-VEGF) treatments

  4. Diaphragmatic pathology: a cause of clinically unexplained death in the perinatal/paediatric age group.

    PubMed

    Sundararajan, S; Ostojic, N S; Rushton, D I; Cox, P M; Acland, P

    2005-04-01

    Sudden unexpected death in infancy and childhood requires a 'full' post-mortem investigation. Guidance from the Royal College of Pathologists recommends sampling of all the major organs. However, the diaphragm does not feature in this or in most lists of routine histology. Our aim is to emphasize the importance of sampling the diaphragm for histological examination during autopsy. We describe three autopsy cases of clinically unexplained death in the perinatal and paediatric age group that showed significant pathology of the diaphragm. In Case 1, a previously healthy five-year-old girl collapsed suddenly and died four days later. In Case 2, an eight-month-old infant had repeated episodes of respiratory arrest that culminated in death. Autopsy demonstrated a predominantly diaphragmatic myositis. In Case 3 a female neonate had a respiratory arrest three days after birth and died less than a month later. Autopsy showed multiple large calcified necrotic fibres in the diaphragm. The diaphragm is seldom sampled at autopsy. In the first two cases a predominantly diaphragmatic myositis was either the direct or underlying cause of death. In the third case long-standing diaphragmatic pathology of uncertain cause may have contributed to the original respiratory arrest. Had the diaphragm not been examined histologically, the cause of death would have remained unascertained in these cases. In cases of sudden death in infancy and childhood, failure to reach a diagnosis may lead to undue suspicion falling upon the child's carers. This underscores the need for full histology at post-mortem in child deaths, including diaphragmatic sampling.

  5. Gamma-delta T cell responses in subclinical and clinical stages of Bovine Mycobacterium Avium Paratuberculosis infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The early immune response to Mycobacterium avium subsp. paratuberculosis (MAP) in cattle is characterized by a Th1-like immune response effective in controlling bacterial proliferation during the subclinical stage of infection. In young calves nearly 60% of circulating lymphocytes are gamma delta T ...

  6. Circulating ECV-Associated miRNAs as Potential Clinical Biomarkers in Early Stage HBV and HCV Induced Liver Fibrosis

    PubMed Central

    Lambrecht, Joeri; Jan Poortmans, Pieter; Verhulst, Stefaan; Reynaert, Hendrik; Mannaerts, Inge; van Grunsven, Leo A.

    2017-01-01

    Introduction: Chronic hepatitis B (HBV) and C (HCV) virus infection is associated with the activation of hepatic stellate cells (HSCs) toward a myofibroblastic phenotype, resulting in excessive deposition of extracellular matrix, the development of liver fibrosis, and its progression toward cirrhosis. The gold standard for the detection and staging of liver fibrosis remains the liver biopsy, which is, however, associated with some mild and severe drawbacks. Other non-invasive techniques evade these drawbacks, but lack inter-stage specificity and are unable to detect early stages of fibrosis. We investigated whether circulating vesicle-associated miRNAs can be used in the diagnosis and staging of liver fibrosis in HBV and HCV patients. Methods: Plasma samples were obtained from 14 healthy individuals and 39 early stage fibrotic patients (F0–F2) with chronic HBV or HCV infection who underwent transient elastography (Fibroscan). Extracellular vesicles were extracted from the plasma and the level of miRNA-122, -150, -192, -21, -200b, and -92a was analyzed by qRT-PCR in total plasma and circulating vesicles. Finally, these same miRNAs were also quantified in vesicles extracted from in vitro activating primary HSCs. Results: In total plasma samples, only miRNA-200b (HBV: p = 0.0384; HCV: p = 0.0069) and miRNA-122 (HBV: p < 0.0001; HCV: p = 0.0007) were significantly up-regulated during early fibrosis. In circulating vesicles, miRNA-192 (HBV: p < 0.0001; HCV: p < 0.0001), -200b (HBV: p < 0.0001; HCV: p < 0.0001), -92a (HBV: p < 0.0001; HCV: p < 0.0001), and -150 (HBV: p = 0.0016; HCV: p = 0.004) displayed a significant down-regulation in both HBV and HCV patients. MiRNA expression profiles in vesicles isolated from in vitro activating primary mouse HSCs resembled the miRNA expression profile in circulating vesicles. Conclusion: Our analysis revealed a distinct miRNA expression pattern in total plasma and its circulating vesicles. The expression profile of miRNAs in

  7. Circulating ECV-Associated miRNAs as Potential Clinical Biomarkers in Early Stage HBV and HCV Induced Liver Fibrosis.

    PubMed

    Lambrecht, Joeri; Jan Poortmans, Pieter; Verhulst, Stefaan; Reynaert, Hendrik; Mannaerts, Inge; van Grunsven, Leo A

    2017-01-01

    Introduction: Chronic hepatitis B (HBV) and C (HCV) virus infection is associated with the activation of hepatic stellate cells (HSCs) toward a myofibroblastic phenotype, resulting in excessive deposition of extracellular matrix, the development of liver fibrosis, and its progression toward cirrhosis. The gold standard for the detection and staging of liver fibrosis remains the liver biopsy, which is, however, associated with some mild and severe drawbacks. Other non-invasive techniques evade these drawbacks, but lack inter-stage specificity and are unable to detect early stages of fibrosis. We investigated whether circulating vesicle-associated miRNAs can be used in the diagnosis and staging of liver fibrosis in HBV and HCV patients. Methods: Plasma samples were obtained from 14 healthy individuals and 39 early stage fibrotic patients (F0-F2) with chronic HBV or HCV infection who underwent transient elastography (Fibroscan). Extracellular vesicles were extracted from the plasma and the level of miRNA-122, -150, -192, -21, -200b, and -92a was analyzed by qRT-PCR in total plasma and circulating vesicles. Finally, these same miRNAs were also quantified in vesicles extracted from in vitro activating primary HSCs. Results: In total plasma samples, only miRNA-200b (HBV: p = 0.0384; HCV: p = 0.0069) and miRNA-122 (HBV: p < 0.0001; HCV: p = 0.0007) were significantly up-regulated during early fibrosis. In circulating vesicles, miRNA-192 (HBV: p < 0.0001; HCV: p < 0.0001), -200b (HBV: p < 0.0001; HCV: p < 0.0001), -92a (HBV: p < 0.0001; HCV: p < 0.0001), and -150 (HBV: p = 0.0016; HCV: p = 0.004) displayed a significant down-regulation in both HBV and HCV patients. MiRNA expression profiles in vesicles isolated from in vitro activating primary mouse HSCs resembled the miRNA expression profile in circulating vesicles. Conclusion: Our analysis revealed a distinct miRNA expression pattern in total plasma and its circulating vesicles. The expression profile of miRNAs in

  8. Hypofractionated High-Dose Proton Beam Therapy for Stage I Non-Small-Cell Lung Cancer: Preliminary Results of A Phase I/II Clinical Study

    SciTech Connect

    Hata, Masaharu . E-mail: mhata@syd.odn.ne.jp; Tokuuye, Koichi; Kagei, Kenji; Sugahara, Shinji; Nakayama, Hidetsugu; Fukumitsu, Nobuyoshi; Hashimoto, Takayuki; Mizumoto, Masashi; Ohara, Kiyoshi; Akine, Yasuyuki

    2007-07-01

    Purpose: To present treatment outcomes of hypofractionated high-dose proton beam therapy for Stage I non-small-cell lung cancer (NSCLC). Methods and Materials: Twenty-one patients with Stage I NSCLC (11 with Stage IA and 10 with Stage IB) underwent hypofractionated high-dose proton beam therapy. At the time of irradiation, patient age ranged from 51 to 85 years (median, 74 years). Nine patients were medically inoperable because of comorbidities, and 12 patients refused surgical resection. Histology was squamous cell carcinoma in 6 patients, adenocarcinoma in 14, and large cell carcinoma in 1. Tumor size ranged from 10 to 42 mm (median, 25 mm) in maximum diameter. Three and 18 patients received proton beam irradiation with total doses of 50 Gy and 60 Gy in 10 fractions, respectively, to primary tumor sites. Results: Of 21 patients, 2 died of cancer and 2 died of pneumonia at a median follow-up period of 25 months. The 2-year overall and cause-specific survival rates were 74% and 86%, respectively. All but one of the irradiated tumors were controlled during the follow-up period. Five patients showed recurrences 6-29 months after treatment, including local progression and new lung lesions outside of the irradiated volume in 1 and 4 patients, respectively. The local progression-free and disease-free rates were 95% and 79% at 2 years, respectively. No therapy-related toxicity of Grade {>=}3 was observed. Conclusions: Hypofractionated high-dose proton beam therapy seems feasible and effective for Stage I NSCLC. Proton beams may contribute to enhanced efficacy and lower toxicity in the treatment of patients with Stage I NSCLC.

  9. Healing of 400 intra-alveolar root fractures. 1. Effect of pre-injury and injury factors such as sex, age, stage of root development, fracture type, location of fracture and severity of dislocation.

    PubMed

    Andreasen, J O; Andreasen, F M; Mejàre, I; Cvek, M

    2004-08-01

    This retrospective study consisted of 400 root-fractured, splinted or non-splinted incisors in young individuals aged 7-17 years (mean = 11.5 +/- 2.7 SD) who were treated in the period 1959-1995 at the Department of Pediatric Dentistry, Eastman Dental Institute, Stockholm. Four hundred of these root fractures were diagnosed at the time of injury; and 344 teeth were splinted with either cap-splints, orthodontic appliances, bonded metal wires, proximal bonding with composite resin or bonding with a Kevlar or glass fiber splint. In 56 teeth, no splinting was carried out for various reasons. In the present study, only pre-injury and injury factors were analyzed. In a second study, treatment variables will be analyzed. The average observation period was 3.1 years +/- 2.6 SD. The clinical and radiographic findings showed that 120 teeth out of 400 teeth (30%) had healed by hard tissue fusion of the fragments. Interposition of periodontal ligament (PDL) and bone between fragments was found in 22 teeth (5%), whereas interposition of PDL alone was found in 170 teeth (43%). Finally, non-healing, with pulp necrosis and inflammatory changes between fragments, was seen in 88 teeth (22%). In a univariate and multivariate stratified analysis, a series of clinical factors were analyzed for their relation to the healing outcome with respect to pulp healing vs. pulp necrosis and type of healing (hard tissue vs. interposition of bone and/or PDL or pulp necrosis). Young age, immature root formation and positive pulp sensibility at the time of injury were found to be significantly and positively related to both pulpal healing and hard tissue repair of the fracture. The same applied to concussion or subluxation (i.e. no displacement) of the coronal fragment compared to extrusion or lateral luxation (i.e. displacement). Furthermore, no mobility vs. mobility of the coronal fragment. Healing was progressively worsened with increased millimeter diastasis between fragments. Sex was a

  10. Stage IV and age over 45 years are the only prognostic factors of the International Prognostic Score for the outcome of advanced Hodgkin lymphoma in the Spanish Hodgkin Lymphoma Study Group series.

