Breast cancer in Kurdish women of northern Iraq: incidence, clinical stage, and case control analysis of parity and family risk.

PubMed

Majid, Runnak A; Mohammed, Hazha A; Saeed, Heshu M; Safar, Banaz M; Rashid, Rekawt M; Hughson, Michael D

2009-12-11

Breast cancer in the Middle-East occurs in relatively young women and frequently presents as advanced disease. A protective effect of multiparity is not apparent, and high familial risk is reported in some countries. This study investigates breast cancer rates and clinical stage related to age in the Kurdish region of Iraq and evaluates risk associated with parity and family history. Findings are compared with nearby countries and the West. Sulaimaniyah Directorate of Health records identified 539 women diagnosed with breast cancer during 2006-2008. Clinical survey forms were completed on 296 patients and on 254 age-matched controls. Age specific incidence rates were calculated from Directorate of Health population estimates. Average patient age was 47.4 +/- 11 years and 59.5% were pre-menopausal. Diagnosis was at clinical stage 1 for 4.1%, stage 2 for 43.5%, stage 3 for 26.0%, and stage 4 for 8.1% of patients. For 18.2%, stage was unknown. Annual breast cancer incidence rates per 100,000 women peaked at 168.9 at age 55 to 59 and declined to 57.3 at 60 and above. Patients had an average of 5.0 +/- 3.3 children compared to 5.4 +/- 3.5 for controls, P = 0.16. A first degree family member had breast cancer among 11.1% of patients and 2.1% of controls (P < 0.001) with > 50% of these patients and controls being > or =50 years old. No statistically significant relationship was found between tumor stage and age, P = 0.59. In Kurdish Iraq, breast cancer is predominantly a disease of pre-menopausal women having multiple pregnancies. For younger patients, breast cancer incidence was similar to the West and possibly higher than many Middle-Eastern countries, but unlike the West, the estimated rates declined markedly in the elderly. The familial breast cancer risk for both older and younger women was within the general population risk of Western countries. Clinical stages were advanced and indicated delays in diagnosis that were unrelated to patient age.

Implications of inaccurate clinical nodal staging in pancreatic adenocarcinoma.

PubMed

Swords, Douglas S; Firpo, Matthew A; Johnson, Kirsten M; Boucher, Kenneth M; Scaife, Courtney L; Mulvihill, Sean J

2017-07-01

Many patients with stage I-II pancreatic adenocarcinoma do not undergo resection. We hypothesized that (1) clinical staging underestimates nodal involvement, causing stage IIB to have a greater percent of resected patients and (2) this stage-shift causes discrepancies in observed survival. The Surveillance, Epidemiology, and End Results (SEER) research database was used to evaluate cause-specific survival in patients with pancreatic adenocarcinoma from 2004-2012. Survival was compared using the log-rank test. Single-center data on 105 patients who underwent resection of pancreatic adenocarcinoma without neoadjuvant treatment were used to compare clinical and pathologic nodal staging. In SEER data, medium-term survival in stage IIB was superior to IB and IIA, with median cause-specific survival of 14, 9, and 11 months, respectively (P < .001). Seventy-two percent of stage IIB patients underwent resection vs 28% in IB and 36% in IIA (P < .001). In our institutional data, 12.4% of patients had clinical evidence of nodal involvement vs 69.5% by pathologic staging (P < .001). Among clinical stage IA-IIA patients, 71.6% had nodal involvement by pathologic staging. Both SEER and institutional data support substantial underestimation of nodal involvement by clinical staging. This finding has implications in decisions regarding neoadjuvant therapy and analysis of outcomes in the absence of pathologic staging. Copyright © 2017 Elsevier Inc. All rights reserved.

Retrospective cohort study of the clinical performance of 1-stage dental implants.

PubMed

Carr, Alan B; Choi, Yong-Geun; Eckert, Steven E; Desjardins, Ronald P

2003-01-01

To evaluate long-term clinical performance of 1-stage dental implant prostheses at a single clinic, emphasizing clinical and demographic characteristics that affect implant survival. Dental records of all 308 patients (674 implants) treated with 1-stage implants at Mayo Clinic from October 1993 through May 2000 were reviewed from implant placement to last visit. Exposure and outcome variables affecting performance were collected separately to control bias in the data collection process. Additional confounding factors (age and sex) were adjusted with the stratified Cox proportional hazards model. Implant survival was determined by means of a Kaplan-Meier survival estimate. The log-rank test was used to determine the role of clinical and demographic variables in implant survival. The relative risk associated with the possible effect of clinical and demographic variables on implant survival was estimated with the Cox proportional hazards model. The implant survival rate (n = 654 implants) was 97% (mean +/- SD follow-up, 21.0 +/- 18.8 months; range, 1 to 78 months). Performance bias was limited because nearly all patients were treated by 1 prosthodontist. Two implants failed after loading (6 and 9 months). The incidence of complications was less than 4%. Among the implant failures, use of heterogeneous bone graft was associated with 4.8 times more failures than was use of autogenous bone graft (P = .04). After augmentation, delaying implant placement for 5 to 6 months resulted in 8.6 times more failures than the rate after earlier placement (P < .001). Retrospective review of the clinical performance of a 1-stage dental implant system yielded a 97% survival rate, with no failures noted after 13 months. Prosthetic complications were low, especially for fixed implant prostheses. Clinical performance of 1-stage dental implant prostheses between 1993 and 2000 demonstrated a high level of predictability.

Early and intermediate age-related macular degeneration: update and clinical review.

PubMed

García-Layana, Alfredo; Cabrera-López, Francisco; García-Arumí, José; Arias-Barquet, Lluís; Ruiz-Moreno, José M

2017-01-01

Age-related macular degeneration (AMD) is the leading cause of irreversible central vision loss in developed countries. With the aging of population, AMD will become globally an increasingly important and prevalent disease worldwide. It is a complex disease whose etiology is associated with both genetic and environmental risk factors. An extensive decline in the quality of life and progressive need of daily living assistance resulting from AMD among those most severely affected highlights the essential role of preventive strategies, particularly advising patients to quit smoking. In addition, maintaining a healthy diet, controlling other risk factors (such as hypertension, obesity, and atherosclerosis), and the use of nutritional supplements (antioxidants) are recommendable. Genetic testing may be especially important in patients with a family history of AMD. Recently, unifying criteria for the clinical classification of AMD, defining no apparent aging changes; normal aging changes; and early, intermediate, and late AMD stages, are of value in predicting AMD risk of progression and in establishing recommendations for the diagnosis, therapeutic approach, and follow-up of patients. The present review is focused on early and intermediate AMD and presents a description of the clinical characteristics and ophthalmological findings for these stages, together with algorithms for the diagnosis and management of patients, which are easily applicable in daily clinical practice.

Early and intermediate age-related macular degeneration: update and clinical review

PubMed Central

García-Layana, Alfredo; Cabrera-López, Francisco; García-Arumí, José; Arias-Barquet, Lluís; Ruiz-Moreno, José M

2017-01-01

Age-related macular degeneration (AMD) is the leading cause of irreversible central vision loss in developed countries. With the aging of population, AMD will become globally an increasingly important and prevalent disease worldwide. It is a complex disease whose etiology is associated with both genetic and environmental risk factors. An extensive decline in the quality of life and progressive need of daily living assistance resulting from AMD among those most severely affected highlights the essential role of preventive strategies, particularly advising patients to quit smoking. In addition, maintaining a healthy diet, controlling other risk factors (such as hypertension, obesity, and atherosclerosis), and the use of nutritional supplements (antioxidants) are recommendable. Genetic testing may be especially important in patients with a family history of AMD. Recently, unifying criteria for the clinical classification of AMD, defining no apparent aging changes; normal aging changes; and early, intermediate, and late AMD stages, are of value in predicting AMD risk of progression and in establishing recommendations for the diagnosis, therapeutic approach, and follow-up of patients. The present review is focused on early and intermediate AMD and presents a description of the clinical characteristics and ophthalmological findings for these stages, together with algorithms for the diagnosis and management of patients, which are easily applicable in daily clinical practice. PMID:29042759

Endemic chronic kidney disease of unknown etiology in Sri Lanka: Correlation of pathology with clinical stages.

PubMed

Wijetunge, S; Ratnatunga, N V I; Abeysekera, T D J; Wazil, A W M; Selvarajah, M

2015-01-01

Chronic kidney disease of unknown etiology (CKDU) is endemic among the rural farming communities in several localities in and around the North Central region of Sri Lanka. This is an interstitial type renal disease and typically has an insidious onset and slow progression. This study was conducted to identify the pathological features in the different clinical stages of CKDU. This is a retrospective study of 251 renal biopsies identified to have a primary interstitial disease from regions endemic for CKDU. Pathological features were assessed and graded in relation to the clinical stage. The mean age of those affected by endemic CKDU was 37.3 ± 12.5 years and the male to female ratio was 3.3:1. The predominant feature of stage I disease was mild and moderate interstitial fibrosis; most did not have interstitial inflammation. The typical stage II disease had moderate interstitial fibrosis with or without mild interstitial inflammation. Stage III disease had moderate and severe interstitial fibrosis, moderate interstitial inflammation, tubular atrophy and some glomerulosclerosis. Stage IV disease typically had severe interstitial fibrosis and inflammation, tubular atrophy and glomerulosclerosis. The mean age of patients with stage I disease (27 ± 10.8 years) was significantly lower than those of the other stages. About 79.2%, 55%, 49.1% and 50% in stage I, II, III and IV disease respectively were asymptomatic at the time of biopsy.

Breast cancer in kurdish women of northern Iraq: incidence, clinical stage, and case control analysis of parity and family risk

PubMed Central

2009-01-01

Background Breast cancer in the Middle-East occurs in relatively young women and frequently presents as advanced disease. A protective effect of multiparity is not apparent, and high familial risk is reported in some countries. This study investigates breast cancer rates and clinical stage related to age in the Kurdish region of Iraq and evaluates risk associated with parity and family history. Findings are compared with nearby countries and the West. Methods Sulaimaniyah Directorate of Health records identified 539 women diagnosed with breast cancer during 2006-2008. Clinical survey forms were completed on 296 patients and on 254 age-matched controls. Age specific incidence rates were calculated from Directorate of Health population estimates. Results Average patient age was 47.4 ± 11 years and 59.5% were pre-menopausal. Diagnosis was at clinical stage 1 for 4.1%, stage 2 for 43.5%, stage 3 for 26.0%, and stage 4 for 8.1% of patients. For 18.2%, stage was unknown. Annual breast cancer incidence rates per 100,000 women peaked at 168.9 at age 55 to 59 and declined to 57.3 at 60 and above. Patients had an average of 5.0 ± 3.3 children compared to 5.4 ± 3.5 for controls, P = 0.16. A first degree family member had breast cancer among 11.1% of patients and 2.1% of controls (P < 0.001) with > 50% of these patients and controls being ≥50 years old. No statistically significant relationship was found between tumor stage and age, P = 0.59. Conclusions In Kurdish Iraq, breast cancer is predominantly a disease of pre-menopausal women having multiple pregnancies. For younger patients, breast cancer incidence was similar to the West and possibly higher than many Middle-Eastern countries, but unlike the West, the estimated rates declined markedly in the elderly. The familial breast cancer risk for both older and younger women was within the general population risk of Western countries. Clinical stages were advanced and indicated delays in diagnosis that were unrelated to

Staging reproductive aging using Stages of Reproductive Aging Workshop + 10 in black urban African women in the Study of Women Entering and in Endocrine Transition.

PubMed

Jaff, Nicole G; Snyman, Tracy; Norris, Shane A; Crowther, Nigel J

2014-11-01

There has been limited research on accurate staging of the menopausal transition in sub-Saharan African women. Our aim was to assess the usefulness of the Stages of Reproductive Aging Workshop + 10 (STRAW + 10) criteria in staging ovarian aging in black South African women, examining whether obesity has any effect on the menopausal transition. The study enrolled 702 women aged 40 to 60 years. STRAW + 10 criteria were used to categorize the stages of reproductive aging. The Menopause Rating Scale was used to measure the prevalence of vasomotor symptoms. Follicle-stimulating hormone (FSH) and estradiol levels were used as supportive criteria for staging. Human immunodeficiency virus status was assessed using a point-of-care method. Reported age at final menstrual period (FMP) was higher in women interviewed within 4 years of FMP (mean [SD], 49.0 [3.80] y) than in women interviewed 10 years or more after FMP (mean [SD], 42.0 [4.06] y; P < 0.0005). In women within 4 years of FMP, lower body mass index was associated with earlier age at FMP. FSH levels increased and estradiol levels decreased (P < 0.0005 for both trends) across seven staging groups. Human immunodeficiency virus status had no effect on menopause symptoms. Obesity (body mass index ≥35.0 kg/m) was associated with severe vasomotor symptoms. Reporting of age at FMP is unreliable in women interviewed 4 years or more after the event. STRAW + 10 seems accurate in staging reproductive aging, as confirmed by the strong association of FSH and estradiol levels with the menopausal transition stage. STRAW + 10 may be appropriate for use in resource-limited settings in the absence of biomarkers. Biocultural methods may be useful in assessing the menopausal transition in culturally diverse women.

Histology-based Combination Induction Chemotherapy for Elderly Patients with Clinical Stage III Non-small Cell Lung Cancer.

PubMed

Banna, Giuseppe L; Parra, Hector Josè Soto; Castaing, Marine; Dieci, Maria Vittoria; Anile, Giuseppe; Nicolosi, Maurizio; Strano, Salvatore; Marletta, Francesco; Guarneri, Valentina; Conte, Pierfranco; Lal, Rohit

2017-07-01

To explore the feasibility and activity of a histology-based induction combination chemotherapy for elderly patients with clinical stage III non-small cell lung cancer (NSCLC). Patients aged ≥70 years with stage IIIA and IIIB lung squamous cell carcinoma (SCC) or adenocarcinoma were treated with three cycles of carboplatin and gemcitabine or pemetrexed, respectively, followed by definitive radiotherapy or surgery. The primary endpoint was the overall response rate (ORR) following induction. Twenty-seven patients, with a median age of 74 years (range=70-80 years) were treated for adenocarcinoma in 14 (52%) and SCC in 13 (48%), clinical stage IIIA in eight (30%) and IIIB in 19 (70%). Grade 3 or 4 toxicity was reported for five patients (18.5%). The ORR was 46% in 12 (partial responses) out of 26 assessable patients. Histology-based induction combination chemotherapy is active and feasible in elderly patients with stage III NSCLC. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Endemic chronic kidney disease of unknown etiology in Sri Lanka: Correlation of pathology with clinical stages

PubMed Central

Wijetunge, S.; Ratnatunga, N. V. I.; Abeysekera, T. D. J.; Wazil, A. W. M.; Selvarajah, M.

2015-01-01

Chronic kidney disease of unknown etiology (CKDU) is endemic among the rural farming communities in several localities in and around the North Central region of Sri Lanka. This is an interstitial type renal disease and typically has an insidious onset and slow progression. This study was conducted to identify the pathological features in the different clinical stages of CKDU. This is a retrospective study of 251 renal biopsies identified to have a primary interstitial disease from regions endemic for CKDU. Pathological features were assessed and graded in relation to the clinical stage. The mean age of those affected by endemic CKDU was 37.3 ± 12.5 years and the male to female ratio was 3.3:1. The predominant feature of stage I disease was mild and moderate interstitial fibrosis; most did not have interstitial inflammation. The typical stage II disease had moderate interstitial fibrosis with or without mild interstitial inflammation. Stage III disease had moderate and severe interstitial fibrosis, moderate interstitial inflammation, tubular atrophy and some glomerulosclerosis. Stage IV disease typically had severe interstitial fibrosis and inflammation, tubular atrophy and glomerulosclerosis. The mean age of patients with stage I disease (27 ± 10.8 years) was significantly lower than those of the other stages. About 79.2%, 55%, 49.1% and 50% in stage I, II, III and IV disease respectively were asymptomatic at the time of biopsy. PMID:26628792

Clinical Practice of Adjuvant Chemotherapy in Patients with Early-Stage Epithelial Ovarian Cancer.

PubMed

Frielink, Lindy M J; Pijlman, Brenda M; Ezendam, Nicole P M; Pijnenborg, Johanna M A

2016-01-01

Adjuvant platinum-based chemotherapy improves survival in women with early-stage epithelial ovarian cancer (EOC). Yet, there is a wide variety in clinical practice. All patients diagnosed with FIGO I and IIa EOC (2006-2010) in the south of the Netherlands were analyzed. The percentage of patients that received adjuvant chemotherapy was determined as well as the comprehensiveness of staging and outcome. Forty percent (54/135) of the patients with early-stage EOC received adjuvant chemotherapy. Treatment with adjuvant chemotherapy was associated with FIGO stage, clear-cell histology and nonoptimal staging. Optimal staging was achieved in 50%, and nonoptimal staging was associated with advanced age, comorbidity and treatment in a non-referral hospital. Overall, there was no difference in outcome between patients with and without adjuvant chemotherapy. Yet, in grade 3 tumors, adjuvant chemotherapy seems beneficial. Selective treatment of patients with early-stage EOC might reduce adjuvant chemotherapy without compromising outcome. © 2016 S. Karger AG, Basel.

Clinical stage of oral cancer patients at the time of initial diagnosis.

PubMed

Shah, Irfan; Sefvan, Omer; Luqman, Uzair; Ibrahim, Waseem; Mehmood, Sana; Alamgir, Wajiha

2010-01-01

Squamous cell carcinoma is the most common oral cancer. Early diagnosis ensures better prognosis. Late diagnosis is however common around the world and contributes to the high morbidity and mortality related to oral cancer. The objective of this study was to determine the clinical stage of oral cancer patients at the time of diagnosis. This retrospective study was carried out on 334 oral cancer patients who presented to the outdoor departments of Armed Forces Institute of Dentistry, and Armed Forces Institute of Pathology, Rawalpindi from July 2008 to December 2009. The records that were reviewed included history and clinical examination findings. OPG and CT scans of the head and neck region, chest X-rays, abdominal ultrasounds and liver function tests. Size of the primary tumour, the size, number and laterality of the involved cervical lymph nodes and the presence/absence of distant metastases were documented and statistically analysed using SPSS-17. Out of the 334 patients, 203 (60.8%) were males and 131 (39.2%) females. The age range was from 21 to 88 years. Buccal mucosa was the most commonly involved site (32%). The primary tumour was 4 Cm or more in size, (T3/T4) 71.25% of the cases. Cervical lymph nodes were involved in 211 patients (63.2%) and distant metastases were present in 39 patients (11.7%). Overall, clinical stage IV was the most common (57.18%) followed by stage III (24.55%), stage II (13.77%) and stage I (4.49%). Oral cancers are diagnosed late (Stage III and IV) in Pakistan and need immediate public and professional attention.

Idiopathic Pulmonary Fibrosis: Gender-Age-Physiology Index Stage for Predicting Future Lung Function Decline.

PubMed

Salisbury, Margaret L; Xia, Meng; Zhou, Yueren; Murray, Susan; Tayob, Nabihah; Brown, Kevin K; Wells, Athol U; Schmidt, Shelley L; Martinez, Fernando J; Flaherty, Kevin R

2016-02-01

Idiopathic pulmonary fibrosis is a progressive lung disease with variable course. The Gender-Age-Physiology (GAP) Index and staging system uses clinical variables to stage mortality risk. It is unknown whether clinical staging predicts future decline in pulmonary function. We assessed whether the GAP stage predicts future pulmonary function decline and whether interval pulmonary function change predicts mortality after accounting for stage. Patients with idiopathic pulmonary fibrosis (N = 657) were identified retrospectively at three tertiary referral centers, and baseline GAP stages were assessed. Mixed models were used to describe average trajectories of FVC and diffusing capacity of the lung for carbon monoxide (Dlco). Multivariable Cox proportional hazards models were used to assess whether declines in pulmonary function ≥ 10% in 6 months predict mortality after accounting for GAP stage. Over a 2-year period, GAP stage was not associated with differences in yearly lung function decline. After accounting for stage, a 10% decrease in FVC or Dlco over 6 months independently predicted death or transplantation (FVC hazard ratio, 1.37; Dlco hazard ratio, 1.30; both, P ≤ .03). Patients with GAP stage 2 with declining pulmonary function experienced a survival profile similar to patients with GAP stage 3, with 1-year event-free survival of 59.3% (95% CI, 49.4-67.8) vs 56.9% (95% CI, 42.2-69.1). Baseline GAP stage predicted death or lung transplantation but not the rate of future pulmonary function decline. After accounting for GAP stage, a decline of ≥ 10% over 6 months independently predicted death or lung transplantation. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Clinical staging: its importance in therapeutic decisions and clinical trials.

PubMed

Denis, L J

1992-02-01

International collaboration has resulted in a revised and unified 1987 formulation for the TNM classification in solid tumors. The simplification and eliminations of most variables caused difficulties for the clinical use of the system in some tumors such as bladder cancer. The approval of the proposed adaptation covering the tumor mass, subdividing the T4 category and adapting the stage grouping, resolves these difficulties. Published reports demonstrate support for the TNM system as a clinical base for treatment decisions and prognosis. The TNMG stage and grade are important basic prognostic factors, but other prognostic factors, especially biologic tumor activity, are under clinical investigation. The TNM classification is the initial evaluation after histologic confirmation of cancer to guide treatment and prognosis. The quality of the evaluation is enhanced by precise communication on the employed methodology.

[Study on the difference of corresponding age at cervical vertebral maturation stages among different skeletal malocclusions].

PubMed

Zuo, Changyan; Cong, Chao; Wang, Shihui; Gu, Yan

2015-10-01

To compare the difference of corresponding age at cervical vertebral maturation (CVM) stages among different skeletal malocclusions and provide clinic guideline on optimal treatment timing for skeletal malocclusion. Based on ANB angle, 2 575 cephalograms collected from Department of Orthodontics, Peking University School and Hospital of Stomatology from May, 2006 to November, 2014 were classified into skeletal Class I (ANB 0°~5°, 1 317 subjects), Class II (ANB > 5°, 685 subjects) and Class III (ANB < 0°, 573 subjects) groups. CVM stages were evaluated with the modified version of CVM method. Independent sample t test was performed to analyze the difference of age at different CVM stages among various skeletal groups. Significant gender difference of age was found at CS3 to CS6 for skeletal Class I group (P < 0.05), at CS5 and CS6 for skeletal Class II group (P < 0.05), and at CS3 and CS5 for skeletal Class III group (P < 0.05). At CS3 stage, the average age of male in skeletal Class II and skeletal Class III groups was (11.6 ± 1.5) years old and (10.3 ± 1.9) years old, respectively; the average age of females in those two groups was (11.7 ± 1.3) years old and (9.3 ± 1.5) years old, respectively, and significant difference was found in both comparisons (P < 0.05). Compared average age at CS5 and CS6 between skeletal Class II and skeletal Class III groups [the ages of male was (15.1 ± 1.7) and (16.8 ± 1.6) years old, the ages of male was (14.6 ± 1.2) and (15.7 ± 2.5) years old], significant difference was also found (P < 0.05). Significant gender differences were found when evaluated CVM stage and age in skeletal Class I, II and III groups. Significant differences of age at different CVM stage was noted when skeletal Class II was compared with skeletal Class III groups.

Worldwide Esophageal Cancer Collaboration: clinical staging data.

PubMed

Rice, T W; Apperson-Hansen, C; DiPaola, L M; Semple, M E; Lerut, T E M R; Orringer, M B; Chen, L-Q; Hofstetter, W L; Smithers, B M; Rusch, V W; Wijnhoven, B P L; Chen, K N; Davies, A R; D'Journo, X B; Kesler, K A; Luketich, J D; Ferguson, M K; Räsänen, J V; van Hillegersberg, R; Fang, W; Durand, L; Allum, W H; Cecconello, I; Cerfolio, R J; Pera, M; Griffin, S M; Burger, R; Liu, J-F; Allen, M S; Law, S; Watson, T J; Darling, G E; Scott, W J; Duranceau, A; Denlinger, C E; Schipper, P H; Ishwaran, H; Blackstone, E H

2016-10-01

To address uncertainty of whether clinical stage groupings (cTNM) for esophageal cancer share prognostic implications with pathologic groupings after esophagectomy alone (pTNM), we report data-simple descriptions of patient characteristics, cancer categories, and non-risk-adjusted survival-for clinically staged patients from the Worldwide Esophageal Cancer Collaboration (WECC). Thirty-three institutions from six continents submitted data using variables with standard definitions: demographics, comorbidities, clinical cancer categories, and all-cause mortality from first management decision. Of 22,123 clinically staged patients, 8,156 had squamous cell carcinoma, 13,814 adenocarcinoma, 116 adenosquamous carcinoma, and 37 undifferentiated carcinoma. Patients were older (62 years) men (80%) with normal body mass index (18.5-25 mg/kg 2 , 47%), little weight loss (2.4 ± 7.8 kg), 0-1 ECOG performance status (67%), and history of smoking (67%). Cancers were cT1 (12%), cT2 (22%), cT3 (56%), cN0 (44%), cM0 (95%), and cG2-G3 (89%); most involved the distal esophagus (73%). Non-risk-adjusted survival for squamous cell carcinoma was not distinctive for early cT or cN; for adenocarcinoma, it was distinctive for early versus advanced cT and for cN0 versus cN+. Patients with early cancers had worse survival and those with advanced cancers better survival than expected from equivalent pathologic categories based on prior WECC pathologic data. Thus, clinical and pathologic categories do not share prognostic implications. This makes clinically based treatment decisions difficult and pre-treatment prognostication inaccurate. These data will be the basis for the 8th edition cancer staging manuals following risk adjustment for patient characteristics, cancer categories, and treatment characteristics and should direct 9th edition data collection. © 2016 International Society for Diseases of the Esophagus.

Worldwide Esophageal Cancer Collaboration: clinical staging data

PubMed Central

Rice, T. W.; Apperson-Hansen, C.; DiPaola, L. M.; Semple, M. E.; Lerut, T. E. M. R.; Orringer, M. B.; Chen, L.-Q.; Hofstetter, W. L.; Smithers, B. M.; Rusch, V. W.; Wijnhoven, B. P. L.; Chen, K. N.; Davies, A. R.; D’Journo, X. B.; Kesler, K. A.; Luketich, J. D.; Ferguson, M. K.; Räsänen, J. V.; van Hillegersberg, R.; Fang, W.; Durand, L.; Allum, W. H.; Cecconello, I.; Cerfolio, R. J.; Pera, M.; Griffin, S. M.; Burger, R.; Liu, J.-F; Allen, M. S.; Law, S.; Watson, T. J.; Darling, G. E.; Scott, W. J.; Duranceau, A.; Denlinger, C. E.; Schipper, P. H.; Ishwaran, H.; Blackstone, E. H.

2017-01-01

SUMMARY To address uncertainty of whether clinical stage groupings (cTNM) for esophageal cancer share prognostic implications with pathologic groupings after esophagectomy alone (pTNM), we report data—simple descriptions of patient characteristics, cancer categories, and non-risk-adjusted survival—for clinically staged patients from the Worldwide Esophageal Cancer Collaboration (WECC). Thirty-three institutions from six continents submitted data using variables with standard definitions: demographics, comorbidities, clinical cancer categories, and all-cause mortality from first management decision. Of 22,123 clinically staged patients, 8,156 had squamous cell carcinoma, 13,814 adenocarcinoma, 116 adenosquamous carcinoma, and 37 undifferentiated carcinoma. Patients were older (62 years) men (80%) with normal body mass index (18.5–25 mg/kg2, 47%), little weight loss (2.4 ± 7.8 kg), 0–1 ECOG performance status (67%), and history of smoking (67%). Cancers were cT1 (12%), cT2 (22%), cT3 (56%), cNO (44%), cMO (95%), and cG2–G3 (89%); most involved the distal esophagus (73%). Non-risk-adjusted survival for squamous cell carcinoma was not distinctive for early cT or cN; for adenocarcinoma, it was distinctive for early versus advanced cT and for cNO versus cN+. Patients with early cancers had worse survival and those with advanced cancers better survival than expected from equivalent pathologic categories based on prior WECC pathologic data. Thus, clinical and pathologic categories do not share prognostic implications. This makes clinically based treatment decisions difficult and pre-treatment prognostication inaccurate. These data will be the basis for the 8th edition cancer staging manuals following risk adjustment for patient characteristics, cancer categories, and treatment characteristics and should direct 9th edition data collection. PMID:27731549

Clinical longitudinal standards for height, weight, height velocity, weight velocity, and stages of puberty.

PubMed Central

Tanner, J M; Whitehouse, R H

1976-01-01

New charts for height, weight, height velocity, and weight velocity are presented for clinical (as opposed to population survey) use. They are based on longitudinal-type growth curves, using the same data as in the British 1965 growth standards. In the velocity standards centiles are given for children who are early- and late-maturing as well as for those who mature at the average age (thus extending the use of the previous charts). Limits of normality for the age of occurrence of the adolescent growth spurt are given and also for the successive stages of penis, testes, and pubic hair development in boys, and for stages of breast and pubic hair development in girls. PMID:952550

Differential impact of current diagnosis and clinical stage on attendance at a youth mental health service.

PubMed

Cross, Shane P M; Hermens, Daniel F; Scott, Jan; Salvador-Carulla, Luis; Hickie, Ian B

2017-06-01

To examine whether clinical stage of illness and current diagnosis influence appointment behaviour in a specialized primary-level youth mental health service. Factors associated with attendance at 8697 appointments made by 828 young people (females = 497) aged 12-25 years over a 1-year period were analysed. The number of appointments made did not correlate with the rates of attendance. However, those with more severe psychiatric morbidity made significantly more appointments and missed significantly more appointments than those with less severe presentations. Impaired social functioning was the best predictor of female attendance rates, whereas age and clinical stage of illness best predicted male attendance rates. Current diagnosis rather than functional impairment appeared to influence the level of input offered by clinicians. Age, gender, severity of illness, functioning and psychological distress had differential associations with both planned treatment intensity and attendance rates. These differences are likely to have implications for service provision in this youth population. © 2016 John Wiley & Sons Australia, Ltd.

Validation of World Health Organisation HIV/AIDS clinical staging in predicting initiation of antiretroviral therapy and clinical predictors of low CD4 cell count in Uganda.

PubMed

Baveewo, Steven; Ssali, Francis; Karamagi, Charles; Kalyango, Joan N; Hahn, Judith A; Ekoru, Kenneth; Mugyenyi, Peter; Katabira, Elly

2011-05-12

The WHO clinical guidelines for HIV/AIDS are widely used in resource limited settings to represent the gold standard of CD4 counts for antiviral therapy initiation. The utility of the WHO-defined stage 1 and 2 clinical factors used in WHO HIV/AIDS clinical staging in predicting low CD4 cell count has not been established in Uganda. Although the WHO staging has shown low sensitivity for predicting CD4<200 cells/mm(3), it has not been evaluated at for CD4 cut-offs of <250 cells/mm(3) or <350 cells/mm(3). To validate the World Health Organisation HIV/AIDS clinical staging in predicting initiation of antiretroviral therapy in a low-resource setting and to determine the clinical predictors of low CD4 cell count in Uganda. Data was collected on 395 participants from the Joint Clinical Research Centre, of whom 242 (61.3%) were classified as in stages 1 and 2 and 262 (68%) were females. Participants had a mean age of 36.8 years (SD 8.5). We found a significant inverse correlation between the CD4 lymphocyte count and WHO clinical stages. The sensitivity the WHO clinical staging at CD4 cell count of 250 cells/mm(3) and 350 cells/mm(3) was 53.5% and 49.1% respectively. Angular cheilitis, papular pruritic eruptions and recurrent upper respiratory tract infections were found to be significant predictors of low CD4 cell count among participants in WHO stage 1 and 2. The WHO HIV/AIDS clinical staging guidelines have a low sensitivity and about half of the participants in stages 1 and 2 would be eligible for ART initiation if they had been tested for CD4 count. Angular cheilitis and papular pruritic eruptions and recurrent upper respiratory tract infections may be used, in addition to the WHO staging, to improve sensitivity in the interim, as access to CD4 machines increases in Uganda.

Stage line diagram: an age-conditional reference diagram for tracking development.

PubMed

van Buuren, Stef; Ooms, Jeroen C L

2009-05-15

This paper presents a method for calculating stage line diagrams, a novel type of reference diagram useful for tracking developmental processes over time. Potential fields of applications include: dentistry (tooth eruption), oncology (tumor grading, cancer staging), virology (HIV infection and disease staging), psychology (stages of cognitive development), human development (pubertal stages) and chronic diseases (stages of dementia). Transition probabilities between successive stages are modeled as smoothly varying functions of age. Age-conditional references are calculated from the modeled probabilities by the mid-P value. It is possible to eliminate the influence of age by calculating standard deviation scores (SDS). The method is applied to the empirical data to produce reference charts on secondary sexual maturation. The mean of the empirical SDS in the reference population is close to zero, whereas the variance depends on age. The stage line diagram provides quick insight into both status (in SDS) and tempo (in SDS/year) of development of an individual child. Other measures (e.g. height SDS, body mass index SDS) from the same child can be added to the chart. Diagrams for sexual maturation are available as a web application at http://vps.stefvanbuuren.nl/puberty. The stage line diagram expresses status and tempo of discrete changes on a continuous scale. Wider application of these measures scores opens up new analytic possibilities. (c) 2009 John Wiley & Sons, Ltd.

Dental Age Estimation (DAE): Data management for tooth development stages including the third molar. Appropriate censoring of Stage H, the final stage of tooth development.

PubMed

Roberts, Graham J; McDonald, Fraser; Andiappan, Manoharan; Lucas, Victoria S

2015-11-01

The final stage of dental development of third molars is usually helpful to indicate whether or not a subject is aged over 18 years. A complexity is that the final stage of development is unlimited in its upper border. Investigators usually select an inappropriate upper age limit or censor point for this tooth development stage. The literature was searched for appropriate data sets for dental age estimation and those that provided the count (n), the mean (x¯), and the standard deviation (sd) for each of the tooth development stages. The Demirjian G and Demirjian H were used for this study. Upper and lower limits of the Stage G and Stage H data were calculated limiting the data to plus or minus three standard deviations from the mean. The upper border of Stage H was limited by appropriate censoring at the maximum value for Stage G. The maximum age at attainment from published data, for Stage H, ranged from 22.60 years to 34.50 years. These data were explored to demonstrate how censoring provides an estimate for the correct maximum age for the final stage of Stage H as 21.64 years for UK Caucasians. This study shows that confining the data array of individual tooth developments stages to ± 3sd provides a reliable and logical way of censoring the data for tooth development stages with a Normal distribution of data. For Stage H this is inappropriate as it is unbounded in its upper limit. The use of a censored data array for Stage H using Percentile values is appropriate. This increases the reliability of using third molar Stage H alone to determine whether or not an individual is over 18 years old. For Stage H, individual ancestral groups should be censored using the same technique. Copyright © 2015 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

Clinical Trials Targeting Aging and Age-Related Multimorbidity

PubMed Central

Crimmins, Eileen M; Grossardt, Brandon R; Crandall, Jill P; Gelfond, Jonathan A L; Harris, Tamara B; Kritchevsky, Stephen B; Manson, JoAnn E; Robinson, Jennifer G; Rocca, Walter A; Temprosa, Marinella; Thomas, Fridtjof; Wallace, Robert; Barzilai, Nir

2017-01-01

Abstract Background There is growing interest in identifying interventions that may increase health span by targeting biological processes underlying aging. The design of efficient and rigorous clinical trials to assess these interventions requires careful consideration of eligibility criteria, outcomes, sample size, and monitoring plans. Methods Experienced geriatrics researchers and clinical trialists collaborated to provide advice on clinical trial design. Results Outcomes based on the accumulation and incidence of age-related chronic diseases are attractive for clinical trials targeting aging. Accumulation and incidence rates of multimorbidity outcomes were developed by selecting at-risk subsets of individuals from three large cohort studies of older individuals. These provide representative benchmark data for decisions on eligibility, duration, and assessment protocols. Monitoring rules should be sensitive to targeting aging-related, rather than disease-specific, outcomes. Conclusions Clinical trials targeting aging are feasible, but require careful design consideration and monitoring rules. PMID:28364543

Classification of hepatocellular carcinoma stages from free-text clinical and radiology reports

PubMed Central

Yim, Wen-wai; Kwan, Sharon W; Johnson, Guy; Yetisgen, Meliha

2017-01-01

Cancer stage information is important for clinical research. However, they are not always explicitly noted in electronic medical records. In this paper, we present our work on automatic classification of hepatocellular carcinoma (HCC) stages from free-text clinical and radiology notes. To accomplish this, we defined 11 stage parameters used in the three HCC staging systems, American Joint Committee on Cancer (AJCC), Barcelona Clinic Liver Cancer (BCLC), and Cancer of the Liver Italian Program (CLIP). After aggregating stage parameters to the patient-level, the final stage classifications were achieved using an expert-created decision logic. Each stage parameter relevant for staging was extracted using several classification methods, e.g. sentence classification and automatic information structuring, to identify and normalize text as cancer stage parameter values. Stage parameter extraction for the test set performed at 0.81 F1. Cancer stage prediction for AJCC, BCLC, and CLIP stage classifications were 0.55, 0.50, and 0.43 F1.

Clinical stage, therapy, and prognosis in canine anal sac gland carcinoma.

PubMed

Polton, Gerry A; Brearley, Malcolm J

2007-01-01

Reports of canine anal sac gland carcinoma (ASGC) describe varied clinical presentations and management and differing responses to therapy. A unifying approach to clinical stage determination and management of this disease has yet to be presented. An ordinal clinical staging scheme for canine ASGC can be devised on the basis of responses to therapy for a retrospective cohort of affected dogs. 130 dogs with naturally occurring ASGC. A simplified clinical stage system and a management algorithm for canine ASGC were derived from retrospective evaluation of a cohort of 80 dogs; applicability of both was then prospectively evaluated in a cohort of 50 dogs. Retrospective evaluation revealed 4 statistically significant negative prognostic indicators for survival: lack of therapy, presence of distant metastases, presence of lymph node metastases, and primary tumor size. Lymph node extirpation was a statistically significant positive prognostic indicator by bivariate analysis. In both retrospective and prospective analyses, the modified clinical stage scheme revealed a significant association with survival time. The clinical staging scheme permits differentiation between groups in terms of prognosis and, therefore, decisions on therapy. This will facilitate application of appropriate therapy and enhanced communication and collaboration in further investigations of ASGC.

Management of clinical stage I testicular pure seminoma. Report on 42 patients and review of the literature.

PubMed

Porcaro, Antonio B; Antoniolli, Stefano Zecchini; Schiavone, Dionisio; Maffei, Nicola; Bassetto, Maria A; Curti, Pierpaolo

2002-06-01

Testis cancer is the most common tumor detected in men aged from 20 to 35 years accounting for 1-2%. About 20-30% of patients presenting with clinical stage I pure seminoma of the testis, which accounts for 45-50% of all germ cell tumors, present with occult metastases in the retroperitoneal lymph nodes. Currently, treatment options for clinical stage I seminoma include adjuvant radiotherapy (RT) as well as surveillance and adjuvant single agent chemotherapy. Herein, we review our experience in the management of 42 patients with clinical stage I pure seminoma of the testis and review the literature concerning this topic. Between January 1977 and December 2000, of 56 patients with pure seminoma of the testis 42 (75%) were assessed as clinical stage I disease. Adjuvant RT was performed in 41 patients and surveillance in 1. Radiations fields included the para-aortic and ipsilateral pelvic lymph nodes. A radiation dose of 25 Gy in 20 daily fractions was given. All patients were followed up. Average age was 41.2 years (range 24-67). Mean follow-up was 85.3 months (range 12-279). Histopathology assessed classic seminoma in 41 cases (98%) and spermatocytic seminoma in 1 (2%). Small vessel invasion was detected in 8 cases (19%). Overall relapse rate was 4.7%. Overall survival rate resulted 97%. Adjuvant radiotherapy (RT) is a safe standard of care in controlling microscopic retroperitoneal disease in patients with clinical stage I seminoma. About 3 to 5% of patients undergo relapses, mostly after the first 18 months after orchiectomy. Overall cause-specific survival rates range between 96% to 100%. An alternative optional treatment for compliant patients presenting with low risk factors for relapse is surveillance with recurrences rates ranging between 15% to 20%. Surveillance avoids unnecessary treatment in about 80% of patients, thus it could be offered as a safe alternative option to adjuvant RT since imaging detects relapses at their early stages. Adjuvant chemotherapy

Oncofertility in patients with stage I epithelial ovarian cancer: fertility-sparing surgery in young women of reproductive age.