    PubMed

    Guisado-Vasco, Pablo; Arranz-Saez, Reyes; Canales, Miguel; Cánovas, Araceli; Garcia-Laraña, José; García-Sanz, Ramón; Lopez, Andrés; López, José Luis; Llanos, Marta; Moraleda, José Maria; Rodriguez, José; Rayón, Consuelo; Sabin, Pilar; Salar, Antonio; Marín-Niebla, Ana; Morente, Manuel; Sánchez-Godoy, Pedro; Tomás, José Francisco; Muriel, Alfonso; Abraira, Victor; Piris, Miguel A; Garcia, Juán F; Montalban, Carlos

    2012-05-01

    The International Prognostic Score (IPS) is the most widely used system to date for identifying risk groups for the outcome of patients with advanced Hodgkin lymphoma, although important limitations have been recognized. We analyzed the value of the IPS in a series of 311 patients with advanced classical Hodgkin lymphoma (cHL) (Ann Arbor stage III, IV or stage II with B symptoms and/or bulky masses) treated with first-line chemotherapy including adriamycin (adriamycin, bleomycin, vinblastine, dacarbazine [ABVD] or equivalent variants). In univariate and multivariate analyses, stage IV disease and age ≥ 45 years were the only factors with independent predictive significance for overall survival (OS) (p = 0.002 and p < 0.001, respectively). Stage IV was still significant for freedom from progression (FFP) (p = 0.001) and age ≥ 45 years was borderline significant (p = 0.058). IPS separates prognostic groups, as in the original publication, but this is mainly due to the high statistical significance of stage IV and age ≥ 45 years. Moreover, the combination of these two factors enables a simpler system to be constructed that separates groups with different FFP and OS. In conclusion, in our series, stage IV and age ≥ 45 years are the key prognostic factors for the outcome of advanced cHL.

  11. Clinical outcomes of CyberKnife stereotactic radiosurgery for elderly patients with presumed primary stage I lung cancer

    PubMed Central

    Wang, Zhen; Li, Ao-Mei; Gao, Jie; Li, Jing; Li, Bing; Lee, Percy; Simone, Charles B.; Song, Yong

    2017-01-01

    Background In certain situations, especially in the elderly patient population, a tissue diagnosis of a suspected pulmonary neoplasm is not feasible. Often, a definitive treatment such as stereotactic body radiosurgery is recommended, rather than active surveillance. The aim of this study is to evaluate the efficacy and tolerability of stereotactic body radiotherapy (SBRT) for elderly patients with presumed primary stage I lung cancer without pathological tissue confirmation. Methods We performed a retrospective analysis of 25 elderly patients (≥75 years) with presumed primary stage I lung cancer treated with SBRT from 2009–2015. The primary end point was local control (LC); secondary end points were survival and toxicity. Results The median follow-up (FU) was 36.0 months (range, 4 to 84 months). The 1-year LC rate was 100%, 3-year LC rate was 78.8%, and 5-year LC rate was 65.7%. The median progression-free survival (PFS) time was 48.0 months (95% CI: 31.2–64.8). The 1-, 3-, and 5-year overall survival (OS) rates were 96.0%, 70.2%, and 50.7%, respectively. The 1-, 3-, and 5-year cancer-specific survival (CSS) rates were 100%, 81.3%, and 67.0%, respectively. No grade 4 or higher toxicity was encountered. Conclusions SBRT is safe and effective treatment for patients with presumed primary stage I lung cancer where obtaining pathological confirmation of malignancy is challenging. PMID:28331819

  12. Long-term Survival and Clinical Benefit from Adoptive T-cell Transfer in Stage IV Melanoma Patients Is Determined by a Four-Parameter Tumor Immune Signature.

    PubMed

    Melief, Sara M; Visconti, Valeria V; Visser, Marten; van Diepen, Merel; Kapiteijn, Ellen H W; van den Berg, Joost H; Haanen, John B A G; Smit, Vincent T H B M; Oosting, Jan; van der Burg, Sjoerd H; Verdegaal, Els M E

    2017-02-01

    The presence of tumor-infiltrating immune cells is associated with longer survival and a better response to immunotherapy in early-stage melanoma, but a comprehensive study of the in situ immune microenvironment in stage IV melanoma has not been performed. We investigated the combined influence of a series of immune factors on survival and response to adoptive cell transfer (ACT) in stage IV melanoma patients. Metastases of 73 stage IV melanoma patients, 17 of which were treated with ACT, were studied with respect to the number and functional phenotype of lymphocytes and myeloid cells as well as for expression of galectins-1, -3, and -9. Single factors associated with better survival were identified using Kaplan-Meier curves and multivariate Cox regression analyses, and those factors were used for interaction analyses. The results were validated using The Cancer Genome Atlas database. We identified four parameters that were associated with a better survival: CD8(+) T cells, galectin-9(+) dendritic cells (DC)/DC-like macrophages, a high M1/M2 macrophage ratio, and the expression of galectin-3 by tumor cells. The presence of at least three of these parameters formed an independent positive prognostic factor for long-term survival. Patients displaying this four-parameter signature were found exclusively among patients responding to ACT and were the ones with sustained clinical benefit. Cancer Immunol Res; 5(2); 170-9. ©2017 AACR.

  13. Radiotherapy With 8-MHz Radiofrequency-Capacitive Regional Hyperthermia for Stage III Non-Small-Cell Lung Cancer: The Radiofrequency-Output Power Correlates With the Intraesophageal Temperature and Clinical Outcomes

    SciTech Connect

    Ohguri, Takayuki Imada, Hajime; Yahara, Katsuya; Morioka, Tomoaki; Nakano, Keita; Terashima, Hiromi; Korogi, Yukunori

    2009-01-01

    Purpose: To assess the efficacy of radiotherapy (RT) combined with regional hyperthermia (HT) guided by radiofrequency (RF)-output power and intraesophageal temperature and evaluate the potential contribution of HT to clinical outcomes in patients with Stage III non-small-cell lung cancer (NSCLC). Methods and Materials: Thirty-five patients with Stage III NSCLC treated with RT plus regional HT were retrospectively analyzed. Twenty-two of the 35 patients underwent intraesophageal temperature measurements. Patients with subcutaneous fat of 2.5 cm or greater, older age, or other serious complications did not undergo this therapy. The 8-MHz RF-capacitive heating device was applied, and in all patients, both the upper and lower electrodes were 30 cm in diameter, placed on opposite sides of the whole thoracic region, and treatment posture was the prone position. The HT was applied within 15 minutes after RT once or twice a week. Results: All thermal parameters, minimum, maximum, and mean of the four intraesophageal temperature measurements at the end of each session and the proportion of the time during which at least one of the four intraesophageal measurements was 41{sup o}C or higher in the total period of each session of HT, of the intraesophageal temperature significantly correlated with median RF-output power. Median RF-output power ({>=}1,200 W) was a statistically significant prognostic factor for overall, local recurrence-free, and distant metastasis-free survival. Conclusions: The RT combined with regional HT using a higher RF-output power could contribute to better clinical outcomes in patients with Stage III NSCLC. The RF-output power thus may be used as a promising parameter to assess the treatment of deep regional HT if deep heating using this device is performed with the same size electrodes and in the same body posture.

  14. Age-dependent parathormone levels and different CKD-MBD treatment practices of dialysis patients in Hungary - results from a nationwide clinical audit

    PubMed Central

    2013-01-01

    Background Achieving target levels of laboratory parameters of bone and mineral metabolism in chronic kidney disease (CKD) patients is important but also difficult in those living with end-stage kidney disease. This study aimed to determine if there are age-related differences in chronic kidney disease-mineral and bone disorder (CKD-MBD) characteristics, including treatment practice in Hungarian dialysis patients. Methods Data were collected retrospectively from a large cohort of dialysis patients in Hungary. Patients on hemodialysis and peritoneal dialysis were also included. The enrolled patients were allocated into two groups based on their age (<65 years and ≥65 years). Characteristics of the age groups and differences in disease-related (epidemiology, laboratory, and treatment practice) parameters between the groups were analyzed. Results A total of 5008 patients were included in the analysis and the mean age was 63.4±14.2 years. A total of 47.2% of patients were women, 32.8% had diabetes, and 11.4% were on peritoneal dialysis. Diabetes (37.9% vs 27.3%), bone disease (42.9% vs 34.1%), and soft tissue calcification (56.3% vs 44.7%) were more prevalent in the older group than the younger group (p<0.001 for all). We found an inverse relationship between age and parathyroid hormone (PTH) levels (p<0.001). Serum PTH levels were lower in patients with diabetes compared with those without diabetes below 80 years (p<0.001). Diabetes and age were independently associated with serum PTH levels (interaction: diabetes × age groups, p=0.138). Older patients were more likely than younger patients to achieve laboratory target ranges for each parameter (Ca: 66.9% vs 62.1%, p<0.001; PO4: 52.6% vs 49.2%, p<0.05; and PTH: 50.6% vs 46.6%, p<0.01), and for combined parameters (19.8% vs 15.8%, p<0.001). Older patients were less likely to receive related medication than younger patients (66.9% vs 79.7%, p<0.001). Conclusions The achievement of laboratory target ranges for bone

  15. [Clinical curative efficacy of inducing remission for the newly diagnosed aged AML patients by chemotherapy with IA and DA regimens].

    PubMed

    Tian, Dong-Hua; Gan, Si-Lin; Xing, Hai-Zhou; Liu, Yan-Fang; Xie, Xin-Sheng; Sun, Hui

    2014-10-01

    This study was aimed to explore the clinical efficacy and toxicity of idarubicin (IA regimen) and daunoru-bicin combined with cytarabine (DA regimen) for treating aged patients with AML as induction chemotherapy. The clinical data of 60 newly diagnosed AML aged patients treated with IA or DA regimen were analyzed retrospectively. IA regimen group included 22 patients (8 male and 14 females with median age of 66 yrs), while the DA regimen group included 38 patients (20 males and 18 females with median age of 64 yrs). The complete remission rate, total effective rate and adverse effects after one chemotherapy course were compared. The results showed that the CR rate in IA regimen group was 63.63%, which was significantly higer than that in DA regimen group (31.58%) (P < 0.05). The total effective rate was 63.63% and 36.84% respectively in IA and DA regimen groups, there was significant difference between the two groups (P < 0.05). Both the hematological and non-hematological adverse effects were observed and no difference was found in the two regimen groups, neither in myelosupression (P > 0.05), the major hematological adverse effects, nor in non-hematological adverse effects (P > 0.05). It is concluded that for aged AML patients, IA regimen can achieve a higher CR rate and higher total effective rate than that in DA regimen without increase of adverse effects after one induction chemotherapy course.