PubMed

Jiang, Xuan; Yang, Jiaxin; Yu, Mei; Xie, Weimin; Cao, Dongyan; Wu, Ming; Pan, Lingya; Huang, Huifang; You, Yan; Shen, Keng

2017-08-15

Fertility-sparing surgery is indicated for patients with stage I epithelial ovarian cancers. We sought to evaluate the clinical outcomes and oncofertility in a cohort of patients of reproductive age with stage I epithelial ovarian cancer (EOC). Overall, 108 patients of reproductive age (≤ 40 years) diagnosed with stage I EOC who were treated at Peking Union Medical College Hospital between 1999 and 2013 were included in the study. The Kaplan-Meier model and Cox regression analyses were used for the survival analysis. The type of surgery included fertility-sparing surgery (FSS) (48.1%) and radical surgery (RS) (51.9%). After a median follow-up of 83 months, we observed that grade 3 or clear-cell carcinoma was the only independent risk factor for disease-free survival and tumor-specific survival in the multivariate analysis. Patients with grade 3 or clear-cell carcinoma tended to be older than 30 years, have endometriosis, and undergo RS (p < 0.05). Fertility-sparing surgery did not affect disease-free survival or tumor-specific survival among patients of reproductive age with stage I EOC and among high-risk patients with stage IC2-3, grade 3, or clear-cell carcinoma. Thirty-four out of 52 (65.4%) FSS patients attempted to get pregnant. Twenty-eight (82.4%) achieved a successful pregnancy with a full-term delivery. Grade 3 or clear-cell carcinoma was the only independent risk factor for survival of patients of reproductive age with stage I EOC. FSS can be safely performed on patients of reproductive age with grade 1-2, stage I EOC. The safety of FSS for grade 3 and clear-cell carcinoma warrants further investigation.

Lymph node metastasis in grossly apparent clinical stage Ia epithelial ovarian cancer: Hacettepe experience and review of literature

PubMed Central

2010-01-01

Background Lymphadenectomy is an integral part of the staging system of epithelial ovarian cancer. However, the extent of lymphadenectomy in the early stages of ovarian cancer is controversial. The objective of this study was to identify the lymph node involvement in unilateral epithelial ovarian cancer apparently confined to the one ovary (clinical stage Ia). Methods A prospective study of clinical stage I ovarian cancer patients is presented. Patient's characteristics and tumor histopathology were the variables evaluated. Results Thirty three ovarian cancer patients with intact ovarian capsule were evaluated. Intraoperatively, neither of the patients had surface involvement, adhesions, ascites or palpable lymph nodes (supposed to be clinical stage Ia). The mean age of the study group was 55.3 ± 11.8. All patients were surgically staged and have undergone a systematic pelvic and paraaortic lymphadenectomy. Final surgicopathologic reports revealed capsular involvement in seven patients (21.2%), contralateral ovarian involvement in two (6%) and omental metastasis in one (3%) patient. There were two patients (6%) with lymph node involvement. One of the two lymph node metastasis was solely in paraaortic node and the other metastasis was in ipsilateral pelvic lymph node. Ovarian capsule was intact in all of the patients with lymph node involvement and the tumor was grade 3. Conclusion In clinical stage Ia ovarian cancer patients, there may be a risk of paraaortic and pelvic lymph node metastasis. Further studies with larger sample size are needed for an exact conclusion. PMID:21114870

Correlation between chronological age and third molar developmental stages in an Iranian population (Demirjian method).

PubMed

Khosronejad, Aria; Navabi, Manijeh; Sakhdari, Shirin; Rakhshan, Vahid

2017-01-01

Third molar development is the only available tool for estimating the age of individuals after puberty. Since this tooth has very high interethnic variability, formulas calculated to estimate the age from its development stages cannot be generalized to other populations and should be adjusted for each region. Therefore, this study was conducted to evaluate this method in a sample of Tehran individuals for the first time, and also to compare the development of third molars across sexes and arches, and to estimate cutoff developmental stages for legal minor/major identification. A total of 150 dental patients aged between 15 and 25 years old were prospectively enrolled, and their Demirjian stages were recorded. The associations between chronological age and Demirjian stages were evaluated. Dental formation was compared between sexes and jaws. Cutoff stages were determined to identify legal minor/major cases (above or below 18 years old). Age estimation formula was found for this population. Of the 150 included patients, 56 were males. The difference between the ages of males and females at each given developmental stage was nonsignificant ( P > 0.05), except for the H stage. Age difference between same stage teeth of the maxilla and mandible was nonsignificant. Each of the G and H stages was significantly above 18 years old ( P < 0.001). Furthermore, E and F stages were below 18 years old ( P < 0.001). All the correlations between Demirjian stages and age were above 90% (all P < 0.001). Third molar development was positively affected by the chronological age ( P = 0.000) and being maxillary ( P = 0.000) but not sex ( P = 0.113). Regression formula for age estimation was: age = 6.52+ (0.64 × sex) + (0.32 × arch) + (1.86 × Demirjian stage). Development of third molar might complete after the age 22. Iranian individuals with third molars at the G and H stages are likely above 18 while those at E and F are likely below 18. Pace of molar development differs for jaws

Initial stage of physical ageing in network glasses

NASA Astrophysics Data System (ADS)

Golovchak, R.; Ingram, A.; Kozdras, A.; Vlcek, M.; Roiland, C.; Bureau, B.; Shpotyuk, O.

2012-11-01

An atomistic view on Johari-Goldstein secondary β-relaxation processes responsible for structural relaxation far below the glass transition temperature (Tg ) in network glasses is developed for the archetypal chalcogenide glass, As20Se80, using positron annihilation lifetime, differential scanning calorimetry, Raman scattering and nuclear magnetic resonance techniques. Increased density fluctuations are shown to be responsible for the initial stage of physical ageing in these materials at the temperatures below Tg . They are correlated with changes in thermodynamic parameters of structural relaxation through the glass-to-supercooled liquid transition interval. General shrinkage, occurred during the next stage of physical ageing, is shown to be determined by the ability of system to release these redundant open volumes from the glass bulk through the densification process of glass network.

Correlation between chronological age and third molar developmental stages in an Iranian population (Demirjian method)

PubMed Central

Khosronejad, Aria; Navabi, Manijeh; Sakhdari, Shirin; Rakhshan, Vahid

2017-01-01

Background: Third molar development is the only available tool for estimating the age of individuals after puberty. Since this tooth has very high interethnic variability, formulas calculated to estimate the age from its development stages cannot be generalized to other populations and should be adjusted for each region. Therefore, this study was conducted to evaluate this method in a sample of Tehran individuals for the first time, and also to compare the development of third molars across sexes and arches, and to estimate cutoff developmental stages for legal minor/major identification. Materials and Methods: A total of 150 dental patients aged between 15 and 25 years old were prospectively enrolled, and their Demirjian stages were recorded. The associations between chronological age and Demirjian stages were evaluated. Dental formation was compared between sexes and jaws. Cutoff stages were determined to identify legal minor/major cases (above or below 18 years old). Age estimation formula was found for this population. Results: Of the 150 included patients, 56 were males. The difference between the ages of males and females at each given developmental stage was nonsignificant (P > 0.05), except for the H stage. Age difference between same stage teeth of the maxilla and mandible was nonsignificant. Each of the G and H stages was significantly above 18 years old (P < 0.001). Furthermore, E and F stages were below 18 years old (P < 0.001). All the correlations between Demirjian stages and age were above 90% (all P < 0.001). Third molar development was positively affected by the chronological age (P = 0.000) and being maxillary (P = 0.000) but not sex (P = 0.113). Regression formula for age estimation was: age = 6.52+ (0.64 × sex) + (0.32 × arch) + (1.86 × Demirjian stage). Conclusion: Development of third molar might complete after the age 22. Iranian individuals with third molars at the G and H stages are likely above 18 while those at E and F are likely below

Staging in bipolar disorder: from theoretical framework to clinical utility.

PubMed

Berk, Michael; Post, Robert; Ratheesh, Aswin; Gliddon, Emma; Singh, Ajeet; Vieta, Eduard; Carvalho, Andre F; Ashton, Melanie M; Berk, Lesley; Cotton, Susan M; McGorry, Patrick D; Fernandes, Brisa S; Yatham, Lakshmi N; Dodd, Seetal

2017-10-01

Illness staging is widely utilized in several medical disciplines to help predict course or prognosis, and optimize treatment. Staging models in psychiatry in general, and bipolar disorder in particular, depend on the premise that psychopathology moves along a predictable path: an at-risk or latency stage, a prodrome progressing to a first clinical threshold episode, and one or more recurrences with the potential to revert or progress to late or end-stage manifestations. The utility and validity of a staging model for bipolar disorder depend on its linking to clinical outcome, treatment response and neurobiological measures. These include progressive biochemical, neuroimaging and cognitive changes, and potentially stage-specific differences in response to pharmacological and psychosocial treatments. Mechanistically, staging models imply the presence of an active disease process that, if not remediated, can lead to neuroprogression, a more malignant disease course and functional deterioration. Biological elements thought to be operative in bipolar disorder include a genetic diathesis, physical and psychic trauma, epigenetic changes, altered neurogenesis and apoptosis, mitochondrial dysfunction, inflammation, and oxidative stress. Many available agents, such as lithium, have effects on these targets. Staging models also suggest the utility of stage-specific treatment approaches that may not only target symptom reduction, but also impede illness neuroprogression. These treatment approaches range from prevention for at-risk individuals, to early intervention strategies for prodromal and newly diagnosed individuals, complex combination therapy for rapidly recurrent illness, and palliative-type approaches for those at chronic, late stages of illness. There is hope that prompt initiation of potentially disease modifying therapies may preclude or attenuate the cognitive and structural changes seen in the later stages of bipolar disorder. The aims of this paper are to: a

Relationship between age at menarche and skeletal maturation stages in Taiwanese female orthodontic patients.

PubMed

Lai, Eddie Hsiang-Hua; Chang, Jenny Zwei-Chieng; Jane Yao, Chung-Chen; Tsai, Shih-Jaw; Liu, Jen-Pei; Chen, Yi-Jane; Lin, Chun-Pin

2008-07-01

The age at menarche reflects a pubertal girl's physiologic maturity. The aims of this study were to evaluate the relationship between the age at menarche and skeletal maturation in female orthodontic patients. Hand-wrist radiographs and lateral cephalometric radiographs from 304 adolescent female subjects (age, 8-18.9 years) were selected from the files of the Department of Orthodontics, National Taiwan University Hospital (NTUH). Hand-wrist bone maturation stages were assessed using the NTUH Skeletal Maturation Index (NTUH-SMI). Cervical vertebral maturation stages (CVMS) were determined using the latest CVMS Index. Menarcheal ages were self-reported by the patients and verified by the patients' mothers. The relationships between the NTUH-SMI or CVM stages and menarcheal status were investigated. More than 90% of the 148 subjects who had already attained menstruation had skeletal maturation beyond the NTUH-SMI stage four or CVMS III. However, the subjects who had never experienced menarche mostly had skeletal maturation before NTUH-SMI stage five or CVMS IV. During the period of orthodontic treatment, 19 females experienced their menarche. The mean age at menarche for the 167 female patients in total was 11.97 years. In average, menarche occurred between NTUH-SMI stages four and five or between CVM stages III and IV. The percentage of girls with menses increased from 1.2% at age 9 to 6.6% at age 10, 39.5% at age 11, 81.4% at age 12, 97% at age 13, and 100% at age 14. Compared with the results obtained 20 years previously, we found a downward shift of 0.47 years per decade for the mean age at menarche in female orthodontic patients. The majority of female orthodontic patients have passed the pubertal growth spurt when they experience their menarche. Menarche usually follows the pubertal growth spurt by about 1 year and occurs after NTUH-SMI stage four or CVMS III.

Forensic age estimation based on magnetic resonance imaging of third molars: converting 2D staging into 3D staging.

PubMed

De Tobel, Jannick; Hillewig, Elke; Verstraete, Koenraad

2017-03-01

Established methods to stage development of third molars for forensic age estimation are based on the evaluation of radiographs, which show a 2D projection. It has not been investigated whether these methods require any adjustments in order to apply them to stage third molars on magnetic resonance imaging (MRI), which shows 3D information. To prospectively study root stage assessment of third molars in age estimation using 3 Tesla MRI and to compare this with panoramic radiographs, in order to provide considerations for converting 2D staging into 3D staging and to determine the decisive root. All third molars were evaluated in 52 healthy participants aged 14-26 years using MRI in three planes. Three staging methods were investigated by two observers. In sixteen of the participants, MRI findings were compared with findings on panoramic radiographs. Decisive roots were palatal in upper third molars and distal in lower third molars. Fifty-seven per cent of upper third molars were not assessable on the radiograph, while 96.9% were on MRI. Upper third molars were more difficult to evaluate on radiographs than on MRI (p < .001). Lower third molars were equally assessable on both imaging techniques (93.8% MRI, 98.4% radiograph), with no difference in level of difficulty (p = .375). Inter- and intra-observer agreement for evaluation was higher in MRI than in radiographs. In both imaging techniques lower third molars showed greater inter- and intra-observer agreement compared to upper third molars. MR images in the sagittal plane proved to be essential for staging. In age estimation, 3T MRI of third molars could be valuable. Some considerations are, however, necessary to transfer known staging methods to this 3D technique.

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. Copyright © 2016 John Wiley & Sons, Ltd.

Relationship of psychological factors with physical activity stage of change in prime-and middle-aged Japanese.

PubMed

Mori, Keiko; Suzuki, Hisao; Wang, Da-Hong; Takaki, Jiro; Takigawa, Tomoko; Ogino, Keiki

2009-04-01

The present study aimed to investigate the status of physical activity and the differences in psychological factors associated with physical activity from the perspective of transtheoretical model stages between prime- and middle-aged Japanese. The study involved 375 prime-aged volunteers (175 men, 200 women) and 557 middle-aged volunteers (247 men, 310 women) living in Kuse, a town in Okayama Prefecture, Japan. We found that the prime-aged men at the preparation stage had significantly higher self-efficacy scores than at the contemplation stage (p<0.01). Middle-aged men had significantly higher self-efficacy scores at the contemplation stage than at the precontemplation stage (p<0.001). Middle-aged women, meanwhile, had significantly higher self-efficacy scores at the maintenance stage than at the action stage (p<0.01), and at the contemplation stage than at the precontemplation stage (p<0.001). The present findings provide valuable information about the differences in psychological factors affecting physical activity between prime-aged and middle-aged community-dwelling Japanese. This information may be useful to health professionals as they develop effective community-based intervention programs for target populations.

Staging in bipolar disorder: from theoretical framework to clinical utility

PubMed Central

Berk, Michael; Post, Robert; Ratheesh, Aswin; Gliddon, Emma; Singh, Ajeet; Vieta, Eduard; Carvalho, Andre F.; Ashton, Melanie M.; Berk, Lesley; Cotton, Susan M.; McGorry, Patrick D.; Fernandes, Brisa S.; Yatham, Lakshmi N.; Dodd, Seetal

2017-01-01

Illness staging is widely utilized in several medical disciplines to help predict course or prognosis, and optimize treatment. Staging models in psychiatry in general, and bipolar disorder in particular, depend on the premise that psychopathology moves along a predictable path: an at‐risk or latency stage, a prodrome progressing to a first clinical threshold episode, and one or more recurrences with the potential to revert or progress to late or end‐stage manifestations. The utility and validity of a staging model for bipolar disorder depend on its linking to clinical outcome, treatment response and neurobiological measures. These include progressive biochemical, neuroimaging and cognitive changes, and potentially stage‐specific differences in response to pharmacological and psychosocial treatments. Mechanistically, staging models imply the presence of an active disease process that, if not remediated, can lead to neuroprogression, a more malignant disease course and functional deterioration. Biological elements thought to be operative in bipolar disorder include a genetic diathesis, physical and psychic trauma, epigenetic changes, altered neurogenesis and apoptosis, mitochondrial dysfunction, inflammation, and oxidative stress. Many available agents, such as lithium, have effects on these targets. Staging models also suggest the utility of stage‐specific treatment approaches that may not only target symptom reduction, but also impede illness neuroprogression. These treatment approaches range from prevention for at‐risk individuals, to early intervention strategies for prodromal and newly diagnosed individuals, complex combination therapy for rapidly recurrent illness, and palliative‐type approaches for those at chronic, late stages of illness. There is hope that prompt initiation of potentially disease modifying therapies may preclude or attenuate the cognitive and structural changes seen in the later stages of bipolar disorder. The aims of this paper

Disorganization at the stage of schizophrenia clinical outcome: Clinical-biological study.

PubMed

Nestsiarovich, A; Obyedkov, V; Kandratsenka, H; Siniauskaya, M; Goloenko, I; Waszkiewicz, N

2017-05-01

According to the multidimensional model of schizophrenia, three basic psychopathological dimensions constitute its clinical structure: positive symptoms, negative symptoms and disorganization. The latter one is the newest and the least studied. Our aim was to discriminate disorganization in schizophrenia clinical picture and to identify its distinctive biological and socio-psychological particularities and associated genetic and environmental factors. We used SAPS/SANS psychometrical scales, scales for the assessment of patient's compliance, insight, social functioning, life quality. Neuropsychological tests included Wisconsin Card Sorting Test (WCST), Stroop Color-Word test. Neurophysiological examination included registration of P300 wave of the evoked cognitive auditory potentials. Environmental factors related to patient's education, family, surrounding and nicotine use, as well as subjectively significant traumatic events in childhood and adolescence were assessed. Using PCR we detected SNP of genes related to the systems of neurotransmission (COMT, SLC6A4 and DRD2), inflammatory response (IL6, TNF), cellular detoxification (GSTM1, GSTT1), DNA methylation (MTHFR, DNMT3b, DNMT1). Disorganization is associated with early schizophrenia onset and history of psychosis in family, low level of insight and compliance, high risk of committing delicts, distraction errors in WCST, lengthened P300 latency of evoked cognitive auditory potentials, low-functional alleles of genes MTHFR (rs1801133) and DNMT3b (rs2424913), high level of urbanicity and psychotraumatic events at early age. Severe disorganization at the stage of schizophrenia clinical outcome is associated with the set of specific biological and social-psychological characteristics that indicate its epigenetic nature and maladaptive social significance. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Estimation of legal age using calcification stages of third molars in living individuals.

PubMed

Streckbein, Philipp; Reichert, Isabelle; Verhoff, Marcel A; Bödeker, Rolf-Hasso; Kähling, Christopher; Wilbrand, Jan-Falco; Schaaf, Heidrun; Howaldt, Hans-Peter; May, Andreas

2014-12-01

The increased number of adolescents and young adults with unknown or inaccurately given date of birth is a current issue in justice and legal medicine. The objective of this study was to determine the extent to which third molar calcification stages assessed on panoramic X-rays could be useful as additional criteria for forensic age estimation in living individuals, focusing on the legally important ages 17 and 18. In a retrospective multi-center study, the developmental stage of each individual's third molar was analyzed using Demirjian's scale in 2360 cases. Additionally, sex, age and ancestry were assessed. Individuals with the lowest calcification stage of all present molars in stage H were ≥18 years with a likelihood of ≥99.05% in the female (n=388), and ≥99.24% in the male (n=482) population. The lowest calcification stage of all present third molars proved to be useful as an additional reliable criterion for the determination of an age ≥18 years. Copyright © 2014 Forensic Science Society. Published by Elsevier Ireland Ltd. All rights reserved.

Health system delay and its effect on clinical stage of breast cancer: Multicenter study.

PubMed

Unger-Saldaña, Karla; Miranda, Alfonso; Zarco-Espinosa, Gelasio; Mainero-Ratchelous, Fernando; Bargalló-Rocha, Enrique; Miguel Lázaro-León, Jesús

2015-07-01

The objective of this study was to determine the correlation between health system delay and clinical disease stage in patients with breast cancer. This was a cross-sectional study of 886 patients who were referred to 4 of the largest public cancer hospitals in Mexico City for the evaluation of a probable breast cancer. Data on time intervals, sociodemographic factors, and clinical stage at diagnosis were retrieved. A logistic regression model was used to estimate the average marginal effects of delay on the probability of being diagnosed with advanced breast cancer (stages III and IV). The median time between problem identification and the beginning of treatment was 7 months. The subinterval with the largest delay was that between the first medical consultation and diagnosis (median, 4 months). Only 15% of the patients who had cancer were diagnosed with stage 0 and I disease, and 48% were diagnosed with stage III and IV disease. Multivariate analyses confirmed independent correlations for the means of problem identification, patient delay, health system delay, and age with a higher probability that patients would begin cancer treatment in an advanced stage. In the sample studied, the majority of patients with breast cancer began treatment after a delay. Both patient delays and provider delays were associated with advanced disease. Research aimed at identifying specific access barriers to medical services is much needed to guide the design of tailored health policies that go beyond the promotion of breast care awareness and screening participation to include improvements in health services that facilitate access to timely diagnosis and treatment. © 2015 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

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

Dental age estimation from the developmental stage of the third molars in western Chinese population.

PubMed

Li, Guo; Ren, Jiayin; Zhao, Shuping; Liu, Yuanyuan; Li, Na; Wu, Wanhong; Yuan, Shanshan; Wang, Hu

2012-06-10

The purpose of this study is to provide reference data about estimating dental age from third molars of the western Chinese population for comparing with other populations and being applied to the age estimation of western Chinese juveniles and adolescents. A total of 2078 digital panoramic radiographs of 989 male and 1089 female Chinese subjects aged between 5 and 23 years were examined. The mineralization status of the third molars was assessed using the formation stages described by Demirjian et al. with two modifications. The results showed that the development of third molars in the western Chinese population was likely to begin at age 5 in both males and females. The third molars 28 and 48 showed significantly higher frequency in females than in males. The third molars 18 in the stage 1, 38 in the stages 1, A and G, and 48 in the stage H showed significantly older average age in females than in males. The Demirjian's stages C and D could be used as a reference stage to determine dichotomously whether a western Chinese is more likely to be under or above age 14 or 16, respectively. This study provided reference data for the age estimation of western Chinese juveniles and adolescents by the mineralization stages of the third molar. Apart from forensic age determination in living subjects, the presented reference data can also be used for age estimations of unidentified corpses and skeletons. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Age is not a prognostic factor in children with Wilms tumor beyond stage I in Africa.

PubMed

Aronson, D C; Hadley, G P

2014-06-01

Patients under age 4 with stage I favorable histology (FH) Wilms tumor have a reported survival advantage. Among children above 10 years, a poorer prognosis has been associated with a higher prevalence of diffuse anaplasia. To determine if, in our practice, patients with Wilms tumors >8 years of age (stage II-V) have a poorer prognosis than those aged <8 years or <4 years. Case-control study of 19 patients >8 years with Wilms tumor stages II-V who were identified from a cohort of 192 new patients (2002-2012). For each patient two controls were chosen matched for stage and histology, one 0-3 years and one 4-7 years. Neo-adjuvant chemotherapy was offered to all, combined with intensive supportive care. Postoperative treatment was determined by local stage and histology. OS and EFS at 5 years for the different age groups were compared. Each age group contained 19 patients, of whom 6 had stage II tumors, 3 stage III, 8 stage IV, and 2 stage V. Histology was intermediate risk (IR) in 17 and high risk (HR) in 2. OS at 5 years was 80.8% and EFS was 79.2% for the whole group. No significant difference in outcome could be shown between age groups. Loss to follow up was 6/57 (11%). The survival advantage of young age (<4 years) associated with stage I FH could not be demonstrated in higher stages. Age had no significant impact on prognosis although a trend to better outcome was seen in children <4 years. © 2014 Wiley Periodicals, Inc.

To evaluate disparity between clinical and pathological tumor-node-metastasis staging in oral cavity squamous cell carcinoma patients and its impact on overall survival: An institutional study.

PubMed

Gupta, Karan; Panda, Naresh K; Bakshi, Jaimanti; Das, Ashim

2015-01-01

Accurate clinical staging is important for patient counseling, treatment planning, prognostication, and rational design of clinical trials. In head and neck squamous cell carcinoma, discrepancy between clinical and pathological staging has been reported. To evaluate any disparity between clinical and pathological tumor-node-metastasis (TNM) staging in oral cavity squamous cell carcinoma (OCSCC) patients and any impact of the same on survival. Retrospective chart review from year 2007 to 2013, at a tertiary care center. All survival analyses were performed using SPSS for Windows version 15 (Chicago, IL, USA). Disease-free survival curves were generated using Kaplan-Meier algorithm. One hundred and twenty-seven patients with OCSCC were analyzed. Seventy-nine (62.2%) were males and 48 (37.8%) females with a mean age at presentation 43.6 years (29-79 years). The highest congruence between clinical and pathological T-staging seen for clinical stage T1 and T4 at 76.9% and 73.4% with pathological T-stage. Similarly, the highest congruence between clinical and pathological N-stage seen for clinical N0 and N3 at 86.4% and 91.7% with pathological N-stage. Of clinically early stage patients, 67.5% remained early stage, and 32.5% were upstaged to advanced stage following pathological analysis. Of the clinically advanced stage patients, 75% remained advanced, and 25% were pathologically downstaged. This staging discrepancy did not significantly alter the survival. Some disparity exists in clinical and pathological TNM staging of OCSCC, which could affect treatment planning and survival of patients. Hence, more unified and even system of staging for the disease is required for proper decision-making.

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. Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

Estimating stage-specific daily survival probabilities of nests when nest age is unknown

USGS Publications Warehouse

Stanley, T.R.

2004-01-01

Estimation of daily survival probabilities of nests is common in studies of avian populations. Since the introduction of Mayfield's (1961, 1975) estimator, numerous models have been developed to relax Mayfield's assumptions and account for biologically important sources of variation. Stanley (2000) presented a model for estimating stage-specific (e.g. incubation stage, nestling stage) daily survival probabilities of nests that conditions on “nest type” and requires that nests be aged when they are found. Because aging nests typically requires handling the eggs, there may be situations where nests can not or should not be aged and the Stanley (2000) model will be inapplicable. Here, I present a model for estimating stage-specific daily survival probabilities that conditions on nest stage for active nests, thereby obviating the need to age nests when they are found. Specifically, I derive the maximum likelihood function for the model, evaluate the model's performance using Monte Carlo simulations, and provide software for estimating parameters (along with an example). For sample sizes as low as 50 nests, bias was small and confidence interval coverage was close to the nominal rate, especially when a reduced-parameter model was used for estimation.

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.

Hippocampal sclerosis in advanced age: clinical and pathological features

PubMed Central

Schmitt, Frederick A.; Lin, Yushun; Abner, Erin L.; Jicha, Gregory A.; Patel, Ela; Thomason, Paula C.; Neltner, Janna H.; Smith, Charles D.; Santacruz, Karen S.; Sonnen, Joshua A.; Poon, Leonard W.; Gearing, Marla; Green, Robert C.; Woodard, John L.; Van Eldik, Linda J.; Kryscio, Richard J.

2011-01-01

degeneration TAR DNA protein 43. To help sharpen our ability to discriminate patients with hippocampal sclerosis associated with ageing clinically, the longitudinal cognitive profile of 43 patients with hippocampal sclerosis associated with ageing was compared with the profiles of 75 controls matched for age, gender, education level and apolipoprotein E genotype. These individuals were followed from intake assessment, with 8.2 (average) longitudinal cognitive assessments. A neuropsychological profile with relatively high-verbal fluency but low word list recall distinguished the hippocampal sclerosis associated with ageing group at intake (P < 0.015) and also 5.5–6.5 years before death (P < 0.005). This may provide a first step in clinical differentiation of hippocampal sclerosis associated with ageing versus pure Alzheimer’s disease in their earliest stages. In summary, in the largest series of autopsy-verified patients with hippocampal sclerosis to date, we characterized the clinical and pathological features associated with hippocampal sclerosis associated with ageing. PMID:21596774

Recommendations for clinical staging (cTNM) of cancer of the esophagus and esophagogastric junction for the 8th edition AJCC/UICC staging manuals.

PubMed

Rice, Thomas W; Ishwaran, Hemant; Blackstone, Eugene H; Hofstetter, Wayne L; Kelsen, David P; Apperson-Hansen, Carolyn

2016-11-01

We report analytic and consensus processes that produced recommendations for clinical stage groups (cTNM) of esophageal and esophagogastric junction cancer for the AJCC/UICC cancer staging manuals, 8th edition. The Worldwide Esophageal Cancer Collaboration (WECC) provided data on 22,123 clinically staged patients with epithelial esophageal cancers. Risk-adjusted survival for each patient was developed using random survival forest analysis from which (1) data-driven clinical stage groups were identified wherein survival decreased monotonically and was distinctive between and homogeneous within groups and (2) data-driven anatomic clinical stage groups based only on cTNM. The AJCC Upper GI Task Force, by smoothing, simplifying, expanding, and assessing clinical applicability, produced (3) consensus clinical stage groups. Compared with pTNM, cTNM survival was "pinched," with poorer survival for early cStage groups and better survival for advanced ones. Histologic grade was distinctive for data-driven grouping of cT2N0M0 squamous cell carcinoma (SCC) and cT1-2N0M0 adenocarcinoma, but consensus removed it. Grouping was different by histopathologic cell type. For SCC, cN0-1 was distinctive for cT3 but not cT1-2, and consensus removed cT4 subclassification and added subgroups 0, IVA, and IVB. For adenocarcinoma, N0-1 was distinctive for cT1-2 but not cT3-4a, cStage II subgrouping was necessary (T1N1M0 [IIA] and T2N0M0 [IIB]), advanced cancers cT3-4aN0-1M0 plus cT2N1M0 comprised cStage III, and consensus added subgroups 0, IVA, and IVB. Treatment decisions require accurate cStage, which differs from pStage. Understaging and overstaging are problematic, and additional factors, such as grade, may facilitate treatment decisions and prognostication until clinical staging techniques are uniformly applied and improved. © 2016 International Society for Diseases of the Esophagus.

Recommendations for clinical staging (cTNM) of cancer of the esophagus and esophagogastric junction for the 8th edition AJCC/UICC staging manuals

PubMed Central

Rice, Thomas W.; Ishwaran, Hemant; Blackstone, Eugene H.; Hofstetter, Wayne L.; Kelsen, David P.; Apperson-Hansen, Carolyn

2017-01-01

SUMMARY We report analytic and consensus processes that produced recommendations for clinical stage groups (cTNM) of esophageal and esophagogastric junction cancer for the AJCC/UICC cancer staging manuals, 8th edition. The Worldwide Esophageal Cancer Collaboration (WECC) provided data on 22,123 clinically staged patients with epithelial esophageal cancers. Risk-adjusted survival for each patient was developed using random survival forest analysis from which (1) data-driven clinical stage groups were identified wherein survival decreased monotonically and was distinctive between and homogeneous within groups and (2) data-driven anatomic clinical stage groups based only on cTNM. The AJCC Upper GI Task Force, by smoothing, simplifying, expanding, and assessing clinical applicability, produced (3) consensus clinical stage groups. Compared with pTNM, cTNM survival was “pinched,” with poorer survival for early cStage groups and better survival for advanced ones. Histologic grade was distinctive for data-driven grouping of cT2N0M0 squamous cell carcinoma (SCC) and cT1-2N0M0 adenocarcinoma, but consensus removed it. Grouping was different by histopathologic cell type. For SCC, cN0-1 was distinctive for cT3 but not cT1-2, and consensus removed cT4 subclassification and added subgroups 0, IVA, and IVB. For adenocarcinoma, N0-1 was distinctive for cT1-2 but not cT3-4a, cStage II subgrouping was necessary (T1N1M0 [IIA] and T2N0M0 [IIB]), advanced cancers cT3-4aN0-1M0 plus cT2N1M0 comprised cStage III, and consensus added subgroups 0, IVA, and IVB. Treatment decisions require accurate cStage, which differs from pStage. Understaging and overstaging are problematic, and additional factors, such as grade, may facilitate treatment decisions and prognostication until clinical staging techniques are uniformly applied and improved. PMID:27905171

Effect of age on survival benefit of adjuvant chemotherapy in elderly patients with Stage III colon cancer.

PubMed

Zuckerman, Ilene H; Rapp, Thomas; Onukwugha, Ebere; Davidoff, Amy; Choti, Michael A; Gardner, James; Seal, Brian; Mullins, C Daniel

2009-08-01

To estimate the modifying effect of age on the survival benefit associated with adjuvant chemotherapy receipt in elderly patients with a diagnosis of Stage III colon cancer. Observational, retrospective cohort study using two samples: an overall sample of 7,182 patients to provide externally valid analyses and a propensity score-matched sample of 3,016 patients to provide more internally valid analyses by reducing the presence of treatment endogeneity. An interval-censored survival model with a complementary log-log link was used. Hazard ratios and 95% confidence intervals were obtained for all regressions. Data from the National Cancer Institute's Surveillance, Epidemiology and End Results database and the linked Medicare enrollment and claims database were used. Selected patients were aged 66 and older and had a diagnosis of Stage III colon cancer. Patients were followed from surgery to time of death or censorship. The outcome was colon cancer-specific death during the follow-up period. Receipt of adjuvant chemotherapy was measured according to the presence of a claim for 5-fluorouracil or leucovorin within 6 months after surgery. All elderly patients had a significant survival benefit associated with adjuvant chemotherapy receipt, although the survival benefit of adjuvant chemotherapy was not uniform across all age groups. These findings have important clinical and policy implications for the risk-benefit calculation induced by treatment in older patients with Stage III colon cancer. The results suggest that there is a benefit from chemotherapy, but the benefit is lower with older age.

Hippocampal sclerosis in advanced age: clinical and pathological features.

PubMed

Nelson, Peter T; Schmitt, Frederick A; Lin, Yushun; Abner, Erin L; Jicha, Gregory A; Patel, Ela; Thomason, Paula C; Neltner, Janna H; Smith, Charles D; Santacruz, Karen S; Sonnen, Joshua A; Poon, Leonard W; Gearing, Marla; Green, Robert C; Woodard, John L; Van Eldik, Linda J; Kryscio, Richard J

2011-05-01

DNA protein 43. To help sharpen our ability to discriminate patients with hippocampal sclerosis associated with ageing clinically, the longitudinal cognitive profile of 43 patients with hippocampal sclerosis associated with ageing was compared with the profiles of 75 controls matched for age, gender, education level and apolipoprotein E genotype. These individuals were followed from intake assessment, with 8.2 (average) longitudinal cognitive assessments. A neuropsychological profile with relatively high-verbal fluency but low word list recall distinguished the hippocampal sclerosis associated with ageing group at intake (P<0.015) and also 5.5-6.5 years before death (P<0.005). This may provide a first step in clinical differentiation of hippocampal sclerosis associated with ageing versus pure Alzheimer's disease in their earliest stages. In summary, in the largest series of autopsy-verified patients with hippocampal sclerosis to date, we characterized the clinical and pathological features associated with hippocampal sclerosis associated with ageing.

Influence of age on the outcome of single stage reconstructive surgery for congenital dislocation of the hip joint.

PubMed

Bhatti, Anisuddin; Jamali, A R; Mehboob, Ghulam

2009-01-01

This study was conducted to assess the effect of age on the ultimate outcome measures following single stage surgical procedure of soft tissue release, relocation, capsulorrhaphy, femoral shortening with varus/derotation osteotomy and pelvic osteotomy. A case series. The study with two groups of pretest-posttest design was conducted at Department of Orthopaedic Surgery, Jinnah Postgraduate Medical Centre (JPMC), Karachi, from 1993 to January 2008. Patients included were having neglected, congenital dislocation of the hip joint, aged over 3 years. Patients with failed previous surgery, paralytic, teratological, traumatic or septic dislocations and patients with less than 5 years follow-up were excluded from the study. The patients were divided into two groups, 3-7 years (37 hip joints) and over 7 years (13 hip joints). The single stage surgical procedure of open relocation, femoral shortening/derotation/ varus osteotomy and pelvic osteotomy was the dependent variable; whereas, the final clinico-radiological results based upon Tonnis grading, Severin's clinical/radiological grading, Klisic's overall rating and acetabular index were the independent variables of the study. Pre- and postoperative data was assessed for overall improvement and the difference in outcome measures between the two age groups. Significant overall improvement on all parameters was achieved after surgery. When results were compared between two age groups, there was no significant difference in the final outcome as per Tonnis grading and Severin's clinical typing as modified by Gibson (97.3% versus 84.4% normal hip joints or Tonnis grade 1 and 78.37% versus 53.85% Severin's type 1) but the results based upon Severin's radiological grading (62.16% versus 15.38%) and Klisic's overall rating (62.16% versus 15.38%) were significantly better in 3-7 years as compared to those over 7 years. There was no significant difference between the two age groups when compared for improvement in acetabular index

"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…

Comprehensive Clinical Staging for Resectable Lung Cancer: Clinicopathological Correlations and the Role of Brain MRI.

PubMed

Vernon, Jordyn; Andruszkiewicz, Nicole; Schneider, Laura; Schieman, Colin; Finley, Christian J; Shargall, Yaron; Fahim, Christine; Farrokhyar, Forough; Hanna, Waël C

2016-11-01

In our model of comprehensive clinical staging (CCS) for lung cancer, patients with a computerized tomography scan of the chest and upper abdomen not showing distant metastases will then routinely undergo whole body positron emission tomography/computerized tomography and magnetic resonance imaging (MRI) of the brain before any therapeutic decision. Our aim was to determine the accuracy of CCS and the value of brain MRI in this population. A retrospective analysis of a prospectively entered database was performed for all patients who underwent lung cancer resection from January 2012 to June 2014. Demographics, clinical and pathological stage (seventh edition of the American Joint Committee on Cancer/Union for International Cancer Control tumor, node, and metastasis staging manual), and costs of staging were collected. Correlation between clinical and pathological stage was determined. Of 315 patients with primary lung cancer, 55.6% were female and the mean age was 70 ± 9.6 years. When correlation was analyzed without consideration for substages A and B, 49.8% of patients (158 of 315) were staged accurately, 39.7% (125 of 315) were overstaged, and 10.5% (32 of 315) were understaged. Only 4.7% of patients (15 of 315) underwent surgery without appropriate neoadjuvant treatment. Preoperative brain MRI detected asymptomatic metastases in four of 315 patients (1.3%). At a median postoperative follow-up of 19 months (range 6-43), symptomatic brain metastases developed in seven additional patients. The total cost of CCS in Canadian dollars was $367,292 over the study period, with $117,272 (31.9%) going toward brain MRI. CCS is effective for patients with resectable lung cancer, with less than 5% of patients being denied appropriate systemic treatment before surgery. Brain MRI is a low-yield and high-cost intervention in this population, and its routine use should be questioned. Copyright © 2016 International Association for the Study of Lung Cancer. Published by

The Effect of Aging on the Stages of Processing in a Choice Reaction Time Task

ERIC Educational Resources Information Center

Simon, J. Richard; Pouraghabagher, A. Reza

1978-01-01

Two experiments were conducted to determine the effect of aging on encoding and response selection stages of a choice reaction time task. Results suggested reducing stimulus discriminability may affect information processing prior to the encoding stage, but the encoding stage is the primary locus of the slowing which accompanied aging. (Author)

Clinical radiobiology of stage T2-T3 bladder cancer.