  16. Spontaneous Pathology and Routine Clinical Pathology Parameters in Aging Beagle Dogs: A Comparison With Adolescent and Young Adults.

    PubMed

    Barnes, J; Cotton, P; Robinson, S; Jacobsen, M

    2016-03-01

    AstraZeneca ran a bespoke study to generate age-matched clinical pathology and histopathology data from a cohort of Beagle dogs aged between 25 and 37 months to support the use of these older animals in routine preclinical toxicology studies. As the upper age range of Beagle dogs routinely used in toxicology studies does not normally exceed 24 months, there is an absence of appropriate age-matched historical control data. The generation of such data was crucial to understand whether age-related differences in spontaneous findings might confound the interpretation of toxicology study data. While the majority of the histopathology findings in all the older dogs occurred at a similar prevalence as those expected in young adult dogs (<24 months), a number of differences were observed in the thymus (involution), bone marrow (increased adiposity), testes (degenerative changes), and lung (fibrosis, pigment and alveolar hyperplasia) that could be misinterpreted as a test article effect. Minor differences in some clinical pathology values (hemoglobin, alkaline phosphatase, absolute reticulocytes) were of a small magnitude and considered unlikely to affect the interpretation of study data.

  17. Targeting chronic lymphocytic leukemia using CIGB-300, a clinical-stage CK2-specifc cell-permeable peptide inhibitor

    PubMed Central

    Martins, Leila R.; Perera, Yasser; Lúcio, Paulo; Silva, Maria G.; Perea, Silvio E.; Barata, João T.

    2014-01-01

    Chronic lymphocytic leukemia (CLL) remains an incurable malignancy, urging for the identifcation of new molecular targets for therapeutic intervention. CLL cells rely on overexpression and hyperactivation of the ubiquitous serine/threonine protein kinase CK2 for their viability in vitro. CIGB-300 is a cell-permeable selective CK2 inhibitor peptide undergoing clinical trials for several cancers. Here, we show that CIGB-300 promotes activation of the tumor suppressor PTEN and abrogates PI3K-mediated downstream signaling in CLL cells. In accordance, CIGB-300 decreases the viability and proliferation of CLL cell lines, promotes apoptosis of primary leukemia cells and displays antitumor efcacy in a xenograft mouse model of human CLL. Our studies provide pre-clinical support for the testing and possible inclusion of CK2 inhibitors in the clinical arsenal against CLL. PMID:24473900

  18. Management of multivessel coronary disease after primary angioplasty: staged reintervention versus optimized clinical treatment and two-year follow-up

    PubMed Central

    de Paula, José Guilherme Rodrigues; de Godoy, Moacir Fernandes; dos Santos, Márcio Antônio; Pivatelli, Flávio Corrêa; Osti, Alan Vinicius Gamero; Trindade, Luciano Folchine; Novelli, Diego; Nakazone, Marcelo Arruda

    2014-01-01

    Objective In the clinical scenario of ST-segment elevation acute myocardial infarction, several patients with multivessel coronary atherosclerotic disease are discharged without a defined strategy to monitor the residual atherosclerotic lesions. The clinical endpoints evaluated were cardiovascular death, symptoms of angina pectoris, rehospitalization for a new acute coronary syndrome, and the necessity of reintervention during the two-year follow-up. Methods This observational, prospective, and historical study included multivessel coronary atherosclerotic disease patients who were admitted to a tertiary care university hospital with ST-segment elevation acute myocardial infarction and underwent primary percutaneous coronary intervention with stent implantation only at the culprit lesion site; these patients were monitored in the outpatient clinic according to two treatments: the Clinical Group - CG (optimized pharmacological therapy associated with counseling for a healthy diet and cardiac rehabilitation) or the Intervention Group - IG (new staged percutaneous coronary intervention or surgical coronary artery bypass graft surgery combined with the previously prescribed treatment). Results Of 143 patients consecutively admitted with ST-segment elevation acute myocardial infarction, 57 were eligible for the study (CG=44 and IG=13). Regarding the clinical endpoints, the cardiovascular death rate did not differ between the CG and IG. The symptom of angina pectoris and the rehospitalization rate for a new episode of acute coronary syndrome were accentuated in the CG (P=0.020 and P=0.049, respectively) mainly in individuals with evidence of ischemia evidenced by myocardial scintigraphy (P<0.001 and P=0.001, respectively) which culminated in an even greater need for reintervention (P=0.001) in this subgroup of patients. Conclusion The staged intervention was demonstrated to be safe and able to reduce angina pectoris and rehospitalization for a new episode of acute

  19. Clinical intervention in aging: ethicolegal issues in assessing risk and benefit

    PubMed Central

    Mallia, Pierre

    2010-01-01

    The ethical dimension of treating the elderly, including risk–benefit analysis, focuses mainly on quality of life and end-of-life issues. These include arguments on advance directives and the concept of extraordinary treatments. This paper looks more closely at the philosophical approach to aging in order to address questions on the direction of research and issues such as longevity and social construction of the aging process. It is the way society moves to understand the value-laden choices on aging that directs the goals of treatment and research. Whilst these vary culturally, one has to reckon with a postmodern view of aging which may, in turn, reflect on the course of action of future care and research in aging. The paper canvasses how, in reality, four principles act as guidelines for moral discourse, and discusses how changing values in society decide this course of action. PMID:21152239

  20. [Postoperative Adjuvant Chemotherapy for Stage III Colon Cancer--Drug Selection, Tolerability, and Safety in Clinical Practice].

    PubMed

    Okada, Kazutake; Sadahiro, Sotaro; Saito, Gota; Tanaka, Akira; Suzuki, Toshiyuki

    2016-05-01

    In the National Comprehensive Cancer Network (NCCN) guidelines, oxaliplatin (L-OHP)-based chemotherapeutic regimens, including 5-fluorouracil, Leucovorin (LV), and L-OHP (FOLFOX); capecitabine and L-OHP (CapeOX); and 5-fluorouracil, folinic acid, and L-OHP (FLOX) are designated as category 1 recommendations for postoperative adjuvant chemotherapy in Stage III colon cancer, followed by capecitabine and 5-fluorouracil plus LV as category 2A recommendations. We studied the selection of drugs for adjuvant chemotherapy and assessed the tolerability and safety of CapeOX and tegafur-uracil (UFT) plus LV (UFT/LV) in patients with Stage III colon cancer. The study group included 104 consecutive patients with Stage III colon cancer who underwent curative surgery. One patient changed hospitals immediately after surgery. Among the remaining 103 patients, 82 (80%) received adjuvant chemotherapy and 21 (20%) did not. CapeOX was administered to 32 patients (31%), UFT/LV to 49 patients (48%), and capecitabine to 1 patient (1%). In 59 patients, the treatment choice was determined according to the patient's preference; 32 patients (54%) selected CapeOX, 26 (44%) selected UFT/LV, and 1 (2%) selected no chemotherapy. The treatment completion rate was 80% for CapeOX and 84% for UFT/LV. Among patients who completed chemotherapy, dose reduction and drug withdrawal were not required in 22% of patients who received CapeOX and 80% of those who received UFT/LV. Neither CapeOX nor UFT/LV was associated with any serious adverse events. The tolerability and safety of CapeOX and UFT/LV were acceptable. However, CapeOX dose had to be carefully adjusted according to each patient's condition.

  1. Detection of Occult Micrometastases in Patients With Clinical Stage I Non–Small-Cell Lung Cancer: A Prospective Analysis of Mature Results of CALGB 9761 (Alliance)

    PubMed Central

    D’Cunha, Jonathan; Wang, Xiaofei; Herzan, Debra; Gu, Lin; Abraham, Naif; Demmy, Todd L.; Detterbeck, Frank C.; Groth, Shawn S.; Harpole, David H.; Krasna, Mark J.; Kernstine, Kemp; Kohman, Leslie J.; Patterson, G. Alexander; Sugarbaker, David J.; Vollmer, Robin T.; Maddaus, Michael A.; Kratzke, Robert A.

    2016-01-01

    Purpose Outcomes after resection of stage I non–small-cell lung cancer (NSCLC) are variable, potentially due to undetected occult micrometastases (OM). Cancer and Leukemia Group B 9761 was a prospectively designed study aimed at determining the prognostic significance of OM. Materials and Methods Between 1997 and 2002, 502 patients with suspected clinical stage I (T1-2N0M0) NSCLC were prospectively enrolled at 11 institutions. Primary tumor and lymph nodes (LNs) were collected and sent to a central site for molecular analysis. Both were assayed for OM using immunohistochemistry (IHC) for cytokeratin (AE1/AE3) and real-time reverse transcriptase polymerase chain reaction (RT-PCR) for carcinoembryonic antigen. Results Four hundred eighty-nine of the 502 enrolled patients underwent complete surgical staging. Three hundred four patients (61%) had pathologic stage I NSCLC (T1, 58%; T2, 42%) and were included in the final analysis. Fifty-six percent had adenocarcinomas, 34% had squamous cell carcinomas, and 10% had another histology. LNs from 298 patients were analyzed by IHC; 41 (14%) were IHC-positive (42% in N1 position, 58% in N2 position). Neither overall survival (OS) nor disease-free survival was associated with IHC positivity; however, patients who had IHC-positive N2 LNs had statistically significantly worse survival rates (hazard ratio, 2.04, P = .017). LNs from 256 patients were analyzed by RT-PCR; 176 (69%) were PCR-positive (52% in N1 position, 48% in N2 position). Neither OS nor disease-free survival was associated with PCR positivity. Conclusion NSCLC tumor markers can be detected in histologically negative LNs by AE1/AE3 IHC and carcinoembryonic antigen RT-PCR. In this prospective, multi-institutional trial, the presence of OM by IHC staining in N2 LNs of patients with NSCLC correlated with decreased OS. The clinical significance of this warrants further investigation. PMID:26926677

  2. Impact of multiple caregiving roles on elevated depressed mood in early-stage breast cancer patients and same-age controls

    PubMed Central

    Bailey, Ellen H.; Pérez, Maria; Aft, Rebecca L.; Liu, Ying; Schootman, Mario; Jeffe, Donna B.

    2010-01-01

    The effect of caregiving roles on risk of elevated depressed mood over 12 months was examined in early-stage (0–IIA) breast cancer patients and same-aged women without breast cancer. Women were interviewed 4–6 weeks, 6 months, and 12 months following definitive surgical treatment (patients) or routine screening mammogram (controls). The Center for Epidemiologic Studies-Depression Scale was administered at each interview and dichotomized for analysis (<16 [little/no depressed mood] vs. ≥16 [elevated depressed mood]). Participants were categorized as having no caregiving responsibilities, care-giving for children or other persons, or caregiving for both children and others (multiple caregiving roles). Two multivariable marginal logistic regression models with repeated measures were fit (one each for patients and controls) to examine the effect of caregiving roles on elevated depressed mood, using generalized estimating equations to account for intra-individual correlations. Of 1096 participants (mean age 58; 76% white), 1019 with caregiving data were included in the analysis. Compared with baseline, patients with multiple caregiving roles (23/521 patients) were at increased risk of elevated depressed mood at 6 months (adjusted odds ratio [aOR], 7.20; 95% confidence interval [CI], 1.17–44.46; P = 0.034), and controls with multiple caregiving roles (15/498 controls) were at decreased risk of elevated depressed mood at 12-month follow-up (aOR, 0.12; 95% CI, 0.02–0.97; P = 0.047). Patients with multiple caregiving roles were more likely while controls were less likely to report elevated depressed mood over time, suggesting a need to identify patients with multiple caregiving roles early during their treatment. PMID:19936914

  3. Links between Disorganized Attachment Classification and Clinical Symptoms in School-Aged Children

    ERIC Educational Resources Information Center

    Borelli, Jessica L.; David, Daryn H.; Crowley, Michael J.; Mayes, Linda C.

    2010-01-01

    Research examining the links between disorganized attachment and clinical symptoms largely has neglected middle childhood due to lack of available measurement tools. The few studies that have examined these links in other developmental phases have found higher clinical symptoms in disorganized individuals. Our study extended this research by using…

  4. Clinical Approach to the Heavy Cannabis User in the Age of Medical Marijuana.

    PubMed

    Cermak, Timmen L

    2016-01-01

    This article begins with a case vignette exemplifying the common clinical problem of heavy marijuana users. The epidemiology and basic science underlying cannabis dependence is outlined, followed by clinical strategies for basing a therapeutic alliance on known research findings and using motivational interviewing to deal with typical patterns of denial.

  5. Stimulating Healthy Aging with a Model Nurse-Managed Free Clinic in a Senior Center.

    ERIC Educational Resources Information Center

    Franklin, Ruth H.

    As part of a Geriatric Education and Health Management program, a model nurse-managed free clinic has been established at an urban senior center by faculty and students of the University of New Mexico College of Nursing. Funded by a 3-year grant from the Department of Health and Human Services, the weekly clinic is based on Orem's self-care theory…

  6. Clinical aspects of pregnancy after the age of 35 years: a review of the literature.

    PubMed

    van Katwijk, C; Peeters, L L

    1998-01-01

    The objective of this report is to provide an update of our current knowledge about the impact of maternal age on pregnancy outcome. Pregnancy in women > or =35 years old is associated with a higher maternal and perinatal mortality. The older gravida also has a higher chance of being delivered by Caesarean section. Most of the complications associated with older age are caused by age-related confounders such as leiomyomas, type II diabetes, hypertension and multiparity. Diabetes and hypertension increase almost linearly with age. Pregnant women with diabetes or hypertension are at increased risk of adverse pregnancy outcome irrespective of age. The currently available literature indicates that premenopausal pregnant women of advanced age who are in good health do not need special care besides the normal obstetric practice. At present, establishing pregnancy in postmenopausal women is more an ethical than a medical issue, partly because the information reported on pregnancy in postmenopausal women is insufficient to determine a reliable risk profile. In these women cardiovascular ageing accelerates. Therefore, until proven otherwise, postmenopausal women should be considered particularly at increased risk for vascular complications during pregnancy. This risk is likely to increase progressively with the number of years elapsed since the onset of postmenopause.

  7. A randomized two-stage design for phase II clinical trials based on a Bayesian predictive approach.

    PubMed

    Cellamare, Matteo; Sambucini, Valeria

    2015-03-15

    The rate of failure in phase III oncology trials is surprisingly high, partly owing to inadequate phase II studies. Recently, the use of randomized designs in phase II is being increasingly recommended, to avoid the limits of studies that use a historical control. We propose a two-arm two-stage design based on a Bayesian predictive approach. The idea is to ensure a large probability, expressed in terms of the prior predictive probability of the data, of obtaining a substantial posterior evidence in favour of the experimental treatment, under the assumption that it is actually more effective than the standard agent. This design is a randomized version of the two-stage design that has been proposed for single-arm phase II trials by Sambucini. We examine the main features of our novel design as all the parameters involved vary and compare our approach with Jung's minimax and optimal designs. An illustrative example is also provided online as a supplementary material to this article.

  8. Dosimetric and Clinical Outcomes of Involved-Field Intensity-Modulated Radiotherapy After Chemotherapy for Early-Stage Hodgkin's Lymphoma With Mediastinal Involvement

    SciTech Connect

    Lu Ningning; Li Yexiong; Wu Runye; Zhang Ximei; Wang Weihu; Jin Jing; Song Yongwen; Fang Hui; Ren Hua; Wang Shulian; Liu Yueping; Liu Xinfan; Chen Bo; Dai Jianrong; Yu Zihao

    2012-09-01

    Purpose: To evaluate the dosimetric and clinical outcomes of involved-field intensity-modulated radiotherapy (IF-IMRT) for patients with early-stage Hodgkin's lymphoma (HL) with mediastinal involvement. Methods and Materials: Fifty-two patients with early-stage HL that involved the mediastinum were reviewed. Eight patients had Stage I disease, and 44 patients had Stage II disease. Twenty-three patients (44%) presented with a bulky mediastinum, whereas 42 patients (81%) had involvement of both the mediastinum and either cervical or axillary nodes. All patients received combination chemotherapy followed by IF-IMRT. The prescribed radiation dose was 30-40 Gy. The dose-volume histograms of the target volume and critical normal structures were evaluated. Results: The median mean dose to the primary involved regions (planning target volume, PTV1) and boost area (PTV2) was 37.5 Gy and 42.1 Gy, respectively. Only 0.4% and 1.3% of the PTV1 and 0.1% and 0.5% of the PTV2 received less than 90% and 95% of the prescribed dose, indicating excellent PTV coverage. The median mean lung dose and V20 to the lungs were 13.8 Gy and 25.9%, respectively. The 3-year overall survival, local control, and progression-free survival rates were 100%, 97.9%, and 96%, respectively. No Grade 4 or 5 acute or late toxicities were reported. Conclusions: Despite the large target volume, IF-IMRT gave excellent dose coverage and a favorable prognosis, with mild toxicity in patients with early-stage mediastinal HL.

  9. Trends in 'cure' fraction from colorectal cancer by age and tumour stage between 1975 and 2000, using population-based data, Osaka, Japan.

    PubMed

    Ito, Yuri; Nakayama, Tomio; Miyashiro, Isao; Sugimoto, Tomoyuki; Ioka, Akiko; Tsukuma, Hideaki; Abdel-Rahman, Manar E; Rachet, Bernard

    2012-10-01

    Since the 1960s, Japan has experienced a striking increase in the incidence of colorectal cancer, now the second most common cancer in the country. Meanwhile, the management of colorectal cancer has changed dramatically with the implementation of, for example, screening, endoscopy and adjuvant chemotherapy. It is therefore of interest to monitor the long-term trends in population 'cure' in Japan. We analysed 33 885 colorectal cancer cases diagnosed between 1975 and 2000 in Osaka. We applied the multivariable mixture cure model to estimate cure fraction and median survival time (MST) for 'uncured' patients, by sex, age, stage, period at diagnosis and subsite. For colon cancer, the cure fraction increased by about 25%, while MST for the uncured was prolonged from 8 to 12 months. The cure fraction was 5% higher in men than in women, while MST was similar in both. The cure fraction also increased for localized and regional tumours. For rectal cancer, the cure fraction increased by about 25-30%, but remained lower than for colon cancer. From the late 1970s, the cure fraction for colorectal cancer increased dramatically due to better management of detection and care for colorectal cancer. This improvement was obtained at the cost of shorter MST for uncured patients.

  10. Age-related changes in protein metabolism of beech (Fagus sylvatica L.) seeds during alleviation of dormancy and in the early stage of germination.

    PubMed

    Ratajczak, Ewelina; Kalemba, Ewa M; Pukacka, Stanislawa

    2015-09-01

    The long-term storage of seeds generally reduces their viability and vigour. The aim of this work was to evaluate the effect of long-term storage on beech (Fagus sylvatica L.) seeds at optimal conditions, over 9 years, on the total and soluble protein levels and activity of proteolytic enzymes, including endopeptidases, carboxypeptidases and aminopeptidases, as well as free amino acid levels and protein synthesis, in dry seeds, after imbibition and during cold stratification leading to dormancy release and germination. The same analyses were conducted in parallel on seeds gathered from the same tree in the running growing season and stored under the same conditions for only 3 months. The results showed that germination capacity decreased from 100% in freshly harvested seeds to 75% in seeds stored for 9 years. The levels of total and soluble proteins were highest in freshly harvested seeds and decreased significantly during storage, these proportions were retained during cold stratification and germination of seeds. Significant differences between freshly harvested and stored seeds were observed in the activities of proteolytic enzymes, including endopeptidases, aminopeptidases and carboxypeptidases, and in the levels of free amino acids. The neosynthesis of proteins during dormancy release and in the early stage of seed germination was significantly weaker in stored seeds. These results confirm the importance of protein metabolism for seed viability and the consequences of its reduction during seed ageing.