PubMed

Majewski, Wojciech; Maciejewski, Boguslaw; Majewski, Stanislaw; Suwinski, Rafal; Miszczyk, Leszek; Tarnawski, Rafal

2004-09-01

To evaluate the relationship between total radiation dose and overall treatment time (OTT) with the treatment outcome, with adjustment for selected clinical factors, in patients with Stage T2-T3 bladder cancer treated with curative radiotherapy (RT). The analysis was based on 480 patients with Stage T2-T3 bladder cancer who were treated at the Center of Oncology in Gliwice between 1975 and 1995. The mean total radiation dose was 65.5 Gy, and the mean OTT was 51 days. In 261 patients (54%), planned and unplanned gaps occurred during RT. Four fractionation schedules were used: (1) conventional fractionation (once daily, 1.8-2.5 Gy/fraction); (2) protracted fractionation (pelvic RT, once daily, 1.6-1.7 Gy/fraction, boost RT, once daily, 2.0 Gy/fraction); (3) accelerated hyperfractionated boost (pelvic RT, once daily, 2.0 Gy/fraction; boost RT, twice daily, 1.3-1.4 Gy/fraction); and (4) accelerated hyperfractionation (pelvic and boost RT, twice daily, 1.2-1.5 Gy/fraction). In all fractionation schedules, the total radiation dose was similar (average 65.5 Gy), but the OTT was different (mean 53 days for conventional fractionation, 62 days for protracted fractionation, 45 days for accelerated hyperfractionated boost, and 41 days for accelerated hyperfractionation). A Cox proportional hazard model and maximum likelihood logistic model were used to evaluate the relationship between the treatment-related parameters (total radiation dose, dose per fraction, and OTT) and clinical factors (clinical T stage, hemoglobin level and bladder capacity before RT) and treatment outcome. With a median follow-up of 76 months, the actuarial 5-year local control rate was 47%, and the overall survival rate was 40%. The logistic analysis, which included the total dose, OTT, and T stage, revealed that all of these factors were significantly related to tumor control probability (p = 0.021 for total radiation dose, p = 0.038 for OTT, and p = 0.00068 for T stage). A multivariate Cox model, which

Significance of clinical and biologic features in Stage 3 neuroblastoma: a report from the International Neuroblastoma Risk Group project.

PubMed

Meany, Holly J; London, Wendy B; Ambros, Peter F; Matthay, Katherine K; Monclair, Tom; Simon, Thorsten; Garaventa, Alberto; Berthold, Frank; Nakagawara, Akira; Cohn, Susan L; Pearson, Andrew D J; Park, Julie R

2014-11-01

International Neuroblastoma Staging System (INSS) Stage 3 neuroblastoma is a heterogeneous disease. Data from the International Neuroblastoma Risk Group (INRG) database were analyzed to define patient and tumor characteristics predictive of outcome. Of 8,800 patients in the INRG database, 1,483 with INSS Stage 3 neuroblastoma and complete follow-up data were analyzed. Secondary analysis was performed in 1,013 patients (68%) with MYCN-non-amplified (NA) tumors. Significant prognostic factors were identified via log-rank test comparisons of survival curves. Multivariable Cox proportional hazards regression model was used to identify factors independently predictive of event-free survival (EFS). Age at diagnosis (P < 0.0001), tumor MYCN status (P < 0.0001), and poorly differentiating/undifferentiated histology (P = 0.03) were independent predictors of EFS. Compared to other Stage 3 subgroups, outcome was inferior for patients ≥ 547 days with MYCN-NA neuroblastoma (P < 0.0001), and within this cohort, serum ferritin ≥ 96 ng/ml was associated with inferior EFS (P = 0.02). For patients <547 days of age with MYCN-NA tumors, serum ferritin levels were prognostic of overall survival (OS) (P = 0.04) and chromosome 11q aberration was prognostic of EFS (P = 0.03). Among patients with INSS Stage 3 neuroblastoma patients, age at diagnosis, MYCN status and histology predict outcome. Patients <547 days of age with MYCN-NA tumors that lack chromosome 11q aberrations or those with serum ferritin <96 ng/ml have excellent prognosis and should be considered for therapy reduction. Prospective clinical trials are needed to identify optimal therapy for those patients ≥ 547 days of age with undifferentiated histology or elevated serum ferritin. © 2014 Wiley Periodicals, Inc.

Ethnic differences in breast cancer in Hawai'i: age, stage, hormone receptor status, and survival.

PubMed

Braun, Kathryn L; Fong, Megan; Gotay, Carolyn C; Chong, Clayton D K

2004-09-01

Previous examinations of breast cancer and survival in Hawai'i's 5 major ethnic groups have found that Native Hawaiian women have the highest breast cancer mortality rates. Although ethnic disparities in survival are reduced when age and stage at diagnosis are controlled for statistically, prior studies could not explain ethnic variation in survival among women who were diagnosed at the same stage. We examined variations in breast tumor characteristics for a multiethnic sample of 4,583 women diagnosed in 1990-1997 by stage and age group and extended previous multivariate analyses by adding a new prognostic variable: estrogen receptor (ER) and progesterone receptor (PR) status. Logistic regression was used to examine the influence of age, stage, and hormone status on 5-year survival. With a few exceptions, greater proportions of Native Hawaiian women were diagnosed both in later stages of disease and at earlier ages compared to women of other ethnicities, and smaller proportions of Native Hawaiians survived 5 years post diagnosis in each stage and age group. Surprisingly, greater proportions of Native Hawaiian women in all age groups had ER/PR positive tumors, which is a prognostic indicator for better, not worse, survival. Native Hawaiian women had an increased risk of death and Japanese women had an increased chance of survival after controlling for age, stage, and ER/PR status. Future studies should examine other reasons for better survival of Japanese women and worse survival of Native Hawaiian women, including socioeconomic status, access to health insurance, adequacy of recommended screening frequency, co-morbid conditions, treatment appropriateness and compliance, and genetic markers of tumor aggressiveness.

Value analysis of postoperative staging imaging for asymptomatic, early-stage breast cancer: implications of clinical variation on utility and cost.

PubMed

Pellet, Andrew C; Erten, Mujde Z; James, Ted A

2016-06-01

Routine staging imaging for early-stage breast cancer is not recommended. Despite this, there is clinical practice variation with imaging studies obtained for asymptomatic patients with a positive sentinel node (SN+). We characterize the utility, cost, and clinical implications of imaging studies obtained in asymptomatic SN+ patients. A retrospective review was performed of asymptomatic, clinically node-negative patients who were found to have a positive sentinel node after surgery. The type of imaging, subsequent tests/interventions, frequency of additional malignancy detected, and costs were recorded. From April 2009 to April 2013, a total of 50 of 113 (44%) asymptomatic patients underwent staging imaging for a positive sentinel node; 11 (22%) patients had at least 1 subsequent imaging study or diagnostic intervention. No instance of metastatic breast cancer was identified, with a total cost of imaging calculated at $116,905. Staging imaging for asymptomatic SN+ breast cancer demonstrates clinical variation. These tests were associated with low utility, increased costs, and frequent false positives leading to subsequent testing/intervention. Evidence-based standardization may help increase quality by decreasing unnecessary variation and cost. Copyright © 2015 Elsevier Inc. All rights reserved.

Atrophy of the cholinergic basal forebrain over the adult age range and in early stages of Alzheimer´s disease

PubMed Central

Grothe, Michel; Heinsen, Helmut; Teipel, Stefan J.

2013-01-01

Background The basal forebrain cholinergic system (BFCS) is known to undergo moderate neurodegenerative changes during normal aging as well as severe atrophy in Alzheimer´s disease (AD). However, there is a controversy on how the cholinergic lesion in AD relates to early and incipient stages of the disease. In-vivo imaging studies on the structural integrity of the BFCS in normal and pathological aging are still rare. Methods We applied automated morphometry techniques in combination with high-dimensional image warping and a cytoarchitectonic map of BF cholinergic nuclei to a large cross-sectional dataset of high-resolution MRI scans, covering the whole adult age-range (20–94 years; N=211) as well as patients with very mild AD (vmAD; CDR=0.5; N=69) and clinically manifest AD (AD; CDR=1; N=28). For comparison, we investigated hippocampus volume using automated volumetry. Results Volume of the BFCS declined from early adulthood on and atrophy aggravated in advanced age. Volume reductions in vmAD were most pronounced in posterior parts of the nucleus basalis Meynert, while in AD atrophy was more extensive and included the whole BFCS. In clinically manifest AD, the diagnostic accuracy of BFCS volume reached the diagnostic accuracy of hippocampus volume. Conclusions Our findings indicate that cholinergic degeneration in AD occurs against a background of age-related atrophy and that exacerbated atrophy in AD can be detected at earliest stages of cognitive impairment. Automated in-vivo morphometry of the BFCS may become a useful tool to assess BF cholinergic degeneration in normal and pathological aging. PMID:21816388

Clinical significance of preoperative carcinoembryonic antigen level in patients with clinical stage IA non-small cell lung cancer.

PubMed

Maeda, Ryo; Suda, Takashi; Hachimaru, Ayumi; Tochii, Daisuke; Tochii, Sachiko; Takagi, Yasushi

2017-01-01

The objective of this study was to assess the preoperative serum carcinoembryonic antigen (CEA) level in patients with clinical stage IA non-small cell lung cancer (NSCLC) and to evaluate its clinical significance. Between January 2005 and December 2014, a total of 378 patients with clinical stage IA NSCLC underwent complete resection with systematic node dissection. The survival rate was estimated starting from the date of surgery to the date of either death or the last follow-up by the Kaplan-Meier method. Univariate analyses by log-rank tests were used to determine prognostic factors. Cox proportional hazards ratios were used to identify independent predictors of poor prognosis. Clinicopathological predictors of lymph node metastases were evaluated by logistic regression analyses. The 5-year survival rate of patients with an elevated preoperative serum CEA level was significantly lower than that of patients with a normal CEA level (75.5% vs. 87.7%; P=0.02). However, multivariate analysis did not show the preoperative serum CEA level to be an independent predictor of poor prognosis. Postoperative pathological factors, including lymphatic permeation, visceral pleural invasion, and lymph node metastases, tended to be positive in patients with an elevated preoperative serum CEA level. In addition, the CEA level was a statistically significant independent clinical predictor of lymph node metastases. The preoperative serum CEA level was not an independent predictor of poor prognosis in patients with pathological stage IA NSCLC but was an important clinical predictor of tumor invasiveness and lymph node metastases in patients with clinical stage IA NSCLC. Therefore, measurement of the preoperative serum CEA level should be considered even for patients with early-stage NSCLC.

Determinants of stage at diagnosis of breast cancer in Nigerian women: sociodemographic, breast cancer awareness, health care access and clinical factors.

PubMed

Jedy-Agba, Elima; McCormack, Valerie; Olaomi, Oluwole; Badejo, Wunmi; Yilkudi, Monday; Yawe, Terna; Ezeome, Emmanuel; Salu, Iliya; Miner, Elijah; Anosike, Ikechukwu; Adebamowo, Sally N; Achusi, Benjamin; Dos-Santos-Silva, Isabel; Adebamowo, Clement

2017-07-01

Advanced stage at diagnosis is a common feature of breast cancer in Sub-Saharan Africa (SSA), contributing to poor survival rates. Understanding its determinants is key to preventing deaths from this cancer in SSA. Within the Nigerian Integrative Epidemiology of Breast Cancer Study, a multicentred case-control study on breast cancer, we studied factors affecting stage at diagnosis of cases, i.e. women diagnosed with histologically confirmed invasive breast cancer between January 2014 and July 2016 at six secondary and tertiary hospitals in Nigeria. Stage was assessed using clinical and imaging methods. Ordinal logistic regression was used to examine associations of sociodemographic, breast cancer awareness, health care access and clinical factors with odds of later stage (I, II, III or IV) at diagnosis. A total of 316 women were included, with a mean age (SD) of 45.4 (11.4) years. Of these, 94.9% had stage information: 5 (1.7%), 92 (30.7%), 157 (52.4%) and 46 (15.3%) were diagnosed at stages I, II, III and IV, respectively. In multivariate analyses, lower educational level (odds ratio (OR) 2.35, 95% confidence interval: 1.04, 5.29), not believing in a cure for breast cancer (1.81: 1.09, 3.01), and living in a rural area (2.18: 1.05, 4.51) were strongly associated with later stage, whilst age at diagnosis, tumour grade and oestrogen receptor status were not. Being Muslim (vs. Christian) was associated with lower odds of later stage disease (0.46: 0.22, 0.94). Our findings suggest that factors that are amenable to intervention concerning breast cancer awareness and health care access, rather than intrinsic tumour characteristics, are the strongest determinants of stage at diagnosis in Nigerian women.

Evaluation of the 8th AJCC staging system for pathologically versus clinically staged pancreatic adenocarcinoma: A time to revisit a dogma?

PubMed

Abdel-Rahman, Omar

2018-02-01

The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for pancreatic exocrine adenocarcinoma has been released. The current study seeks to assess the 7th and 8th editions among patients registered within the surveillance, epidemiology and end results (SEER) database. SEER database (2010-2013) has been accessed through SEER*Stat program and AJCC 8th edition stages were reconstructed utilizing the collaborative stage descriptions. Kaplan-Meier analysis of overall survival and pancreatic cancer-specific survival analyses (according to both 7th and 8th editions and according to whether pathological or clinical staging were conducted) has been performed. Multivariate analysis of factors affecting pancreatic cancer-specific survival was also conducted through a Cox proportional hazard model. A total of 18  948 patients with pancreatic adenocarcinoma were identified in the period from 2010-2013. Pancreatic cancer-specific survival among pathologically staged patients and according to the 8th edition showed significant differences for all pair wise comparisons among different stages (P < 0.0001) except for the comparison between stage IA and stage IB (P = 0.307) and the comparison between stage IB and stage IIA (P = 0.116). Moreover, P value for stage IA vs IIA was 0.014; while pancreatic cancer-specific survival according to the 7th edition among pathologically staged patients showed significant differences for all pair wise comparisons among different stages (P < 0.0001) except for the comparison between IA and IB (P = 0.072), the comparison between stage IIA and stage IIB (P = 0.065), the comparison between stage IIA and stage III (P = 0.059) and the comparison between IIB and III (P = 0.595). Among clinically staged patients (i.e. those who did not undergo initial radical surgery), the prognostic performance of both 7th and 8th stages for both overall survival and pancreatic cancer-specific survival was

Ages and Career Stages: Considerations in Providing Support for Mid-Late Career Stage Doctoral Students

ERIC Educational Resources Information Center

Robertson, Margaret J.

2017-01-01

This article raises two inter-related issues: firstly there is a correlation between the needs of doctoral students that are strongly related to age and career stage; and secondly, because these needs differ according to their demographic, the current discourse of developing work-readiness skills of doctoral students is misplaced for the growing…

[Depressive states at the stage of broad clinical presentations of anorexia nervosa in adolescents].

PubMed

Grachev, V V

2014-01-01

To specify psychopathological features and dynamics of depression developed at the stage of broad clinical presentations of anorexia nervosa (AN) in adolescent patients. Authors studied 61 young women, aged from 14 to 18 years, mean age 16.6 ± .9 years. Depressive states manifested during the first year of AN in all patients. Two variants of depressive episodes were described. The first variant was characterized by asthenic/depressive, somatic and autonomic presentations, with the leading role of exogenous/organic and somatogenic factors. In the second variant, affective disorders were characterized by the anxiety affect concomitant with adynamia, dysphoria and melancholia that most probably may be caused by endogenous constitutional/biological factors. The follow-up data (0,5-6 years) indicated that most of the patients with the second variant of depressive episodes had recurrent depressive states. During the course of disease, eating disorders acquired an atypical character and gradually decreased while the affective pathology became dominating. Depressive symptomatology in AN patients of pubertal age corresponded to main mechanisms of development of the clinical picture and dynamics of adolescent depression as atypical depressive triad, predominance of anxiety and asthenic/adynamic affect, a trend towards protracted course and substantial frequency of dysmorphophobic symptoms and over-valued ideas.

Intake of key micronutrients and food groups in patients with late-stage age-related macular degeneration compared with age-sex-matched controls.

PubMed

Gopinath, Bamini; Liew, Gerald; Russell, Joanna; Cosatto, Victoria; Burlutsky, George; Mitchell, Paul

2017-08-01

Knowledge of the risk factor profile of patients presenting with late-stage age-related macular degeneration (AMD) could help identify the most frequent modifiable AMD precursors among people who are referred for treatment. We aimed to assess dietary behaviours by comparing adjusted mean intakes of micronutrients and major food groups (fruits, vegetables, fish) among patients with AMD and a sample of age-sex-matched controls. Cross-sectional analysis of 480 late AMD cases and 518 population-based age-sex-matched controls with no AMD signs. AMD cases (aged 60+ years) were those presenting for treatment to a hospital eye clinic in Sydney, Australia, during 2012-2015. The comparator group were obtained from a cohort study (Blue Mountains Eye Study; Sydney, Australia) during 2002-2009. Dietary intake was assessed using a semiquantitative food-frequency questionnaire. AMD lesions were assessed from retinal photographs. After multivariable adjustment, patients with late-stage AMD compared with controls had significantly lower intakes of vitamin E (7.4 vs 9.8 mg/day; p<0.0001), beta-carotene (6232 vs 7738 μg/day; p<0.0001), vitamin C (161 vs 184 mg/day; p=0.0002) and folate (498.3 vs 602 μg/day; p<0.0001); but had higher intakes of zinc (13.0 vs 11.9 mg/day; p<0.0001). A significantly lower proportion of patients with late AMD met the recommended intake of vegetables than controls: 52.9% versus 64.5%; p=0.0002. This study showed significant differences in intakes of vitamins C and E, beta-carotene, folate and vegetables between patients with late-stage AMD and healthy controls, and thus has provided a better understanding of the nutritional intake of patients presenting with advanced AMD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Clinical Characteristics and Prognosis of End-stage Hypertrophic Cardiomyopathy.

PubMed

Xiao, Yan; Yang, Kun-Qi; Yang, Yan-Kun; Liu, Ya-Xin; Tian, Tao; Song, Lei; Jiang, Xiong-Jing; Zhou, Xian-Liang

2015-06-05

End-stage hypertrophic cardiomyopathy (HCM) is complicated by substantial adverse events. However, few studies have focused on electrocardiographic features and their prognostic values in HCM. This study aimed to evaluate the clinical manifestations and prognostic value of electrocardiography in patients with end-stage HCM. End-stage HCM patients were enrolled from a total of 1844 consecutive HCM patients from April 2002 to November 2013 at Fuwai Hospital. Clinical data, including medical history, electrocardiography, and echocardiography, were analyzed. Cox hazards regression analysis was used to assess the risk factors for cardiovascular mortality. End-stage HCM was identified in 99 (5.4%) patients, averaged at 52 ± 16 years old at entry. Atrial fibrillation was observed in 53 patients and mural thrombus in 19 patients. During 3.9 ± 3.0 years of follow-up, embolic stroke, refractory heart failure, and death or transplantation were observed in 20, 39, and 51 patients, respectively. The incidence of annual mortality was 13.2%. Multivariate Cox hazards regression analysis identified New York Heart Association Class (NYHA) III/IV at entry (hazard ratio [HR]: 1.99; 95% confidence interval [CI]: 1.05-3.80; P = 0.036), left bundle branch block (LBBB) (HR: 2.80; 95% CI: 1.47-5.31; P = 0.002), and an abnormal Q wave (HR: 2.21; 95% CI: 1.16-4.23; P = 0.016) as independent predictors of cardiovascular death, in accordance with all-cause death and heart failure-related death. LBBB and an abnormal Q wave are risk factors of cardiovascular mortality in end-stage HCM and provide new evidence for early intervention. Susceptibility of end-stage HCM patients to mural thrombus and embolic events warrants further attention.

Neurofibrillary Tangle Stage and the Rate of Progression of Alzheimer Symptoms: Modeling Using an Autopsy Cohort and Application to Clinical Trial Design

PubMed Central

Qian, Jing; T.Hyman, Bradley; Betensky, Rebecca A.

2017-01-01

Importance The heterogeneity of rate of clinical progression among patients with Alzheimer disease leads to difficulty in providing clinical counseling and diminishes the power of clinical trials using disease-modifying agents. Objective To gain a better understanding of the factors that affect the natural history of progression in Alzheimer disease for the purpose of improving both clinical care and clinical trial design. Design, Setting, and Participants A longitudinal cohort study of aging from 2005 to 2014 in the National Alzheimer Coordinating Center. Clinical evaluation of the participants was conducted in 31 National Institute on Aging’s Alzheimer Disease Centers. Nine hundred eighty-four participants in the National Alzheimer Coordinating Center cohort study who died and underwent autopsy and met inclusion and exclusion criteria. Main Outcomes and Measures We sought to model the possibility that knowledge of neurofibrillary tangle burden in the presence of moderate or frequent plaques would add to the ability to predict clinical rate of progression during the ensuing 2 to 3 years. We examined the National Alzheimer Coordinating Center autopsy data to evaluate the effect of different neurofibrillary tangle stages on the rates of progression on several standard clinical instruments: the Clinical Dementia Rating Scale sum of boxes, a verbal memory test (logical memory), and a controlled oral word association task (vegetable naming), implementing a reverse-time longitudinal modeling approach in conjunction with latent class estimation to adjust for unmeasured sources of heterogeneity. Results Several correlations between clinical variables and neurocognitive performance suggest a basis for heterogeneity: Higher education level was associated with lower Clinical Dementia Rating Scale sum of boxes (β = −0.19; P < .001), and frequent vs moderate neuritic plaques were associated with higher Clinical Dementia Rating Scale sum of boxes (β = 1.64; P

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

PubMed

Chen, Jian; Yang, Wei-Jun; Sun, Hai-Jian; Yang, Xia; Wu, Yu-Zhang

2016-08-01

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.

The impact of eliminating age inequalities in stage at diagnosis on breast cancer survival for older women.

PubMed

Rutherford, M J; Abel, G A; Greenberg, D C; Lambert, P C; Lyratzopoulos, G

2015-03-31

Older women with breast cancer have poorer relative survival outcomes, but whether achieving earlier stage at diagnosis would translate to substantial reductions in mortality is uncertain. We analysed data on East of England women with breast cancer (2006-2010) aged 70+ years. We estimated survival for different stage-deprivation-age group strata using both the observed and a hypothetical stage distribution (assuming that all women aged 75+ years acquired the stage distribution of those aged 70-74 years). We subsequently estimated deaths that could be postponed beyond 5 years from diagnosis if women aged 75+ years had the hypothetical stage distribution. We projected findings to the English population using appropriate age and socioeconomic group weights. For a typically sized annual cohort in the East of England, 27 deaths in women with breast cancer aged 75+ years can be postponed within 5 years from diagnosis if their stage distribution matched that of the women aged 70-74 years (4.8% of all 566 deaths within 5 years post diagnosis in this population). Under assumptions, we estimate that the respective number for England would be 280 deaths (5.0% of all deaths within 5 years post diagnosis in this population). The findings support ongoing development of targeted campaigns aimed at encouraging prompt presentation in older women.

Clinical Presentation and Outcomes of Stage III or Stage IV Retinoblastoma in 80 Asian Indian Patients.

PubMed

Kaliki, Swathi; Patel, Anamika; Iram, Sadiya; Palkonda, Vijay Anand Reddy

2017-05-01

To describe the clinical features and outcomes of patients with stage III or IV retinoblastoma. This was a retrospective study of 80 patients. Based on the International Retinoblastoma Staging System (IRSS), the tumors (n = 81) belonged to stage IIIa (n = 38, 47%), IIIb (n = 1, 1%), IVa2 (n = 10, 12%), IVb1 (n = 14, 17%), and IVb3 (n = 18, 22%). Of 80 patients, 42 (53%) were compliant to treatment and 38 (47%) were non-compliant. All 38 patients who were non-compliant to treatment died of the disease at a mean duration of 13 months from diagnosis. Of the 42 patients compliant to treatment, 22 (52%) died before completion of treatment. Twenty patients with stage III disease (25%) could complete the multimodal treatment and 17 (71%) were alive and well at a median follow-up duration of 77 months. Compliant multimodality treatment is beneficial in patients with IRSS stage III disease. IRSS stage IV retinoblastoma has poor prognosis despite treatment. [J Pediatr Ophthalmol Strabismus. 2017;54(3):177-184.]. Copyright 2017, SLACK Incorporated.

Clinical Characteristics and Current Treatment of Age-Related Macular Degeneration

PubMed Central

Yonekawa, Yoshihiro; Kim, Ivana K.

2015-01-01

Age-related macular degeneration (AMD) is a multifactorial degeneration of photoreceptors and retinal pigment epithelium. The societal impact is significant, with more than 2 million individuals in the United States alone affected by advanced stages of AMD. Recent progress in our understanding of this complex disease and parallel developments in therapeutics and imaging have translated into new management paradigms in recent years. However, there are many unanswered questions, and diagnostic and prognostic precision and treatment outcomes can still be improved. In this article, we discuss the clinical features of AMD, provide correlations with modern imaging and histopathology, and present an overview of treatment strategies. PMID:25280900

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.

The multisystem degeneration amyotrophic lateral sclerosis - neuropathological staging and clinical translation.

PubMed

Verde, Federico; Del Tredici, Kelly; Braak, Heiko; Ludolph, Albert

2017-12-01

Amyotrophic lateral sclerosis (ALS) is traditionally considered a disease affecting exclusively motor neurons. However, much evidence points towards additional involvement of brain systems other than the motor. As much as half of ALS patients display cognitive-behavioral disturbances. ALS shares with a considerable proportion of FTD cases the same neuropathological substrate, namely, inclusions of abnormally phosphorylated protein TDP-43 (pTDP-43). In analogy with pathological staging systems elaborated in the past decades for Alzheimer's disease (AD) and Parkinson's disease (PD), a model of staging of pTDP-43 pathology in sporadic ALS (sALS) has been recently proposed. According to it, 4 stages can be recognized, where pTDP-43 inclusions are found in the agranular motor cortex and α-motor neurons of the brain stem and spinal cord (stage 1), in prefrontal neocortex (middle frontal gyrus), reticular formation, and precerebellar nuclei (stage 2), in further areas of the prefrontal neocortex (gyrus rectus and orbitofrontal gyri), postcentrally located sensory cortex, and basal ganglia (stage 3), and in the anteromedial temporal lobe including the hippocampus (stage 4). Based on this staging effort, a corticofugal axonal model for spreading of pathology can be hypothesized, whereby pathology starts in the primary motor cortex and spreads from there via axonal projections to lower motor neurons and to subcortical structures. Recent neuroradiological evidence seems to support the proposed staging system. From the clinical standpoint, a proportion of ALS patients display extramotor deficits (namely cognitive-behavioural disturbances, impaired ocular movements, and extrapyramidal alterations), which seem to correspond to the pathological involvement of the relevant cerebral structures. This review describes neuropathological sALS staging and addresses clinical evidence corresponding to this staging, pointing towards the concept of ALS as a multisystem brain degeneration

A Bayesian-frequentist two-stage single-arm phase II clinical trial design.

PubMed

Dong, Gaohong; Shih, Weichung Joe; Moore, Dirk; Quan, Hui; Marcella, Stephen

2012-08-30

It is well-known that both frequentist and Bayesian clinical trial designs have their own advantages and disadvantages. To have better properties inherited from these two types of designs, we developed a Bayesian-frequentist two-stage single-arm phase II clinical trial design. This design allows both early acceptance and rejection of the null hypothesis ( H(0) ). The measures (for example probability of trial early termination, expected sample size, etc.) of the design properties under both frequentist and Bayesian settings are derived. Moreover, under the Bayesian setting, the upper and lower boundaries are determined with predictive probability of trial success outcome. Given a beta prior and a sample size for stage I, based on the marginal distribution of the responses at stage I, we derived Bayesian Type I and Type II error rates. By controlling both frequentist and Bayesian error rates, the Bayesian-frequentist two-stage design has special features compared with other two-stage designs. Copyright © 2012 John Wiley & Sons, Ltd.

Validation of the Mayo Clinic Staging System in Determining Prognoses of Patients With Perihilar Cholangiocarcinoma.

PubMed

Coelen, Robert J S; Gaspersz, Marcia P; Labeur, Tim A; van Vugt, Jeroen L A; van Dieren, Susan; Willemssen, François E J A; Nio, Chung Y; IJzermans, Jan N M; Klümpen, Heinz-Josef; Groot Koerkamp, Bas; van Gulik, Thomas M

2017-12-01

Most systems for staging perihilar cholangiocarcinoma (PHC) have been developed for the minority of patients with resectable disease. The recently developed Mayo Clinic system for staging PHC requires only clinical and radiologic variables, but has not yet been validated. We performed a retrospective study to validate the Mayo Clinic staging system. We identified consecutive patients with suspected PHC who were evaluated and treated at 2 tertiary centers in The Netherlands, from January 2002 through December 2014. Baseline characteristics (performance status, carbohydrate antigen 19-9 level) used in the staging system were collected from medical records and imaging parameters (tumor size, suspected vascular involvement, and metastatic disease) were reassessed by 2 experienced abdominal radiologists. Overall survival was analyzed using the Kaplan-Meier method and comparison of staging groups was performed using the log-rank test and Cox proportional hazard regression analysis. Discriminative performance was quantified by the concordance index and compared with the radiologic TNM staging of the American Joint Committee on Cancer (7th ed). PHCs from 600 patients were staged according to the Mayo Clinic model (23 stage I, 80 stage II, 357 stage III, and 140 stage IV). The median overall survival time was 11.6 months. The median overall survival times for patients with stages I, II, III, and IV were 33.2 months, 19.7 months, 12.1 months, and 6.0 months, respectively; with hazard ratios of 1.0 (reference), 2.02 (95% confidence interval [CI], 1.14-3.58), 2.71 (95% CI, 1.59-4.64), and 4.00 (95% CI, 2.30-6.95), respectively (P < .001). The concordance index score was 0.59 for the entire cohort (95% CI, 0.56-0.61). The Mayo Clinic model performed slightly better than the radiologic American Joint Committee on Cancer TNM system. In a retrospective study of 600 patients with PHC, we validated the Mayo Clinic system for staging PHC. This 4-tier staging system may aid

Contemporary, age-based trends in the incidence and management of patients with early-stage kidney cancer.

PubMed

Tan, Hung-Jui; Filson, Christopher P; Litwin, Mark S

2015-01-01

Although kidney cancer incidence and nephrectomy rates have risen in tandem, clinical advances have generated new uncertainty regarding the optimal management of patients with small renal tumors, especially the elderly. To clarify existing practice patterns, we assessed contemporary trends in the incidence and management of patients with early-stage kidney cancer. Using Surveillance, Epidemiology, and End Results data, we identified adult patients diagnosed with T1aN0M0 kidney cancer from 2000 to 2010. We determined age-adjusted and age-specific incidence and management rates (i.e., nonoperative, ablation, partial nephrectomy [PN], and radical nephrectomy) per 100,000 adults and determined the average annual percent change (AAPC). Finally, we compared management groups using multinomial logistic regression accounting for patient characteristics, cancer information, and county-level measures for health. From 2000 to 2010, we identified 41,645 adults diagnosed with T1aN0M0 kidney cancer. Overall incidence increased from 3.7 to 7.0 per 100,000 adults (AAPC = 7.0%, P<0.001). Over the study interval, rates of PN (AAPC = 13.1%, P<0.001) increased substantially, becoming the most used treatment by 2010. Among the elderly, rates of nonoperative management and ablation approached nephrectomy rates for those aged 75 to 84 years and became the predominant strategy for patients older than 84 years. Adjusting for clinical, oncological, and environmental factors, older patients less frequently underwent PN and more often received ablative or nonoperative management (P<0.001). As the incidence of early-stage kidney cancer rises, patients are increasingly treated with nonoperative and nephron-sparing strategies, especially among the most elderly. The broader array of treatment options suggests opportunities to better personalize kidney cancer care for seniors. Published by Elsevier Inc.

Effect of transmission intensity and age on subclass antibody responses to Plasmodium falciparum pre-erythrocytic and blood-stage antigens.

PubMed

Noland, Gregory S; Jansen, Paul; Vulule, John M; Park, Gregory S; Ondigo, Bartholomew N; Kazura, James W; Moormann, Ann M; John, Chandy C

2015-02-01

Cytophilic immunoglobulin (IgG) subclass responses (IgG1 and IgG3) to Plasmodium falciparum antigens have been associated with protection from malaria, yet the relative importance of transmission intensity and age in generation of subclass responses to pre-erythrocytic and blood-stage antigens have not been clearly defined. We analyzed IgG subclass responses to the pre-erythrocytic antigens CSP, LSA-1, and TRAP and the blood-stage antigens AMA-1, EBA-175, and MSP-1 in asymptomatic residents age 2 years or older in stable (n=116) and unstable (n=96) transmission areas in Western Kenya. In the area of stable malaria transmission, a high prevalence of cytophilic (IgG1 and IgG3) antibodies to each antigen was seen in all age groups. Prevalence and levels of cytophilic antibodies to pre-erythrocytic and blood-stage P. falciparum antigens increased with age in the unstable transmission area, yet IgG1 and IgG3 responses to most antigens for all ages in the unstable transmission area were less prevalent and lower in magnitude than even the youngest age group from the stable transmission area. The dominance of cytophilic responses over non-cytophilic (IgG2 and IgG4) was more pronounced in the stable transmission area, and the ratio of IgG3 over IgG1 generally increased with age. In the unstable transmission area, the ratio of cytophilic to non-cytophilic antibodies did not increase with age, and tended to be IgG3-biased for pre-erythrocytic antigens yet IgG1-biased for blood-stage antigens. The differences between areas could not be attributed to active parasitemia status, as there were minimal differences in antibody responses between those positive and negative for Plasmodium infection by microscopy in the stable transmission area. Individuals in areas of unstable transmission have low cytophilic to non-cytophilic IgG subclass ratios and low IgG3:IgG1 ratios to P. falciparum antigens. These imbalances could contribute to the persistent risk of clinical malaria in these

Clinical Factors and Outcomes of Dialysis-Dependent End-Stage Renal Disease Patients with Emergency Department Septic Shock.

PubMed

Lowe, Kevin M; Heffner, Alan C; Karvetski, Colleen H

2018-01-01

Infection is the second leading cause of death in end-stage renal disease (ESRD) patients. Prior investigations of acute septic shock in this specific population are limited. We aimed to evaluate the clinical presentation and factors associated with outcome among ESRD patients with acute septic shock. We reviewed patients prospectively enrolled in an emergency department (ED) septic shock treatment pathway registry between January 2014 and May 2016. Clinical and treatment variables for ESRD patients were compared with non-ESRD patients. A second analysis focused on ESRD septic shock survivors and nonsurvivors. Among 4126 registry enrollees, 3564 (86.4%) met inclusion for the study. End-stage renal disease was present in 3.8% (n = 137) of ED septic shock patients. Hospital mortality was 20.4% and 17.1% for the ESRD and non-ESRD septic shock patient groups (p = 0.31). Septic shock patients with ESRD had a higher burden of chronic illness, but similar admission clinical profiles to non-ESRD patients. End-stage renal disease status was independently associated with lower fluid resuscitation dose, even when controlling for severity of illness. Age and admission lactate were independently associated with mortality in ESRD septic shock patients. ESRD patients comprise a small but important portion of patients with ED septic shock. Although presentation clinical profiles are similar to patients without ESRD, ESRD status is independently associated with lower fluid dose and compliance with the 30-mL/kg fluid goal. Hyperlactatemia is a marker of mortality in ESRD septic shock. Copyright © 2017 Elsevier Inc. All rights reserved.

The reliability of clinical decisions based on the cervical vertebrae maturation staging method.

PubMed

Sohrabi, Aydin; Babay Ahari, Sahar; Moslemzadeh, Hossein; Rafighi, Ali; Aghazadeh, Zahra

2016-02-01

Of the various techniques used to determine the optimum timing for growth modification treatments, the cervical vertebrae maturation method has great advantages, including validity and no need for extra X-ray exposure. Recently, the reproducibility of this method has been questioned. The aim of this study was to investigate the cause of poor reproducibility of this method and to assess the reproducibility of the clinical decisions made based on it. Seventy lateral cephalograms of Iranian patients aged 9‒15 years were observed twice by five experienced orthodontists. In addition to determining the developmental stage, each single parameter involved in this method was assessed in terms of inter- and intra-observer reproducibility. In order to evaluate the reproducibility of clinical decisions based on this method, cervical vertebrae maturation staging (CVMS) I and II were considered as phase 1 and CVMS IV and V were considered as phase 3. By considering the clinical approach of the CVMS method, inter-observer reproducibility of this method increased from 0.48 to 0.61 (moderate to substantial) and intra-observer reproducibility enhanced from 0.72 to 0.74. 1. Complete visualization of the first four cervical vertebrae was an inclusion criterion, which also limits the clinical application of CVMS method. 2. These results can be generalized when determining growth modification treatments solely for Class II patients. Difficulty in determining the morphology of C3 and C4 leads to poor reproducibility of the CVMS method. Despite this, it has acceptable reproducibility in determining the timing of functional treatment for Class II patients. © The Author 2015. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Forensic age estimation based on development of third molars: a staging technique for magnetic resonance imaging.

PubMed

De Tobel, J; Phlypo, I; Fieuws, S; Politis, C; Verstraete, K L; Thevissen, P W

2017-12-01

The development of third molars can be evaluated with medical imaging to estimate age in subadults. The appearance of third molars on magnetic resonance imaging (MRI) differs greatly from that on radiographs. Therefore a specific staging technique is necessary to classify third molar development on MRI and to apply it for age estimation. To develop a specific staging technique to register third molar development on MRI and to evaluate its performance for age estimation in subadults. Using 3T MRI in three planes, all third molars were evaluated in 309 healthy Caucasian participants from 14 to 26 years old. According to the appearance of the developing third molars on MRI, descriptive criteria and schematic representations were established to define a specific staging technique. Two observers, with different levels of experience, staged all third molars independently with the developed technique. Intra- and inter-observer agreement were calculated. The data were imported in a Bayesian model for age estimation as described by Fieuws et al. (2016). This approach adequately handles correlation between age indicators and missing age indicators. It was used to calculate a point estimate and a prediction interval of the estimated age. Observed age minus predicted age was calculated, reflecting the error of the estimate. One-hundred and sixty-six third molars were agenetic. Five percent (51/1096) of upper third molars and 7% (70/1044) of lower third molars were not assessable. Kappa for inter-observer agreement ranged from 0.76 to 0.80. For intra-observer agreement kappa ranged from 0.80 to 0.89. However, two stage differences between observers or between staging sessions occurred in up to 2.2% (20/899) of assessments, probably due to a learning effect. Using the Bayesian model for age estimation, a mean absolute error of 2.0 years in females and 1.7 years in males was obtained. Root mean squared error equalled 2.38 years and 2.06 years respectively. The performance to

Analysis of Stage and Clinical/Prognostic Factors for Lung Cancer from SEER Registries: AJCC Staging and Collaborative Stage Data Collection System

PubMed Central

Chen, Vivien W.; Ruiz, Bernardo A.; Hsieh, Mei-Chin; Wu, Xiao-Cheng; Ries, Lynn; Lewis, Denise R.

2014-01-01

Introduction The American Joint Committee on Cancer (AJCC) 7th edition introduced major changes in the staging of lung cancer, including Tumor (T), Node (N), Metastasis (M) (TNM) system and new stage/prognostic site-specific factors (SSFs), collected under the Collaborative Stage Version 2 (CSv2) Data Collection System. The intent was to improve the stage precision which could guide treatment options and ultimately lead to better survival. This report examines stage trends, the change in stage distributions from the AJCC 6th to the 7th edition, and findings of the prognostic SSFs for 2010 lung cancer cases. Methods Data were from the November 2012 submission of 18 Surveillance, Epidemiology, and End Results (SEER) Program population-based registries. A total of 344 797 cases of lung cancer, diagnosed in 2004–2010, were analyzed. Results The percentages of small tumors and early stage lung cancer cases increased from 2004 to 2010. The AJCC 7th edition, implemented for 2010 diagnosis year, subclassified tumor size and reclassified multiple tumor nodules, pleural effusions, and involvement of tumors in the contralateral lung, resulting in a slight decrease in stage IB and stage IIIB and a small increase in stage IIA and stage IV. Overall about 80% of cases remained the same stage group in AJCC 6th and 7th editions. About 21% of lung cancer patients had separate tumor nodules in the ipsilateral (same) lung, and 23% of the surgically resected patients had visceral pleural invasion, both adverse prognostic factors. Conclusion It is feasible for high quality population-based registries such as the SEER Program to collect more refined staging and prognostic SSFs that allows better categorization of lung cancer patients with different clinical outcomes and to assess their survival. PMID:25412390

The power of personality in discriminating between healthy aging and early-stage Alzheimer's disease.