  11. Age, Predisposing Diseases, and Ultrasonographic Findings in Determining Clinical Outcome of Acute Acalculous Inflammatory Gallbladder Diseases in Children

    PubMed Central

    2016-01-01

    We evaluated clinical factors such as age, gender, predisposing diseases and ultrasonographic findings that determine clinical outcome of acute acalculous inflammatory gallbladder diseases in children. The patients were divided into the four age groups. From March 2004 through February 2014, clinical data from 131 children diagnosed as acute acalculous inflammatory gallbladder disease by ultrasonography were retrospectively reviewed. Systemic infectious diseases were the most common etiology of acute inflammatory gallbladder disease in children and were identified in 50 patients (38.2%). Kawasaki disease was the most common predisposing disease (28 patients, 21.4%). The incidence was highest in infancy and lowest in adolescence. The age groups were associated with different predisposing diseases; noninfectious systemic disease was the most common etiology in infancy and early childhood, whereas systemic infectious disease was the most common in middle childhood and adolescence (P = 0.001). Gallbladder wall thickening was more commonly found in malignancy (100%) and systemic infection (94.0%) (P = 0.002), whereas gallbladder distension was more frequent in noninfectious systemic diseases (60%) (P = 0.000). Ascites seen on ultrasonography was associated with a worse clinical course compared with no ascites (77.9% vs. 37.7%, P = 0.030), and the duration of hospitalization was longer in patients with ascites (11.6 ± 10.7 vs. 8.0 ± 6.6 days, P = 0.020). In conclusion, consideration of age and predisposing disease in addition to ultrasonographic gallbladder findings in children suspected of acute acalculous inflammatory gallbladder disease might result in better outcomes. PMID:27550491

  12. Influence of Age and Dose of African Swine Fever Virus Infections on Clinical Outcome and Blood Parameters in Pigs.

    PubMed

    Post, Jacob; Weesendorp, Eefke; Montoya, Maria; Loeffen, Willie L

    African swine fever (ASF) is a fatal disease for domestic pigs, leading to serious economic losses in countries where ASF is endemic. Despite extensive research, efficient vaccines against ASF are lacking. Since peripheral blood cells are important mediators for vaccines, we study the impact of ASF on blood parameters in pigs with different ages and infected with different doses of ASF virus. Four different groups were studied: (1) 12 weeks of age/low virus dose; (2) 12 weeks of age/high virus dose; (3) 18 weeks of age/low virus dose; and (4) 18 weeks of age/high virus dose. By varying in age and/or ASFV inoculation dose, we monitor blood parameters during different degrees of disease. Thirty percent of the pigs survived the infection with a moderately virulent strain of African swine fever virus (ASFV). Animals that did survive infection were generally older, independent from the inoculation dose used. A firm reduction in many different cell types at 3-5 days postinfection (DPI) was accompanied by an increase in body temperature, followed by clinical signs and mortality from day 6 PI. While blood parameters generally normalized in survivors, γδ T cells and IL-10 levels could be related to mortality. These conclusions should be considered in new approaches for protection against ASF.

  13. Does aging of mesenchymal stem cells limit their potential application in clinical practice?

    PubMed

    Bajek, Anna; Czerwinski, Mateusz; Olkowska, Joanna; Gurtowska, Natalia; Kloskowski, Tomasz; Drewa, Tomasz

    2012-10-01

    Mesenchymal stem cells (MSCs) are in the center of attention of many investigators due to easy isolation from many tissues. MSC capability to differentiate into many cell types makes them a starting point of many new therapies, especially in tissue engineering. However, understanding the process of MSC aging is crucial for selecting donors for cellular therapies, which is necessary for successful treatment. Cell changes can be divided into three major groups. Changes which affect their proliferate rate, differentiation capability and genome stability lead to decrease of their usefulness in new therapies. There are many tools that can be used to describe and measure some features of aging in MSCs but the essence of this process is still unclear. The aim of this review is to take a deep look into the influence of donor age and in vitro aging on MSC properties.

  14. The controversy over the age of blood: what do the clinical trials really teach us?

    PubMed

    Belpulsi, Danamarie; Spitalnik, Steven L; Hod, Eldad A

    2017-03-01

    Red blood cell transfusions have been used in clinical practice for decades and represent the most common therapeutic procedure performed in hospitalised patients. Depending on the storage solution and national regulatory requirements, red blood cells can be stored in the refrigerator up to 42 days before transfusion. We reviewed five of the most recent randomised clinical trials that examined clinical outcomes in specific patient populations. Although these studies provide some comfort regarding our current standard of care, they do not address whether the oldest blood is associated with harm in certain patient populations.

  15. The controversy over the age of blood: what do the clinical trials really teach us?

    PubMed Central

    Belpulsi, Danamarie; Spitalnik, Steven L.; Hod, Eldad A.

    2017-01-01

    Red blood cell transfusions have been used in clinical practice for decades and represent the most common therapeutic procedure performed in hospitalised patients. Depending on the storage solution and national regulatory requirements, red blood cells can be stored in the refrigerator up to 42 days before transfusion. We reviewed five of the most recent randomised clinical trials that examined clinical outcomes in specific patient populations. Although these studies provide some comfort regarding our current standard of care, they do not address whether the oldest blood is associated with harm in certain patient populations. PMID:28263167

  16. Developmental stages in human embryos: revised and new measurements.

    PubMed

    O'Rahilly, Ronan; Müller, Fabiola

    2010-01-01

    The staging of human embryos, as distinct from seriation, depends on a morphological scheme devised by Streeter and completed by O'Rahilly, who proposed the term Carnegie stages. To avoid misconceptions and errors, and to place new findings in perspective, it is necessary to summarize the essentials of the Carnegie system: (1) Twenty-three stages cover the embryonic period, i. e. the first 8 postfertilizational weeks of development. (2) The system is based on internal as well as external features, and the use of only external criteria is subject to serious limitations. For example, precise delineation of stages 19-23 and of the embryonic-fetal transition depends on histological examination. (3) Prenatal measurements are not an integral component of the staging system, and hence a stage should never be assigned merely on the basis of embryonic length. A 20-mm embryo, for example, could belong to any of three stages. Measurements, however, are important for the assessment of age, and very few measurements are available for staged embryos. Presented here and based on accurate staging are the maximum diameter of the chorionic sac, the crown-heel length, the greatest length exclusive of the lower limbs, the biparietal diameter, the head circumference, the length of the hindbrain, the total length of the brain, and the lengths of the limbs as well as of their segments, including the foot length. (4) Prenatal ages are also not an integral part of the staging system and hence a stage should never be assigned merely on the basis of prenatal age. Ages, however, are of clinical importance and their estimate has been rendered more precise by accurate timing of fertilization followed by ultrasonography. Prenatal age is postfertilizational and hence some 2 weeks less than the postmenstrual interval. The term gestational age is ambiguous and should be discarded. Presented here is a new graph showing proposed estimates of age in relation to stages and based on current information.

  17. [Clinical, biochemical and anthropometric studies and determination of biological age in relation to body mass in a longitudinal study].

    PubMed

    Hunecke, I; Reuter, W; Sauer, I; Ries, W

    1989-01-15

    On 46 adipose persons (25 males and 21 females) and 53 test persons with normal weight (35 males and 18 females) at the age of 25-40 years since 1976 clinical, biochemical and anthropometric investigations as well as the determination of the biological age have annually been performed. Several of the parameters established (e.g. cholesterol, triglycerides, fasting blood sugar, blood pressure among others) in the course of 9 years within the well-known normal regions draw towards the adequate valid limit value to the pathological entity. The results of the study distinctly show the central role of obesity for the development of risk factors. Despite the partly only with a certain tendency recognizable behaviour of single parameters after 9 years from our point of view the longitudinal method represents itself as a very well suitable method for establishing dynamic processes and risk factors of age.

  18. Clinical evidence of intravitreal triamcinolone acetonide in the management of age-related macular degeneration.

    PubMed

    Becerra, E M; Morescalchi, F; Gandolfo, F; Danzi, P; Nascimbeni, G; Arcidiacono, B; Semeraro, F

    2011-02-01

    Triamcinolone acetonide (TA) is one of the first pharmacologic compounds evaluated for the treatment of choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). The most important effects of TA consist in the stabilisation of the blood-retinal barrier and the down-regulation of inflammation. TA also has anti-angiogenic and anti-fibrotic properties. The peculiar characteristic of being well tolerated by ocular tissues and the capability to remain active for many months after a single intravitreal injection, make this drug a safe and effective alternative. In the past decade, intravitreal injection of TA (IVTA) has emerged as a useful treatment of several ocular diseases such as uveitis, macular edema secondary to retinal vasculature disease, neovascularisation and vitreoretinopathy. In this paper, we review all the available evidence of its use in AMD as mono-therapy or in combination with other treatments, and we discuss which role TA will play in the treatment of AMD in the future. The first experiences with IVTA as monotherapy for the treatment of exudative AMD reported a positive outcome in transiently reducing the leakage from CNV. However, in the long-term follow-up, IVTA as monotherapy had no effect on the risk of severe visual acuity loss, despite a significant anti-angiogenic effect found 3 months after the treatment. Consequently, studies using the combination of IVTA and photodynamic therapy (PDT), which acts synergistically, were performed. They reported to improve vision and to reduce the number of re-treatments with PDT. A large number of publications confirmed the positive synergic role of combining TA and PDT (therapies) for the treatment of all types of CNV: classic or predominantly classic, occult or minimally classic and RAP (Retinal Angiomatous Proliferation) lesions. The advantages registered with the use of IVTA plus PDT compared to PDT alone were partially limited by the side effects, such as the rapid evolution

  19. Clustering of Subgingival Microbiota Reveals Microbial Disease Ecotypes Associated with Clinical Stages of Periodontitis in a Cross-Sectional Study

    PubMed Central

    Boutin, Sébastien; Hagenfeld, Daniel; Zimmermann, Heiko; El Sayed, Nihad; Höpker, Tanja; Greiser, Halina K.; Becher, Heiko; Kim, Ti-Sun; Dalpke, Alexander H.

    2017-01-01

    Periodontitis is characterized by chronic inflammation associated with alteration of the oral microbiota. In contrast to previous microbiome studies focusing a priori on comparison between extreme phenotypes, our study analyzed a random sample of 85 people. The aim of this study was to link microbial differences to disease’s prevalence and severity. Using next generation sequencing of 16S rRNA amplicons and cluster analysis, we observed that the population can be divided into two major ecotypes: One mainly contained periodontal healthy/mild periodontitis individuals whereas the second ecotype showed a heterogeneous microbial distribution and clustered into three distinct sub-ecotypes. Those sub-ecotypes differed with respect to the frequency of diseased patients and displayed a gradual change in distinct subgingival microbiota that goes along with clinical disease symptoms. In ecotype 2, the subgroup with no clinical signs of disease was linked to an increase of F. nucleatum vincentii but also several other species, while only in “end-stage” dysbiosis classical red complex bacteria gained overweight. Therefore, the microbial disease ecotypes observed in our population can lead to an establishment of an early microbial risk profile for clinically healthy patients. PMID:28298910

  20. Transforming Clinical Education in Obstetrics and Gynecology: Gone Is the Day of the Sage on the Stage.

    PubMed

    Smith, Marshall L; Foley, Michael R

    2016-04-01

    Many traditional approaches to clinical education today are outdated and inefficient with disruptive changes on the horizon. Millennials are the new wave of learners in health care and do not learn the same way as their older faculty. Merging health care systems are moving to standardizations of care and reduction of errors, and health care providers are going to be increasingly held more accountable for their clinical outcomes. Computers, digitalization, and connectivity are revolutionizing learning environments, and simulation learning in the form of trainers, mannequins, and team training is already widespread. Newer technologies like virtual and augmented reality are beginning to be used for clinical education and will be a more efficient and standardized way of providing simulation learning. Emerging technologies like holograms and head-mounted displays will follow soon after and be even more disruptive. Faculty and mentors will always be crucial to learning in health care but will be empowered to teach in more focused and comprehensive ways. The educational model of the future will be a hybrid model of experienced faculty, interactive learning, and innovative and emerging technology. It is time we start to train health care providers for their future, not our past.

  1. Non-Randomized Confirmatory Trial of Laparoscopy-Assisted Total Gastrectomy and Proximal Gastrectomy with Nodal Dissection for Clinical Stage I Gastric Cancer: Japan Clinical Oncology Group Study JCOG1401

    PubMed Central

    Kataoka, Kozo; Mizusawa, Junki; Katayama, Hiroshi; Nakamura, Kenichi; Morita, Shinji; Yoshikawa, Takaki; Ito, Seiji; Kinoshita, Takahiro; Fukagawa, Takeo; Sasako, Mitsuru

    2016-01-01

    Several prospective studies on laparoscopy-assisted distal gastrectomy for early gastric cancer have been initiated, but no prospective study evaluating laparoscopy-assisted total gastrectomy or laparoscopy-assisted proximal gastrectomy has been completed to date. A non-randomized confirmatory trial was commenced in April 2015 to evaluate the safety of laparoscopy-assisted total gastrectomy and laparoscopy-assisted proximal gastrectomy for clinical stage I gastric cancer. A total of 245 patients will be accrued from 42 Japanese institutions over 3 years. The primary endpoint is the proportion of patients with anastomotic leakage. The secondary endpoints are overall survival, relapse-free survival, proportion of patients with completed laparoscopy-assisted total gastrectomy or laparoscopy-assisted proximal gastrectomy, proportion of patients with conversion to open surgery, adverse events, and short-term clinical outcomes. The UMIN Clinical Trials Registry number is UMIN000017155. PMID:27433394

  2. Treatment response for acute depression is not associated with number of previous episodes: lack of evidence for a clinical staging model for major depressive disorder.

    PubMed

    Dodd, Seetal; Berk, Michael; Kelin, Katarina; Mancini, Michele; Schacht, Alexander

    2013-09-05

    Mental illness has been observed to follow a neuroprogressive course, commencing with prodrome, then onset, recurrence and finally chronic illness. In bipolar disorder and schizophrenia responsiveness to treatment mirrors these stages of illness progression, with greater response to treatment in the earlier stages of illness and greater treatment resistance in chronic late stage illness. Using data from 5627 participants in 15 controlled trials of duloxetine, comparator arm (paroxetine, venlafaxine, escitalopram) or placebo for the treatment of an acute depressive episode, the relationship between treatment response and number of previous depressive episodes was determined. Data was dichotomised for comparisons between participants who had >3 previous episodes (n=1697) or ≤3 previous episodes (n=3930), and additionally for no previous episodes (n=1381) or at least one previous episode (n=4246). Analyses were conducted by study arm for each clinical trial, and results were then pooled. There was no significant difference between treatment response and number of previous depressive episodes. This unexpected finding suggests that treatments to reduce symptoms of depression during acute illness do not lose efficacy for patients with a longer history of illness.

  3. Analysis of the pX region of bovine leukemia virus in different clinical stages of Enzootic Bovine Leukemia in Argentine Holstein cattle.

    PubMed

    Panei, Carlos Javier; Serena, María Soledad; Metz, Germán Ernesto; Bravi, María Emilia; González, Ester Teresa; Echeverría, María Gabriela

    2013-01-01

    Bovine leukemia virus (BLV) infection in cattle causes Enzootic Bovine Leukemia (EBL). About 30% of infected cattle develop persistent lymphocytosis (PL), a 0.1-5% develops tumors, and a 70% remains asymptomatic in an aleukemic stage (AL). Regulatory genes of BLV (Tax, Rex, R3 and G4) are located in a region known as pX(BLV). The variability of those genes had been postulated with the progression of the disease. The aim of this work was to compare the wild-type proviral pX(BLV) region at different stages of BLV natural infected cattle from Argentine Holstein. Pairs of primers were designed to amplify the proviral pX region of 12 cattle by PCR, and products were then sequenced, aligned and compared both with each other and with the reference sequence. Results show a divergence percentage from 0 to 6.1 for the Tax gene, from 0 to 9.4% for the Rex gene, from 0 to 12.1% for the R3 gene and finally from 0 to 6.5% for the G4 gene. Results obtained with hierarchical clustering showed two clusters well differentiated, where the members of each cluster are cattle that had tumor, PL and AL, not allowing differentiate those two cluster by clinical stage.

  4. Incidence and Effects of Polypharmacy on Clinical Outcome among Patients Aged 80+: A Five-Year Follow-Up Study

    PubMed Central

    Fan, Li; Gao, Dewei; Liang, Zhiru; He, Jing; Gong, Weiqin; Gao, Linggen

    2015-01-01

    Objectives Polypharmacy is a problem of growing interest in geriatrics with the increase in drug consumption in recent years, is defined according to the WHO criteria as the, ‘‘concurrent use of five or more different prescription medication”. We investigated the clinical characteristics of polypharmacy and identified the effects of polypharmacy on clinical outcome among patients aged 80+ admitted to Chinese PLA general hospital. Methods Older men aged ≥80 years (n = 1562) were included in this study. The included participants attended a structured clinical examination and an interview carried out by a geriatrician and trained nurses. A follow-up survey in 2014 was carried out on survivors in the same way as in 2009. The clinical outcome measured were adverse drug reactions, falls, frailty, disability, cognitive impairment, mortality. The association between polypharmacy and clinical outcome was assessed by logistic regression. Results The mean (range) age of the included participants was 85.2 (80–104) years. Medication exposure was reported by 100% of the population. Mean number of medications reported in this population was 9.56±5.68. The prevalence of polypharmacy (≥6 medications) in the present study was 70%. At the time of the follow-up survey, an increase in the number of taken medicines had occurred among half of the survivors. The risk of different outcomes in relation to number of medications rises significantly, the odds ratios were 1.21 (95% confidence interval [CI]1.17–1.28) for adverse drug reactions, 1.18 (95% CI 1.10–1.26) for falls, 1.16 (95% CI 1.09–1.24) for disability, and 1.19 (95% CI 1.12–1.23) for mortality. There was no association between increasing number of medications and cognitive impairment. Conclusions Our study demonstrates that polypharmacy is very common in the very old patients, and observed that number of medications was a factor associated with difference clinical outcome independently of the age, type of

  5. Clinical pharmacokinetics of new-generation antiepileptic drugs at the extremes of age: an update.

    PubMed

    Italiano, Domenico; Perucca, Emilio

    2013-08-01

    Epilepsies occur across the entire age range, and their incidence peaks in the first years of life and in the elderly. Therefore, antiepileptic drugs (AEDs) are commonly used at the extremes of age. Rational prescribing in these age groups requires not only an understanding of the drugs' pharmacodynamic properties, but also careful consideration of potential age-related changes in their pharmacokinetic profile. The present article, which updates a review published in 2006 in this journal, focuses on recent findings on the pharmacokinetics of new-generation AEDs in neonates, infants, children, and the elderly. Significant new information on the pharmacokinetics of new AEDs in the perinatal period has been acquired, particularly for lamotrigine and levetiracetam. As a result of slow maturation of the enzymes involved in glucuronide conjugation, lamotrigine elimination occurs at a particularly slow rate in neonates, and becomes gradually more efficient during the first months of life. In the case of levetiracetam, elimination occurs primarily by renal excretion and is also slow at birth, but drug clearance increases rapidly thereafter and can even double within 1 week. In general, infants older than 2-3 months and children show higher drug clearance (normalized for body weight) than adults. This pattern was confirmed in recent studies that investigated the pediatric pharmacokinetics of several new AEDs, including levetiracetam, rufinamide, stiripentol, and eslicarbazepine acetate. At the other extreme of age, in the elderly, drug clearance is generally reduced compared with younger adults because of less efficient drug-metabolizing activity, decreased renal function, or both. This general pattern, described previously for several AEDs, was confirmed in recent studies on the effect of old age on the clearance of felbamate, levetiracetam, pregabalin, lacosamide, and retigabine. For those drugs which are predominantly eliminated by renal excretion, aging

  6. Clinical Value of Natriuretic Peptides in Predicting Time to Dialysis in Stage 4 and 5 Chronic Kidney Disease Patients

    PubMed Central

    Sundqvist, Sofia; Larson, Thomas; Cauliez, Bruno; Bauer, Fabrice; Dumont, Audrey; Le Roy, Frank; Hanoy, Mélanie; Fréguin-Bouilland, Caroline; Godin, Michel

    2016-01-01

    Background Anticipating the time to renal replacement therapy (RRT) in chronic kidney disease (CKD) patients is an important but challenging issue. Natriuretic peptides are biomarkers of ventricular dysfunction related to poor outcome in CKD. We comparatively investigated the value of B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) as prognostic markers for the risk of RRT in stage 4 and 5 CKD patients, and in foretelling all-cause mortality and major cardiovascular events within a 5-year follow-up period. Methods Baseline plasma BNP (Triage, Biosite) and NT-proBNP (Elecsys, Roche) were measured at inclusion. Forty-three patients were followed-up during 5 years. Kaplan-Meier analysis, with log-rank testing and hazard ratios (HR), were calculated to evaluate survival without RRT, cardiovascular events or mortality. The independent prognostic value of the biomarkers was estimated in separate Cox multivariate analysis, including estimated glomerular filtration rate (eGFR), creatininemia and comorbidities. Results During the first 12-month follow-up period, 16 patients started RRT. NT-proBNP concentration was higher in patients who reached endpoint (3221 ng/L vs 777 ng/L, p = 0.02). NT-proBNP concentration > 1345 ng/L proved significant predictive value on survival analysis for cardiovascular events (p = 0.04) and dialysis within 60 months follow-up (p = 0.008). BNP concentration > 140 ng/L was an independent predictor of RRT after 12 months follow-up (p<0.005), and of significant predictive value for initiation of dialysis within 60 months follow-up. Conclusions Our results indicate a prognostic value for BNP and NT-proBNP in predicting RRT in stage 4 and 5 CKD patients, regarding both short- and long-term periods. NT-proBNP also proved a value in predicting cardiovascular events. Natriuretic peptides could be useful predictive biomarkers for therapeutic guidance in CKD. PMID:27548064