PubMed

Duchek, Janet M; Balota, David A; Storandt, Martha; Larsen, Randy

2007-11-01

This study examined differences in personality in the earliest stages of dementia of the Alzheimer type (DAT) relative to healthy aging, and the power of personality in discriminating healthy aging from early-stage DAT. Four groups of participants (middle-aged controls, older controls, persons with very mild DAT, and persons with mild DAT) and their families were administered Costa and McCrae's NEO Five-Factor Inventory. On the basis of both self-report and informant report, there was an increase in neuroticism and a decrease in conscientiousness in persons with very mild DAT relative to healthy individuals without it, and in persons with mild DAT relative to those with very mild DAT. Moreover, informant reports of neuroticism and conscientiousness capture substantial unique variance in discriminating healthy aging and very mild DAT, above and beyond standard neuropsychological tests. Discussion focuses on the importance of personality traits as a noncognitive indicator of early-stage DAT.

Age-related inequalities in health and healthcare: the life stages approach.

PubMed

Jecker, Nancy S

2018-06-01

How should healthcare systems prepare to care for growing numbers and proportions of older people? Older people generally suffer worse health than younger people do. Should societies take steps to reduce age-related health inequalities? Some express concern that doing so would increase age-related inequalities in healthcare. This paper addresses this debate by (1) presenting an argument in support of three principles for distributing scarce resources between age groups; (2) framing these principles of age group justice in terms of life stages; and (3) indicating policy implications that merit further attention in light of rapidly aging societies. © 2017 John Wiley & Sons Ltd.

Age- or stage-appropriate? Recreation and the relevance of Piaget's theory in dementia care.

PubMed

Mahoney, Alison E J

2003-01-01

In this study, the immediate effects (within 10 minutes) of age- and stage-appropriate activities and two control activities were observed in 56 dementia sufferers. Compared with the control activities, the two experimental treatment conditions elicited greater reductions in agitation and negative emotion and increases in positive emotion and duration of activity. Stage-appropriate activity was superior to age-appropriate activity in increasing positive emotion and had about the same effect in reducing negative emotion and agitation. The study also addressed the idea that people with Alzheimer's disease may regress through Piaget's stages of cognitive development and thus display the play interests associated with each stage. There was a significant relationship between cognitive level and type of Piagetian play observed; however, Piaget's descriptions of play were not entirely appropriate for persons with with Alzheimer's disease.

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.

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

Propensity score-matching analysis of hybrid video-assisted thoracoscopic surgery and thoracoscopic lobectomy for clinical stage I lung cancer†.

PubMed

Iwata, Hisashi; Shirahashi, Koyo; Yamamoto, Hirotaka; Marui, Tsutomu; Matsumoto, Shinsuke; Mizuno, Yoshimasa; Matsumoto, Mitsuyoshi; Mitta, Shohei; Miyamoto, Yusaku; Komuro, Hiroyasu

2016-04-01

Video-assisted thoracoscopic surgery (VATS) lobectomy is classified into hybrid VATS (direct and video vision) and thoracoscopic VATS (video vision only). In this study, the outcomes of hybrid VATS and thoracoscopic VATS for clinical stage I lung cancer were compared using a propensity score-matching analysis. Hybrid and thoracoscopic VATS were performed in 178 and 76 patients, respectively. Propensity scores were calculated using logistic regression analysis and matched within a score of ±0.03 for age, sex, size of tumour, Charlson comorbidity index, preoperative therapy, percent vital capacity, forced expiratory volume in 1 s, clinical stage, pathological stage and histology. In the non-matched analysis, the results for hybrid and thoracoscopic VATS, respectively, were as follows: mean age, 69 ± 9 and 66 ± 10 years (P = 0.04); tumour size, 24 ± 10 and 20 ± 7 mm (P < 0.01); 2-deoxy-2 [F-18]fluorodeoxyglucose positron emission tomography SUV, 5.6 ± 4.4 and 3.6 ± 3.2 (P < 0.01); clinical stage (IA/IB), 130/48 and 69/7 (P < 0.01); pathological stage (IA/IB/IIA and IIB/IIIA and IIIB), 89/56/15/18 and 57/14/2/3 (P < 0.01); postoperative complications, 66 (37.1%) and 16 (21.1%; P = 0.01); respiratory complications, 32 (18.0%) and 6 (7.9%; P = 0.04); 5-year overall survival (OS), 77.0 and 88.8% (log-rank P = 0.045); and 5-year disease-free survival (DFS), 67.2 and 81.1% (log-rank P = 0.02). In 66 matched cases, the results for hybrid and thoracoscopic VATS, respectively, were as follows: mean operative time, 245 ± 96 and 285 ± 85 min (P = 0.01); blood loss, 95 ± 100 and 86 ± 123 ml (P = 0.67); mean duration of drainage, 3.6 ± 2.7 and 3.2 ± 2.2 days (P = 0.37); postoperative complications, 21 (31.8%) and 14 (21.2%; P = 0.17); respiratory complications, 11 (16.7%) and 5 (7.6%; P = 0.11); 5-year OS, 72.5 and 86.0% (log-rank P = 0.25); and 5-year DFS, 68.4 and 77.2% (log-rank P = 0.17). In this single-institution, propensity score-matched study, hybrid VATS

Clinical, radiological and laboratory findings in 185 children with tuberculous meningitis at a single centre and relationship with the stage of the disease.

PubMed

Güneş, Ali; Uluca, Ünal; Aktar, Fesih; Konca, Çapan; Şen, Velat; Ece, Aydın; Hoşoğlu, Salih; Taş, Mehmet Ali; Gürkan, Fuat

2015-10-15

A delay in the diagnosis and treatment of tuberculosis meningitis (TBM) may lead to increased mortality and morbidity. The aim of this study was to describe the clinical, radiological and laboratory findings of TBM on a cohort of 185 pediatric patients at a single centre over a 10 year period and to investigate relationship between the stage of the disease. The hospital records of 185 TBM children that presented to the Pediatric Clinics of Dicle University Hospital were retrospectively evaluated. The age, gender, family history of tuberculosis, result of Mantoux skin test, status of BCG vaccination, stage of TBM at hospitalization, and clinical, laboratory and radiological features were recorded. Clinical staging of TBM was defined as follows: Stage I, no focal neurological findings and Glasgow Coma Scale (GCS) score 15; Stage II, GCS 15 presenting with focal neurological deficit or all the patients with GCS 10-14; Stage III, all the patients with GCS < 10. Relationships between results and stages of TBM were investigated. The mean age of the patients was 53.5 ± 44.9 months (4 months-18 years). 121 (65.4 %) of the patients were male and 64 (34.6 %) female. Family history of tuberculosis was defined in 62 (33.5 %) patients. Forty five (24.3 %) children had BCG vaccination scar. Mantoux skin test was interpreted as positive in 35 (18.9 %) patients. Sixty-eight (36.8 %) children were at stage I TBM, 57 (30.8 %) at stage II and 60 (32.4 %) were at stage III on admission. Mean duration of hospitalization was 23.9 ± 14.1 days. Totally, 90 patients (48.6 %) had abnormal chest X-ray findings (parenchymal infiltration in 46 (24.9 %), mediastinal lymphadenopathy in 36 (19.5 %), miliary opacities in 25 (13.5 %), pleural effusion in 2 (1.1 %), and atelectasis in 2 (1.1 %) patients). One hundred sixty seven (90.3 %) patients had hydrocephalus in cranial computerized tomography. There were 24 (13.0 %) patients with positive culture for

At-risk studies and clinical antecedents of psychosis, bipolar disorder and depression: a scoping review in the context of clinical staging.

PubMed

Hartmann, Jessica A; Nelson, Barnaby; Ratheesh, Aswin; Treen, Devi; McGorry, Patrick D

2018-06-04

Identifying young people at risk of developing serious mental illness and identifying predictors of onset of illness has been a focus of psychiatric prediction research, particularly in the field of psychosis. Work in this area has facilitated the adoption of the clinical staging model of early clinical phenotypes, ranging from at-risk mental states to chronic and severe mental illness. It has been a topic of debate if these staging models should be conceptualised as disorder-specific or transdiagnostic. In order to inform this debate and facilitate cross-diagnostic discourse, the present scoping review provides a broad overview of the body of literature of (a) longitudinal at-risk approaches and (b) identified antecedents of (homotypic) illness progression across three major mental disorders [psychosis, bipolar disorder (BD) and depression], and places these in the context of clinical staging. Stage 0 at-risk conceptualisations (i.e. familial high-risk approaches) were identified in all three disorders. However, formalised stage 1b conceptualisations (i.e. ultra-high-risk approaches) were only present in psychosis and marginally in BD. The presence of non-specific and overlapping antecedents in the three disorders may support a general staging model, at least in the early stages of severe psychotic or mood disorders.

Clinical stages in patients with primary and subsequent cancers based on the czech cancer registry 1976-2005.

PubMed

Geryk, Edvard; Stampach, Radim; Dítě, Petr; Kozel, Jiří; Horváth, Teodor; Kubíček, Petr

2013-01-01

Of 1,486,984 new cancers registered in the Czech Cancer Registry in 1976-2005, 290,312 (19.5%) were multiple malignant neoplasms (MMNs), of which there were 65,292 primary and 89,796 subsequent cases in men and 59,970 primary and 75,254 subsequent cases in women. The duplicities were higher in women, and the triplicities and others (3-6 MMNs) were higher in men. The most frequent diagnoses were the primary cancers of skin, gastrointestinal and urinary tract, male genital organs, respiratory tract in men, and cancers of skin, breast, female genital organs, and gastrointestinal tract in women. The analysis of the early and advanced clinical stages shows that the number of subsequent advanced stages increased after primary advanced stages. Their time-age-space distributions visualized maps of MMNs in 14 Czech regions. These results support the improvement of algorithms of dispensary care for the early detection of the subsequent neoplasms.

Ages & Stages Questionnaire–Brazil–2011

PubMed Central

Santana, Cristina M. T.; Filgueiras, Alberto; Landeira-Fernandez, J.

2015-01-01

Introduction. Professionals who assess early childhood development highly benefit from reliable development screening measures. The Ages & Stages Questionnaire was adapted Brazil in 2010 and named ASQ-BR. Modifications in some items were required to improve the instrument’s psychometric properties. The present study modified the ASQ-BR to verify if those changes increase its characteristics. Method. This study researched 67 522 children from 972 public day care centers and preschools. Changes in items were made considering Cronbach’s α and item-to-total correlations. Reliability, dimensionality, and item-to-total correlations were calculated. Results. Regarding dimensionality, 86.2% of the scales in ASQ-BR-2011 were unidimensional. Internal consistency showed improvement from 2010 to 2011: 53.8% of the scales increased the α statistics against 41.2% that decreased, and 5.0% remained the same. Finally, 65.2% of the modified items showed improvement. Conclusions. Overall, the instrument’s psychometrics improved from 2010 to 2011, especially in the personal/social domain. However, it still leaves room for improvement in future studies. PMID:27335984

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.

International neuroblastoma staging system stage 1 neuroblastoma: a prospective study and literature review.

PubMed

Kushner, B H; Cheung, N K; LaQuaglia, M P; Ambros, P F; Ambros, I M; Bonilla, M A; Ladanyi, M; Gerald, W L

1996-07-01

To gain insight into the management of non-metastatic neuroblastoma by examining clinical and biologic features of International Neuroblastoma Staging System (INSS) stage 1 tumors. Patients were staged by both the INSS and the Evans staging system and were evaluated for biologic prognostic factors. Patients with INSS stage 1 received no cytotoxic therapy. The literature was reviewed for clinical and biologic data about INSS stage 1. We evaluated 10 consecutive patients (median age, 17.5 months) with INSS stage 1; all remain disease-free (median follow-up duration, > 5 years). Tumors were in the abdomen (n = 6), chest (n = 3), or pelvis (n = 1). Neuroblastoma involved margins of resection in six tumors. Poor-prognostic biologic findings included tumor-cell diploidy (n = 2) and unfavorable Shimada histopathology (n = 2). Two patients were to receive chemotherapy for, respectively, a tumor deemed unresectable and a tumor classified as Evans stage III; second opinions resulted in surgical management alone in each case. Published reports confirm that some INSS stage 1 patients (1) are at risk for overtreatment, and (2) have poor-prognostic biologic findings yet do well. Surgery alone suffices for INSS stage 1 neuroblastoma, even if biologic prognostic factors are unfavorable, microscopic disease remains after surgery, and tumor size is suggestive of "advanced-stage" status in other staging systems. Attempts to resect regionally confined neuroblastomas should take precedence over immediate use of cytotoxic therapy; otherwise, some patients may receive chemotherapy or radiotherapy unnecessarily.

Early Childhood Psychosocial Screening in Culturally Diverse Populations: A Survey of Clinical Experience With the Ages and Stages Questionnaires: Social-Emotional (ASQ:SE)

ERIC Educational Resources Information Center

Lyman, D. Russell; Njoroge, Wanjiku F. M.; Willis, David W.

2007-01-01

The authors developed a qualitative study to seek the feedback of service providers with regard to the usefulness of the Ages and Stages Questionnaire: Social Emotional as a screening tool for multicultural populations. They addressed provider satisfaction with the tool by surveying a multidisciplinary sample of practitioners who provide a range…

Clinical Pathways: A Catalyst for the Adoption of Hypofractionation for Early-Stage Breast Cancer

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

Chapman, Bhavana V.; Rajagopalan, Malolan S.; Heron, Dwight E.

2015-11-15

Purpose: Hypofractionated whole-breast irradiation (HF-WBI) remains underutilized in the United States despite support by multiple clinical trials. We evaluated the success of iterative modifications of our breast cancer clinical pathway on the adoption of HF-WBI in a large, integrated radiation oncology network. Methods and Materials: The breast clinical pathway was modified in January 2011 (Amendment 1) to recommend HF-WBI as the first option for women ≥70 of age with stages 0 to IIA, while maintaining conventional fractionation (CF) as a pathway-concordant secondary option. In January 2013 (Amendment 2), the pathway's HF-WBI recommendation was extended to women ≥50 years of age.more » In January 2014 (Amendment 3), the pathway mandated HF-WBI as the only pathway-concordant option in women ≥50 years of age, and all pathway-discordant plans were subject to peer review and justification. Women ≥50 years of age with ductal carcinoma in situ or invasive breast cancer who underwent breast conserving surgery and adjuvant WBI were included in this analysis. Results: We identified 5112 patients from 2009 to 2014 who met inclusion criteria. From 2009 to 2012, the overall HF-WBI use rate was 8.3%. Following Amendments 2 and 3 (2013 and 2014, respectively), HF-WBI use significantly increased to 21.8% (17.3% in the community, 39.7% at academic sites) and 76.7% (75.5% in the community, 81.4% at academic sites), respectively (P<.001). Compared to 2009 to 2012, the relative risk of using HF-WBI was 7.9 (95% confidence interval: 7.1-8.6, P<.001) and 10.7 (95% CI: 10.3-11.0, P<.001), respectively, after Amendments 2 and 3, respectively. Age ≥70 and treatment at an academic site increased the likelihood of receiving HF-WBI in 2009 to 2012 and following Amendment 2 (P<.001). Conclusions: This study demonstrates the transformative effect of a clinical pathway on patterns of care for breast radiation therapy. Although our initial HF-WBI use rate was low (8%-22%) and

Systematic genomic identification of colorectal cancer genes delineating advanced from early clinical stage and metastasis

PubMed Central

2013-01-01

Background Colorectal cancer is the third leading cause of cancer deaths in the United States. The initial assessment of colorectal cancer involves clinical staging that takes into account the extent of primary tumor invasion, determining the number of lymph nodes with metastatic cancer and the identification of metastatic sites in other organs. Advanced clinical stage indicates metastatic cancer, either in regional lymph nodes or in distant organs. While the genomic and genetic basis of colorectal cancer has been elucidated to some degree, less is known about the identity of specific cancer genes that are associated with advanced clinical stage and metastasis. Methods We compiled multiple genomic data types (mutations, copy number alterations, gene expression and methylation status) as well as clinical meta-data from The Cancer Genome Atlas (TCGA). We used an elastic-net regularized regression method on the combined genomic data to identify genetic aberrations and their associated cancer genes that are indicators of clinical stage. We ranked candidate genes by their regression coefficient and level of support from multiple assay modalities. Results A fit of the elastic-net regularized regression to 197 samples and integrated analysis of four genomic platforms identified the set of top gene predictors of advanced clinical stage, including: WRN, SYK, DDX5 and ADRA2C. These genetic features were identified robustly in bootstrap resampling analysis. Conclusions We conducted an analysis integrating multiple genomic features including mutations, copy number alterations, gene expression and methylation. This integrated approach in which one considers all of these genomic features performs better than any individual genomic assay. We identified multiple genes that robustly delineate advanced clinical stage, suggesting their possible role in colorectal cancer metastatic progression. PMID:24308539

Challenges of assessing the clinical efficacy of asexual blood-stage Plasmodium falciparum malaria vaccines.

PubMed

Sheehy, Susanne H; Douglas, Alexander D; Draper, Simon J

2013-09-01

In the absence of any highly effective vaccine candidate against Plasmodium falciparum malaria, it remains imperative for the field to pursue all avenues that may lead to the successful development of such a formulation. The development of a subunit vaccine targeting the asexual blood-stage of Plasmodium falciparum malaria infection has proven particularly challenging with only limited success to date in clinical trials. However, only a fraction of potential blood-stage vaccine antigens have been evaluated as targets, and a number of new promising candidate antigen formulations and delivery platforms are approaching clinical development. It is therefore essential that reliable and sensitive methods of detecting, or ruling out, even modest efficacy of blood-stage vaccines in small clinical trials be established. In this article we evaluate the challenges facing blood-stage vaccine developers, assess the appropriateness and limitations of various in vivo approaches for efficacy assessment and suggest future directions for the field.

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. © The Author(s) 2016.

Identifying the most appropriate age threshold for TNM stage grouping of well-differentiated thyroid cancer.

PubMed

Hendrickson-Rebizant, J; Sigvaldason, H; Nason, R W; Pathak, K A

2015-08-01

Age is integrated in most risk stratification systems for well-differentiated thyroid cancer (WDTC). The most appropriate age threshold for stage grouping of WDTC is debatable. The objective of this study was to evaluate the best age threshold for stage grouping by comparing multivariable models designed to evaluate the independent impact of various prognostic factors, including age based stage grouping, on the disease specific survival (DSS) of our population-based cohort. Data from population-based thyroid cancer cohort of 2125 consecutive WDTC, diagnosed during 1970-2010, with a median follow-up of 11.5 years, was used to calculate DSS using the Kaplan Meier method. Multivariable analysis with Cox proportional hazard model was used to assess independent impact of different prognostic factors on DSS. The Akaike information criterion (AIC), a measure of statistical model fit, was used to identify the most appropriate age threshold model. Delta AIC, Akaike weight, and evidence ratios were calculated to compare the relative strength of different models. The mean age of the patients was 47.3 years. DSS of the cohort was 95.6% and 92.8% at 10 and 20 years respectively. A threshold of 55 years, with the lowest AIC, was identified as the best model. Akaike weight indicated an 85% chance that this age threshold is the best among the compared models, and is 16.8 times more likely to be the best model as compared to a threshold of 45 years. The age threshold of 55 years was found to be the best for TNM stage grouping. Copyright © 2015 Elsevier Ltd. All rights reserved.

Clinical and histopathological factors affecting failed sentinel node localization in axillary staging for breast cancer.

PubMed

Dordea, Matei; Colvin, Hugh; Cox, Phil; Pujol Nicolas, Andrea; Kanakala, Venkat; Iwuchukwu, Obi

2013-04-01

Sentinel lymph node biopsy (SLNB) has become the standard of care in axillary staging of clinically node-negative breast cancer patients. To analyze reasons for failure of SLN localization by means of a multivariate analysis of clinical and histopathological factors. We performed a review of 164 consecutive breast cancer patients who underwent SLNB. A superficial injection technique was used. 9/164 patients failed to show nodes. In 7/9 patients no evidence of radioactivity or blue dye was observed. Age and nodal status were the only statistically significant factors (p < 0.05). For every unit increase in age there was a 9% reduced chance of failed SLN localization. Patients with negative nodal status have 90% reduced risk of failed sentinel node localization than patients with macro or extra capsular nodal invasion. The results suggest that altered lymphatic dynamics secondary to tumour burden may play a role in failed sentinel node localization. We showed that in all failed localizations the radiocolloid persisted around the injection site, showing limited local diffusion only. While clinical and histopathological data may provide some clues as to why sentinel node localization fails, we further hypothesize that integrity of peri-areolar lymphatics is important for successful localization. Copyright © 2012 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.

Thoroughness of Mediastinal Staging in Stage IIIA Non-Small Cell Lung Cancer

PubMed Central

Vest, Michael T.; Tanoue, Lynn; Soulos, Pamela R.; Kim, Anthony W.; Detterbeck, Frank; Morgensztern, Daniel; Gross, Cary P.

2011-01-01

Introduction Guidelines recommend that patients with clinical stage IIIA non-small cell lung cancer (NSCLC) undergo histologic confirmation of pathologic lymph nodes. Studies have suggested that invasive mediastinal staging is underutilized, though practice patterns have not been rigorously evaluated. Methods We used the Surveillance, Epidemiology, and End Results-Medicare database to identify patients with stage IIIA NSCLC diagnosed from 1998 through 2005. Invasive staging and use of positron emission tomography (PET) scanning were assessed using Medicare claims. Multivariable logistic regression was used to identify patient characteristics associated with use of invasive staging. Results Of 7583 stage IIIA NSCLC patients, 1678 (22%) underwent invasive staging. Patients who received curative intent cancer treatment were more likely to undergo invasive staging than patients who did not receive cancer specific therapy (30% vs. 9.8%, adjusted odds ratio [OR} 3.31, 95% CI 2.78–3.95). The oldest patients (age 85–94) were less likely to receive invasive staging than the youngest ((age 67–69) (27.6 % vs. 11.9%, OR 0.46, 95% CI 0.34–0.61)). Sex, marital status, income and race were not associated with the use of the invasive staging. The use of invasive staging was stable throughout the study period, despite an increase in the use of PET scanning from less than 10% of patients prior to 2000 to almost 70% in 2005. Conclusion Nearly 80% of Medicare beneficiaries with stage IIIA NSCLC do not receive guideline adherent mediastinal staging; this failure cannot be entirely explained by patient factors or a reliance on PET imaging. Incentives to encourage use of invasive staging may improve care. PMID:22134069

Development and validation of a clinically applicable score to classify cachexia stages in advanced cancer patients

PubMed Central

Zhou, Ting; Wang, Bangyan; Liu, Huiquan; Yang, Kaixiang; Thapa, Sudip; Zhang, Haowen; Li, Lu

2018-01-01

Abstract Background Cachexia is a multifactorial syndrome that is highly prevalent in advanced cancer patients and leads to progressive functional impairments. The classification of cachexia stages is essential for diagnosing and treating cachexia. However, there is a lack of simple tools with good discrimination for classifying cachexia stages. Therefore, our study aimed to develop a clinically applicable cachexia staging score (CSS) and validate its discrimination of clinical outcomes for different cachexia stages. Methods Advanced cancer patients were enrolled in our study. A CSS comprising the following five components was developed: weight loss, a simple questionnaire of sarcopenia (SARC‐F), Eastern Cooperative Oncology Group, appetite loss, and abnormal biochemistry. According to the CSS, patients were classified into non‐cachexia, pre‐cachexia, cachexia, and refractory cachexia stages, and clinical outcomes were compared among the four groups. Results Of the 297 participating patients, data from 259 patients were ultimately included. Based on the CSS, patients were classified into non‐cachexia (n = 69), pre‐cachexia (n = 68), cachexia (n = 103), and refractory cachexia (n = 19) stages. Patients with more severe cachexia stages had lower skeletal muscle indexes (P = 0.002 and P = 0.004 in male and female patients, respectively), higher prevalence of sarcopenia (P = 0.017 and P = 0.027 in male and female patients, respectively), more severe symptom burden (P < 0.001), poorer quality of life (P < 0.001 for all subscales except social well‐being), and shorter survival times (P < 0.001). Conclusions The CSS is a simple and clinically applicable tool with excellent discrimination for classifying cachexia stages. This score is extremely useful for the clinical treatment and prognosis of cachexia and for designing clinical trials. PMID:29372594

Clinical outcome of fiducial-less CyberKnife radiosurgery for stage I non-small cell lung cancer

PubMed Central

Jung, In-Hye; Jung, Jinhong; Cho, Byungchul; Kwak, Jungwon; Je, Hyoung Uk; Choi, Wonsik; Jung, Nuri Hyun; Kim, Su Ssan; Choi, Eun Kyung

2015-01-01

Purpose To evaluate the treatment results in early stage non-small cell lung cancer patients who have undergone fiducial-less CyberKnife radiosurgery (CKRS). Materials and Methods From June 2011 to November 2013, 58 patients underwent CKRS at Asan Medical Center for stage I lung cancer. After excluding 14 patients, we retrospectively reviewed the records of the remaining 44 patients. All analyses were performed using SPSS ver. 21. Results The median age at diagnosis was 75 years. Most patients had inoperable primary lung cancer with a poor pulmonary function test with comorbidity or old age. The clinical stage was IA in 30 patients (68.2%), IB in 14 (31.8%). The mean tumor size was 2.6 cm (range, 1.2 to 4.8 cm), and the tumor was smaller than 2 cm in 12 patients (27.3%). The radiation dose given was 48-60 Gy in 3-4 fractions. In a median follow-up of 23.1 months, local recurrence occurred in three patients (2-year local recurrence-free survival rate, 90.4%) and distant metastasis occurred in 13 patients. All patients tolerated the radiosurgery well, only two patients developing grade 3 dyspnea. The most common complications were radiation-induced fibrosis and pneumonitis. Eight patients died due to cancer progression. Conclusion The results showed that fiducial-less CKRS shows comparable local tumor control and survival rates to those of LINAC-based SABR or CKRS with a fiducial marker. Thus, fiducial-less CKRS using Xsight lung tracking system can be effectively and safely performed for patients with medically inoperable stage I non-small cell lung cancer without any risk of procedure-related complication. PMID:26157678

[Impact of microdose clinical trials in the preclinical stage].

PubMed

Kim, Soonih

2014-01-01

A microdose clinical trial may be useful as a safe early-phase exploratory study using doses as low as 100 μg or less for determination of the disposition of a candidate compound in humans in a short period of time. This may increase confidence in candidate compounds, especially those for which it is difficult to predict disposition based on the results of in vitro or preclinical studies. In this study, we examined microdose trials performed in the preclinical stage for two first-in-class compounds with a new mechanism of action. These compounds showed species difference in first pass metabolism in the digestive tract and liver, causing uncertainty in prediction of disposition in humans. For this reason, first-in-human microdose clinical trials were performed. The results showed that the two compounds had effective blood concentrations after oral administration at a dose of 100 mg qd. Administration of an extremely small dose of one (14)C-labeled compound permitted identification of major metabolites. No toxic metabolites were detected. The preclinical toxic dose was determined based on prediction of blood exposure at the estimated maximum clinical dose. For the other candidate compound, the findings of the microdose trial indicated a high bioavailability after oral administration and low hepatic clearance after intravenous administration. These results suggested only a small risk of a change in disposition in patients with hepatic disorder. The data obtained for the two compounds suggest that microdose clinical trials can be useful for improving the process of candidate selection in the preclinical stage.

8th edition AJCC/UICC staging of cancers of the esophagus and esophagogastric junction: application to clinical practice.

PubMed

Rice, Thomas W; Patil, Deepa T; Blackstone, Eugene H

2017-03-01

The 8th edition of the American Joint Committee on Cancer (AJCC) staging of epithelial cancers of the esophagus and esophagogastric junction (EGJ) presents separate classifications for clinical (cTNM), pathologic (pTNM), and postneoadjuvant (ypTNM) stage groups. Histopathologic cell type markedly affects survival of clinically and pathologically staged patients, requiring separate groupings for each cell type, but ypTNM groupings are identical for both cell types. Clinical categories, typically obtained by imaging with minimal histologic information, are limited by resolution of each method. Strengths and shortcomings of clinical staging methods should be recognized. Complementary cytology or histopathology findings may augment imaging and aid initial treatment decision-making. However, prognostication using clinical stage groups remains coarse and inaccurate compared with pTNM. Pathologic staging is losing its relevance for advanced-stage cancer as neoadjuvant therapy replaces esophagectomy alone. However, it remains relevant for early-stage cancers and as a staging and survival reference point. Although pathologic stage could facilitate decision-making, its use to direct postoperative adjuvant therapy awaits more effective treatment. Prognostication using pathologic stage groups is the most refined of all classifications. Postneoadjuvant staging (ypTNM) is introduced by the AJCC but not adopted by the Union for International Cancer Control (UICC). Drivers of this addition include absence of equivalent pathologic (pTNM) categories for categories peculiar to the postneoadjuvant state (ypT0N0-3M0 and ypTisN0-3M0), dissimilar stage group compositions, and markedly different survival profiles. Thus, prognostication is specific for patients undergoing neoadjuvant therapy. The role of ypTNM classification in additional treatment decision-making is currently limited. Precision cancer care advances are necessary for this information to be clinically useful.

Stage of visual field loss and age at diagnosis in 1988 patients with different glaucomas: implications for glaucoma screening and driving ability.

PubMed

Gramer, Gwendolyn; Gramer, Eugen

2018-04-01

To compare stage of visual field loss (VFL) and age at diagnosis between patients with different types of glaucoma with regard to glaucoma screening and driving ability. In a cross-sectional study of 1988 consecutive patients with different types of glaucoma VFL at diagnosis and age at diagnosis were assessed. Patients with binocular advanced or severe VFL were classified unable, patients with no VFL in one eye and VFL I-V (Aulhorn classification) in the other eye able, all other constellations questionably able to drive. There were significant differences in age at diagnosis between different glaucomas and between patients with different stages of VFL at diagnosis. Age-related assessment of VFL at diagnosis in normal tension glaucoma (NTG) compared to primary open-angle glaucoma (POAG) showed that NTG is not a disease of the elderly but a disease with late diagnosis at severe VFL. In POAG a solely age-related glaucoma screening, e.g. from the age of 50 years, does not sufficiently lead to diagnosis at an early stage of the disease. In POAG solely based on binocular VFL 11.5% of patients were judged unable, 29.2% questionably able to drive, in NTG 19.6%/43.1%, pigmentary glaucoma 16%/22%, pseudoexfoliation glaucoma 9.1%/16.7%, and in primary angle-closure glaucoma 14.6%/30%. Depending on type of glaucoma more than 50% of patients require counselling regarding safe driving as part of clinical care. A disease-specific, age-related perimetric examination considering additional risk factors like family history of glaucoma is essential for early detection of glaucoma and road safety.

Inflammation-based scoring is a useful prognostic predictor of pulmonary resection for elderly patients with clinical stage I non-small-cell lung cancer.

PubMed

Miyazaki, Takuro; Yamasaki, Naoya; Tsuchiya, Tomoshi; Matsumoto, Keitaro; Kunizaki, Masaki; Taniguchi, Daisuke; Nagayasu, Takeshi

2015-04-01

The number of elderly lung cancer patients requiring surgery has been increasing due to the ageing society and less invasive perioperative procedures. Elderly people usually have various comorbidities, but there are few simple and objective tools that can be used to determine prognostic factors for elderly patients with clinical stage I non-small-cell lung cancer (NSCLC). The aim of this retrospective study was to evaluate the prognostic factors of surgically treated, over 80-year old patients with clinical stage I NSCLC. The preoperative data of 97 over 80-year old patients with clinical stage I NSCLC were collected at Nagasaki University Hospital from 1990 to 2012. As prognostic factors, inflammation-based scoring systems, including the Glasgow Prognostic Score (GPS) determined by serum levels of C-reactive protein and albumin, the neutrophil lymphocyte ratio (NLR) and the platelet lymphocyte ratio (PLR) were evaluated, as well as other clinicopathological factors, including performance status, body mass index, carcinoembryonic antigen, Charlson comorbidity index and type of surgical procedure. The median age was 82 (range, 80-93) years. There were 62 (64.0%) clinical stage IA cases and 35 IB cases. Operations included 64 (66.0%) lobectomies, 15 segmentectomies and 18 wedge resections. The pathological stage was I in 76 (78.4%) patients, II in 12 (12.4%), III in 8 (8.2%) and IV in 1 (1.0%). Twelve (12.4%) patients underwent mediastinal lymph node dissection. Overall survival and disease-specific 5-year survival rates were 55.5 and 70.0%, respectively. The average GPS score was 0.4 (0-2). Disease-specific 5-year survival was significantly longer with GPS 0 than with GPS 1-2. (74.2%, 53.7%, respectively, P = 0.03). Overall 5-year survival was significantly longer with GPS 0 than with GPS 1-2. (59.7%, 43.1%, respectively, P = 0.005). Both the NLR (median value = 1.9) and the PLR (median value = 117) were not correlated with disease-specific and overall 5-year

Early two-stage double opposing Z-plasty or one-stage push-back palatoplasty?: comparisons in maxillary development and speech outcome at 4 years of age.

PubMed

Yamanishi, Tadashi; Nishio, Juntaro; Sako, Michiyo; Kohara, Hiroshi; Hirano, Yoshiko; Yamanishi, Yukiko; Adachi, Tadafumi; Miya, Shigenori; Mukai, Takao

2011-02-01

Determining the optimal timing and procedure of palatal surgery for children with cleft lip and palate has long raised a major controversy. An early two-stage palatoplasty protocol has been a recent trend in an attempt to obtain preferable maxillary growth without compromising adequate speech development. In this study, we aim to address whether the resulting maxillofacial growth and speech development obtained by an early 2-stage palatoplasty protocol are better than those obtained by conventional 1-stage push-back palatoplasty. Seventy-two nonsyndromic children with complete unilateral cleft lip and palate were enrolled in this study. They were divided into 2 groups: 30 children, who were treated with early 2-stage palatoplasty, in which soft palate closure was performed using a modified Furlow's procedure at 12 months of age and hard palate closure was performed at 18 months of age (Early Tow Stage [ETS] group: 22 boys, 8 girls), and 42 children, who underwent 1-stage Wardill-Kilner push-back palatoplasty at 12 months of age (Push Back [PB] group: 31 boys, 11 girls). Cephalometric analysis for maxillofacial growth and assessments of speech development were performed for each child at 4 years of age. The ETS group showed a lager maxillary length than the PB group [anterior nasal spine (ANS)-ptm': ETS, 46.7 ± 2.0 mm; PB, 43.6 ± 2.3 mm]. The ANS in the ETS group was positioned more anteriorly than that in the PB group (N'-ANS: ETS, 2.5 ± 1.8 mm; PB, 0.26 ± 2.5 mm), whereas the posterior edge of the maxilla positioned anteroposteiorly was comparable between the 2 groups. The anterior facial height was significantly greater in the ETS group than in the PB group (N-N': ETS, 43.3 ± 2.9 mm; PB, 40.1 ± 2.3 mm, S-S': ETS, 29.7 ± 3.2 mm; PB, 31.0 ± 3.2 mm). No statistically significant differences were observed in the incidence of either velopharyngeal incompetence or articulation errors between the 2 groups at 4 years of age. Our results show that the early 2

The Earliest Stage of Cognitive Impairment in Transition From Normal Aging to Alzheimer Disease Is Marked By Prominent RNA Oxidation in Vulnerable Neurons

PubMed Central

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

2012-01-01

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 approach to 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 clinical dementia rating score and postmortem brain pathological 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. PMID:22318126

The changes of stage distribution of seminiferous epithelium cycle and its correlations with Leydig cell stereological parameters in aging men.

PubMed

Huang, Rui; Zhu, Wei-Jie; Li, Jing; Gu, Yi-Qun

2014-12-01

To evaluate the changes of stage distribution of seminiferous epithelium cycle and its correlations with Leydig cell stereological parameters in aging men. Point counting method was used to analyze the stereological parameters of Leydig cells. The stage number of seminiferous epithelium cycle was calculated in the same testicular tissue samples which were used for Leydig cell stereological analysis. The aging group had shown more severe pathological changes as well as higher pathologic scores than the young group. Compared with the control group, the volume density (VV) and surface density (NA) of Leydig cells in the aging group were increased significantly. The stage number of seminiferous epithelium cycle in the aging group was decreased coincidently compared to the young group. Leydig cell Vv in the young group has a positive relationship with stages I, II, III, V and VI of seminiferous epithelium cycle, and Leydig cell NA and numerical density (NV) were positively related to stage IV. However, only the correlation between NV and stage II was found in the aging group. The stage number of seminiferous epithelium cycle was decreased in aging testes. Changes in the stage distribution in aging testes were related to the Leydig cell stereological parameters which presented as a sign of morphological changes. Copyright © 2014 Elsevier GmbH. All rights reserved.

OPEC/OJEC for stage 4 neuroblastoma in children over 1 year of age.

PubMed

Tweddle, D A; Pinkerton, C R; Lewis, I J; Ellershaw, C; Cole, M; Pearson, A D

2001-01-01

This paper reports the toxicity of OPEC/OJEC chemotherapy in stage 4 neuroblastoma patients over 1 year of age. Ninety-five patients with stage 4 neuroblastoma received alternating courses of OPEC/OJEC--vincristine 1.5 mg/m2 (O), cisplatin 80 mg/m2 (P), etoposide 200 mg/m2 (E), cyclophosphamide 600 mg/m2 (C), and carboplatin 500 mg/m2 (J), every 21 days if there was haematological recovery. Seventy out of ninety-five (74%) patients completed seven or more courses and were evaluable for toxicity. Of these 70 patients, 33% had more than three episodes of fever and sepsis, 35% required more than five blood or platelet transfusions, 36% had grade 2 or more gastrointestinal toxicity and 9% had neurotoxicity. There was a median reduction in GFR of 32 ml/min/1.73 m2 (-46 to 134) and there was one toxic death. OPEC/OJEC is a well-tolerated therapy for stage 4 neuroblastoma over 1 year of age.

Validation of Photoplethysmography-Based Sleep Staging Compared With Polysomnography in Healthy Middle-Aged Adults.

PubMed

Fonseca, Pedro; Weysen, Tim; Goelema, Maaike S; Møst, Els I S; Radha, Mustafa; Lunsingh Scheurleer, Charlotte; van den Heuvel, Leonie; Aarts, Ronald M

2017-07-01

To compare the accuracy of automatic sleep staging based on heart rate variability measured from photoplethysmography (PPG) combined with body movements measured with an accelerometer, with polysomnography (PSG) and actigraphy. Using wrist-worn PPG to analyze heart rate variability and an accelerometer to measure body movements, sleep stages and sleep statistics were automatically computed from overnight recordings. Sleep-wake, 4-class (wake/N1 + N2/N3/REM) and 3-class (wake/NREM/REM) classifiers were trained on 135 simultaneously recorded PSG and PPG recordings of 101 healthy participants and validated on 80 recordings of 51 healthy middle-aged adults. Epoch-by-epoch agreement and sleep statistics were compared with actigraphy for a subset of the validation set. The sleep-wake classifier obtained an epoch-by-epoch Cohen's κ between PPG and PSG sleep stages of 0.55 ± 0.14, sensitivity to wake of 58.2 ± 17.3%, and accuracy of 91.5 ± 5.1%. κ and sensitivity were significantly higher than with actigraphy (0.40 ± 0.15 and 45.5 ± 19.3%, respectively). The 3-class classifier achieved a κ of 0.46 ± 0.15 and accuracy of 72.9 ± 8.3%, and the 4-class classifier, a κ of 0.42 ± 0.12 and accuracy of 59.3 ± 8.5%. The moderate epoch-by-epoch agreement and, in particular, the good agreement in terms of sleep statistics suggest that this technique is promising for long-term sleep monitoring, although more evidence is needed to understand whether it can complement PSG in clinical practice. It also offers an improvement in sleep/wake detection over actigraphy for healthy individuals, although this must be confirmed on a larger, clinical population. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

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.

Stage-specific incidence rates and trends of prostate cancer by age, race, and ethnicity, United States, 2004-2014.

PubMed

Li, Jun; Siegel, David A; King, Jessica B

2018-05-01

Current literature shows different findings on the contemporary trends of distant-stage prostate cancer incidence, in part, due to low study population coverage and wide age groupings. This study aimed to examine the stage-specific incidence rates and trends of prostate cancer by age (5-year grouping), race, and ethnicity using nationwide cancer registry data. Data on prostate cancer cases came from the 2004-2014 United States Cancer Statistics data set. We calculated stage-specific incidence and 95% confidence intervals by age (5-year age grouping), race, and ethnicity. To measure the changes in rates over time, we calculated annual percentage change (APC). We identified 2,137,054 incident prostate cancers diagnosed during 2004-2014, with an age-adjusted incidence rate of 453.8 per 100,000. Distant-stage prostate cancer incidence significantly decreased during 2004-2010 (APC = -1.2) and increased during 2010-2014 (APC = 3.3). Significant increases in distant prostate cancer incidence also occurred in men aged older than or equal to 50 years except men aged 65-74 and older than or equal to 85 years, in men with white race (APC = 3.9), and non-Hispanic ethnicity (APC = 3.5). Using data representing over 99% of U.S. population, we found that incidence rates of distant-stage prostate cancer significantly increased during 2010-2014 among men in certain ages, in white, and with non-Hispanic ethnicity. Published by Elsevier Inc.