  7. Treatment of liver cancer of middle and advanced stages using ultrasound-guided percutaneous ethanol injection combined with radiofrequency ablation: A clinical analysis

    PubMed Central

    SUN, XUE; LI, RU; ZHANG, BOTAO; YANG, YUEJIE; CUI, ZHIFEI

    2016-01-01

    Liver cancer is a malignancy of the digestive system and has a high morbidity and mortality rate. Local intervention has become a viable option in identifying liver treatment. The aim of the present study was to analyze the clinical effects of treating liver cancer in middle and advanced stages using ultrasound-guided percutaneous ethanol injection (PEI) in tumors combined with radiofrequency ablation (RFA). A total of 100 patients with stage III–IV liver cancers were selected to participate in the study. Patients were divided into groups. In group A, treatment was initiated with PEI and after 1–2 weeks RFA was applied while in group B treatment was initiated with RFA and after 1–2 weeks PEI was applied. Patients in group C received PEI and RFA simultaneously. The clinical effects in the 3 groups were compared after 6-month follow ups. The volume of tumor ablation necrosis in group A was significantly greater than that in the groups B and C, while the size was significantly smaller compared to groups B and C after ablation. For group A, the complete ablation rate was significantly higher than that in groups B and C, and the differences were statistically significant (P<0.05). Liver damage indices, including raising levels of glutamic-pyruvic transaminase and total bilirubin, were significantly decreased in group A (P<0.05). The survival rate in group A was also significantly higher than in groups B and C (P<0.05). In conclusion, for patients with liver cancer in middle and advanced stages, the treatment method using PEI followed by RFA was more beneficial in terms of improving the tumor ablation rate, alleviating liver damages and increasing survival rates. PMID:26998128

  8. Quantitative clinical pharmacology for size and age scaling in pediatric drug development: A systematic review.

    PubMed

    Samant, Tanay S; Mangal, Naveen; Lukacova, Viera; Schmidt, Stephan

    2015-11-01

    The establishment of drug dosing in children is often hindered by the lack of actual pediatric efficacy and safety data. To overcome this limitation, scaling approaches are frequently employed to leverage adult clinical information for informing pediatric dosing. The objective of this review is to provide a comprehensive overview of the different scaling approaches used in pediatric pharmacotherapy as well as their proper implementation in drug development and clinical use. We will start out with a brief overview of the current regulatory requirements in pediatric drug development, followed by a review of the most commonly employed scaling approaches in increasing order of complexity ranging from simple body weight-based dosing to physiologically-based pharmacokinetic (PBPK) modeling approaches. Each of the presented approaches has advantages and limitations, which will be highlighted throughout the course of the review by the use of clinically-relevant examples. The choice of the approach employed consequently depends on the clinical question at hand and the availability of sufficient clinical data. The main effort while establishing and qualifying these scaling approaches should be directed towards the development of safe and effective dosing regimens in children rather than identifying the best model, ie models should be fit for purpose.

  9. Aging modifies the effect of GCH1 RS11158026 on DAT uptake and Parkinson's disease clinical severity.

    PubMed

    Webb, Joseph; Willette, Auriel A

    2017-02-01

    Novel single nucleotide polymorphisms within Parkinson's disease (PD) can predict disease risk, but their influence on clinical, cognitive, and neurobiological indices remains unexplored. We investigated differences between functional polymorphisms at RS11158026 coding for guanosine triphosphate cyclohydrolase-1 (GCH1), an essential enzyme for dopamine production in nigrostriatal cells. Among newly diagnosed, untreated PD subjects and age-matched controls from the Parkinson's Progression Markers Initiative, T allele carriers showed higher PD risk (odds ratio = 1.23, p = 0.048), earlier age of onset by 5 years (p = 0.003), and lower striatal dopamine reuptake transporter uptake (p = 0.003). Carriers also had increased cerebrospinal fluid α-synuclein (p = 0.016), worse motor function (p = 0.041), anxiety (p = 0.038), and executive function (p < 0.001). Strikingly, these effects were only in younger T carriers (<50 years), where aging quells the effects of these genetic factors. This suggests GCH1 variants affect early PD risk through altered dopamine uptake, and aging alters how genetic factors contribute to disease development. Future studies should investigate how aging modifies genotypes' contributions on PD risk and sequelae.

  10. The embodied and relational nature of the mind: implications for clinical interventions in aging individuals and populations

    PubMed Central

    Rejeski, W Jack; Gauvin, Lise

    2013-01-01

    Considerable research over the past decade has garnered support for the notion that the mind is both embodied and relational. Jointly, these terms imply that the brain, physical attributes of the self, and features of our interpersonal relationships and of the environments in which we live jointly regulate energy and information flow; they codetermine how we think, feel, and behave both individually and collectively. In addition to direct experience, evidence supports the view that stimuli embedded within past memories trigger multimodal simulations throughout the body and brain to literally recreate lived experience. In this paper, we review empirical support for the concept of an embodied and relational mind and then reflect on the implications of this perspective for clinical interventions in aging individuals and populations. Data suggest that environmental influences literally “get under the skin” with aging; that musculoskeletal and visceral sensations become more prominent in activities of the mind due to aging biological systems and chronic disease. We argue that conceiving the mind as embodied and relational will grow scientific inquiry in aging, transform how we think about the self-system and well-being, and lead us to rethink health promotion interventions aimed at aging individuals and populations. PMID:23776330

  11. Volume cerebral blood flow reduction in pre-clinical stage of Alzheimer disease: evidence from an ultrasonographic study.

    PubMed

    Maalikjy Akkawi, Nabil; Borroni, B; Agosti, C; Magoni, M; Broli, M; Pezzini, A; Padovani, A

    2005-05-01

    The association of decreased cerebral blood flow with the development of Alzheimer's disease (AD) has been a recent target of interest. By using neuroimaging techniques, growing attention has been devoted to the identification of preclinical AD. In this study, color duplex sonography of cervical arteries was used to measure mean cerebral blood flow (CBF) on 55 amnestic Mild Cognitive Impairment (MCI) patients. Two years after enrollment, excluding patients who progressed to dementia other than AD, two subgroups were identified, patients who developed AD (MCI converters) and patients with preserved cognitive and functional level (MCI non-converters). Examining the mean difference of CBF measured at baseline in the two subgroups obtained, a significant difference was noticed (MCI converters 539.3 +/- 114.3 vs MCI non converters 636.0 +/- 143.9, p < 0.05). MCI patients with CBF higher than median value (558 ml/min) had lower risk of developing AD (specificity 72.2%, sensitivity 68.4%) within a two year follow-up. Ultrasonography of the cervical arteries is a simple, non invasive and widespread technique useful in detecting CBF decline during the MCI stage, thus identifying patients who later will convert to AD.

  12. A novel molecular and clinical staging model to predict survival for patients with esophageal squamous cell carcinoma

    PubMed Central

    Zhao, Jun; Wei, Min; Zhu, Xinghua; He, Qi; Ling, Tianlong; Chen, Xiaoyan; Cao, Ziang; Zhang, Yixin; Liu, Lei; Shi, Minxin

    2016-01-01

    Current prognostic factors fail to accurately determine prognosis for patients with esophageal squamous cell carcinoma (ESCC) after surgery. Here, we constructed a survival prediction model for prognostication in patients with ESCC. Candidate molecular biomarkers were extracted from the Gene Expression Omnibus (GEO), and Cox regression analysis was performed to determine significant prognostic factors. The survival prediction model was constructed based on cluster and discriminant analyses in a training cohort (N=205), and validated in a test cohort (N=207). The survival prediction model consisting of two genes (UBE2C and MGP) and two clinicopathological factors (tumor stage and grade) was developed. This model could be used to accurately categorize patients into three groups in the test cohort. Both disease-free survival and overall survival differed among the diverse groups (P<0.05). In summary, we have developed and validated a predictive model that is based on two gene markers in conjunction with two clinicopathological variables, and which can accurately predict outcomes for ESCC patients after surgery. PMID:27556859

  13. A subpopulation that may correspond to granulocytic myeloid-derived suppressor cells reflects the clinical stage and progression of cutaneous melanoma

    PubMed Central

    Miller, Karolina; Kandolf-Sekulovic, Lidija; Mijuskovic, Zeljko; Zolotarevski, Lidija; Jovic, Milena; Gacevic, Milomir; Djukic, Mirjana; Arsenijevic, Nebojsa; Vojvodic, Danilo

    2016-01-01

    Seventy-eight melanoma patients and 10 healthy individuals were examined. Follow-up examinations of all melanoma patients were performed regularly every three months. Myeloid-derived suppressor cells (MDSC) were defined as lineage negative (CD3−, CD19−, CD56−), HLA-DR−/low, CD11b+ and CD33+. Classification of granulocytic (GrMDSC) and monocytic (MoMDSC) subsets was based on the CD15 and CD14 expression, respectively. Unlike the MoMDSC, that were present in 60% of healthy controls and 15% of melanoma patients, the GrMDSC were present in all examined participants, and the melanoma patients were found to have statistically higher frequencies compared with healthy controls. Accordingly, we kept focused on GrMDSC frequencies in relation to the melanoma stages and course of the disease. The GrMDSC values are highest in stage IV melanoma patients, with statistical significance compared with stages IA, IB, IIA and IIB. Patients with progression had statistically higher GrMDSC counts comparing with those with stable disease (P = 0.0079). Patients who had progression-free interval (PFI) < 12 months showed significantly higher GrMDSC values compared with those with PFI > 12 months (P = 0.0333). GrMDSC showed significant negative correlation with PFI intervals (P = 0.0095). The GrMDSC subset was predominant in all our patients. We confirmed that GrMDSC do accumulate early in the peripheral blood of melanoma patients and their frequencies correlate narrowly with the clinical stage and the spread of the disease. The increase in GrMDSC frequencies correlates well with a progressive disease and could be considered a potential predictive biomarker of high-risk melanoma cases that are more likely to have a shorter PFI. PMID:26391013

  14. Challenges and new opportunities for clinical nutrition interventions in the aged

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Nutritional status plays a critical role in the prevention and management of many chronic health conditions that are common in the elderly and are likely to become more prevalent as the population ages. This paper highlights several aspects of nutrition that require additional basic science and clin...

  15. Clinical Study of the Effects of Age on the Physical Health of Adults with Mental Retardation.

    ERIC Educational Resources Information Center

    Cooper, Sally-Ann

    1998-01-01

    Physical disorders and pharmacotherapy for 134 people with mental retardation (ages 65 years and older) living in the United Kingdom were compared to 73 younger adults with mental retardation. Results showed the older group had higher rates of urinary incontinence, immobility, hearing impairments, arthritis, hypertension, and cerebrovascular…

  16. Improving Clinical Practice: A School-Age and School-Based Perspective

    ERIC Educational Resources Information Center

    Wallach, Geraldine P.

    2014-01-01

    Purpose: In this article, the author presents a conceptual framework for intervention at school-age levels reflecting upon a number of aspects raised by Kamhi (2014) in the lead article of this forum. The focus is on the persistence of traditional practices, components of language intervention, and prioritizing goals for students with language…

  17. Assessment of Aging Individuals with Down Syndrome in Clinical Trials: Results of Baseline Measures

    ERIC Educational Resources Information Center

    Sano, Mary; Aisen, Paul S.; Dalton, Arthur J.; Andrews, Howard F.; Tsai, Wei-Yann

    2005-01-01

    A major challenge to developing therapeutic interventions for cognitive loss and dementia in aging individuals with Down syndrome (DS) is the selection of appropriate outcome measures. This report describes the adaptation of the Brief Praxis Test (a nonverbal cognitive test) as a primary outcome measure, as well as the selection of secondary…

  18. Influence of the gestational stage on the clinical course, lesional development and parasite distribution in experimental ovine neosporosis.

    PubMed

    Arranz-Solís, David; Benavides, Julio; Regidor-Cerrillo, Javier; Fuertes, Miguel; Ferre, Ignacio; Ferreras, Maria Del Carmen; Collantes-Fernández, Esther; Hemphill, Andrew; Pérez, Valentín; Ortega-Mora, Luis Miguel

    2015-03-03

    Neospora caninum is considered one of the main causes of abortion in cattle, yet recent studies have also emphasised its relevance as an abortifacient in small ruminants. In order to gain deeper insight into the pathogenesis of ovine neosporosis, pregnant ewes were intravenously inoculated with 10(6) tachyzoites of the Nc-Spain7 isolate at days 40, 90 or 120 of gestation. Infection during the first term resulted in the death of all foetuses between days 19 and 21 post-infection, showing mainly necrotic lesions in foetal liver and the highest parasite DNA detection and burden in both placenta and foetal viscera. After infection at day 90, foetal death was also detected in all ewes, although later (34-48 days post-infection). In this group, lesions were mainly inflammatory. Foetal livers showed the lowest frequency of lesions, as well as the lowest parasite detection and burden. All ewes infected at day 120 delivered viable lambs, although 3 out of 9 showed weakness and recumbency. Neospora DNA was detected in all lambs but one, and parasite burden was similar to that observed in day 90 group. Lesions in this group showed more conspicuous infiltration of inflammatory cells and higher frequency in foetal brain and muscle when compared to both previous groups. These results highlight the crucial role that the stage of gestation plays on the course of ovine neosporosis, similar to that reported in bovine neosporosis, and open the doors to consider sheep as a valid model for exogenous transplacental transmission for ruminant neosporosis.

  19. Different Clinical and Neuroimaging Characteristics in Early Stage Parkinson’s Disease with Dementia and Dementia with Lewy Bodies

    PubMed Central

    Takemoto, Mami; Sato, Kota; Hatanaka, Noriko; Yamashita, Toru; Ohta, Yasuyuki; Hishikawa, Nozomi; Abe, Koji

    2016-01-01

    Parkinson’s disease with dementia (PDD) and dementia with Lewy bodies (DLB) both commonly exhibit brain Lewy body pathology and similar end-stage symptoms, but early symptoms differ. To clarify these differences, we compared the demographic characteristics, symptoms, cognitive and affective functioning, activities of daily life, and neuroimaging results between PDD (n = 52) and DLB (n = 46) patients. In measures of cognitive functioning, PDD patients had worse Hasegawa dementia scale-revised (HDS-R) scores (11.2±4.8) and better frontal assessment battery (FAB) scores (11.3±4.1) compared with DLB (17.0±6.4, p = 0.013 and 8.6±4.7, p = 0.039, respectively). DLB patients performed worse than PDD patients in “orientation to place” tasks. In affective functions, DLB patients had worse GDS (7.6±3.4) and ABS (9.9±5.3) scores than PDD patients (5.1±4.1 and 4.8±3.0, respectively). 99mTc-ECD images showed greater CBF in the whole cingulate gyrus and a lower CBF in the precuneus area in DLB than in PDD. These results suggest that PDD patients’ lower average scores for “repetition” (MMSE), “recent memory” (HDS-R), and “lexical fluency” (FAB) were related to lower CBF in the cingulate gyrus than in DLB. Furthermore, DLB patients’ poorer average subscale scores of “orientation to place” (MMSE) and “similarities”, “conflicting instructions”, and “go-no go” (FAB) tasks may be related to the lower CBF in the precuneus area in DLB than PDD. PMID:27060948

  20. Molecular modeling in the age of clinical genomics, the enterprise of the next generation.

    PubMed

    Prokop, Jeremy W; Lazar, Jozef; Crapitto, Gabrielle; Smith, D Casey; Worthey, Elizabeth A; Jacob, Howard J

    2017-03-01

    Protein modeling and molecular dynamics hold a unique toolset to aide in the characterization of clinical variants that may result in disease. Not only do these techniques offer the ability to study under characterized proteins, but they do this with the speed that is needed for time-sensitive clinical cases. In this paper we retrospectively study a clinical variant in the XIAP protein, C203Y, while addressing additional variants seen in patients with similar gastrointestinal phenotypes as the C203Y mutation. In agreement with the clinical tests performed on the C203Y patient, protein modeling and molecular dynamics suggest that direct interactions with RIPK2 and Caspase3 are altered by the C203Y mutation and subsequent loss of Zn coordination in the second BIR domain of XIAP. Interestingly, the variant does not appear to alter interactions with SMAC, resulting in further damage to the caspase and NOD2 pathways. To expand the computational strategy designed when studying XIAP, we have applied the molecular modeling tools to a list of 140 variants seen in CFTR associated with cystic fibrosis, and a list of undiagnosed variants in 17 different genes. This paper shows the exciting applications of molecular modeling in the classification and characterization of genetic variants identified in next generation sequencing. Graphical abstract XIAP in Caspase 3 and NOD2 signaling pathways.

  1. Clinical and genetic factors associated with progression of geographic atrophy lesions in age-related macular degeneration.

    PubMed

    Grassmann, Felix; Fleckenstein, Monika; Chew, Emily Y; Strunz, Tobias; Schmitz-Valckenberg, Steffen; Göbel, Arno P; Klein, Michael L; Ratnapriya, Rinki; Swaroop, Anand; Holz, Frank G; Weber, Bernhard H F

    2015-01-01

    Worldwide, age-related macular degeneration (AMD) is a serious threat to vision loss in individuals over 50 years of age with a pooled prevalence of approximately 9%. For 2020, the number of people afflicted with this condition is estimated to reach 200 million. While AMD lesions presenting as geographic atrophy (GA) show high inter-individual variability, only little is known about prognostic factors. Here, we aimed to elucidate the contribution of clinical, demographic and genetic factors on GA progression. Analyzing the currently largest dataset on GA lesion growth (N = 388), our findings suggest a significant and independent contribution of three factors on GA lesion growth including at least two genetic factors (ARMS2_rs10490924 [P < 0.00088] and C3_rs2230199 [P < 0.00015]) as well as one clinical component (presence of GA in the fellow eye [P < 0.00023]). These correlations jointly explain up to 7.2% of the observed inter-individual variance in GA lesion progression and should be considered in strategy planning of interventional clinical trials aimed at evaluating novel treatment options in advanced GA due to AMD.

  2. Assessment of Stage of Change, Decisional Balance, Self-Efficacy, and Use of Processes of Change of Low-Income Parents for Increasing Servings of Fruits and Vegetables to Preschool-Aged Children

    ERIC Educational Resources Information Center

    Hildebrand, Deana A.; Betts, Nancy M.

    2009-01-01

    Objective: Use the Transtheoretical Model of Behavior Change (TTM) to determine the proportionate stage of change of low-income parents and primary caregivers (PPC) for increasing accessibility, measured as servings served, of fruits and vegetables (FV) to their preschool-aged children and evaluate response differences for theoretical constructs.…

  3. Second stage of labor.

    PubMed

    Cheng, Yvonne W; Caughey, Aaron B

    2015-06-01

    Current American College of Obstetricians and Gynecologists' definition of prolonged second stage diagnoses 10% to 14% of nulliparous and 3% to 3.5% of multiparous women as having a prolonged second stage. The progression of labor in modern obstetrics may have deviated from the current labor norms established in the 1950s, likely due to differences in obstetric population characteristics and variation in clinical practice. Optimal management of the second stage in women with and without epidural remains debatable. Although prolonged second stage is associated with increased risk of maternal morbidity, conflicting data exist regarding the duration of second stage and associated neonatal morbidity and mortality.

  4. Clinical Impact of Education Provision on Determining Advance Care Planning Decisions among End Stage Renal Disease Patients Receiving Regular Hemodialysis in University Malaya Medical Centre

    PubMed Central

    Hing (Wong), Albert; Chin, Loh Ee; Ping, Tan Li; Peng, Ng Kok; Kun, Lim Soo

    2016-01-01

    Introduction: Advance care planning (ACP) is a process of shared decision-making about future health-care plans between patients, health care providers, and family members, should patients becomes incapable of participating in medical treatment decisions. ACP discussions enhance patient's autonomy, focus on patient's values and treatment preferences, and promote patient-centered care. ACP is integrated as part of clinical practice in Singapore and the United States. Aim: To assess the clinical impact of education provision on determining ACP decisions among end-stage renal disease patients on regular hemodialysis at University Malaya Medical Centre (UMMC). To study the knowledge and attitude of patients toward ACP and end-of-life issues. Materials and Methods: Fifty-six patients were recruited from UMMC. About 43 questions pretest survey adapted from Lyon's ACP survey and Moss's cardiopulmonary resuscitation (CPR) attitude survey was given to patients to answer. An educational brochure is then introduced to these patients, and a posttest survey carried out after that. The results were analyzed using SPSS version 22.0. Results: Opinion on ACP, including CPR decisions, showed an upward trend on the importance percentage after the educational brochure exposure, but this was statistically not significant. Seventy-five percent of participants had never heard of ACP before, and only 3.6% had actually prepared a written advanced directive. Conclusion: The ACP educational brochure clinically impacts patients’ preferences and decisions toward end-of-life care; however, this is statistically not significant. Majority of patients have poor knowledge on ACP. This study lays the foundation for execution of future larger scale clinical trials, and ultimately, the incorporation of ACP into clinical practice in Malaysia. PMID:27803566

  5. The role of proteases and inflammatory molecules in triggering neovascular age-related macular degeneration: basic science to clinical relevance.