Minimal clinically important difference and the effect of clinical variables on the ankle osteoarthritis scale in surgically treated end-stage ankle arthritis.

PubMed

Coe, Marcus P; Sutherland, Jason M; Penner, Murray J; Younger, Alastair; Wing, Kevin J

2015-05-20

There is much debate regarding the best outcome tool for use in foot and ankle surgery, specifically in patients with ankle arthritis. The Ankle Osteoarthritis Scale (AOS) is a validated, disease-specific score. The goals of this study were to investigate the clinical performance of the AOS and to determine a minimal clinically important difference (MCID) for it, using a large cohort of 238 patients undergoing surgery for end-stage ankle arthritis. Patients treated with total ankle arthroplasty or ankle arthrodesis were prospectively followed for a minimum of two years at a single site. Data on demographics, comorbidities, AOS score, Short Form-36 results, and the relationship between expectations and satisfaction were collected at baseline (preoperatively), at six and twelve months, and then yearly thereafter. A linear regression analysis examined the variables affecting the change in AOS scores between baseline and the two-year follow-up. An MCID in the AOS change score was then determined by employing an anchor question, which asked patients to rate their relief from symptoms after surgery. Surgical treatment of end-stage ankle arthritis resulted in a mean improvement (and standard deviation) of 31.2 ± 22.7 points in the AOS score two years after surgery. The MCID of the AOS change score was a mean of 28.0 ± 17.9 points. The change in AOS score was significantly affected by the preoperative AOS score, smoking, back pain, and age. Patients undergoing arthroplasty or arthrodesis for end-stage ankle arthritis experienced a mean improvement in AOS score that was greater than the estimated MCID (31.2 versus 28.0 points). Copyright © 2015 by The Journal of Bone and Joint Surgery, Incorporated.

Histogram analysis of diffusion kurtosis imaging of nasopharyngeal carcinoma: Correlation between quantitative parameters and clinical stage.

PubMed

Xu, Xiao-Quan; Ma, Gao; Wang, Yan-Jun; Hu, Hao; Su, Guo-Yi; Shi, Hai-Bin; Wu, Fei-Yun

2017-07-18

To evaluate the correlation between histogram parameters derived from diffusion-kurtosis (DK) imaging and the clinical stage of nasopharyngeal carcinoma (NPC). High T-stage (T3/4) NPC showed significantly higher Kapp-mean (P = 0.018), Kapp-median (P = 0.029) and Kapp-90th (P = 0.003) than low T-stage (T1/2) NPC. High N-stage NPC (N2/3) showed significantly lower Dapp-mean (P = 0.002), Dapp-median (P = 0.002) and Dapp-10th (P < 0.001) than low N-stage NPC (N0/1). High AJCC-stage NPC (III/IV) showed significantly lower Dapp-10th (P = 0.038) than low AJCC-stage NPC (I/II). ROC analyses indicated that Kapp-90th was optimal for predicting high T-stage (AUC, 0.759; sensitivity, 0.842; specificity, 0.607), while Dapp-10th was best for predicting high N- and AJCC-stage (N-stage, AUC, 0.841; sensitivity, 0.875; specificity, 0.807; AJCC-stage, AUC, 0.671; sensitivity, 0.800; specificity, 0.588). DK imaging data of forty-seven consecutive NPC patients were retrospectively analyzed. Apparent diffusion for Gaussian distribution (Dapp) and apparent kurtosis coefficient (Kapp) were generated using diffusion-kurtosis model. Histogram parameters, including mean, median, 10th, 90th percentiles, skewness and kurtosis of Dapp and Kapp were calculated. Patients were divided into low and high T, N and clinical stage based on American Joint Committee on Cancer (AJCC) staging system. Differences of histogram parameters between low and high T, N and AJCC stages were compared using t test. Multiple receiver operating characteristic (ROC) curves were used to determine and compare the value of significant parameters in predicting high T, N and AJCC stage, respectively. DK imaging-derived parameters correlated well with clinical stage of NPC, therefore could serve as an adjunctive imaging technique for evaluating NPC.

Overcoming Age Limits in Cancer Clinical Trials

Cancer.gov

Adolescents, young adults, and the elderly lag far behind other age groups when it comes to enrolling in clinical trials. Their participation is critical to advancing effective therapies for these age groups.

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

Mild hypercholesterolemia, normal plasma triglycerides, and normal glucose levels across dementia staging in Alzheimer's disease: a clinical setting-based retrospective study.

PubMed

Ramdane, Said; Daoudi-Gueddah, Doria

2011-08-01

We examined retrospectively the concurrent relationships between fasting plasma total cholesterol, triglycerides, and glucose levels, and Alzheimer's disease (AD), in a clinical setting-based study. Total cholesterol level was higher in patients with AD compared to elderly controls; triglycerides or glucose levels did not significantly differ between the 2 groups. Respective plotted trajectories of change in cholesterol level across age were fairly parallel. No significant difference in total cholesterol levels was recorded between patients with AD classified by the Clinical Dementia Rating (CDR) score subgroups. These results suggest that patients with AD have relative mild total hypercholesterolemia, normal triglyceridemia, and normal fasting plasma glucose level. Mild total hypercholesterolemia seems to be permanent across age, and across dementia severity staging, and fairly parallels the trajectory of age-related change in total cholesterolemia of healthy controls. We speculate that these biochemical parameters pattern may be present long before-a decade at least-the symptomatic onset of the disease.

Does posterior cingulate hypometabolism result from disconnection or local pathology across preclinical and clinical stages of Alzheimer's disease?

PubMed

Teipel, Stefan; Grothe, Michel J

2016-03-01

Posterior cingulate cortex (PCC) hypometabolism as measured by FDG PET is an indicator of Alzheimer's disease (AD) in prodromal stages, such as in mild cognitive impairment (MCI), and has been found to be closely associated with hippocampus atrophy in AD dementia. We studied the effects of local and remote atrophy and of local amyloid load on the PCC metabolic signal in patients with different preclinical and clinical stages of AD. We determined the volume of the hippocampus and PCC grey matter based on volumetric MRI scans, PCC amyloid load based on AV45 PET, and PCC metabolism based on FDG PET in 667 subjects participating in the Alzheimer's Disease Neuroimaging Initiative spanning the range from cognitively normal ageing through prodromal AD to AD dementia. In cognitively normal individuals and those with early MCI, PCC hypometabolism was exclusively associated with hippocampus atrophy, whereas in subjects with late MCI it was associated with both local and remote effects of atrophy as well as local amyloid load. In subjects with AD dementia, PCC hypometabolism was exclusively related to local atrophy. Our findings suggest that the effects of remote pathology on PCC hypometabolism decrease and the effects of local pathology increase from preclinical to clinical stages of AD, consistent with a progressive disconnection of the PCC from downstream cortical and subcortical brain regions.

Point estimation following two-stage adaptive threshold enrichment clinical trials.

PubMed

Kimani, Peter K; Todd, Susan; Renfro, Lindsay A; Stallard, Nigel

2018-05-31

Recently, several study designs incorporating treatment effect assessment in biomarker-based subpopulations have been proposed. Most statistical methodologies for such designs focus on the control of type I error rate and power. In this paper, we have developed point estimators for clinical trials that use the two-stage adaptive enrichment threshold design. The design consists of two stages, where in stage 1, patients are recruited in the full population. Stage 1 outcome data are then used to perform interim analysis to decide whether the trial continues to stage 2 with the full population or a subpopulation. The subpopulation is defined based on one of the candidate threshold values of a numerical predictive biomarker. To estimate treatment effect in the selected subpopulation, we have derived unbiased estimators, shrinkage estimators, and estimators that estimate bias and subtract it from the naive estimate. We have recommended one of the unbiased estimators. However, since none of the estimators dominated in all simulation scenarios based on both bias and mean squared error, an alternative strategy would be to use a hybrid estimator where the estimator used depends on the subpopulation selected. This would require a simulation study of plausible scenarios before the trial. © 2018 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

[Clinical observation on acupuncture by stages combined with exercise therapy for treatment of Bell palsy at acute stage].

PubMed

Qu, Yong

2005-08-01

To find out a method for increasing clinical therapeutic effect on Bell palsy at acute stage. Ninety cases of Bell palsy were randomly divided into an observation group, a control group I and a control group II, 30 cases in each group. They were treated respectively with acupuncture plus exercise therapy, simple acupuncture therapy, and simple exercise therapy, and their therapeutic effects were observed. The cured rate was 66.7% in the observation group, 53.3% in the control group I and 46.70% in the control group II, the observation group being better than the two control groups (P<0.05). Acupuncture by stage combined with exercise therapy can increase the therapeutic effect on Bell palsy at acute stage, and it is a better therapy for Bell palsy.

Development and validation of a preoperative prediction model for colorectal cancer T-staging based on MDCT images and clinical information.

PubMed

Sa, Sha; Li, Jing; Li, Xiaodong; Li, Yongrui; Liu, Xiaoming; Wang, Defeng; Zhang, Huimao; Fu, Yu

2017-08-15

This study aimed to establish and evaluate the efficacy of a prediction model for colorectal cancer T-staging. T-staging was positively correlated with the level of carcinoembryonic antigen (CEA), expression of carbohydrate antigen 19-9 (CA19-9), wall deformity, blurred outer edges, fat infiltration, infiltration into the surrounding tissue, tumor size and wall thickness. Age, location, enhancement rate and enhancement homogeneity were negatively correlated with T-staging. The predictive results of the model were consistent with the pathological gold standard, and the kappa value was 0.805. The total accuracy of staging improved from 51.04% to 86.98% with the proposed model. The clinical, imaging and pathological data of 611 patients with colorectal cancer (419 patients in the training group and 192 patients in the validation group) were collected. A spearman correlation analysis was used to validate the relationship among these factors and pathological T-staging. A prediction model was trained with the random forest algorithm. T staging of the patients in the validation group was predicted by both prediction model and traditional method. The consistency, accuracy, sensitivity, specificity and area under the curve (AUC) were used to compare the efficacy of the two methods. The newly established comprehensive model can improve the predictive efficiency of preoperative colorectal cancer T-staging.

Relationship between primary lesion metabolic parameters and clinical stage in lung cancer.

PubMed

Sahiner, I; Atasever, T; Akdemir, U O; Ozturk, C; Memis, L

2013-01-01

The relation of PET-derived parameters as maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG), metabolic tumor volume (MTV) with clinical stage in lung cancer and correlation of SUVmax of primary tumor and that of metastatic lesion was studied in lung cancer patients. Patients with lung cancer who were referred for FDG PET/CT were included in the study. PET/CT scans and pathology reports of 168 patients were assessed. A total of 146 (86.9%) of these patients had a diagnosis of non-small cell lung cancer (NSCLC) and 22 (13.1%) had small cell lung cancer (SCLC). Metabolic parameters such as SUVmax, TLG and MTV showed significant differences in all the stages in NSCLC patients (p<0.001). However, after tumors sizes <25 mm were excluded, no significant differences in SUVmax between stages were observed. No significant differences were found between these metabolic parameters and limited or extended disease SCLC. Tumor diameter correlated with primary tumor SUVmax and significant correlations between primary lesion SUVmax and metastatic lesion SUVmax were found. Although differences were found regarding indices between stages of NSCLC cases, SUVmax differences between stages seem to be caused by underestimation of SUVmax in small lesions. Other glucose metabolism indexes such as MTV and TLG show promising results in terms of prognostic stratification. Future studies are needed for better understanding of their contribution to clinical cases. Copyright © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.

Cure by age and stage at diagnosis for colorectal cancer patients in North West England, 1997-2004: a population-based study.

PubMed

Shack, L G; Shah, A; Lambert, P C; Rachet, B

2012-12-01

Stage and age at diagnosis are important prognostic factors for patients with colorectal cancer. However, the proportion cured by stage and age is unknown in England. This population-based study includes 29,563 adult patients who were diagnosed and registered with colorectal cancer during 1997-2004 and followed till 2007 in North West England. Multiple imputation was used to provide more reliable estimates of stage at diagnosis, when these data were missing. Cure mixture models were used to estimate the proportion 'cured' and the median survival of the uncured by age and stage. For both colon and rectal cancer the proportion of patients cured and median survival time of the uncured decreased with advancing stage and increasing age. Patients aged under 65 years had the highest proportion cured and longest median survival of the uncured. Cure of colorectal cancer patients is dependent on stage and age at diagnosis with younger patients or those with less advanced disease having a better prognosis. Further efforts are required, in order to reduce the proportion of patients presenting with stage III and IV disease and ultimately increase the chance of cure. Copyright © 2012 Elsevier Ltd. All rights reserved.

Clinical presentation of familial exudative vitreoretinopathy.

PubMed

Ranchod, Tushar M; Ho, Lawrence Y; Drenser, Kimberly A; Capone, Antonio; Trese, Michael T

2011-10-01

To describe the clinical characteristics, staging and presentation of patients with familial exudative vitreoretinopathy (FEVR) in our clinical practice over the last 25 years. Case series, retrospective review. We included 273 eyes of 145 patients. Data collected from charts included gender, gestational age at birth, birthweight, age at presentation, referring diagnosis, family history, prior ocular surgery, and clinical presentation in each eye. Eyes with invasive posterior segment procedures before initial presentation were excluded. Demographics on presentation and clinical staging. Patients were slightly male predominant (57%) with a mean birthweight of 2.80 kg (range, 740 g-4.76 kg), mean gestational age of 37.8 weeks (range, 25-42), and mean age at presentation of almost 6 years (range, <1 month-49 years). A positive family history of FEVR was obtained in 18% of patients. A positive family history for ocular disease consistent with but not diagnosed as FEVR was obtained in an additional 19%. Stage 1 FEVR was identified in 45 eyes, stage 2 in 33 eyes, stage 3 in 42 eyes, stage 4 in 89 eyes, and stage 5 in 44 eyes. Radial retinal folds were seen in 77 eyes, 64 of which were temporal or inferotemporal in location. The FEVR patient population is remarkable for the wide range of age at presentation, gestational age, and birthweight. Although a positive family history on presentation may support the diagnosis of FEVR, a negative family history is of little help. The majority of retinal folds extended radially in the temporal quadrants, but radial folds were seen in almost all quadrants. Fellow eyes demonstrated a wide variation in symmetry. The presentation of FEVR may mimic the presentation of other pediatric and adult vitreoretinal disorders, and careful examination is often crucial in making the diagnosis of FEVR. The authors have no proprietary or commercial interest in any of the materials discussed in this article. Copyright © 2011 American Academy of

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.

[Age of onset of puberty in Chilean boys according to testicular volume and Tanner stage].

PubMed

Gaete, Ximena; García, Roberto; Riquelme, Joel; Codner, Ethel

2015-03-01

A secular trend towards a younger age of puberty onset has been reported in Chilean girls. To evaluate the age of onset of puberty and prevalence of early puberty in Chilean boys. A pediatric endocrinologist examined 319 children attending schools in central Santiago. Pubertal development was assessed by testicular volume (TV) and genital inspection (GI) using Tanner graduation. Precocious and early puberty development was diagnosed if TV ≥ 4 ml or GI > stage 2 occurred in boys younger than 9 years and at 9-10 years of age, respectively. Pubertal onset occurred at 10.2 ± 1.5 years according to TV and at 11.1 ± 1.6 years according to GI (p < 0.01). Before the age of nine, 15.2% of children had a VT ≥ 4 ml, 3% had genital changes in GI and only 3% had both changes simultaneously. Early puberty was observed in 23.8% of children according to TV and 9.5% according to GI. However, no child of less than 11 years old had a TV ≥ 4 ml, genital changes and pubic hair simultaneously. Late pubertal stages occurred at the same age according to both criteria used. Body mass index z score was not associated with the age of pubertal onset. Testicular enlargement occurs one year earlier than changes in genitalia according to inspection. Testicular growth, but not late stages of puberty, are occurring one year earlier than previously reported in Chile 10 years ago.

Ocriplasmin for treatment of stage 2 macular holes: early clinical results.

PubMed

Miller, John B; Kim, Leo A; Wu, David M; Vavvas, Demetrios G; Eliott, Dean; Husain, Deeba

2014-01-01

To review clinical and structural outcomes of ocriplasmin for treatment of stage 2 macular holes. A retrospective review of the first patients with stage 2 macular holes to be treated with ocriplasmin at Massachusetts Eye and Ear Infirmary. All patients were imaged with spectral-domain optical coherence tomography (SD-OCT). Eight patients with stage 2 macular holes received a single injection of 125 μg of ocriplasmin. One patient (12.5%) demonstrated macular hole closure. The posterior hyaloid separated from the macula in six eyes (75%). All seven holes that remained open showed enlargement in hole diameters (narrowest, apical, and basal) at 1 week and 1 month. All seven were successfully closed with surgery. Ellipsoid zone disruptions were observed by OCT in four eyes (50%) and persisted throughout follow-up (more than 6 months on average). In early clinical results, the authors found a lower macular hole closure rate with ocriplasmin than previously reported. Enlargement was observed in all holes that failed to close with ocriplasmin. The authors found ellipsoid zone disruptions that persisted through 6 months of follow-up after ocriplasmin injection. Further work is needed to investigate the cause for these ellipsoid zone changes. Copyright 2014, SLACK Incorporated.

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

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

PubMed

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

2015-01-01

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. 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. 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). 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.

Incidence of Intermediate-stage Age-related Macular Degeneration in Patients With Acquired Immunodeficiency Syndrome.

PubMed

Jabs, Douglas A; Van Natta, Mark L; Pak, Jeong Won; Danis, Ronald P; Hunt, Peter W

2017-07-01

To evaluate the incidence of intermediate-stage age-related macular degeneration (AMD) in patients with acquired immunodeficiency syndrome (AIDS). Cohort study. Patients enrolled in the Longitudinal Study of the Ocular Complications of AIDS (LSOCA) underwent 5- and 10-year follow-up retinal photographs. Intermediate-stage AMD (AREDS stage 3) was determined from these photographs by graders at a centralized Reading Center, using the Age-Related Eye Disease Study-2 grading system. The incidence of AMD in LSOCA was compared with that in the Multi-Ethnic Study of Atherosclerosis (MESA), a Human Immunodeficiency Virus (HIV)-uninfected cohort, which used a similar photographic methodology. The incidence of AMD in LSOCA was 0.65/100 person-years (PY). In a multivariate analysis the only significant risk factor for AMD in LSOCA was smoking; the relative risk vs never-smokers was 3.4 for former smokers (95% confidence interval [CI] 1.3, 9.5; P = .02) and 3.3 for current smokers (95% CI 1.1, 9.7; P = .03). Compared with the MESA cohort, the race/ethnicity- and sex-adjusted risk of AMD in LSOCA was 1.75 (95% CI 1.16, 2.64; P = .008), despite the fact that the mean age of the MESA cohort was 17 years greater than the LSOCA cohort (61 ± 9 years vs 44 ± 8 years). Patients with AIDS have a 1.75-fold increased race- and sex-adjusted incidence of intermediate-stage AMD compared with that found in an HIV-uninfected cohort. This increased incidence is consistent with the increased incidence of other age-related diseases in antiretroviral-treated, immune-restored, HIV-infected persons when compared with HIV-uninfected persons. Copyright © 2017 Elsevier Inc. All rights reserved.

Less common clinical manifestations of atopic dermatitis: prevalence by age.

PubMed

Julián-Gónzalez, Rolando Elias; Orozco-Covarrubias, Luz; Durán-McKinster, Carola; Palacios-Lopez, Carolina; Ruiz-Maldonado, Ramon; Sáez-de-Ocariz, Marimar

2012-01-01

The common manifestations of atopic dermatitis (AD) appear sequentially with involvement of the cheeks in infancy, flexural extremities in childhood, and hands in adulthood. Although less common clinical manifestations are well described, they have not been the subject of epidemiologic studies to describe their prevalence in specific age groups. This observational, cross-sectional, comparative study included 131 children younger than 18 of both sexes with AD who attended the clinics of the Dermatology Department of the National Institute of Pediatrics in Mexico City. Patients were examined to determine the presence of infrequent clinical manifestations of AD during infancy, preschool and school age, and adolescence and stratified according to sex, age, and number of clinical signs. A chi-square test was used to detect differences according to age and sex. Logistic regression analysis was also performed. The main findings according to age were genital dermatitis and papular-lichenoid dermatitis variant in infants; atopic feet, prurigo-like, nummular pattern, and erythroderma in preschool and school-aged children; and eyelid eczema and nipple dermatitis in adolescents. The risk of development of nipple dermatitis and eyelid eczema increased with age, and the development of genital dermatitis decreased with age. The knowledge of the prevalence of less common clinical manifestations of AD according to age in different populations might be helpful in diagnosing incipient cases of AD. © 2012 Wiley Periodicals, Inc.

Ages and stages questionnaires: adaptation to an Arabic speaking population and cultural sensitivity.

PubMed

Charafeddine, Lama; Sinno, Durriyah; Ammous, Farah; Yassin, Walid; Al-Shaar, Laila; Mikati, Mohamad A

2013-09-01

Early detection of developmental delay is essential to initiate early intervention. The Ages and Stages Questionnaires (ASQ) correlate well with physician's assessment and have high predictive value. No such tool exists in Arabic. Translate and test the applicability and reliability of Arabic translated Ages and Stages Questionnaires (A-ASQ) in an Arabic speaking population. 733 healthy children were assessed. ASQ-II for 10 age groups (4-60 months) were translated to Arabic, back translations and cultural adaptation were performed. Test-retest reliability and internal consistency were evaluated using Pearson Correlation Coefficient (CC) and Cronbach's alpha (Cα). Mean scores per domain were compared to US normative scores using t-test. A-ASQ, after culturally relevant adaptations, was easily administered for 4-36 months age groups but not for 4-5 year old due to numerous cultural differences in the later. For the 4-36 month age groups Pearson CC ranged from 0.345 to 0.833. The internal consistency coefficients Cα scores ranged from 0.111 to 0.816. Significant differences were found in the mean domain scores of all age groups between Lebanese and US normative sample (p-value <0.001) with some exceptions in gross motor, fine motor and personal social domains. A-ASQ was easily translated and administered with acceptable internal consistency and reliability in the younger age groups. It proved to be culturally sensitive, which should be taken into consideration when adapting such tool to non-western populations. Copyright © 2013 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Structural neuroimaging across early-stage psychosis: Aberrations in neurobiological trajectories and implications for the staging model.

PubMed

Bartholomeusz, Cali F; Cropley, Vanessa L; Wannan, Cassandra; Di Biase, Maria; McGorry, Patrick D; Pantelis, Christos

2017-05-01

This review critically examines the structural neuroimaging evidence in psychotic illness, with a focus on longitudinal imaging across the first-episode psychosis and ultra-high-risk of psychosis illness stages. A thorough search of the literature involving specifically longitudinal neuroimaging in early illness stages of psychosis was conducted. The evidence supporting abnormalities in brain morphology and altered neurodevelopmental trajectories is discussed in the context of a clinical staging model. In general, grey matter (and, to a lesser extent, white matter) declines across multiple frontal, temporal (especially superior regions), insular and parietal regions during the first episode of psychosis, which has a steeper trajectory than that of age-matched healthy counterparts. Although the ultra-high-risk of psychosis literature is considerably mixed, evidence indicates that certain volumetric structural aberrations predate psychotic illness onset (e.g. prefrontal cortex thinning), while other abnormalities present in ultra-high-risk of psychosis populations are potentially non-psychosis-specific (e.g. hippocampal volume reductions). We highlight the advantages of longitudinal designs, discuss the implications such studies have on clinical staging and provide directions for future research.

Influence of age on the pattern and outcome of external beam radiotherapy for clinically localized prostate cancer.

PubMed

Ogawa, Kazuhiko; Nakamura, Katsumasa; Onishi, Hiroshi; Koizumi, Masahiko; Sasaki, Tomonari; Araya, Masayuki; Miyabe, Yuuki; Otani, Yuuki; Teshima, Teruki

2006-01-01

The influence of age on the patterns and outcomes of external beam radiotherapy for clinically localized prostate cancer patients was examined. The Japanese Patterns of Care Study surveys were used to compare the processes and outcomes of radical external beam radiotherapy in 140 elderly patients (>75 years old) and 304 younger patients (<75 years old). Although the Karnofsky performance status was significantly different between elderly and younger patients, there were no significant differences in disease characteristics such as pretreatment PSA level, differentiation, Gleason combined score and clinical T stage. There were also no significant differences in the treatment characteristics such as CT-based treatment planning, conformal therapy, total radiation doses (both a median of 66.0 Gy) and hormonal therapy usage. Moreover, no significant differences in overall survival, biochemical relapse-free survival and late toxicity rates were observed between elderly and younger patients. Age did not influence the disease characteristics, patterns of external beam radiotherapy, survival and late toxicities for clinically localized prostate cancer patients. Therefore, radiotherapy could represent an important treatment modality for elderly patients as well as for younger ones.

One-Stage versus Two-Stage Repair of Asymmetric Bilateral Cleft Lip: A 20-Year Retrospective Study of Clinical Outcome.

PubMed

Chung, Kyung Hoon; Lo, Lun-Jou

2018-05-01

Both one- and two-stage approaches have been widely used for patients with asymmetric bilateral cleft lip. There are insufficient long-term outcome data for comparison of these two methods. The purpose of this retrospective study was to compare the clinical outcome over the past 20 years. The senior author's (L.J.L.) database was searched for patients with asymmetric bilateral cleft lip from 1995 to 2015. Qualified patients were divided into two groups: one-stage and two-stage. The postoperative photographs of patients were evaluated subjectively by surgical professionals and laypersons. Ratios of the nasolabial region were calculated for objective analysis. Finally, the revision procedures in the nasolabial area were reviewed. Statistical analyses were performed. A total of 95 consecutive patients were qualified for evaluation. Average follow-up was 13.1 years. A two-stage method was used in 35 percent of the patients, and a one-stage approach was used in 65 percent. All underwent primary nasal reconstruction. Among the satisfaction rating scores, the one-stage repair was rated significantly higher than two-stage reconstruction (p = 0.0001). Long-term outcomes of the two-stage patients and the unrepaired mini-microform deformities were unsatisfactory according to both professional and nonprofessional evaluators. The revision rate was higher in patients with a greater-side complete cleft lip and palate as compared with those without palatal involvement. The results suggested that one-stage repair provided better results with regard to achieving a more symmetric and smooth lip and nose after primary reconstruction. The revision rate was slightly higher in the two-stage patient group. Therapeutic, III.

Panels of tumor-derived RNA markers in peripheral blood of patients with non-small cell lung cancer: their dependence on age, gender and clinical stages.

PubMed

Chian, Chih-Feng; Hwang, Yi-Ting; Terng, Harn-Jing; Lee, Shih-Chun; Chao, Tsui-Yi; Chang, Hung; Ho, Ching-Liang; Wu, Yi-Ying; Perng, Wann-Cherng

2016-08-02

Peripheral blood mononuclear cell (PBMC)-derived gene signatures were investigated for their potential use in the early detection of non-small cell lung cancer (NSCLC). In our study, 187 patients with NSCLC and 310 age- and gender-matched controls, and an independent set containing 29 patients for validation were included. Eight significant NSCLC-associated genes were identified, including DUSP6, EIF2S3, GRB2, MDM2, NF1, POLDIP2, RNF4, and WEE1. The logistic model containing these significant markers was able to distinguish subjects with NSCLC from controls with an excellent performance, 80.7% sensitivity, 90.6% specificity, and an area under the receiver operating characteristic curve (AUC) of 0.924. Repeated random sub-sampling for 100 times was used to validate the performance of classification training models with an average AUC of 0.92. Additional cross-validation using the independent set resulted in the sensitivity 75.86%. Furthermore, six age/gender-dependent genes: CPEB4, EIF2S3, GRB2, MCM4, RNF4, and STAT2 were identified using age and gender stratification approach. STAT2 and WEE1 were explored as stage-dependent using stage-stratified subpopulation. We conclude that these logistic models using different signatures for total and stratified samples are potential complementary tools for assessing the risk of NSCLC.

Novel histopathologic feature identified through image analysis augments stage II colorectal cancer clinical reporting

PubMed Central

Caie, Peter D.; Zhou, Ying; Turnbull, Arran K.; Oniscu, Anca; Harrison, David J.

2016-01-01

A number of candidate histopathologic factors show promise in identifying stage II colorectal cancer (CRC) patients at a high risk of disease-specific death, however they can suffer from low reproducibility and none have replaced classical pathologic staging. We developed an image analysis algorithm which standardized the quantification of specific histopathologic features and exported a multi-parametric feature-set captured without bias. The image analysis algorithm was executed across a training set (n = 50) and the resultant big data was distilled through decision tree modelling to identify the most informative parameters to sub-categorize stage II CRC patients. The most significant, and novel, parameter identified was the ‘sum area of poorly differentiated clusters’ (AreaPDC). This feature was validated across a second cohort of stage II CRC patients (n = 134) (HR = 4; 95% CI, 1.5– 11). Finally, the AreaPDC was integrated with the significant features within the clinical pathology report, pT stage and differentiation, into a novel prognostic index (HR = 7.5; 95% CI, 3–18.5) which improved upon current clinical staging (HR = 4.26; 95% CI, 1.7– 10.3). The identification of poorly differentiated clusters as being highly significant in disease progression presents evidence to suggest that these features could be the source of novel targets to decrease the risk of disease specific death. PMID:27322148

Age-related monoclonal gammapathies: clinical lessons from the aging C57BL mouse.

PubMed

Radl, J

1990-07-01

In this article the long-held notion that benign monoclonal gammapathy (BMG) is a premalignant stage in the development of multiple myeloma (MM) is attacked. Jiri Radl argues that clinical and experimental observations indicate that they are separate entities which may be distinguished in the laboratory and which should be managed in radically different ways.

End-stage coxarthrosis and gonarthrosis. Aetiology, clinical patterns and radiological features of idiopathic osteoarthritis.

PubMed

Chitnavis, J; Sinsheimer, J S; Suchard, M A; Clipsham, K; Carr, A J

2000-06-01

To determine and compare the aetiological background, clinical patterns and radiological features of idiopathic osteoarthritis (OA) of the hip and the knee warranting arthroplasty. A total of 402 Caucasians consecutively undergoing total hip replacement (THR) or total knee replacement (TKR) for idiopathic OA at a major centre was surveyed. Previous joint injury was more common in the TKR group (P < 0.0001). However, both groups manifested a mixed occupational background, body mass indices similar to the general population and a predominance of females (F:M = 1.3-1.4:1). The TKR group had a significantly younger age of symptom onset (56 yr) than the THR group (61 yr) but both groups had a tendency to bilateral arthroplasty (33%), nodal involvement (54-59%), a significant excess of right-sided replacements (1.8:1, THR; 2.2:1, TKR) and similar levels of pre-operative pain and disability. Up to 40% of hips manifested acetabular dysplasia and 10% possible previous slipped upper femoral epiphyses. Eighty-five per cent with end-stage coxarthrosis or gonarthrosis had an identical pattern of radiographic disease contralaterally. Our data suggest the importance of a constitutional tendency to idiopathic, end-stage OA, a disorder traditionally associated with environmental factors leading to 'wear and tear'.

Demirjian's stages and Cameriere's third molar maturity index to estimate legal adult age in Peruvian population.

PubMed

Quispe Lizarbe, Roselhy Juliana; Solís Adrianzén, Christian; Quezada-Márquez, Milushka Miroslava; Galić, Ivan; Cameriere, Roberto

2017-03-01

To compare the accuracy of Demirjian's stages (DS) and Cameriere's third molar maturity index cut-off value (I 3M <0.08) to estimate the age of majority on panoramic radiographs (OPTs) from the dental clinic of the Scientific University of the South (UCSUR), Lima, Peru. An observational cross-sectional study was conducted on the sample of 208 digital panoramic radiographs of patients aged 14-22years examined during 2015 in UCSUR. The left lower third molars were analyzed using Adobe Photoshop® CS6. An effectiveness of specific DS and I 3M <0.08 was evaluated by using accurate classification, sensitivity, specificity, positive (LR+) and negative (LR-) likelihood ratios and Bayes post-test probability (p). Only G and H stages were practical for classify adults and minors in the tested sample, while I 3M <0.08 showed the best performance in both sexes. For I 3M <0.08, the accurate classification, sensitivity and specificity were 0.96, 0.96, 0.96 and 0.90, 0.84 and 0.95 in males and females, respectively. Values of LR+, LR- and p were 24.96, 0.04, 0.97 and 15.68, 0.17, 0.95 in males and females, respectively. The specific cut-off value of third molar maturity index (I 3M <0.08) showed to be more accurate in discriminating adults and minors in Peruvian sample when a test with high sensitivity and specificity is required. Copyright © 2017 Elsevier B.V. All rights reserved.

Nutritional status according to the stages of Alzheimer's disease.

PubMed

Marino, Larissa Vieira; Ramos, Liliana Figueiredo Andrade de Oliveira; Chiarello, Paula Garcia

2015-08-01

To assess the nutritional status of Alzheimer's disease (AD) patients with no other associated dementia, according to disease stage. Cross-sectional observational study. Neurobehavioral Diseases Outpatient Clinic, Clinical Hospital, Ribeirao Preto Medical School (University of São Paulo). The sample consisted of 36 individuals of both genders with AD diagnosis, and no other associated type of dementia, in various stages of the disease, according to the Clinical Dementia Rating (CDR 0.5-3). Nutritional status was evaluated using the Mini Nutritional Assessment (MNA) and anthropometric measurements such as weight, body mass index (BMI) and arm, waist, abdomen and hip circumferences. In addition, body composition was assessed by bioelectrical impedance analysis (BIA). The mean age of the group was 74.2 ± 10.1 years, 72.2 % of them were women. The MNA showed that most of these individuals were at risk for malnutrition (55.5 %) and many of them (43.7 %) were underweight according to BMI. Data from BIA analysis revealed that 41.7 % of these individuals had a quantity of body fat classified as malnutrition and 11.1 % had a phase angle (PA) below recommended values for age group. There was a negative and significant correlation of lean mass and PA with age, and of global MNA evaluation with CDR, as well as a positive correlation of MNA total score with fat mass and BMI. Worse classifications of nutritional status obtained by MNA scores were also observed in the more severe stages of the disease, according to the CDR. Patients with AD are mostly elderly with changes in body composition that are typical of aging, with signs of peripheral malnutrition and preservation of abdominal fat. However, greater impairment of general nutritional status was observed in the more advanced stages of AD, creating a situation of greater vulnerability for these patients.

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…

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

Nursing values and a changing nurse workforce: values, age, and job stages.

PubMed

McNeese-Smith, Donna K; Crook, Mary

2003-05-01

To identify the extent values are associated with age group and job stage; job satisfaction, productivity, and organizational commitment; as well as education, generation, ethnicity, gender, and role. Values direct the priorities we live by and are related to employee loyalty and commitment. Lack of congruency between a nurse's personal values and those of the organization decrease satisfaction and effectiveness and may lead to burnout and turnover. Little research has been done on whether values differ by age, generations, or job stages. Nurses in all roles (N = 412) in three hospitals in Los Angeles County were randomly surveyed, using valid and reliable instruments to measure the variables of interest. Nurses in the top third for job satisfaction, organizational commitment, and productivity showed higher scores for many values including their associates, creativity, esthetics, and management, while those in the bottom third scored higher in economic returns only. Nurses in different generations differed little; younger generations placed higher values on economic returns and variety. Management strategies to meet nurses' values and increase their satisfaction and retention are presented.

Landing Kinematics in Elite Male Youth Soccer Players of Different Chronologic Ages and Stages of Maturation.

PubMed

Read, Paul J; Oliver, Jon L; De Ste Croix, Mark B A; Myer, Gregory D; Lloyd, Rhodri S

2018-04-01

  Despite the high frequency of knee injuries in athletes, few researchers have studied the effects of chronologic age and stage of maturation on knee-joint kinematics in male youth soccer players.   To use a coach-friendly screening tool to examine knee-valgus scores for players of different ages and at different stages of maturation.   Cross-sectional study.   Academy soccer clubs.   A total of 400 elite male youth soccer players aged 10 to 18 years categorized by chronologic age and stage of maturation based on their years from peak height velocity (PHV).   Knee valgus was evaluated during the tuck-jump assessment via 2-dimensional analysis. Frontal-plane projection angles were subjectively classified as minor (<10°), moderate (10°-20°), or severe (>20°), and using these classifications, we scored knee valgus in the tuck jump as 0 ( no valgus), 1 ( minor), 2 ( moderate), or 3 ( severe).   A trend toward higher valgus scores was observed in the younger age groups and the pre-PHV group. The lowest frequency of no valgus occurred in the U18 and post-PHV groups. The highest percentages of severe scores were in the U13 and pre-PHV groups for the right limb. Knee-valgus scores were lower for both lower extremities in the U18 group than in all other age groups ( P < .001) except the U16 group. Scores were lower for the post-PHV than the pre-PHV group for the right limb ( P < .001) and both pre-PHV and circa-PHV groups for the left limb ( P < .001). Noteworthy interlimb asymmetries were evident in the U14, U15, and circa-PHV groups.   Reductions in knee valgus with incremental age and during the later stages of maturation indicated that this risk factor was more prevalent in younger players. Interlimb asymmetry may also emerge around the time of the peak growth spurt and early adolescence, potentially increasing the risk of traumatic injury.

P38 mitogen-activated protein kinase (p38 MAPK) overexpression in clinical staging of nasopharyngeal carcinoma

NASA Astrophysics Data System (ADS)

Farhat; Asnir, R. A.; Yudhistira, A.; Daulay, E. R.; Muzakkir, M. M.; Yulius, S.

2018-03-01

Molecular biological research on nasopharyngeal carcinoma has been widely practiced, such as VEGF, EGFR, COX-2 expression and so on. MAPK plays a role in cell growth such as proliferation, differentiation, and apoptosis, primarily contributing to gene expression, where p38 MAPK pathway mostly associate with anti-apoptosis and cause cell transformation. The aim of this study is to determine the expression of p38 MAPK in clinical stage of nasopharyngeal carcinoma so that the result can be helpful in prognosis and adjunctive therapy in nasopharyngeal carcinoma. The research design is descriptive. It was done in THT- KL Department of FK USU/RSUP Haji Adam Malik, Medan and Pathology Anatomical Department of FK USU. The study was conducted from December 2011 to May 2012. The Samples are all patients who diagnosed with nasopharyngeal carcinoma in oncology division of Otorhinolaryngology Department. p38 MAPK overexpression was found in 21 samples (70%) from 30 nasopharyngeal carcinoma samples. The elevated of p38 MAPK expression most found on T4 by eight samples (38.1%), N3 lymph node group by nine samples (42.9%), stage IV of clinical staging is as many as 15 samples (71.4%). p38 MAPK most expressed in stage IV clinical staging of patients with nasopharyngeal carcinoma.

[Aging affects early stage direction selectivity of MT cells in rhesus monkeys].

PubMed

Liang, Zhen; Chen, Yue-Ming; Meng, Xue; Wang, Yi; Zhou, Bao-Zhuo; Xie, Ying-Ying; He, Wen-Sheng

2012-10-01

The middle temporal area (MT/V5) plays an important role in motion processing. Neurons in this area have a strongly selective response to the moving direction of objects and as such, the selectivity of MT neurons was proposed to be a neural mechanism for the perception of motion. Our previous studies have found degradation in direction selectivity of MT neurons in old monkeys, but this direction selectivity was calculated during the whole response time and the results were not able to uncover the mechanism of motion perception over a time course. Furthermore, experiments have found that direction selectivity was enhanced by attention at a later stage. Therefore, the response should be excluded in experiments with anesthesia. To further characterize the neural mechanism over a time course, we investigated the age-related changes of direction selectivity in the early stage by comparing the proportions of direction selective MT cells in old and young macaque monkeys using in vivo single-cell recording techniques. Our results show that the proportion of early-stage-direction-selective cells is lower in old monkeys than in young monkeys, and that the early stage direction bias (esDB) of old MT cells decreased relative to young MT cells. Furthermore, the proportion of MT cells having strong early stage direction selectivity in old monkeys was decreased. Accordingly, the functional degradation in the early stage of MT cells may mediate perceptual declines of old primates in visual motion tasks.

Comparison of age estimation between 15-25 years using a modified form of Demirjian’s ten stage method and two teeth regression formula

NASA Astrophysics Data System (ADS)

Amiroh; Priaminiarti, M.; Syahraini, S. I.

2017-08-01

Age estimation of individuals, both dead and living, is important for victim identification and legal certainty. The Demirjian method uses the third molar for age estimation of individuals above 15 years old. The aim is to compare age estimation between 15-25 years using two Demirjian methods. Development stage of third molars in panoramic radiographs of 50 male and female samples were assessed by two observers using Demirjian’s ten stages and two teeth regression formula. Reliability was calculated using Cohen’s kappa coefficient and the significance of the observations was obtained from Wilcoxon tests. Deviations of age estimation were calculated using various methods. The deviation of age estimation with the two teeth regression formula was ±1.090 years; with ten stages, it was ±1.191 years. The deviation of age estimation using the two teeth regression formula was less than with the ten stages method. The age estimations using the two teeth regression formula or the ten stages method are significantly different until the age of 25, but they can be applied up to the age of 22.

Contemporary Treatment Patterns and Outcomes for Clinical Stage IS Testicular Cancer.

PubMed

Kamran, Sophia C; Seisen, Thomas; Markt, Sarah C; Preston, Mark A; Trinh, Quoc-Dien; Frazier, Lindsay A; Choueiri, Toni K; Martin, Neil E; Nguyen, Paul L; Beard, Clair J

2018-02-01

Controversy exists regarding the optimal management strategy for clinical stage IS seminomatous (SGCT) and nonseminomatous germ cell tumors (NSGCT) of the testis. To assess contemporary treatment patterns and outcomes for clinical stage IS testicular cancer. Using the National Cancer Data Base (2004-2012), we identified 1362 patients with clinical stage IS SGCT and NSGCT of the testis, treated with either adjuvant treatment (AT) or observation. We calculated the annual percent change (APC) to assess treatment trends. Inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier curves and Cox regression analyses were used to compare overall survival (OS) between AT and observation groups. Analyses were stratified by histologic type. Overall, there were 581 (43%) and 781 (57%) men with SGCT and NSGCT, respectively. Among men with SGCT, the use of AT decreased over the study period (APC=-2.7, 95% confidence interval [CI]: -4.4, -1.1, p=0.001). The 5-yr IPTW-adjusted rates of OS were 99% and 97% in the AT and observation groups, respectively (hazard ratio = 0.36, 95% CI: 0.12, 1.14, p=0.08). Among men with NSGCT, the use of AT remained stable over the study period (APC = +0.8, 95% CI: -0.7, +2.2, p=0.29). The 5-yr IPTW-adjusted rates of OS were 97% and 95% in the AT and observation groups, respectively (HR=0.66, 95% CI: 0.27, 1.61, p=0.36). Limitations include the lack of full treatment details and cancer-specific survival information. Trends in the use of AT significantly decreased over time for SGCT, while it remained stable for NSGCT. Nonetheless, we report 5-yr OS rates of ≥95% for both histologies without any significant benefit with the use of AT. Further studies are warranted to confirm these findings. We evaluated treatment trends and outcomes for stage IS testicular cancer. We found that treatment changed over time for seminoma and remained stable for nonseminoma; there was no significant survival benefit in the use of adjuvant treatment versus

Uterine cervix cancer treatment at Radiumhemmet: 90 years′ experience. Time trends of age, stage, and histopathology distribution

PubMed Central

Hellman, Kristina; Hellström, Ann-Cathrin; Pettersson, B Folke

2014-01-01

Since the introduction of screening programs for cervical cancer (CC) the incidence has decreased and CC is discovered at an earlier stage. The purpose of this study was to analyze time trends in age, stage, and histopathology over a 90-year period and to our knowledge this is the largest single institutional series in the literature of invasive cervical carcinoma (CC) cases. This is a retrospective study comprising 18,472 women treated for CC from 1914 until 2004 at Radiumhemmet, Stockholm. The material is part of the international CC statistics published since 1937 in the League of Nations' Annual Reports, and since 1958 under the patronage of International Federation of Gynecology and Obstetrics (FIGO). During the 90-year study period, the annual number of cases treated increased to over 400 up until 1965, after which there was a gradual drop to less than 100 cases in 2004. A pronounced shift toward earlier stages at diagnosis was noted. The mean age at diagnosis increased in all stages, predominantly in advanced stages. A reduction in squamous cell carcinoma (SCC) cases and a sixfold increase in the proportion of adenocarcinoma (AC) cases were observed. The mean age at diagnosis for squamous and AC cases shifted after 1970, when the SCC cases ultimately became 3 years older than the AC cases in contrast to around 1950 when they were 3 years younger than the AC cases. The changes in the distribution by age, stage, and histopathology during this 90-year period are probably associated with: improved social conditions and increased access to health care, the introduction of screening programs for CC in the 1960s, and a change in the risk factors for CC (changed sexual behavior, introduction of contraceptive pills, and changed smoking habits). This is a study on changes in the distribution by age, stage, and histopathology in a large series of cervical cancer treated in Sweden during a 90-year period. It also includes an historical review about the development of

Predictors of clinical-pathologic stage discrepancy in oral cavity squamous cell carcinoma: A National Cancer Database study.

PubMed

Kılıç, Sarah S; Kılıç, Suat; Crippen, Meghan M; Varughese, Denny; Eloy, Jean Anderson; Baredes, Soly; Mahmoud, Omar M; Park, Richard Chan Woo

2018-04-01

Few studies have examined the frequency and survival implications of clinicopathologic stage discrepancy in oral cavity squamous cell carcinoma (SCC). Oral cavity SCC cases with full pathologic staging information were identified in the National Cancer Database (NCDB). Clinical and pathologic stages were compared. Multivariate logistic regressions were performed to identify factors associated with stage discrepancy. There were 9110 cases identified, of which 67.3% of the cases were stage concordant, 19.9% were upstaged, and 12.8% were downstaged. The N classification discordance (28.5%) was more common than T classification discordance (27.6%). In cases of T classification discordance, downstaging is more common than upstaging (15.4% vs 12.1% of cases), but in cases of N classification discordance, the reverse is true; upstaging is much more common than downstaging (20.1 vs 8.4% of cases). Clinicopathologic stage discrepancy in oral cavity SCC is a common phenomenon that is associated with a number of clinical factors and has survival implications. © 2018 Wiley Periodicals, Inc.

The newly proposed clinical and post-neoadjuvant treatment staging classifications for gastric adenocarcinoma for the American Joint Committee on Cancer (AJCC) staging.

PubMed

In, Haejin; Ravetch, Ethan; Langdon-Embry, Marisa; Palis, Bryan; Ajani, Jaffer A; Hofstetter, Wayne L; Kelsen, David P; Sano, Takeshi

2018-01-01

New stage grouping classifications for clinical (cStage) and post-neoadjuvant treatment (ypStage) stage for gastric adenocarcinoma have been proposed for the eighth edition of the AJCC manual. This article summarizes the analysis for these stages. Gastric adenocarcinoma patients diagnosed in 2004-2009 were identified from the National Cancer Database (NCDB). The cStage cohort included both surgical and nonsurgical cases, and the ypStage cohort included only patients who had chemotherapy or radiation therapy before surgery. Survival differences between the stage groups were determined by the log-rank test and prognostic accuracy was assessed by concordance index. Analysis was performed using SAS 9.4 (SAS, Cary, NC, USA). Five strata for cStage and four strata for ypStage were developed. The 5-year survival rates for cStages were 56.77%, 47.39%, 33.1%, 25.9%, and 5.0% for stages I, IIa, IIb, III, and IV, respectively, and the rates for ypStage were 74.2%, 46.3%, 19.2%, and 11.6% for stages I, II, III, and IV, respectively. The log-rank test showed that survival differences were well stratified and stage groupings were ordered and distinct (p < 0.0001). The proposed cStage and ypStage classification was sensitive and specific and had high prognostic accuracy (cStage: c index = 0.81, 95% CI, 0.79-0.83; ypStage: c index = 0.80, 95% CI, 0.73-0.87). The proposed eighth edition establishes two new staging schemata that provide essential prognostic data for patients before treatment and for patients who have undergone surgery following neoadjuvant therapy. These additions are a significant advance to the AJCC staging manual and will provide critical guidance to clinicians in making informed decisions throughout the treatment course.

An automated technique to stage lower third molar development on panoramic radiographs for age estimation: a pilot study.

PubMed

De Tobel, J; Radesh, P; Vandermeulen, D; Thevissen, P W

2017-12-01

Automated methods to evaluate growth of hand and wrist bones on radiographs and magnetic resonance imaging have been developed. They can be applied to estimate age in children and subadults. Automated methods require the software to (1) recognise the region of interest in the image(s), (2) evaluate the degree of development and (3) correlate this to the age of the subject based on a reference population. For age estimation based on third molars an automated method for step (1) has been presented for 3D magnetic resonance imaging and is currently being optimised (Unterpirker et al. 2015). To develop an automated method for step (2) based on lower third molars on panoramic radiographs. A modified Demirjian staging technique including ten developmental stages was developed. Twenty panoramic radiographs per stage per gender were retrospectively selected for FDI element 38. Two observers decided in consensus about the stages. When necessary, a third observer acted as a referee to establish the reference stage for the considered third molar. This set of radiographs was used as training data for machine learning algorithms for automated staging. First, image contrast settings were optimised to evaluate the third molar of interest and a rectangular bounding box was placed around it in a standardised way using Adobe Photoshop CC 2017 software. This bounding box indicated the region of interest for the next step. Second, several machine learning algorithms available in MATLAB R2017a software were applied for automated stage recognition. Third, the classification performance was evaluated in a 5-fold cross-validation scenario, using different validation metrics (accuracy, Rank-N recognition rate, mean absolute difference, linear kappa coefficient). Transfer Learning as a type of Deep Learning Convolutional Neural Network approach outperformed all other tested approaches. Mean accuracy equalled 0.51, mean absolute difference was 0.6 stages and mean linearly weighted kappa was

A Bayesian predictive two-stage design for phase II clinical trials.

PubMed

Sambucini, Valeria

2008-04-15

In this paper, we propose a Bayesian two-stage design for phase II clinical trials, which represents a predictive version of the single threshold design (STD) recently introduced by Tan and Machin. The STD two-stage sample sizes are determined specifying a minimum threshold for the posterior probability that the true response rate exceeds a pre-specified target value and assuming that the observed response rate is slightly higher than the target. Unlike the STD, we do not refer to a fixed experimental outcome, but take into account the uncertainty about future data. In both stages, the design aims to control the probability of getting a large posterior probability that the true response rate exceeds the target value. Such a probability is expressed in terms of prior predictive distributions of the data. The performance of the design is based on the distinction between analysis and design priors, recently introduced in the literature. The properties of the method are studied when all the design parameters vary.

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

Clinical diagnosis and staging of cholangiocarcinoma

PubMed Central

Blechacz, Boris; Komuta, Mina; Roskams, Tania; Gores, Gregory J.

2012-01-01

Cholangiocarcinoma is the most frequent biliary malignancy. It is difficult to diagnose owing to its anatomic location, growth patterns and lack of definite diagnostic criteria. Currently, cholangiocarcinoma is classified into the following types according to its anatomic location along the biliary tree: intrahepatic, perihilar or distal extrahepatic cholangiocarcinoma. These cholangiocarcinoma types differ in their biological behavior and management. The appropriate stratification of patients with regard to the anatomic location and stage of cholangiocarcinoma is a key determinate in their management. Staging systems can guide this stratification and provide prognostic information. In addition, staging systems are essential in order to compare and contrast the outcomes of different therapeutic approaches. A number of staging systems exist for cholangiocarcinoma—several early ones have been updated, and new ones are being developed. We discuss the emerging diagnostic criteria as well as the different staging systems for cholangiocarcinoma, and provide a critical appraisal regarding these advances in biliary tract malignancies. PMID:21808282

Considerations in the Design of Clinical Trials for Cognitive Aging

PubMed Central

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

2012-01-01

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. PMID:22573913

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.

Personality in the cockroach Diploptera punctata: Evidence for stability across developmental stages despite age effects on boldness.

PubMed

Stanley, Christina R; Mettke-Hofmann, Claudia; Preziosi, Richard F

2017-01-01

Despite a recent surge in the popularity of animal personality studies and their wide-ranging associations with various aspects of behavioural ecology, our understanding of the development of personality over ontogeny remains poorly understood. Stability over time is a central tenet of personality; ecological pressures experienced by an individual at different life stages may, however, vary considerably, which may have a significant effect on behavioural traits. Invertebrates often go through numerous discrete developmental stages and therefore provide a useful model for such research. Here we test for both differential consistency and age effects upon behavioural traits in the gregarious cockroach Diploptera punctata by testing the same behavioural traits in both juveniles and adults. In our sample, we find consistency in boldness, exploration and sociality within adults whilst only boldness was consistent in juveniles. Both boldness and exploration measures, representative of risk-taking behaviour, show significant consistency across discrete juvenile and adult stages. Age effects are, however, apparent in our data; juveniles are significantly bolder than adults, most likely due to differences in the ecological requirements of these life stages. Size also affects risk-taking behaviour since smaller adults are both bolder and more highly explorative. Whilst a behavioural syndrome linking boldness and exploration is evident in nymphs, this disappears by the adult stage, where links between other behavioural traits become apparent. Our results therefore indicate that differential consistency in personality can be maintained across life stages despite age effects on its magnitude, with links between some personality traits changing over ontogeny, demonstrating plasticity in behavioural syndromes.

Personality in the cockroach Diploptera punctata: Evidence for stability across developmental stages despite age effects on boldness

PubMed Central

Mettke-Hofmann, Claudia; Preziosi, Richard F.

2017-01-01

Despite a recent surge in the popularity of animal personality studies and their wide-ranging associations with various aspects of behavioural ecology, our understanding of the development of personality over ontogeny remains poorly understood. Stability over time is a central tenet of personality; ecological pressures experienced by an individual at different life stages may, however, vary considerably, which may have a significant effect on behavioural traits. Invertebrates often go through numerous discrete developmental stages and therefore provide a useful model for such research. Here we test for both differential consistency and age effects upon behavioural traits in the gregarious cockroach Diploptera punctata by testing the same behavioural traits in both juveniles and adults. In our sample, we find consistency in boldness, exploration and sociality within adults whilst only boldness was consistent in juveniles. Both boldness and exploration measures, representative of risk-taking behaviour, show significant consistency across discrete juvenile and adult stages. Age effects are, however, apparent in our data; juveniles are significantly bolder than adults, most likely due to differences in the ecological requirements of these life stages. Size also affects risk-taking behaviour since smaller adults are both bolder and more highly explorative. Whilst a behavioural syndrome linking boldness and exploration is evident in nymphs, this disappears by the adult stage, where links between other behavioural traits become apparent. Our results therefore indicate that differential consistency in personality can be maintained across life stages despite age effects on its magnitude, with links between some personality traits changing over ontogeny, demonstrating plasticity in behavioural syndromes. PMID:28489864

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

ASSOCIATION BETWEEN DENTAL AND SKELETAL MATURATION STAGES IN CROATIAN SUBJECTS.

PubMed

Srkoc, Tamara; Mestrović, Senka; Anić-Milosević, Sandra; Slaj, Mladen

2015-12-01

This study investigated the relationships between the stages of calcification of teeth and cervical vertebral maturation. The sample consisted of 295 subjects (129 male and 166 female), mean age 13.36 ± 2.65 (range 7-18) years. Dental age was evaluated from panoramic radiographs according to the method of Demirjian. Cervical vertebral maturation was determined on lateral cephalometric radiographs using cervical vertebrae maturation stages (CVS). For assessing the relationship between cervical vertebral and dental maturation, percentage distributions of the stages of calcification for each studied tooth were calculated. Only in the first CVS stage, boys and girls were of the same age. In all other stages (CVS 2-CVS 6) girls were by 0.98 (range 0.23-1.86) younger than boys. Gender differences in the mineralization pattern were also observed. It was found that dental maturation was finished earlier in female subjects. The highest correlation coefficient between dental and skeletal maturity was found for second premolars. Mineralization pattern of second premolars could be considered as a guideline for prediction of the pubertal growth spurt. Dental maturation stages might be clinically useful as a reliable indicator of facial growth.

Clinical classification of age-related macular degeneration.

PubMed

Ferris, Frederick L; Wilkinson, C P; Bird, Alan; Chakravarthy, Usha; Chew, Emily; Csaky, Karl; Sadda, SriniVas R

2013-04-01

To develop a clinical classification system for age-related macular degeneration (AMD). Evidence-based investigation, using a modified Delphi process. Twenty-six AMD experts, 1 neuro-ophthalmologist, 2 committee chairmen, and 1 methodologist. Each committee member completed an online assessment of statements summarizing current AMD classification criteria, indicating agreement or disagreement with each statement on a 9-step scale. The group met, reviewed the survey results, discussed the important components of a clinical classification system, and defined new data analyses needed to refine a classification system. After the meeting, additional data analyses from large studies were provided to the committee to provide risk estimates related to the presence of various AMD lesions. Delphi review of the 9-item set of statements resulting from the meeting. Consensus was achieved in generating a basic clinical classification system based on fundus lesions assessed within 2 disc diameters of the fovea in persons older than 55 years. The committee agreed that a single term, age-related macular degeneration, should be used for the disease. Persons with no visible drusen or pigmentary abnormalities should be considered to have no signs of AMD. Persons with small drusen (<63 μm), also termed drupelets, should be considered to have normal aging changes with no clinically relevant increased risk of late AMD developing. Persons with medium drusen (≥ 63-<125 μm), but without pigmentary abnormalities thought to be related to AMD, should be considered to have early AMD. Persons with large drusen or with pigmentary abnormalities associated with at least medium drusen should be considered to have intermediate AMD. Persons with lesions associated with neovascular AMD or geographic atrophy should be considered to have late AMD. Five-year risks of progressing to late AMD are estimated to increase approximately 100 fold, ranging from a 0.5% 5-year risk for normal aging changes to a

Vulvovaginitis in a pediatric population: relationship among etiologic agents, age and Tanner staging of breast development.

PubMed

Giugno, Silvina; Risso, Paula; Ocampo, Dolores; Rahman, Gisel; Rubinstein, Dra Anahí V

2014-02-01

Vulvovaginitis accounts for 25% of all pediatric gynecology consultations. To assess the etiology of vulvovaginitis based on age and Tanner staging of breast development. Descriptive, cross-sectional study conducted between January 1st and December 31st, 2011. Patients with vulvovaginitis were assessed based on two outcome measures: age group (GI: 0 to 8.9 years old, GII: 9 to 15.9 years old, and GIII: 16 to 18 years old), and the Tanner staging of breast development (I, II-III, IV-V). Results. Two hundred and twenty-nine patients were included, 78 girls in the GI group, 134 in the GII group, and 17 in the GIII group; 81 girls were classified as TI, 36 as TII-III, and 112 as TIV-V based on Tanner staging. Shigella and Oxyuris were the most commonly found etiologic agents in younger girls. Candida albicans, other Candida species, Gardnerella and Ureaplasma urealyticum were the germs most commonly observed in older patients. Oxyuris was predominant in prepubertal girls, while Candida albicans, in postpubertal girls. Hormonal influence was more relevant than the patient's age in terms of vulvovaginitis etiology.

[Clinical, morphological and molecular biological characteristics of the aging eye].

PubMed

Böhm, M R R; Thomasen, H; Parnitzke, F; Steuhl, K-P

2017-02-01

The physiological aging of the eye is associated with loss of visual function. Age-related changes of the eye can result in ophthalmological diseases. The aim of this article is to display morphological, histological and molecular biological alterations of the aging eye. A web-based search and review of the literature for aging of the visual system including cornea, lens, vitreous humor, retina, retinal pigment epithelium (RPE), choroidea and optic nerve were carried out. The most important results related to morphological, histological and molecular biological changes are summarized. Age-related, morphological alterations can be found in preretinal structures, e. g. cornea, lens and vitreous humor, as well as neuronal structures, such as the retina. In addition to negligible clinical signs of the aging eye, there are clinically relevant changes which can develop into pathological ophthalmological diseases. These transitions from age-related alterations to relevant ophthalmological diseases, e. g. age-related macular degeneration and glaucoma are continuous. An understanding of aging could provide predictive factors to detect the conversion of physiological aging into pathological conditions. The derivation of physiological markers or new approaches to detection and treatment of disease-related entities associated with the risk factor aging are desirable. Translational approaches in clinical and basic science are necessary to provide new therapeutic options for relevant ophthalmological diseases in the future.

Systemic Therapy for Stage IV Non–Small-Cell Lung Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update

PubMed Central

Masters, Gregory A.; Temin, Sarah; Azzoli, Christopher G.; Giaccone, Giuseppe; Baker, Sherman; Brahmer, Julie R.; Ellis, Peter M.; Gajra, Ajeet; Rackear, Nancy; Schiller, Joan H.; Smith, Thomas J.; Strawn, John R.; Trent, David; Johnson, David H.

2015-01-01

Purpose To provide evidence-based recommendations to update the American Society of Clinical Oncology guideline on systemic therapy for stage IV non–small-cell lung cancer (NSCLC). Methods An Update Committee of the American Society of Clinical Oncology NSCLC Expert Panel based recommendations on a systematic review of randomized controlled trials from January 2007 to February 2014. Results This guideline update reflects changes in evidence since the previous guideline. Recommendations There is no cure for patients with stage IV NSCLC. For patients with performance status (PS) 0 to 1 (and appropriate patient cases with PS 2) and without an EGFR-sensitizing mutation or ALK gene rearrangement, combination cytotoxic chemotherapy is recommended, guided by histology, with early concurrent palliative care. Recommendations for patients in the first-line setting include platinum-doublet therapy for those with PS 0 to 1 (bevacizumab may be added to carboplatin plus paclitaxel if no contraindications); combination or single-agent chemotherapy or palliative care alone for those with PS 2; afatinib, erlotinib, or gefitinib for those with sensitizing EGFR mutations; crizotinib for those with ALK or ROS1 gene rearrangement; and following first-line recommendations or using platinum plus etoposide for those with large-cell neuroendocrine carcinoma. Maintenance therapy includes pemetrexed continuation for patients with stable disease or response to first-line pemetrexed-containing regimens, alternative chemotherapy, or a chemotherapy break. In the second-line setting, recommendations include docetaxel, erlotinib, gefitinib, or pemetrexed for patients with nonsquamous cell carcinoma; docetaxel, erlotinib, or gefitinib for those with squamous cell carcinoma; and chemotherapy or ceritinib for those with ALK rearrangement who experience progression after crizotinib. In the third-line setting, for patients who have not received erlotinib or gefitinib, treatment with erlotinib is

Estimation of age- and stage-specific Catalan breast cancer survival functions using US and Catalan survival data

PubMed Central

2009-01-01

Background During the last part of the 1990s the chance of surviving breast cancer increased. Changes in survival functions reflect a mixture of effects. Both, the introduction of adjuvant treatments and early screening with mammography played a role in the decline in mortality. Evaluating the contribution of these interventions using mathematical models requires survival functions before and after their introduction. Furthermore, required survival functions may be different by age groups and are related to disease stage at diagnosis. Sometimes detailed information is not available, as was the case for the region of Catalonia (Spain). Then one may derive the functions using information from other geographical areas. This work presents the methodology used to estimate age- and stage-specific Catalan breast cancer survival functions from scarce Catalan survival data by adapting the age- and stage-specific US functions. Methods Cubic splines were used to smooth data and obtain continuous hazard rate functions. After, we fitted a Poisson model to derive hazard ratios. The model included time as a covariate. Then the hazard ratios were applied to US survival functions detailed by age and stage to obtain Catalan estimations. Results We started estimating the hazard ratios for Catalonia versus the USA before and after the introduction of screening. The hazard ratios were then multiplied by the age- and stage-specific breast cancer hazard rates from the USA to obtain the Catalan hazard rates. We also compared breast cancer survival in Catalonia and the USA in two time periods, before cancer control interventions (USA 1975–79, Catalonia 1980–89) and after (USA and Catalonia 1990–2001). Survival in Catalonia in the 1980–89 period was worse than in the USA during 1975–79, but the differences disappeared in 1990–2001. Conclusion Our results suggest that access to better treatments and quality of care contributed to large improvements in survival in Catalonia. On

Clinical potentials of methylator phenotype in stage 4 high-risk neuroblastoma: an open challenge.

PubMed

Banelli, Barbara; Merlo, Domenico Franco; Allemanni, Giorgio; Forlani, Alessandra; Romani, Massimo

2013-01-01

Approximately 20% of stage 4 high-risk neuroblastoma patients are alive and disease-free 5 years after disease onset while the remaining experience rapid and fatal progression. Numerous findings underline the prognostic role of methylation of defined target genes in neuroblastoma without taking into account the clinical and biological heterogeneity of this disease. In this report we have investigated the methylation of the PCDHB cluster, the most informative member of the "Methylator Phenotype" in neuroblastoma, hypothesizing that if this epigenetic mark can predict overall and progression free survival in high-risk stage 4 neuroblastoma, it could be utilized to improve the risk stratification of the patients, alone or in conjunction with the previously identified methylation of the SFN gene (14.3.3sigma) that can accurately predict outcome in these patients. We have utilized univariate and multivariate models to compare the prognostic power of PCDHB methylation in terms of overall and progression free survival, quantitatively determined by pyrosequencing, with that of other markers utilized for the patients' stratification utilizing methylation thresholds calculated on neuroblastoma at stage 1-4 and only on stage 4, high-risk patients. Our results indicate that PCDHB accurately distinguishes between high- and intermediate/low risk stage 4 neuroblastoma in agreement with the established risk stratification criteria. However PCDHB cannot predict outcome in the subgroup of stage 4 patients at high-risk whereas methylation levels of SFN are suggestive of a "methylation gradient" associated with tumor aggressiveness as suggested by the finding of a higher threshold that defines a subset of patients with an extremely severe disease (OS <24 months). Because of the heterogeneity of neuroblastoma we believe that clinically relevant methylation markers should be selected and tested on homogeneous groups of patients rather than on patients at all stages.

Uterine cervix cancer treatment at Radiumhemmet: 90 years' experience. Time trends of age, stage, and histopathology distribution.

PubMed

Hellman, Kristina; Hellström, Ann-Cathrin; Pettersson, B Folke

2014-04-01

Since the introduction of screening programs for cervical cancer (CC) the incidence has decreased and CC is discovered at an earlier stage. The purpose of this study was to analyze time trends in age, stage, and histopathology over a 90-year period and to our knowledge this is the largest single institutional series in the literature of invasive cervical carcinoma (CC) cases. This is a retrospective study comprising 18,472 women treated for CC from 1914 until 2004 at Radiumhemmet, Stockholm. The material is part of the international CC statistics published since 1937 in the League of Nations' Annual Reports, and since 1958 under the patronage of International Federation of Gynecology and Obstetrics (FIGO). During the 90-year study period, the annual number of cases treated increased to over 400 up until 1965, after which there was a gradual drop to less than 100 cases in 2004. A pronounced shift toward earlier stages at diagnosis was noted. The mean age at diagnosis increased in all stages, predominantly in advanced stages. A reduction in squamous cell carcinoma (SCC) cases and a sixfold increase in the proportion of adenocarcinoma (AC) cases were observed. The mean age at diagnosis for squamous and AC cases shifted after 1970, when the SCC cases ultimately became 3 years older than the AC cases in contrast to around 1950 when they were 3 years younger than the AC cases. The changes in the distribution by age, stage, and histopathology during this 90-year period are probably associated with: improved social conditions and increased access to health care, the introduction of screening programs for CC in the 1960s, and a change in the risk factors for CC (changed sexual behavior, introduction of contraceptive pills, and changed smoking habits). © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Appendiceal goblet cell carcinoid: common errors in staging and clinical interpretation with a proposal for an improved terminology.

PubMed

Wen, Kwun Wah; Hale, Gillian; Shafizadeh, Nafis; Hosseini, Mojgan; Huang, Anne; Kakar, Sanjay

2017-07-01

Goblet cell carcinoid (GCC) is staged and treated as adenocarcinoma (AC) and not as neuroendocrine tumor (NET) or neuroendocrine carcinoma. The term carcinoid may lead to incorrect interpretation as NET. The aim of the study was to explore pitfalls in staging and clinical interpretation of GCC and mixed GCC-AC, and propose strategies to avoid common errors. Diagnostic terminology, staging, and clinical interpretation were evaluated in 58 cases (27 GCCs, 31 mixed GCC-ACs). Opinions were collected from 23 pathologists using a survey. Clinical notes were reviewed to assess the interpretation of pathology diagnoses by oncologists. NET staging was incorrectly used for 25% of GCCs and 5% of mixed GCC-ACs. In the survey, 43% of pathologists incorrectly indicated that NET staging is applicable to GCCs, and 43% incorrectly responded that Ki-67 proliferation index is necessary for GCC grading. Two cases each of GCC and mixed GCC-AC were incorrectly interpreted as neuroendocrine neoplasms by oncologists, and platinum-based therapy was considered for 2 GCC-AC cases because of the mistaken impression of neuroendocrine carcinoma created by use of the World Health Organization 2010 term mixed adenoneuroendocrine carcinoma. The term carcinoid in GCC and use of mixed adenoneuroendocrine carcinoma for mixed GCC-AC lead to errors in staging and treatment. We propose that goblet cell carcinoid should be changed to goblet cell carcinoma, whereas GCC with AC should be referred to as mixed GCC-AC with a comment about the proportion of each component and the histologic subtype of AC. This terminology will facilitate appropriate staging and clinical management, and avoid errors in interpretation. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

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

Development and testing of a de novo clinical staging system for podoconiosis (endemic non-filarial elephantiasis)

PubMed Central

Tekola, Fasil; Ayele, Zewdu; HaileMariam, Dereje; Fuller, Claire; Davey, Gail

2010-01-01

Summary Background Podoconiosis (endemic non-filarial elephantiasis) is a geochemical disease in individuals exposed to red-clay soil. Despite the prevalence and public health importance of podoconiosis, there is as yet no accepted clinical staging system. Objective We aimed to develop and test a robust clinical staging system for podoconiosis. Methods We adapted the Dreyer system for staging filarial lymphoedema and tested it in four re-iterative field tests conducted in an area of high podoconiosis prevalence in Southern Ethiopia. The system finally arrived at has five stages according to proximal spread of disease and presence of dermal nodules, ridges and bands. We measured the one-week repeatability and the inter-observer agreement of the final staging system. Results We have developed a five-stage system that is readily understood by community workers with little health training. Kappa for one-week repeatability was 0.88 (95% CI 0.80 to 0.96), Kappa for agreement between health professionals was 0.71 (95% CI 0.60 to 0.82), while that between health professionals and community podoconiosis agents without formal health training averaged 0.64 (95% CI 0.52 to 0.78). Conclusions A simple staging system with good inter-observer agreement and repeatability has been developed to assist in the management and further study of podoconiosis. PMID:18721188

7-year follow-up after stereotactic ablative radiotherapy for patients with stage I non-small cell lung cancer: Results of a phase 2 clinical trial.

PubMed

Sun, Bing; Brooks, Eric D; Komaki, Ritsuko U; Liao, Zhongxing; Jeter, Melenda D; McAleer, Mary F; Allen, Pamela K; Balter, Peter A; Welsh, James D; O'Reilly, Michael S; Gomez, Daniel; Hahn, Stephen M; Roth, Jack A; Mehran, Reza J; Heymach, John V; Chang, Joe Y

2017-08-15

The authors evaluated the efficacy, patterns of failure, and toxicity of stereotactic ablative radiotherapy (SABR) for patients with medically inoperable, clinical stage I non-small cell lung cancer (NSCLC) in a prospective clinical trial with 7 years of follow-up. Clinical staging was performed according to the seventh edition of the American Joint Committee on Cancer TNM staging system. Eligible patients with histologically confirmed NSCLC of clinical stage I as determined using positron emission tomography staging were treated with SABR (50 grays in 4 fractions). The primary endpoint was progression-free survival. Patients were followed with computed tomography and/or positron emission tomography/computed tomography every 3 months for the first 2 years, every 6 months for the next 3 years, and then annually thereafter. A total of 65 patients were eligible for analysis. The median age of the patients was 71 years, and the median follow-up was 7.2 years. A total of 18 patients (27.7%) developed disease recurrence at a median of 14.5 months (range, 4.3-71.5 months) after SABR. Estimated incidences of local, regional, and distant disease recurrence using competing risk analysis were 8.1%, 10.9%, and 11.0%, respectively, at 5 years and 8.1%, 13.6%, and 13.8%, respectively, at 7 years. A second primary lung carcinoma developed in 12 patients (18.5%) at a median of 35 months (range, 5-67 months) after SABR. Estimated 5-year and 7-year progression-free survival rates were 49.5% and 38.2%, respectively; the corresponding overall survival rates were 55.7% and 47.5%, respectively. Three patients (4.6%) experienced grade 3 treatment-related adverse events. No patients developed grade 4 or 5 adverse events (toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 3.0]). With long-term follow-up, the results of the current prospective study demonstrated outstanding local control and low toxicity after SABR in

Ascites and alpha-fetoprotein improve prognostic performance of Barcelona Clinic Liver Cancer staging

PubMed Central

Gomaa, Asmaa I; Al-Khatib, Alzhraa; Abdel-Razek, Wael; Hashim, Mohammed Saad; Waked, Imam

2015-01-01

AIM: To assess how ascites and alpha-fetoprotein (AFP) added to the Barcelona Clinic Liver Cancer (BCLC) staging predict hepatocellular carcinoma survival. METHODS: The presence of underlying cirrhosis, ascites and encephalopathy, Child-Turcotte-Pugh (CTP) score, the number of nodules, and the maximum diameter of the largest nodule were determined at diagnosis for 1060 patients with hepatocellular carcinoma at a tertiary referral center for liver disease in Egypt. Demographic information, etiology of liver disease, and biochemical data (including serum bilirubin, albumin, international normalized ratio, alanine and aspartate aminotransferases, and AFP) were evaluated. Staging of the tumor was determined at the time of diagnosis using the BCLC staging system; 496 patients were stage A and 564 patients were stage B. Patients with mild ascites on initial ultrasound, computed tomography, or clinical examination, and who had a CTP score ≤ 9 were included in this analysis. All patients received therapy according to the recommended treatment based on the BCLC stage, and were monitored from the time of diagnosis to the date of death or date of data collection. The effect of the presence of ascites and AFP level on survival was analyzed. RESULTS: At the time the data were censored, 123/496 (24.8%) and 218/564 (38.6%) patients with BCLC stages A and B, respectively, had died. Overall mean survival of the BCLC A and B patients during a three-year follow-up period was 31 mo [95% confidence interval (95%CI): 29.7-32.3] and 22.7 mo (95%CI: 20.7-24.8), respectively. The presence of ascites, multiple focal lesions, large tumor size, AFP level and CTP score were independent predictors of survival for the included patients on multivariate analysis (P < 0.001). Among stage A patients, 18% had ascites, 33% had AFP ≥ 200 ng/mL, and 8% had both. Their median survival in the presence of ascites was shorter if AFP was ≥ 200 ng/mL (19 mo vs 24 mo), and in the absence of ascites

Ascites and alpha-fetoprotein improve prognostic performance of Barcelona Clinic Liver Cancer staging.

PubMed

Gomaa, Asmaa I; Al-Khatib, Alzhraa; Abdel-Razek, Wael; Hashim, Mohammed Saad; Waked, Imam

2015-05-14

To assess how ascites and alpha-fetoprotein (AFP) added to the Barcelona Clinic Liver Cancer (BCLC) staging predict hepatocellular carcinoma survival. The presence of underlying cirrhosis, ascites and encephalopathy, Child-Turcotte-Pugh (CTP) score, the number of nodules, and the maximum diameter of the largest nodule were determined at diagnosis for 1060 patients with hepatocellular carcinoma at a tertiary referral center for liver disease in Egypt. Demographic information, etiology of liver disease, and biochemical data (including serum bilirubin, albumin, international normalized ratio, alanine and aspartate aminotransferases, and AFP) were evaluated. Staging of the tumor was determined at the time of diagnosis using the BCLC staging system; 496 patients were stage A and 564 patients were stage B. Patients with mild ascites on initial ultrasound, computed tomography, or clinical examination, and who had a CTP score ≤ 9 were included in this analysis. All patients received therapy according to the recommended treatment based on the BCLC stage, and were monitored from the time of diagnosis to the date of death or date of data collection. The effect of the presence of ascites and AFP level on survival was analyzed. At the time the data were censored, 123/496 (24.8%) and 218/564 (38.6%) patients with BCLC stages A and B, respectively, had died. Overall mean survival of the BCLC A and B patients during a three-year follow-up period was 31 mo [95% confidence interval (95%CI): 29.7-32.3] and 22.7 mo (95%CI: 20.7-24.8), respectively. The presence of ascites, multiple focal lesions, large tumor size, AFP level and CTP score were independent predictors of survival for the included patients on multivariate analysis (P < 0.001). Among stage A patients, 18% had ascites, 33% had AFP ≥ 200 ng/mL, and 8% had both. Their median survival in the presence of ascites was shorter if AFP was ≥ 200 ng/mL (19 mo vs 24 mo), and in the absence of ascites, patients with AFP ≥ 200

Poverty dynamics, poverty thresholds and mortality: An age-stage Markovian model

PubMed Central

Rehkopf, David; Tuljapurkar, Shripad; Horvitz, Carol C.

2018-01-01

Recent studies have examined the risk of poverty throughout the life course, but few have considered how transitioning in and out of poverty shape the dynamic heterogeneity and mortality disparities of a cohort at each age. Here we use state-by-age modeling to capture individual heterogeneity in crossing one of three different poverty thresholds (defined as 1×, 2× or 3× the “official” poverty threshold) at each age. We examine age-specific state structure, the remaining life expectancy, its variance, and cohort simulations for those above and below each threshold. Survival and transitioning probabilities are statistically estimated by regression analyses of data from the Health and Retirement Survey RAND data-set, and the National Longitudinal Survey of Youth. Using the results of these regression analyses, we parameterize discrete state, discrete age matrix models. We found that individuals above all three thresholds have higher annual survival than those in poverty, especially for mid-ages to about age 80. The advantage is greatest when we classify individuals based on 1× the “official” poverty threshold. The greatest discrepancy in average remaining life expectancy and its variance between those above and in poverty occurs at mid-ages for all three thresholds. And fewer individuals are in poverty between ages 40-60 for all three thresholds. Our findings are consistent with results based on other data sets, but also suggest that dynamic heterogeneity in poverty and the transience of the poverty state is associated with income-related mortality disparities (less transience, especially of those above poverty, more disparities). This paper applies the approach of age-by-stage matrix models to human demography and individual poverty dynamics. In so doing we extend the literature on individual poverty dynamics across the life course. PMID:29768416

Clinical predictors of elective total joint replacement in persons with end-stage knee osteoarthritis.

PubMed

Zeni, Joseph A; Axe, Michael J; Snyder-Mackler, Lynn

2010-05-06

Arthritis is a leading cause of disability in the United States. Total knee arthroplasty (TKA) has become the gold standard to manage the pain and disability associated with knee osteoarthritis (OA). Although more than 400,000 primary TKA surgeries are performed each year in the United States, not all individuals with knee OA elect to undergo the procedure. No clear consensus exists on criteria to determine who should undergo TKA. The purpose of this study was to determine which clinical factors will predict the decision to undergo TKA in individuals with end-stage knee OA. Knowledge of these factors will aid in clinical decision making for the timing of TKA. Functional data from one hundred twenty persons with end-stage knee OA were obtained through a database. All of the individuals complained of knee pain during daily activities and had radiographic evidence of OA. Functional and clinical tests, collectively referred to as the Delaware Osteoarthritis Profile, were completed by a physical therapist. This profile consisted of measuring height, weight, quadriceps strength and active knee range of motion, while functional mobility was assessed using the Timed Up and Go (TUG) test and the Stair Climbing Task (SCT). Self-perceived functional ability was measured using the activities of daily living subscale of the Knee Outcome Survey (KOS-ADLS). A logistic regression model was used to identify variables predictive of TKA use. Forty subjects (33%) underwent TKA within two years of evaluation. These subjects were significantly older and had significantly slower TUG and SCT times (p < 0.05). Persons that underwent TKA were also significantly weaker, had lower self-reported function and had less knee extension than persons who did not undergo TKA. No differences between groups were seen for BMI, gender, knee flexion ROM and unilateral versus bilateral joint disease. Using backward regression, age, knee extension ROM and KOS-ADLS together significantly predicted whether or

Estimation of Direct Melanoma-related Costs by Disease Stage and by Phase of Diagnosis and Treatment According to Clinical Guidelines.

PubMed

Buja, Alessandra; Sartor, Gino; Scioni, Manuela; Vecchiato, Antonella; Bolzan, Mario; Rebba, Vincenzo; Sileni, Vanna Chiarion; Palozzo, Angelo Claudio; Montesco, Maria; Del Fiore, Paolo; Baldo, Vincenzo; Rossi, Carlo Riccardo

2018-02-07

Cutaneous melanoma is a major concern in terms of healthcare systems and economics. The aim of this study was to estimate the direct costs of melanoma by disease stage, phase of diagnosis, and treatment according to the pre-set clinical guidelines drafted by the AIOM (Italian Medical Oncological Association). Based on the AIOM guidelines for malignant cutaneous melanoma, a highly detailed decision-making model was developed describing the patient's pathway from diagnosis through the subsequent phases of disease staging, surgical and medical treatment, and follow-up. The model associates each phase potentially involving medical procedures with a likelihood measure and a cost, thus enabling an estimation of the expected costs by disease stage and clinical phase of melanoma diagnosis and treatment according to the clinical guidelines. The mean per-patient cost of the whole melanoma pathway (including one year of follow-up) ranged from €149 for stage 0 disease to €66,950 for stage IV disease. The costs relating to each phase of the disease's diagnosis and treatment depended on disease stage. It is essential to calculate the direct costs of managing malignant cutaneous melanoma according to clinical guidelines in order to estimate the economic burden of this disease and to enable policy-makers to allocate appropriate resources.

The relations of age and pubertal development with cortisol and daily stress in youth at clinical risk for psychosis.

PubMed

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

2016-04-01

Prodromal syndromes often begin in adolescence - a period of neurodevelopmental changes and heightened stress sensitivity. Research has shown elevated stress and cortisol in individuals at clinical high risk (CHR) for psychosis. This cross-sectional study examined relations of age and pubertal status with cortisol and self-reported stress in healthy controls (HCs) and CHR adolescents. It was hypothesized that the relations of age and pubertal stage with cortisol and stress would be more pronounced in CHR youth. Participants were 93 HCs and 348 CHR adolescents from the North American Prodrome Longitudinal Study (NAPLS). At baseline, measures of stress (Daily Stress Inventory - DSI), Tanner stage (TS), and salivary cortisol were obtained. ANCOVA revealed increased DSI scores with age for both groups, and higher DSI scores in CHR adolescents than HCs, with a more pronounced difference for females. Contrary to prediction, with age controlled, HCs showed greater TS-related DSI increases. Analysis of cortisol showed no significant interactions, but a main effect of age and a trend toward higher cortisol in the CHR group. Correlations of cortisol with TS were higher in HC than CHR group. Stress measures increased with age in HC and CHR adolescents, and DSI scores also increased with TS in HCs. The results do not support a more pronounced age or TS increase in stress measures in CHR adolescents, but instead suggest that stress indices tend to be elevated earlier in adolescence in the CHR group. Potential determinants of findings and future directions are discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

Placental cord drainage in the third stage of labor: Randomized clinical trial.

PubMed

Vasconcelos, Fernanda Barros; Katz, Leila; Coutinho, Isabela; Lins, Vanessa Laranjeiras; de Amorim, Melania Maria

2018-01-01

An open randomized clinical trial was developed at Instituto de Medicina Integral Prof. Fernando Figueira (IMIP) in Recife and at Petronila Campos Municipal Hospital in São Lourenço da Mata, both in Pernambuco, northeastern Brazil, including 226 low-risk pregnant women bearing a single, full-term, live fetus after delayed cord clamping, 113 randomized to placental cord drainage and 113 to a control group not submitted to this procedure. Women incapable of understanding the study objectives and those who went on to have an instrumental or cesarean delivery were excluded. Duration of the third stage of labor did not differ between the two groups (14.2±12.9 versus 13.7±12.1 minutes (mean ± SD), p = 0.66). Likewise, there was no significant difference in mean blood loss (248±254 versus 208±187ml, p = 0.39) or in postpartum hematocrit levels (32.3±4.06 versus 32.8±4.25mg/dl, p = 0.21). Furthermore, no differences were found between the groups for any of the secondary outcomes (postpartum hemorrhage >500 or >1000ml, therapeutic use of oxytocin, third stage >30 or 60 minutes, digital evacuation of the uterus or curettage, symptoms of postpartum anemia and maternal satisfaction). Placental cord drainage had no effect in reducing duration or blood loss during the third stage of labor. ClinicalTrials.gov: www.clinicaltrial.gov, NCT01655576.

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

Genome-Level Determination of Plasmodium falciparum Blood-Stage Targets of Malarial Clinical Immunity in the Peruvian Amazon

PubMed Central

Torres, Katherine J.; Castrillon, Carlos E.; Moss, Eli L.; Saito, Mayuko; Tenorio, Roy; Molina, Douglas M.; Davies, Huw; Neafsey, Daniel E.; Felgner, Philip; Vinetz, Joseph M.; Gamboa, Dionicia

2015-01-01

Background. Persons with blood-stage Plasmodium falciparum parasitemia in the absence of symptoms are considered to be clinically immune. We hypothesized that asymptomatic subjects with P. falciparum parasitemia would differentially recognize a subset of P. falciparum proteins on a genomic scale. Methods and Findings. Compared with symptomatic subjects, sera from clinically immune, asymptomatically infected individuals differentially recognized 51 P. falciparum proteins, including the established vaccine candidate PfMSP1. Novel, hitherto unstudied hypothetical proteins and other proteins not previously recognized as potential vaccine candidates were also differentially recognized. Genes encoding the proteins differentially recognized by the Peruvian clinically immune individuals exhibited a significant enrichment of nonsynonymous nucleotide variation, an observation consistent with these genes undergoing immune selection. Conclusions. A limited set of P. falciparum protein antigens was associated with the development of naturally acquired clinical immunity in the low-transmission setting of the Peruvian Amazon. These results imply that, even in a low-transmission setting, an asexual blood-stage vaccine designed to reduce clinical malaria symptoms will likely need to contain large numbers of often-polymorphic proteins, a finding at odds with many current efforts in the design of vaccines against asexual blood-stage P. falciparum. PMID:25381370

Staging Dementia Using Clinical Dementia Rating Scale Sum of Boxes Scores

PubMed Central

O'Bryant, Sid E.; Waring, Stephen C.; Cullum, C. Munro; Hall, James; Lacritz, Laura; Massman, Paul J.; Lupo, Philip J.; Reisch, Joan S.; Doody, Rachelle

2012-01-01

Background The Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) score is commonly used, although the utility regarding this score in staging dementia severity is not well established. Obiective To investigate the effectiveness of CDRSOB scores in staging dementia severity compared with the global CDR score. Design Retrospective study. Setting Texas Alzheimer's Research Consortium minimum data set cohort. Participants A total of 1577 participants (110 controls, 202 patients with mild cognitive impairment, and 1265 patients with probable Alzheimer disease) were available for analysis. Main Outcome Measures Receiver operating characteristic curves were generated from a derivation sample to determine optimal cutoff scores and ranges, which were then applied to the validation sample. Results Optimal ranges of CDR-SOB scores corresponding to the global CDR scores were 0.5 to 4.0 for a global score of 0.5, 4.5 to 9.0 for a global score of 1.O, 9.5 to 15.5 for a global score of 2.0, and 16.0 to 18.0 for a global score of 3.0. When applied to the validation sample, κ scores ranged from 0.86 to 0.94 (P <.001 for all), with 93.0% of the participants falling within the new staging categories. Conclusions The CDR-SOB score compares well with the global CDR score for dementia staging. Owing to the increased range of values, the CDR-SOB score offers several advantages over the global score, including increased utility in tracking changes within and between stages of dementia severity. Interpretive guidelines for CDR-SOB scores are provided. PMID:18695059

Effect of Habits and Nutritional Status on Clinical Grading and Histopathological Staging in Patients with Oral Sub Mucous Fibrosis.

PubMed

Singh, Abhayjeet; Lanke, Rama Brahmam; Shetty, Rakhith; Akifuddin, Syed; Sahu, Manish; Singh, Navneet; Kaur, Gagandeep; Goyal, Garish

2015-10-01

Oral submucous fibrosis (OSMF) is a chronic progressive debilitating disease affecting the oral, oropharyngeal and sometimes the oesophageal mucosa resulting in inability to eat due to burning, ulcers and stiffness. The study was undertaken, to evaluate the correlation of clinical staging, histological grading and nutritional status using body mass index (BMI) with gutkha (habit) index in OSMF patients. The study group comprised of 50 patients clinically diagnosed and histopathologically confirmed cases of OSMF. Habit (gutkha) index was calculated by multiplying duration and frequency. Body mass index was calculated by dividing weight in kilograms and height in centimetres of the patient. Male to female ratio was 2.8:1. Clinical grading increased with increase in gutkha index, patients with gutkha index 1-50, maximum were in mild stage; with gutkha index 51-100, maximum in moderate and patients with gutkha index 101-150, all were in severe stage. Histological staging showed direct correlation with gutkha index, it increased with increase in gutkha index with p <0.05. Site analysis showed that buccal mucosa and retromolar area were involved in all the patient and floor of mouth in 46% of patients Body mass index analysis revealed that out of 27 patients with moderate clinical staging 3 was underweight; out of 3 with severe clinical staging, 2 was underweight. The duration and frequency of areca nut product use effects on the incidence and severity of OSMF and the patient becomes unable to eat due to burning, ulcers and inability to open mouth which affect the health of the individual. Thus it is important to access the nutritional status to improve the survival rate of patients.

Perceptions of mistreatment among trainees vary at different stages of clinical training.

PubMed

Kulaylat, Afif N; Qin, Danni; Sun, Susie X; Hollenbeak, Christopher S; Schubart, Jane R; Aboud, Antone J; Flemming, Donald J; Dillon, Peter W; Bollard, Edward R; Han, David C

2017-01-14

Mistreatment of trainees remains a frequently reported phenomenon in medical education. One barrier to creating an educational culture of respect and professionalism may be a lack of alignment in the perceptions of mistreatment among different learners. Through the use of clinical vignettes, our aim was to assess the perceptions of trainees toward themes of potential mistreatment at different stages of training. Based on observations from external experts embedded in the clinical learning environment, six thematic areas of potential mistreatment were identified: verbal abuse, specialty-choice discrimination, non-educational tasks, withholding/denying learning opportunities, neglect and gender/racial insensitivity. Corresponding clinical vignettes were created and distributed to 1) medical students, 2) incoming interns, 3) residents/fellows. Perceptions of the appropriateness of the interactions depicted in the vignettes were measured on a 5-point Likert scale. Scores were categorized into neutral or appropriate (≤3) or inappropriate (i.e. mistreatment) (>3) and compared using chi-squared tests. Four hundred twenty seven trainees participated (182 students, 120 interns, 125 residents/fellows). Proportions of students perceiving mistreatment differed significantly from those of interns and residents/fellows in domains of verbal abuse, specialty discrimination and gender/racial insensitivity (p < 0.05). In scenarios comparing interns to residents/fellows, no significant differences were noted in perceptions of mistreatment in the domains of non-educational tasks, withholding learning and neglect. Perceptions of mistreatment differ at different developmental stages of medical training. After exposure to the clinical learning environment, perceptions of incoming interns did not differ from those of residents/fellows, implicating clinical rotations as a key period in indoctrinating students into the prevailing culture. More longitudinal studies are needed to

Biological maturity at birth, the course of the subsequent ontogenetic stages and age at menarche.

PubMed

Szwed, A; Kosińska, M

2012-08-01

The main aim of the study was to assess the influence of biological maturity at birth on growth processes in the subsequent years and during puberty in girls. The material of this study comes from the outpatient clinic cards and cross-sectional research on girls from the province of Wielkopolska in Poland. It includes data of 527 girls. The influence of perinatal maturity on body weight in the later stages of ontogeny was determined with the use of the Kruskal-Wallis test and the Mann-Whitney U test. In order to determine the relationship between perinatal maturity and age at menarche, the survival analysis module was used. The results show a diverse influence of perinatal maturity on the values of body weight achieved in later years of life. The indicated predictive factors included both birth weight and gestational age. In the examined girls menarche occurred between the 10th year and the 17th year of life (X¯=12.87, s=1.26; Me=13 years). The comparison showed a significant variation in age at menarche depending on the length of pregnancy (log-rank χ(2)(2)=27.068, p<0.0001) and birth weight (log-rank χ(2)(2)=23.241, p<0.0001). There was no variation in maturation of the examined girls conditioned by the occurrence of intra-uterine growth retardation (log-rank χ(2)(2)=2.046, p>0.05). Remote prognoses as to the postnatal development of preterm-born children and/or children with low birth weight indicate adverse influence of these variables on age at menarche. Perinatal biological maturity of a newborn conditions the course of postnatal development. Copyright © 2012 Elsevier GmbH. All rights reserved.

Growing Musicians in English Secondary Schools at Key Stage 3 (Age 11-14)

ERIC Educational Resources Information Center

Dalladay, Christopher

2017-01-01

The National Curriculum for Music in England at Key Stage 3 (KS3; age 11-14) declares its purpose that pupils should be inspired to "develop a love of music and their talent as musicians" (DfE, 2013: KS3 Music). The Office for Standards in Education (Ofsted) have criticised secondary schools for a lack of progress in the musical…

Risk Factors for Predicting Occult Lymph Node Metastasis in Patients with Clinical Stage I Non-small Cell Lung Cancer Staged by Integrated Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography.

PubMed

Kaseda, Kaoru; Asakura, Keisuke; Kazama, Akio; Ozawa, Yukihiko

2016-12-01

Lymph nodes in patients with non-small cell lung cancer (NSCLC) are often staged using integrated 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT). However, this modality has limited ability to detect micrometastases. We aimed to define risk factors for occult lymph node metastasis in patients with clinical stage I NSCLC diagnosed by preoperative integrated FDG-PET/CT. We retrospectively reviewed the records of 246 patients diagnosed with clinical stage I NSCLC based on integrated FDG-PET/CT between April 2007 and May 2015. All patients were treated by complete surgical resection. The prevalence of occult lymph node metastasis in patients with clinical stage I NSCLC was analysed according to clinicopathological factors. Risk factors for occult lymph node metastasis were defined using univariate and multivariate analyses. Occult lymph node metastasis was detected in 31 patients (12.6 %). Univariate analysis revealed CEA (P = 0.04), SUV max of the primary tumour (P = 0.031), adenocarcinoma (P = 0.023), tumour size (P = 0.002) and pleural invasion (P = 0.046) as significant predictors of occult lymph node metastasis. Multivariate analysis selected SUV max of the primary tumour (P = 0.049), adenocarcinoma (P = 0.003) and tumour size (P = 0.019) as independent predictors of occult lymph node metastasis. The SUV max of the primary tumour, adenocarcinoma and tumour size were risk factors for occult lymph node metastasis in patients with NSCLC diagnosed as clinical stage I by preoperative integrated FDG-PET/CT. These findings would be helpful in selecting candidates for mediastinoscopy or endobronchial ultrasound-guided transbronchial needle aspiration.

Effects of sleep stage and age on short-term heart rate variability during sleep in healthy infants and children.

PubMed

Villa, M P; Calcagnini, G; Pagani, J; Paggi, B; Massa, F; Ronchetti, R

2000-02-01

Power spectrum analysis of heart rate variability (HRV) is a noninvasive technique that provides a quantitative assessment of cardiovascular neural control. Using this technique, we studied the autonomic nervous system changes induced by sleep in 14 healthy subjects: 7 infants (mean age, 9.40 +/- 2.32 months) and 7 children (mean age, 8.93 +/- 0.65 years) during a standard all-night polysomnographic recording. Our primary aim was to assess the effect of sleep stage and age on short-term HRV during sleep in healthy infants and children. Power spectral density was estimated by autoregressive modeling over 250 consecutive R-R intervals. In this study, we mainly considered two spectral components: the high-frequency (HF) component (0.15 to 0.40 Hz), which reflects parasympathetic cardiovascular modulation; and the low-frequency (LF) component (0.04 to 0.15 Hz), generally considered due to both parasympathetic and sympathetic modulation. Heart rate was higher (p < 0.01 in all sleep stages) and total power lower (p < 0. 02) in infants than in children. HF power was higher in children than in infants (p < 0.05). In infants and children, the ratio between LF and HF powers changed with the various sleep stages (p < 0.02 in infants; p < 0.01 in children): it decreased during deep sleep and increased during rapid eye movement sleep. However, it was invariably lower in children than in infants. These findings show that the sleep stage and age both significantly influence short-term HRV during sleep in healthy infants and children. Hence, to provide unbiased results, HRV studies investigating the effects of age on autonomic nervous system activity should segment sleep into the five stages. In addition, despite a relatively small study sample, our data confirm greater parasympathetic control during sleep in children than in infants.

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.

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

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

PubMed

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

2015-01-01

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

Predictors of clinical course of subacute sclerosing panencephalitis: experience at the Children's Hospital, Lahore.

PubMed

Malik, Muhammad Akbar; Saeed, Muhammad; Qureshi, Ahmad Usaid; Ahmed, Naseer; Akram, Muhammad

2010-10-01

To determine the clinical course of Subacute Sclerosing Panencephalitis (SSPE) and different factors affecting the clinical course. Descriptive study. The Children's Hospital, Lahore, from October 2005 to May 2008. All serologically confirmed patients of SSPE were registered and clinical staging of these patients were done from stage-I to stage-IV. Clinical course of these patients was classified by using neurological disability index as fulminant, acute, subacute, and chronic course. Clinical course was analyzed for any difference with age, gender, immunization for measles, measles infection, nutritional status and correlation with age of onset of SSPE, (Spearman's correlation), using statistic package for social science (SPSS) V. 14. A total of 57 cases (41 males, 16 females) with mean age of 7.45 years were studied. Forty (71.4%) of them were vaccinated with single dose at about 9 months of age, 41% (23/57) had measles infections ≤ 2 years of age. Using the Neurology Disability Index for these patients 10.5% had fulminant, 17.5% had acute, 49.2% subacute and 22.8% had chronic course. Age, gender, age at measles infection, SSPE onset age and nutritional status were poor predictors of clinical course of SSPE. Unvaccinated patients showed significantly more rapid course of disease (p = 0.04). Clinical course of SSPE cannot be predicted at the onset of this catastrophic disorder. Children not immunized against measles had a significant rapid course of disease.

Genome-level determination of Plasmodium falciparum blood-stage targets of malarial clinical immunity in the Peruvian Amazon.

PubMed

Torres, Katherine J; Castrillon, Carlos E; Moss, Eli L; Saito, Mayuko; Tenorio, Roy; Molina, Douglas M; Davies, Huw; Neafsey, Daniel E; Felgner, Philip; Vinetz, Joseph M; Gamboa, Dionicia

2015-04-15

Persons with blood-stage Plasmodium falciparum parasitemia in the absence of symptoms are considered to be clinically immune. We hypothesized that asymptomatic subjects with P. falciparum parasitemia would differentially recognize a subset of P. falciparum proteins on a genomic scale. Compared with symptomatic subjects, sera from clinically immune, asymptomatically infected individuals differentially recognized 51 P. falciparum proteins, including the established vaccine candidate PfMSP1. Novel, hitherto unstudied hypothetical proteins and other proteins not previously recognized as potential vaccine candidates were also differentially recognized. Genes encoding the proteins differentially recognized by the Peruvian clinically immune individuals exhibited a significant enrichment of nonsynonymous nucleotide variation, an observation consistent with these genes undergoing immune selection. A limited set of P. falciparum protein antigens was associated with the development of naturally acquired clinical immunity in the low-transmission setting of the Peruvian Amazon. These results imply that, even in a low-transmission setting, an asexual blood-stage vaccine designed to reduce clinical malaria symptoms will likely need to contain large numbers of often-polymorphic proteins, a finding at odds with many current efforts in the design of vaccines against asexual blood-stage P. falciparum. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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

Changes in Protein Structure and Distribution Observed at Pre-Clinical Stages of Scrapie Pathogenesis

PubMed Central

Kretlow, Ariane; Wang, Qi; Beekes, Michael; Naumann, Dieter; Miller, Lisa M.

2011-01-01

Scrapie is a neurodegenerative disorder that involves the misfolding, aggregation and accumulation of the prion protein (PrP). The normal cellular PrP (PrPC) is rich in α-helical secondary structure, whereas the disease-associated pathogenic form of the protein (PrPSc) has an anomalously high β-sheet content. In this study, protein structural changes were examined in situ in the dorsal root ganglia from perorally 263K scrapie-infected and mock-infected hamsters using synchrotron Fourier Transform InfraRed Microspectroscopy (FTIRM) at four time points over the course of the disease (preclinical, 100 & 130 days post-infection (dpi); first clinical signs (~145 dpi); and terminal (~170 dpi)). Results showed clear changes in the total protein content, structure, and distribution as the disease progressed. At pre-clinical time points, the scrapie-infected animals exhibited a significant increase in protein expression, but the β-sheet protein content was significantly lower than controls. Based on these findings, we suggest that the pre-clinical stages of scrapie are characterized by an overexpression of proteins low in β-sheet content. As the disease progressed, the β-sheet content increased significantly. Immunostaining with a PrP-specific antibody, 3F4, confirmed that this increase was partly – but not solely – due to the formation of PrPSc in the tissue and indicated that other proteins high in β-sheet were produced, either by overexpression or misfolding. Elevated β-sheet was observed near the cell membrane at pre-clinical time points and also in the cytoplasm of infected neurons at later stages of infection. At the terminal stage of the disease, the protein expression declined significantly, likely due to degeneration and death of neurons. These dramatic changes in protein content and structure, especially at pre-clinical time points, emphasize the possibility for identifying other proteins involved in early pathogenesis, which are important for further

Clinical Placement Before or After Simulated Learning Environments?: A Naturalistic Study of Clinical Skills Acquisition Among Early-Stage Paramedicine Students.

PubMed

Mills, Brennen W; Carter, Owen B J; Rudd, Cobie J; Ross, Nathan P; Claxton, Louise A

2015-10-01

There is conflicting evidence surrounding the merit of clinical placements (CPs) for early-stage health-profession students. Some contend that early-stage CPs facilitate contextualization of a subsequently learned theory. Others argue that training in simulated-learning experiences (SLEs) should occur before CP to ensure that students possess at least basic competency. We sought to investigate both claims. First-year paramedicine students (n = 85) undertook 3 days of CP and SLEs as part of course requirements. Students undertook CP either before or after participation in SLEs creating 2 groups (Clin → Sim/Sim → Clin). Clinical skills acquisition was measured via direct scenario-based clinical assessments with expert observers conducted at 4 intervals during the semester. Perceptions of difficulty of CP and SLE were measured via the National Aeronautics and Space Administration Task Load Index. Students' clinical assessment scores in both groups improved significantly from beginning to end of semester (P < 0.001). However, at semester's end, clinical assessment scores for the Sim → Clin group were statistically significantly greater than those of the Clin → Sim group (P = 0.021). Both groups found SLEs more demanding than CP (P < 0.001). However, compared with the Sim → Clin group, the Clin → Sim group rated SLE as substantially more time-demanding than CP (P = 0.003). Differences in temporal demand suggest that the Clin → Sim students had fewer opportunities to practice clinical skills during CP than the Sim → Clin students due to a more limited scope of practice. The Sim → Clin students contextualized SLE within subsequent CP resulting in greater improvement in clinical competency by semester's end in comparison with the Clin → Sim students who were forced to contextualize skills retrospectively.

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.

Clinical outcome of critically ill patients with thrombocytopenia and hypophosphatemia in the early stage of sepsis.

PubMed

Brotfain, Evgeni; Schwartz, Andrei; Boniel, Avi; Koyfman, Leonid; Boyko, Matthew; Kutz, Ruslan; Klein, Moti

2016-01-01

Hypophosphatemia and thrombocytopenia may both be independent risk factors for the development of multiple organ failure and correlate well with the severity of sepsis. In the present study we wanted to analyze the potential clinical role and prognostic significance of both early hypophosphatemia and thrombocytopenia on clinical outcomes of critically ill ICU patients with severe sepsis. We analyzed the clinical data, including the outcome of critically ill ICU patients with severe sepsis who presented during a 5 year period with early hypophosphatemia and thrombocytopenia.This study was retrospective and single centre. All clinical and laboratory data was collected from the patients' ICU and hospital electronic records. All laboratory measurements were done on admission and during the ICU stay. The included patients were distributed into one of three study groups based on the presence of hypophosphatemia and/or thrombocytopenia during the first 24 hours of admission to the ICU: group 1 - early hypophosphatemia; group 2 - early hypophosphatemia and thrombocytopenia and group 3 - early thrombocytopenia. The ICU mortality rate was significantly higher in groups 2 and 3 (25.9% and 22% vs. 9.3%, respectively, P = 0.034). An APACHE II > 27, a TISS > 25 following the first 24 hours of ICU stay , an age higher than 70, male gender and total parenteral nutrition were independent predictors of ICU and hospital mortality in this study population. It may be considered that hypophosphatemia and thrombocytopenia in the early stage of sepsis, even when severe and coexisting, reflect the degree of initial illness severity of sepsis. However, further investigations need to be done for a better understanding of the potential clinical role of these features in the septic critically ill population.

Therapeutic efficacy of three hyaluronic acid formulations in young and middle-aged patients with early-stage meniscal injuries

PubMed Central

Dernek, Bahar; Kesiktas, Fatma Nur; Duymus, Tahir Mutlu; Diracoglu, Demirhan; Aksoy, Cihan

2017-01-01

[Purpose] To investigate and compare the efficacy of three hyaluronic acid formulations in patients with early-stage meniscal injuries. [Subjects and Methods] Male and female patients who were admitted to our clinic between January 2013 and December 2013, diagnosed with early-stage meniscus lesions of the knee, and given a hyaluronic acid treatment were included in this retrospective study. Patients were categorized into 3 groups according to their treatments: MONOVISC, OSTENIL PLUS, or ORTHOVISC. Scores from a Visual Analog Scale and the Western Ontario and McMaster Universities Arthritis Index were evaluated at baseline and one, three, and six months after baseline. [Results] A total of 55 patients were included in this study. Most of the patients were female (55%), and the mean age of the patients was 42.4 (± 8.1) years. Based on the pre- and post-injection data, there was significant reductions both in the Visual Analog Scale score and the Western Ontario and McMaster Universities Arthritis Index score after the injections for all groups. According to intergroup comparisons, no significant difference was observed in terms of efficacy. [Conclusion] Three hyaluronic acid formulations produced a similar efficacy in patients with meniscal injuries, and further studies are needed to evaluate long-term results. PMID:28744035

Age dependence of clinical and pathological manifestations of autoimmune demyelination. Implications for multiple sclerosis.

PubMed

Smith, M E; Eller, N L; McFarland, H F; Racke, M K; Raine, C S

1999-10-01

A prominent feature of the clinical spectrum of multiple sclerosis (MS) is its high incidence of onset in the third decade of life and the relative rarity of clinical manifestations during childhood and adolescence, features suggestive of age-related restriction of clinical expression. Experimental allergic encephalomyelitis (EAE), a model of central nervous system (CNS) autoimmune demyelination with many similarities to MS, has a uniform rapid onset and a high incidence of clinical and pathological disease in adult (mature) animals. Like MS, EAE is most commonly seen and studied in female adults. In this study, age-related resistance to clinical EAE has been examined with the adoptive transfer model of EAE in SJL mice that received myelin basic protein-sensitized cells from animals 10 days (sucklings) to 12 weeks (young adults) of age. A variable delay before expression of clinical EAE was observed between the different age groups. The preclinical period was longest in the younger (<14 days of age) animals, and shortest in animals 6 to 8 weeks old at time of transfer. Young animals initially resistant to EAE eventually expressed well-developed clinical signs by 6 to 7 weeks of age. This was followed by a remitting, relapsing clinical course. For each age at time of sensitization, increased susceptibility of females compared to males was observed. Examination of the CNS of younger animal groups during the preclinical period showed lesions of acute EAE. Older age groups developed onset of signs coincident with acute CNS lesions. This age-related resistance to clinical EAE in developing mice is reminiscent of an age-related characteristic of MS previously difficult to study in vivo. The associated subclinical CNS pathology and age-related immune functions found in young animals may be relevant to the increasing clinical expression of MS with maturation, and may allow study of factors associated with the known occasional poor correlation of CNS inflammation and

Influence of Neuroblastoma Stage on Serum-Based Detection of MYCN Amplification

PubMed Central

Combaret, Valerie; Hogarty, Michael D; London, Wendy B; McGrady, Patrick; Iacono, Isabelle; Brejon, Stephanie; Swerts, Katrien; Noguera, Rosa; Gross, Nicole; Rousseau, Raphael; Puisieux, Alain

2010-01-01

Background MYCN oncogene amplification has been defined as the most important prognostic factor for neuroblastoma, the most common solid extracranial neoplasm in children. High copy numbers are strongly associated with rapid tumor progression and poor outcome, independently of tumor stage or patient age, and this has become an important factor in treatment stratification. Procedure By Real Time Quantitative PCR analysis, we evaluated the clinical relevance of circulating MYCN DNA of 267 patients with locoregional or metastatic neuroblastoma in children less than 18 months of age. Results For patients in this age group with INSS stage 4 or 4S NB and stage 3 patients, serum-based determination of MYCN DNA sequences had good sensitivity (85%, 83% and 75% respectively) and high specificity (100%) when compared to direct tumor gene determination. In contrast, the approach showed low sensitivity patients with stage 1 and 2 disease. Conclusion Our results show that the sensitivity of the serum-based MYCN DNA sequence determination depends on the stage of the disease. However, this simple, reproducible assay may represent a reasonably sensitive and very specific tool to assess tumor MYCN status in cases with stage 3 and metastatic disease for whom a wait and see strategy is often recommended. PMID:19301388

Staging of third molar development in relation to chronological age of 5-16 year old Indian children.

PubMed

Hegde, Sapna; Patodia, Akash; Dixit, Uma

2016-12-01

The usefulness of the developmental status of the third molar has been studied in assessment of the chronological age of adolescents in whom the development of the other permanent teeth is nearly complete. However, little is known about the timing and pattern of third-molar development in the Indian population. This study aimed to stage the third molar development in relation to chronological age of 5-16year old Indian children. In this cross-sectional observational study, the status of third molar development in relation to chronological age of 1139 Indian children aged 5-16 years was evaluated radiographically, using Orhan's modification of Demirjian's method. The frequency of occurrence of the third molars varied from 47% to 70%. Crypt formation, crown completion and root completion occurred as early as 5.4, 8.7 and 15.0 years, respectively. No significant differences based on gender or side were observed in third-molar development (p>0.05). For most stages, maxillary third molars were slightly more advanced than their mandibular counterparts (p>0.05). Considering the high degree of variability observed in third molar genesis and development, the usefulness of this tooth in age determination studies may be very limited in the age group studied. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

An education and motivation intervention to change clinical management of the third stage of labor - the GIRMMAHP Initiative.

PubMed

Figueras, Albert; Narváez, Edgar; Valsecia, Mabel; Vásquez, Susana; Rojas, Germán; Camilo, Angiolina; del Valle, José-María; Aguilera, Cristina

2008-12-01

Hemorrhage and hypertensive disorders are major contributors to death after delivery in developing countries. The GIRMMAHP Initiative was designed to describe the actual delivery care in five Latin American countries and to educate and motivate clinical staff at 17 hospitals with the purpose of implementing their own clinical practice guidelines to prevent postpartum hemorrhage. A multicountry education intervention was developed in four consecutive stages, using two analyses: (a) an observational study of the clinical records in eight teaching and nine nonteaching hospitals and (b) a study of the long-term changes measured 12 months after completion of an education intervention and writing a local clinical guideline. Data from 2,247 pregnant women showed that only 23.3 percent had an active management of the third stage of labor and that 22.7 percent received no prenatal care visit. These data were used to prepare local clinical practice guidelines in each participant hospital. The proportion of active management increased to 72.6 percent of deliveries at 3 months and 58.7 percent 1 year later. Use of oxytocin during the third stage of labor increased to 85.9 percent of included deliveries. The proportion of women who had postpartum hemorrhage decreased from 12.7 percent at baseline to 5 percent at 1 year after the intervention. An education intervention and discussion of actual clinical practice problems with health professionals and their involvement in drafting clinical guidelines helped improve health care quality and practitioners' adherence to these guidelines.

A two-stage clinical decision support system for early recognition and stratification of patients with sepsis: an observational cohort study.

PubMed

Amland, Robert C; Lyons, Jason J; Greene, Tracy L; Haley, James M

2015-10-01

To examine the diagnostic accuracy of a two-stage clinical decision support system for early recognition and stratification of patients with sepsis. Observational cohort study employing a two-stage sepsis clinical decision support to recognise and stratify patients with sepsis. The stage one component was comprised of a cloud-based clinical decision support with 24/7 surveillance to detect patients at risk of sepsis. The cloud-based clinical decision support delivered notifications to the patients' designated nurse, who then electronically contacted a provider. The second stage component comprised a sepsis screening and stratification form integrated into the patient electronic health record, essentially an evidence-based decision aid, used by providers to assess patients at bedside. Urban, 284 acute bed community hospital in the USA; 16,000 hospitalisations annually. Data on 2620 adult patients were collected retrospectively in 2014 after the clinical decision support was implemented. 'Suspected infection' was the established gold standard to assess clinical decision support clinimetric performance. A sepsis alert activated on 417 (16%) of 2620 adult patients hospitalised. Applying 'suspected infection' as standard, the patient population characteristics showed 72% sensitivity and 73% positive predictive value. A postalert screening conducted by providers at bedside of 417 patients achieved 81% sensitivity and 94% positive predictive value. Providers documented against 89% patients with an alert activated by clinical decision support and completed 75% of bedside screening and stratification of patients with sepsis within one hour from notification. A clinical decision support binary alarm system with cross-checking functionality improves early recognition and facilitates stratification of patients with sepsis.

Clinical Training in Aging and Mental Health. Final Report.

ERIC Educational Resources Information Center

Gatz, Margaret; And Others

This report describes the University of Southern California's (USC) gerontology career preparation project, which was funded for the following training activities in mental health and aging: (1) traineeships for graduate students in USC's doctoral track in clinical psychology and aging and in the Leonard Davis School of Gerontology master's track…

Orbital Metastasis Is Associated With Decreased Survival in Stage M Neuroblastoma.

PubMed

Harreld, Julie H; Bratton, Emily M; Federico, Sara M; Li, Xingyu; Grover, William; Li, Yimei; Kerr, Natalie C; Wilson, Matthew W; Hoehn, Mary E

2016-04-01

Approximately 30% of patients with metastatic (stage M) neuroblastoma present with periorbital ecchymosis from orbital osseous disease. Though locoregional disease is staged by imaging, the prognostic significance of metastatic site in stage M disease is unknown. We hypothesize that, compared to nonorbital metastasis, orbital metastasis is associated with decreased survival in patients with stage M neuroblastoma, and that periorbital ecchymosis reflects location and extent of orbital disease. Medical records and imaging from 222 patients with stage M neuroblastoma seen at St. Jude Children's Research Hospital between January 1995 and May 2009 were reviewed. Thirty-seven patients were <18 months of age at diagnosis and 185 were ≥18 months of age. Overall survival (OS) and 5-year survival (5YS) were compared for patients with and without orbital, calvarial and nonorbital osseous metastasis, and with and without periorbital ecchymosis (log-rank test). Associations of periorbital ecchymosis with orbital metastasis location/extent were explored (Fisher's exact test, t-test). In patients ≥18 months of age, only orbital metastasis was associated with decreased 5YS (P = 0.0323) and OS (P = 0.0288). In patients <18 months of age, neither orbital, calvarial, or nonorbital bone metastasis was associated with OS or 5YS. Periorbital ecchymosis was associated with higher number of involved orbital bones (P = 0.0135), but not location or survival. In patients ≥ 18 months of age with stage M neuroblastoma, orbital metastatic disease is associated with decreased 5YS and OS. In future clinical trials, orbital disease may be useful as an imaging-based risk factor for substratification of stage M neuroblastoma. © 2015 Wiley Periodicals, Inc.

Age estimation using development of third molars in South Indian population: A radiological study.

PubMed

Priyadharshini, K Indra; Idiculla, Jose Joy; Sivapathasundaram, B; Mohanbabu, V; Augustine, Dominic; Patil, Shankargouda

2015-05-01

To assess the estimation of chronological age based on the stages of third molar development following the eight stages (A-H) method of Demirjian et al. in Chennai population of South India. A sample consisting of 848 individuals (471 males and 377 females) aged between 14 and 30 years was randomly selected for the clinical evaluation and 323 orthopantomograms with clinically missing third molars were taken for radiological evaluation using Demirjian's method from a Chennai population of known chronological age and sex. Statistical analysis was performed using Pearson's Chi-square test and mean values were compared between the study groups using t-test or analysis of variance (ANOVA) followed by Tukey's highly significant difference (HSD). In the present study, P < 0.05 was considered as the level of significance. The results showed that the mean age of having clinically completely erupted maxillary third molars was 22.41 years in male subjects and 23.81 years in female subjects and that of mandibular third molars was 21.49 years in male subjects and 23.34 years in female subjects. Mandibular third molars were clinically missing more often in females than in males. Eruption of mandibular third molars was generally ahead of the emergence of maxillary third molars into the oral cavity. Third molar development between male and female subjects showed statistically significant differences at calcification stage F and stage G in maxillary third molars and stage F in mandibular third molars (P < 0.05). There are differences indicating that maxillary and mandibular third molar eruption reached Demirjian's formation stages earlier in males than in females. It is suggested that in future studies, to increase the accuracy of age determination, indications of sexual maturity and ossification should also be evaluated in addition to third molar mineralization.

Age estimation using development of third molars in South Indian population: A radiological study

PubMed Central

Priyadharshini, K. Indra; Idiculla, Jose Joy; Sivapathasundaram, B.; Mohanbabu, V.; Augustine, Dominic; Patil, Shankargouda

2015-01-01

Aim: To assess the estimation of chronological age based on the stages of third molar development following the eight stages (A–H) method of Demirjian et al. in Chennai population of South India. Materials and Methods: A sample consisting of 848 individuals (471 males and 377 females) aged between 14 and 30 years was randomly selected for the clinical evaluation and 323 orthopantomograms with clinically missing third molars were taken for radiological evaluation using Demirjian's method from a Chennai population of known chronological age and sex. Statistical analysis was performed using Pearson's Chi-square test and mean values were compared between the study groups using t-test or analysis of variance (ANOVA) followed by Tukey's highly significant difference (HSD). In the present study, P < 0.05 was considered as the level of significance. Results: The results showed that the mean age of having clinically completely erupted maxillary third molars was 22.41 years in male subjects and 23.81 years in female subjects and that of mandibular third molars was 21.49 years in male subjects and 23.34 years in female subjects. Mandibular third molars were clinically missing more often in females than in males. Eruption of mandibular third molars was generally ahead of the emergence of maxillary third molars into the oral cavity. Third molar development between male and female subjects showed statistically significant differences at calcification stage F and stage G in maxillary third molars and stage F in mandibular third molars (P < 0.05). Conclusion: There are differences indicating that maxillary and mandibular third molar eruption reached Demirjian's formation stages earlier in males than in females. It is suggested that in future studies, to increase the accuracy of age determination, indications of sexual maturity and ossification should also be evaluated in addition to third molar mineralization. PMID:25984465

HPV16 variant lineage, clinical stage, and survival in women with invasive cervical cancer

PubMed Central

2011-01-01

Background HPV16 variants are associated with different risks for development of CIN3 and invasive cancer, although all are carcinogenic. The relationship of HPV 16 variants to cancer survival has not been studied. Methods 155 HPV16-positive cervical cancers were categorized according to European and non-European variant patterns by DNA sequencing of the E6 open reading frame. Clinico-pathologic parameters and clinical outcome were collected by chart review and death registry data. Results Of the 155 women (mean age 44.7 years; median follow-up 26.7 months), 85.2% harbored European variants while 14.8% had non-European sequences. HPV16 variants differed by histologic cell type (p = 0.03) and stage (1 vs. 2+; p = 0.03). Overall, 107 women (68.0%) were alive with no evidence of cancer, 42 (27.1%) died from cervical cancer, 2 (1.3%) were alive with cervical cancer, and 4 (2.6%) died of other causes. Death due to cervical cancer was associated with European variant status (p < 0.01). While 31% of women harboring tumors with European variants died from cervical cancer during follow-up, only 1 of 23 (4.4%) non-European cases died of cancer. The better survival for non-European cases was partly mediated by lower stage at diagnosis. Conclusions Overall, invasive cervical cancers with non-European variants showed a less aggressive behavior than those with European variants. These findings should be replicated in a population with more non-European cases. PMID:22035468

Correlation between cervical vertebral maturation and chronological age in a group of Iranian females.

PubMed

Safavi, Seyed Mohammadreza; Beikaii, Hanie; Hassanizadeh, Raheleh; Younessian, Farnaz; Baghban, Alireza Akbarzadeh

2015-01-01

Correlation between chronological age at different stages of cervical vertebral maturation (CVM) is important in clinical orthodontic practice. The objective of this study was to evaluate the correlation between CVM stage and chronological age in a group of Iranian female patients. This study was conducted on 196 digital lateral cephalometry of female patients with the age ranged 9-14 years. The CVM stage was determined with two calibrated examiners, using the method developed by Baccetti and its correlation with mean chronological age was assessed by the Spearman rank-order. The intra and inter-agreements were evaluated by weighted Kappa statistics in overall diagnosis of stages, in addition to determination of presence or absent of concavities at the lower border of second, third and fourth cervical vertebrae and the shapes of the third and fourth vertebrae. P < 0.05 was considered as significant. The correlation coefficient between CVM stages and chronological age was relatively low (r = 0.62). The least amount of inter-observer agreement was determined to be at the clinical decision of the shape of the fourth vertebra. Regarding the low reported correlation, the concomitant usage of other skeletal indicators seems necessary for precise determination of physiological age of the patients.

Cost and Survival Analysis Before and After Implementation of Dana-Farber Clinical Pathways for Patients With Stage IV Non-Small-Cell Lung Cancer.

PubMed

Jackman, David M; Zhang, Yichen; Dalby, Carole; Nguyen, Tom; Nagle, Julia; Lydon, Christine A; Rabin, Michael S; McNiff, Kristen K; Fraile, Belen; Jacobson, Joseph O

2017-04-01

Increasing costs and medical complexity are significant challenges in modern oncology. We explored the use of clinical pathways to support clinical decision making and manage resources prospectively across our network. We created customized lung cancer pathways and partnered with a commercial vendor to provide a Web-based platform for real-time decision support and post-treatment data aggregation. Dana-Farber Cancer Institute (DFCI) Pathways for non-small cell lung cancer (NSCLC) were introduced in January 2014. We identified all DFCI patients who were diagnosed and treated for stage IV NSCLC in 2012 (before pathways) and 2014 (after pathways). Costs of care were determined for 1 year from the time of diagnosis. Pre- and postpathway cohorts included 160 and 210 patients with stage IV NSCLC, respectively. The prepathway group had more women but was otherwise similarly matched for demographic and tumor characteristics. The total 12-month cost of care (adjusted for age, sex, race, distance to DFCI, clinical trial enrollment, and EGFR and ALK status) demonstrated a $15,013 savings after the implementation of pathways ($67,050 before pathways v $52,037 after pathways). Antineoplastics were the largest source of cost savings. Clinical outcomes were not compromised, with similar median overall survival times (10.7 months before v 11.2 months after pathways; P = .08). After introduction of a clinical pathway in metastatic NSCLC, cost of care decreased significantly, with no compromise in survival. In an era where comparative outcomes analysis and value assessment are increasingly important, the implementation of clinical pathways may provide a means to coalesce and disseminate institutional expertise and track and learn from care decisions.

Age of zircons from the xenolith of metapelite in granitoids of the Verkhisetsk massif (Middle Urals): Evidence for granite-related stages of metamorphism

NASA Astrophysics Data System (ADS)

Zinkova, E. A.; Pribavkin, S. V.

2016-02-01

Two age stages in the formation of high-aluminous gneisses related to the major stages of granite formation of the Uralian mobile belt were revealed in this study. The first stage (372 ± 2 Ma) corresponds to the age of metamorphism of the amphibolite facies and is controlled by intrusion of the tonalite-trondhjemite series under the environment of the continental margin. At the second stage (307 ± 3 Ma), gneiss underwent contact metamorphism under the influence of plutons of the adamellite-granite composition formed during the early episodes of collisional metamorphism.

Treatment selection of early stage non-small cell lung cancer: the role of the patient in clinical decision making.

PubMed

Mokhles, S; Nuyttens, J J M E; de Mol, M; Aerts, J G J V; Maat, A P W M; Birim, Ö; Bogers, A J J C; Takkenberg, J J M

2018-01-15

The objective of this study is to investigate the role and experience of early stage non-small cell lung cancer (NSCLC) patient in decision making process concerning treatment selection in the current clinical practice. Stage I-II NSCLC patients (surgery 55 patients, SBRT 29 patients, median age 68) were included in this prospective study and completed a questionnaire that explored: (1) perceived patient knowledge of the advantages and disadvantages of the treatment options, (2) experience with current clinical decision making, and (3) the information that the patient reported to have received from their treating physician. This was assessed by multiple-choice, 1-5 Likert Scale, and open questions. The Decisional Conflict Scale was used to assess the decisional conflict. Health related quality of life (HRQoL) was measured with SF-36 questionnaire. In 19% of patients, there was self-reported perceived lack of knowledge about the advantages and disadvantages of the treatment options. Seventy-four percent of patients felt that they were sufficiently involved in decision-making by their physician, and 81% found it important to be involved in decision making. Forty percent experienced decisional conflict, and one-in-five patients to such an extent that it made them feel unsure about the decision. Subscores with regard to feeling uninformed and on uncertainty, contributed the most to decisional conflict, as 36% felt uninformed and 17% of patients were not satisfied with their decision. HRQoL was not influenced by patient experience with decision-making or patient preferences for shared decision making. Dutch early-stage NSCLC patients find it important to be involved in treatment decision making. Yet a substantial proportion experiences decisional conflict and feels uninformed. Better patient information and/or involvement in treatment-decision-making is needed in order to improve patient knowledge and hopefully reduce decisional conflict.

Real-time in situ nanoclustering during initial stages of artificial aging of Al-Cu alloys

NASA Astrophysics Data System (ADS)

Zatsepin, Nadia A.; Dilanian, Ruben A.; Nikulin, Andrei Y.; Gao, Xiang; Muddle, Barry C.; Matveev, Victor N.; Sakata, Osami

2010-01-01

We report an experimental demonstration of real-time in situ x-ray diffraction investigations of clustering and dynamic strain in early stages of nanoparticle growth in Al-Cu alloys. Simulations involving a simplified model of local strain are well correlated with the x-ray diffraction data, suggesting a redistribution of point defects and the formation of nanoscale clusters in the bulk material. A modal, representative nanoparticle size is determined subsequent to the final stage of artificial aging. Such investigations are imperative for the understanding, and ultimately the control, of nanoparticle nucleation and growth in this technologically important alloy.

Stage progression of congenital cholesteatoma in children.

PubMed

Kim, Young Ho; Yoo, Jae Chul; Lee, Jun Ho; Oh, Seung-Ha; Chang, Sun O; Koo, Ja-Won; Kim, Chong Sun

2012-03-01

This study aimed to investigate the most prevalent stage in each age-group of children with congenital cholesteatoma (CC) and verify the correlation between the stage and the age of the patients for the type of CC ("closed" keratotic cyst and "open" infiltrative types). Patients diagnosed with CC between 2004 and 2009 (n = 156; 116 boys and 40 girls; mean age, 5 years and 5 months; range, 12 months-16 years and 7 months) were enrolled retrospectively. Assessment of stage and type of CC was performed with preoperative high-resolution temporal bone computed tomography and intraoperative findings. The stage of CC was determined using Potsic's staging system classified into four stages according to ossicular involvement and mastoid extension. The patients consisted of groups divided on the basis of a 2-year interval. The prevalence of stage I began to decline from the age-group of 1-2 years. In contrast, the prevalence of stages III increased from the age-group of 3-4 years and that of stage IV from the age-group 5-6 years. The prevalence of "open" infiltrative type CC increased from approximately the age of 7 years, thus showing some correlation with age but not with stage. The prevalence of CC with the advanced stage increased since the age of 2 years. Therefore, the importance of early diagnosis and treatment of CC should be more emphasized.

Age at first sexual activity: Clinical and cognitive associations.

PubMed

Harries, Michael D; Paglia, Helen A; Redden, Sarah A; Grant, Jon E-Mail

2018-05-01

Engagement in sexual activity is common among adolescents and can be considered part of adolescent development, but it carries potential life-changing consequences. This study examined if clinical and cognitive differences existed between adolescents who engaged in voluntary sexual behavior before age 15, between ages 15 to 18, and after age 18. All participants were part of a larger study examining impulsive behavior in young adults. Participants were assessed on measures including demographics, comorbid psychiatric disorders, and clinical scales and cognitive tasks assessing impulsivity, obsessive-compulsive traits, emotion regulation, depression, anxiety, and quality of life. Those who engaged in voluntary sexual activity before age 15 were more likely to have increased depression and anxiety symptoms, to score higher on the Yale Brown Obsessive-Compulsive Scale for Pathologic Gambling, and to make poorer decisions on the Cambridge Gambling Task. The results of this study suggest that the decision to engage in sexual activity at a young age is not an act of thinking before acting or impatience, but rather a decision to engage in sensation-seeking behavior. This finding carries implications for interventions targeting healthy sexual activity in adolescents.

Subjective cognitive concerns and neuropsychiatric predictors of progression to the early clinical stages of Alzheimer disease.

PubMed

Donovan, Nancy J; Amariglio, Rebecca E; Zoller, Amy S; Rudel, Rebecca K; Gomez-Isla, Teresa; Blacker, Deborah; Hyman, Bradley T; Locascio, Joseph J; Johnson, Keith A; Sperling, Reisa A; Marshall, Gad A; Rentz, Dorene M

2014-12-01

To examine neuropsychiatric and neuropsychological predictors of progression from normal to early clinical stages of Alzheimer disease (AD). From a total sample of 559 older adults from the Massachusetts Alzheimer's Disease Research Center longitudinal cohort, 454 were included in the primary analysis: 283 with clinically normal cognition (CN), 115 with mild cognitive impairment (MCI), and 56 with subjective cognitive concerns (SCC) but no objective impairment, a proposed transitional group between CN and MCI. Two latent cognitive factors (memory-semantic, attention-executive) and two neuropsychiatric factors (affective, psychotic) were derived from the Alzheimer's Disease Centers' Uniform Data Set neuropsychological battery and Neuropsychiatric Inventory brief questionnaire. Factors were analyzed as predictors of time to progression to a worse diagnosis using a Cox proportional hazards regression model with backward elimination. Covariates included baseline diagnosis, gender, age, education, prior depression, antidepressant medication, symptom duration, and interaction terms. Higher/better memory-semantic factor score predicted lower hazard of progression (hazard ratio [HR] = 0.4 for 1 standard deviation [SD] increase, p <0.0001), and higher/worse affective factor score predicted higher hazard (HR = 1.3 for one SD increase, p = 0.01). No other predictors were significant in adjusted analyses. Using diagnosis as a sole predictor of transition to MCI, the SCC diagnosis carried a fourfold risk of progression compared with CN (HR = 4.1, p <0.0001). These results identify affective and memory-semantic factors as significant predictors of more rapid progression from normal to early stages of cognitive decline and highlight the subgroup of cognitively normal elderly with SCC as those with elevated risk of progression to MCI. Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

A study of clinical nursing research priorities in aged care: a Hong Kong perspective.

PubMed

Chang, Esther; Ho, Carey Kit Bing; Yuen, Anders Chi Man; Hatcher, Deborah

2003-10-01

The aim of this study was to identify clinical research priorities in aged care from the perspectives of rehabilitation aged care nurses in Hong Kong. The Delphi method was used whereby 33 registered nurses working in an aged care rehabilitation ward identified 28 research questions pertaining to areas in which nurses could take a leadership role: clinical research that is of highest value to patients and nurse specialists; clinical research which would provide improved community care; facilitate health promotion and disease prevention and be of value to the professional needs of clinical nurses. Study findings have implications and provide direction for clinical nursing research in aged care.

An Extended Optional Infinitive Stage in German-Speaking Children with Specific Language Impairment.

ERIC Educational Resources Information Center

Rice, Mabel L.; Noll, Karen Ruff; Grimm, Hannelore

1997-01-01

Predictions were formulated for extended Optional Infinitives (OIs) stage in German-speaking children with specific language impairment and evaluated in clinical sample of 8 SLI German-speaking children, ages 4; 0 to 4; 8; and control group of 8 younger utterance-equivalent children, ages 2; 1 to 2; 7. Samples reveal that affected group more…

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. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For

Third molar development: measurements versus scores as age predictor.

PubMed

Thevissen, P W; Fieuws, S; Willems, G

2011-10-01

Human third molar development is widely used to predict chronological age of sub adult individuals with unknown or doubted age. For these predictions, classically, the radiologically observed third molar growth and maturation is registered using a staging and related scoring technique. Measures of lengths and widths of the developing wisdom tooth and its adjacent second molar can be considered as an alternative registration. The aim of this study was to verify relations between mandibular third molar developmental stages or measurements of mandibular second molar and third molars and age. Age related performance of stages and measurements were compared to assess if measurements added information to age predictions from third molar formation stage. The sample was 340 orthopantomograms (170 females, 170 males) of individuals homogenously distributed in age between 7 and 24 years. Mandibular lower right, third and second molars, were staged following Gleiser and Hunt, length and width measurements were registered, and various ratios of these measurements were calculated. Univariable regression models with age as response and third molar stage, measurements and ratios of second and third molars as predictors, were considered. Multivariable regression models assessed if measurements or ratios added information to age prediction from third molar stage. Coefficients of determination (R(2)) and root mean squared errors (RMSE) obtained from all regression models were compared. The univariable regression model using stages as predictor yielded most accurate age predictions (males: R(2) 0.85, RMSE between 0.85 and 1.22 year; females: R(2) 0.77, RMSE between 1.19 and 2.11 year) compared to all models including measurements and ratios. The multivariable regression models indicated that measurements and ratios added no clinical relevant information to the age prediction from third molar stage. Ratios and measurements of second and third molars are less accurate age predictors

Automated EEG sleep staging in the term-age baby using a generative modelling approach.

PubMed

Pillay, Kirubin; Dereymaeker, Anneleen; Jansen, Katrien; Naulaers, Gunnar; Van Huffel, Sabine; De Vos, Maarten

2018-06-01

We develop a method for automated four-state sleep classification of preterm and term-born babies at term-age of 38-40 weeks postmenstrual age (the age since the last menstrual cycle of the mother) using multichannel electroencephalogram (EEG) recordings. At this critical age, EEG differentiates from broader quiet sleep (QS) and active sleep (AS) stages to four, more complex states, and the quality and timing of this differentiation is indicative of the level of brain development. However, existing methods for automated sleep classification remain focussed only on QS and AS sleep classification. EEG features were calculated from 16 EEG recordings, in 30 s epochs, and personalized feature scaling used to correct for some of the inter-recording variability, by standardizing each recording's feature data using its mean and standard deviation. Hidden Markov models (HMMs) and Gaussian mixture models (GMMs) were trained, with the HMM incorporating knowledge of the sleep state transition probabilities. Performance of the GMM and HMM (with and without scaling) were compared, and Cohen's kappa agreement calculated between the estimates and clinicians' visual labels. For four-state classification, the HMM proved superior to the GMM. With the inclusion of personalized feature scaling, mean kappa (±standard deviation) was 0.62 (±0.16) compared to the GMM value of 0.55 (±0.15). Without feature scaling, kappas for the HMM and GMM dropped to 0.56 (±0.18) and 0.51 (±0.15), respectively. This is the first study to present a successful method for the automated staging of four states in term-age sleep using multichannel EEG. Results suggested a benefit in incorporating transition information using an HMM, and correcting for inter-recording variability through personalized feature scaling. Determining the timing and quality of these states are indicative of developmental delays in both preterm and term-born babies that may lead to learning problems by school age.

Automated EEG sleep staging in the term-age baby using a generative modelling approach

NASA Astrophysics Data System (ADS)

Pillay, Kirubin; Dereymaeker, Anneleen; Jansen, Katrien; Naulaers, Gunnar; Van Huffel, Sabine; De Vos, Maarten

2018-06-01

Objective. We develop a method for automated four-state sleep classification of preterm and term-born babies at term-age of 38-40 weeks postmenstrual age (the age since the last menstrual cycle of the mother) using multichannel electroencephalogram (EEG) recordings. At this critical age, EEG differentiates from broader quiet sleep (QS) and active sleep (AS) stages to four, more complex states, and the quality and timing of this differentiation is indicative of the level of brain development. However, existing methods for automated sleep classification remain focussed only on QS and AS sleep classification. Approach. EEG features were calculated from 16 EEG recordings, in 30 s epochs, and personalized feature scaling used to correct for some of the inter-recording variability, by standardizing each recording’s feature data using its mean and standard deviation. Hidden Markov models (HMMs) and Gaussian mixture models (GMMs) were trained, with the HMM incorporating knowledge of the sleep state transition probabilities. Performance of the GMM and HMM (with and without scaling) were compared, and Cohen’s kappa agreement calculated between the estimates and clinicians’ visual labels. Main results. For four-state classification, the HMM proved superior to the GMM. With the inclusion of personalized feature scaling, mean kappa (±standard deviation) was 0.62 (±0.16) compared to the GMM value of 0.55 (±0.15). Without feature scaling, kappas for the HMM and GMM dropped to 0.56 (±0.18) and 0.51 (±0.15), respectively. Significance. This is the first study to present a successful method for the automated staging of four states in term-age sleep using multichannel EEG. Results suggested a benefit in incorporating transition information using an HMM, and correcting for inter-recording variability through personalized feature scaling. Determining the timing and quality of these states are indicative of developmental delays in both preterm and term-born babies that may

From cottage industry to a dominant mode of primary care: stages in the diffusion of a health care innovation (retail clinics).

PubMed

McKinlay, John B; Marceau, Lisa D

2012-09-01

Primary health care is essential to population health and there is increasing need for it, especially with an aging population with multiple comorbidities. Primary health care in the U.S. is widely considered in an ever-deepening crisis. This paper presents a detailed case study of the recent rise of a "disruptive innovation" - retail clinics - which have the potential to transform the face of primary health care in the US. We describe six stages in the diffusion of retail clinics, from cottage industry to a dominant mode for the delivery of primary health care, and consider sociopolitical influences that facilitate and impede their emerging potential. Retail clinics may provide a strategic opportunity to re-engineer the primary health care system, although they may also produce worrisome unanticipated consequences. Discussion concerning the potential threats and opportunities posed by retail clinics occurs in the absence of sound evidence concerning their comparative effectiveness and quality-of-care. This case study identifies the sociopolitical influences and processes that determine whether health care innovations rise or fall, and highlights critically important points along the pathway to health system change. Copyright © 2012 Elsevier Ltd. All rights reserved.

Age of depressed patient does not affect clinical outcome in collaborative care management.

PubMed

Angstman, Kurt B; MacLaughlin, Kathy L; Rasmussen, Norman H; DeJesus, Ramona S; Katzelnick, David J

2011-09-01

Clinical response and remission for the treatment of depression has been shown to be improved utilizing collaborative care management (CCM). Prior studies have indicated that the presence of mental health comorbidities noted by self-rated screening tools at the intake for CCM are associated with worsening outcomes; few have examined directly the impact of age on clinical response and remission. The hypothesis was that when controlling for other mental health and demographic variables, the age of the patient at implementation of CCM does not significantly impact clinical outcome, and that CCM shows consistent efficacy across the adult age spectrum. We performed a retrospective chart analysis of a cohort of 574 patients with a clinical diagnosis of major depression (not dysthymia) treated in CCM who had 6 months of follow-up data. Using the age group as a categorical variable in logistic regression models demonstrated that while maintaining control of all other variables, age grouping remained a nonsignificant predictor of clinical response (P ≥ 0.1842) and remission (P ≥ 0.1919) after 6 months of treatment. In both models, a lower Generalized Anxiety Disorder-7 score and a negative Mood Disorder Questionnaire score were predictive of clinical response and remission. However, the initial Patient Health Questionnaire-9 score was a statistically significant predictor only for clinical remission (P = 0.0094), not for response (P = 0.0645), at 6 months. In a subset (n = 295) of the study cohort, clinical remission at 12 months was also not associated with age grouping (P ≥ 0.3355). The variables that were predictive of remission at 12 months were the presence of clinical remission at 6 months (odds ratio [OR], 7.4820; confidence interval [CI], 3.9301-14.0389; P < 0.0001), clinical response (with persistent symptoms) (OR, 2.7722; CI, 1.1950-6.4313; P = 0.0176), and a lower initial Patient Health Questionnaire-9 score (OR, 0.9121; CI, 0.8475-0.9816; P = 0.0140). Our

The clinical significance of hyperkalaemia-associated repolarization abnormalities in end-stage renal disease.

PubMed

Green, Darren; Green, Heather D; New, David I; Kalra, Philip A

2013-01-01

Hyperkalaemia is a common potentially fatal complication of chronic kidney disease (CKD). It may manifest as electrocardiogram (ECG) changes, the earliest of which is T-wave 'tenting'. However, this occurs in less than half of episodes of hyperkalaemia. The aim of this study was to determine what other clinical features relate to the probability of T-wave tenting; and if there is a longer-term survival difference between patients who develop tenting and those who do not. One hundred and forty-five patients with end-stage renal disease who had standard 12-lead ECG and concurrent serum potassium measurement were enrolled. The presence of tenting and the ratio of the amplitude of the tallest precordial T-wave and R-wave were determined (T:R). Tenting was as common in normal range serum potassium as hyperkalaemia (33 versus 31%) and less common than in left ventricular hypertrophy (44%). T:R was less sensitive (24 versus 33%) but more specific (85 versus 67%) than tenting at correctly identifying hyperkalaemia ≥ 6.0 mmol/L. Tenting became less common with increasing age. Dialysis patients were more likely to show increased T:R that pre-dialysis Stage 5 CKD. Elevated T:R was not associated with worse cardiovascular outcome but was associated with increased risk of sudden death over a mean follow-up of 3.8 years (hazard ratio = 8.3, P = 0.021). The reason for the variability in T-wave changes is not clear. The ratio of precordial T-wave to R-wave amplitude is a more specific measure than tenting but both are poorly sensitive at detecting hyperkalaemia. The greater risk for sudden death may represent a susceptibility to cardiac arrhythmia during repolarization.

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. Copyright © 2016 Elsevier Inc. All rights reserved.

Lymphatic vessel invasion and lymph node metastasis in patients with clinical stage I non-small cell lung cancer.

PubMed

Kang, Du-Young; Lee, Sungsoo

2014-09-01

The aim of this study was to investigate the association between the presence of lymphatic vessel invasion (LVI) in primary tumors and lymph node (LN) metastasis in clinical stage I non-small cell lung cancer (NSCLC) patients. A total of 76 patients who underwent complete resection for clinical stage I adenocarcinoma and squamous cell carcinoma were retrospectively examined. Tumors consisted of 51 cases of adenocarcinoma and 25 cases of squamous cell carcinoma as determined by histology. LN metastasis was detected in 24.4% (19/76) of patients. Factors associated with LN metastasis on univariate analysis included LVI (p < 0.001) and increased tumor dimensions (p < 0.05). Binary logistic regression analysis showed that the presence of LVI (p < 0.001) was the only predictor of LN metastasis. LVI is significantly associated with LN metastasis in patients with clinical stage I NSCLC. These findings may be helpful in determining the most appropriate operative strategy for patients if preoperative detection of LVI becomes feasible. Georg Thieme Verlag KG Stuttgart · New York.

Conservative care as a treatment option for patients aged 75 years and older with CKD stage V: a National survey in the Netherlands.

PubMed

Susanto, Christopher; Kooman, J; Courtens, A M; Konings, C J A M

2018-01-01

Conservative care for patients aged 75 years and older with CKD stage 5 as a treatment option besides dialysis was proposed officially in the Netherlands in October 2016. This national survey showed the current implementation of this option in Netherlands nephrology departments. A web-based survey was sent to medical managers of 60 nephrology departments in the Netherlands in August 2016. Twenty-one medical managers (35%) completed the survey. The term "conservative care" is frequently used and well known. The estimated number of patients in whom the decision for maximal conservative care was made in 2015 was 310 of 2249 patients with CKD stage 5 age 75 years and older (range 5-50 patients per department). 164 patients became symptomatic and received no dialysis. There is no official registration for this treatment option and patient category. The practice patterns vary widely. Only one of 21 respondents reported a conservative care outpatient clinic. Formal training or education regarding conservative care is not available in most of departments. 95% of respondents discussed this treatment option with their patients. General practitioners are always being informed about their patient's decision. Their main role is providing or organizing palliative care support at the end of life and discussing advance care planning. Most respondents (86%) considered to include their patients in a prospective multicentre observational study, conservative care versus dialysis. Conservative care as a treatment option for patients with CKD stage 5 aged 75 years and older is well established. The practice patterns are varied in the Netherlands. Follow-up studies are needed to see whether the new multidisciplinary guideline facilitates harmonization of practice pattern. Funding is needed to optimize the implementation of conservative care.

Encountering aged care: a mixed methods investigation of medical students' clinical placement experiences.

PubMed

Annear, Michael J; Lea, Emma; Lo, Amanda; Tierney, Laura; Robinson, Andrew

2016-02-04

Residential aged care is an increasingly important health setting due to population ageing and the increase in age-related conditions, such as dementia. However, medical education has limited engagement with this fast-growing sector and undergraduate training remains primarily focussed on acute presentations in hospital settings. Additionally, concerns have been raised about the adequacy of dementia-related content in undergraduate medical curricula, while research has found mixed attitudes among students towards the care of older people. This study explores how medical students engage with the learning experiences accessible in clinical placements in residential aged care facilities (RACFs), particularly exposure to multiple comorbidity, cognitive impairment, and palliative care. Fifth-year medical students (N = 61) completed five-day clinical placements at two Australian aged care facilities in 2013 and 2014. The placements were supported by an iterative yet structured program and academic teaching staff to ensure appropriate educational experiences and oversight. Mixed methods data were collected before and after the clinical placement. Quantitative data included surveys of dementia knowledge and questions about attitudes to the aged care sector and working with older adults. Qualitative data were collected from focus group discussions concerning medical student expectations, learning opportunities, and challenges to engagement. Pre-placement surveys identified good dementia knowledge, but poor attitudes towards aged care and older adults. Negative placement experiences were associated with a struggle to discern case complexity and a perception of an aged care placement as an opportunity cost associated with reduced hospital training time. Irrespective of negative sentiment, post-placement survey data showed significant improvements in attitudes to working with older people and dementia knowledge. Positive student experiences were explained by in

Evaluation of third molar development in the estimation of chronological age.

PubMed

Soares, Caio Belém Rodrigues Barros; Figueiroa, José Natal; Dantas, Renata Moura Xavier; Kurita, Lúcio Mitsuo; Pontual, Andréa dos Anjos; Ramos-Perez, Flávia Maria de Moraes; Perez, Danyel Elias da Cruz; Pontual, Maria Luiza dos Anjos

2015-09-01

The purpose of this study was to evaluate the correlation between chronological age and the degree of third molar mineralization by Demirjian's developmental stages (Demirjian et al., 1973) using panoramic radiography. From a total of 11.396 digital panoramic radiographs of patients from three oral radiology private clinics from the northeast region of Brazil, obtained from January to June 2009, 2097 radiographic images from patients aged between 6 and 22 years were selected. The images were analyzed individually by two obsevers using a 21-inch computer screen and Windows Picture and Fax Viewer. Reliability was achieved by intra- and interobserver evaluation, using the Kappa test. Chronological age, calcification stage, gender and third molar were interrelated using a multiple linear regression model, considering age as a response variable. There was reliability with Demirjian et al.'s developmental stage assesment, displaying a significant relationship between mineralization stages and patients' age (P<0.05). There was no significant difference between the average age and the calcification stage taking gender and localization of the third molar into consideration. It is possible to estimate chronological age based on Demirjian's stage of a third molar, regardless of gender and location. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

A clinically relevant frailty index for aging rats

USDA-ARS?s Scientific Manuscript database

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...

Age and rate of cognitive decline in Alzheimer disease: implications for clinical trials.

PubMed

Bernick, Charles; Cummings, Jeffrey; Raman, Rema; Sun, Xiaoying; Aisen, Paul

2012-07-01

Factors that affect the rate of progression of Alzheimer disease (AD) need to be considered in the clinical trial designs of potential disease-modifying therapies. To determine the influence of age on AD course in a clinical trial setting. Pooled cohort study from 3 AD clinical trials of 18-month duration conducted by the Alzheimer Disease Cooperative Study group. Alzheimer disease research centers from across the United States. Four hundred seventy-one subjects with mild to moderate AD assigned to the placebo arm of 3 clinical trials. The relationships between baseline age and rate of change in the Alzheimer Disease Assessment Scale–cognitive subscale (ADAS-cog) 11, Mini-Mental State Examination, Clinical Dementia Rating scale Sum of Boxes score, Alzheimer Disease Cooperative Study–activities of daily living scale, and Neuropsychiatric Inventory were analyzed using a mixed-effect regression model. Sample size calculation for possible future AD clinical trials lasting 18 months using the results of the change in ADAS-cog 11 by tertiles of age groups. Older age at baseline was associated with a slower rate of decline in the ADAS-cog 11 and the Mini-Mental State Examination scores. Almost twice as many subjects aged 80 years and older compared with those aged younger than 70 years would be required to demonstrate a 30% treatment effect on the ADAS-cog 11 in an 18-month AD trial. Subject age is an important factor to consider when defining the study population in and analyzing data from AD trials of potential disease-modifying therapies.

Cross-modal plasticity in developmental and age-related hearing loss: Clinical implications.

PubMed

Glick, Hannah; Sharma, Anu

2017-01-01

This review explores cross-modal cortical plasticity as a result of auditory deprivation in populations with hearing loss across the age spectrum, from development to adulthood. Cross-modal plasticity refers to the phenomenon when deprivation in one sensory modality (e.g. the auditory modality as in deafness or hearing loss) results in the recruitment of cortical resources of the deprived modality by intact sensory modalities (e.g. visual or somatosensory systems). We discuss recruitment of auditory cortical resources for visual and somatosensory processing in deafness and in lesser degrees of hearing loss. We describe developmental cross-modal re-organization in the context of congenital or pre-lingual deafness in childhood and in the context of adult-onset, age-related hearing loss, with a focus on how cross-modal plasticity relates to clinical outcomes. We provide both single-subject and group-level evidence of cross-modal re-organization by the visual and somatosensory systems in bilateral, congenital deafness, single-sided deafness, adults with early-stage, mild-moderate hearing loss, and individual adult and pediatric patients exhibit excellent and average speech perception with hearing aids and cochlear implants. We discuss a framework in which changes in cortical resource allocation secondary to hearing loss results in decreased intra-modal plasticity in auditory cortex, accompanied by increased cross-modal recruitment of auditory cortices by the other sensory systems, and simultaneous compensatory activation of frontal cortices. The frontal cortices, as we will discuss, play an important role in mediating cognitive compensation in hearing loss. Given the wide range of variability in behavioral performance following audiological intervention, changes in cortical plasticity may play a valuable role in the prediction of clinical outcomes following intervention. Further, the development of new technologies and rehabilitation strategies that incorporate brain

Corrected Age for Preemies

MedlinePlus

... Our Sponsors Ages & Stages Ages & Stages Ages and Stages Prenatal Baby (0-12 mos.) Toddler 1-3yrs. Preschool 3-5yrs Grade School 5-12yrs. Teen 12- ... the Word Shop AAP Find a Pediatrician Ages & Stages Prenatal Baby ... Gradeschool Teen Young Adult Healthy Children > Ages & Stages > ...

One-stage versus two-stage exchange arthroplasty for infected total knee arthroplasty: a systematic review.

PubMed

Nagra, Navraj S; Hamilton, Thomas W; Ganatra, Sameer; Murray, David W; Pandit, Hemant

2016-10-01

Infection complicating total knee arthroplasty (TKA) has serious implications. Traditionally the debate on whether one- or two-stage exchange arthroplasty is the optimum management of infected TKA has favoured two-stage procedures; however, a paradigm shift in opinion is emerging. This study aimed to establish whether current evidence supports one-stage revision for managing infected TKA based on reinfection rates and functional outcomes post-surgery. MEDLINE/PubMed and CENTRAL databases were reviewed for studies that compared one- and two-stage exchange arthroplasty TKA in more than ten patients with a minimum 2-year follow-up. From an initial sample of 796, five cohort studies with a total of 231 patients (46 single-stage/185 two-stage; median patient age 66 years, range 61-71 years) met inclusion criteria. Overall, there were no significant differences in risk of reinfection following one- or two-stage exchange arthroplasty (OR -0.06, 95 % confidence interval -0.13, 0.01). Subgroup analysis revealed that in studies published since 2000, one-stage procedures have a significantly lower reinfection rate. One study investigated functional outcomes and reported that one-stage surgery was associated with superior functional outcomes. Scarcity of data, inconsistent study designs, surgical technique and antibiotic regime disparities limit recommendations that can be made. Recent studies suggest one-stage exchange arthroplasty may provide superior outcomes, including lower reinfection rates and superior function, in select patients. Clinically, for some patients, one-stage exchange arthroplasty may represent optimum treatment; however, patient selection criteria and key components of surgical and post-operative anti-microbial management remain to be defined. III.

[Thyroid diseases in old age. Clinical aspects and therapy. Part 1: Hyperthyroidism].

PubMed

Rudorff, K H; Fahrenkrog, U; Jahnke, K

1981-08-27

The clinical signs of thyroid disease in older people may differ considerably from those in younger patients. The symptoms are often incorrectly interpreted and attributed to old age. The age is also important to the kind of therapy. The normal clinical hyperthyroidism-indices are not relevant in the diagnosis of hyperthyroidism in older patients. Organic symptoms predominate in old age (loss of weight, muscular asthenia, tremor, cardiac arrhythmia, stenocardia, congestive cardiomyopathy). Most of the time they are wrongly interpreted as additional symptoms of old age. Probably it is not the age that causes the difficulties in hyperthyroidism-diagnostics in old age, but the atypical symptoms of solitary or multilocular adenomas, which increase with advancing age. A special symptom of hyperthyroidism in old age, often misinterpreted, is "apathetic" hyperthyroidism. Radioiodotherapy is indicated in older patients with hyperthyroidism.

The International Neuroblastoma Risk Group (INRG) staging system: an INRG Task Force report.

PubMed

Monclair, Tom; Brodeur, Garrett M; Ambros, Peter F; Brisse, Hervé J; Cecchetto, Giovanni; Holmes, Keith; Kaneko, Michio; London, Wendy B; Matthay, Katherine K; Nuchtern, Jed G; von Schweinitz, Dietrich; Simon, Thorsten; Cohn, Susan L; Pearson, Andrew D J

2009-01-10

The International Neuroblastoma Risk Group (INRG) classification system was developed to establish a consensus approach for pretreatment risk stratification. Because the International Neuroblastoma Staging System (INSS) is a postsurgical staging system, a new clinical staging system was required for the INRG pretreatment risk classification system. To stage patients before any treatment, the INRG Task Force, consisting of neuroblastoma experts from Australia/New Zealand, China, Europe, Japan, and North America, developed a new INRG staging system (INRGSS) based on clinical criteria and image-defined risk factors (IDRFs). To investigate the impact of IDRFs on outcome, survival analyses were performed on 661 European patients with INSS stages 1, 2, or 3 disease for whom IDRFs were known. In the INGRSS, locoregional tumors are staged L1 or L2 based on the absence or presence of one or more of 20 IDRFs, respectively. Metastatic tumors are defined as stage M, except for stage MS, in which metastases are confined to the skin, liver, and/or bone marrow in children younger than 18 months of age. Within the 661-patient cohort, IDRFs were present (ie, stage L2) in 21% of patients with stage 1, 45% of patients with stage 2, and 94% of patients with stage 3 disease. Patients with INRGSS stage L2 disease had significantly lower 5-year event-free survival than those with INRGSS stage L1 disease (78% +/- 4% v 90% +/- 3%; P = .0010). Use of the new staging (INRGSS) and risk classification (INRG) of neuroblastoma will greatly facilitate the comparison of risk-based clinical trials conducted in different regions of the world.

The International Neuroblastoma Risk Group (INRG) Staging System: An INRG Task Force Report

PubMed Central

Monclair, Tom; Brodeur, Garrett M.; Ambros, Peter F.; Brisse, Hervé J.; Cecchetto, Giovanni; Holmes, Keith; Kaneko, Michio; London, Wendy B.; Matthay, Katherine K.; Nuchtern, Jed G.; von Schweinitz, Dietrich; Simon, Thorsten; Cohn, Susan L.; Pearson, Andrew D.J.

2009-01-01

Purpose The International Neuroblastoma Risk Group (INRG) classification system was developed to establish a consensus approach for pretreatment risk stratification. Because the International Neuroblastoma Staging System (INSS) is a postsurgical staging system, a new clinical staging system was required for the INRG pretreatment risk classification system. Methods To stage patients before any treatment, the INRG Task Force, consisting of neuroblastoma experts from Australia/New Zealand, China, Europe, Japan, and North America, developed a new INRG staging system (INRGSS) based on clinical criteria and image-defined risk factors (IDRFs). To investigate the impact of IDRFs on outcome, survival analyses were performed on 661 European patients with INSS stages 1, 2, or 3 disease for whom IDRFs were known. Results In the INGRSS, locoregional tumors are staged L1 or L2 based on the absence or presence of one or more of 20 IDRFs, respectively. Metastatic tumors are defined as stage M, except for stage MS, in which metastases are confined to the skin, liver, and/or bone marrow in children younger than 18 months of age. Within the 661-patient cohort, IDRFs were present (ie, stage L2) in 21% of patients with stage 1, 45% of patients with stage 2, and 94% of patients with stage 3 disease. Patients with INRGSS stage L2 disease had significantly lower 5-year event-free survival than those with INRGSS stage L1 disease (78% ± 4% v 90% ± 3%; P = .0010). Conclusion Use of the new staging (INRGSS) and risk classification (INRG) of neuroblastoma will greatly facilitate the comparison of risk-based clinical trials conducted in different regions of the world. PMID:19047290

Clinical Phenotype Predicts Early Staged Bilateral Deep Brain Stimulation in Parkinson’s Disease

PubMed Central

Sung, Victor W.; Watts, Ray L.; Schrandt, Christian J.; Guthrie, Stephanie; Wang, Deli; Amara, Amy W.; Guthrie, Barton L.; Walker, Harrison C.

2014-01-01

Object While many centers place bilateral DBS systems simultaneously, unilateral STN DBS followed by a staged contralateral procedure has emerged as a treatment option for many patients. However little is known about whether the preoperative phenotype predicts when staged placement of a DBS electrode in the opposite subthalamic nucleus will be required. We aimed to determine whether preoperative clinical phenotype predicts early staged placement of a second subthalamic deep brain stimulation (DBS) electrode in patients who undergo unilateral subthalamic DBS for Parkinson's disease (PD). Methods Eighty-two consecutive patients with advanced PD underwent unilateral subthalamic DBS contralateral to the most affected hemibody and had at least 2 years of follow-up. Multivariate logistic regression determined preoperative characteristics that predicted staged placement of a second electrode in the opposite subthalamic nucleus. Preoperative measurements included aspects of the Unified Parkinson Disease Rating Scale (UPDRS), motor asymmetry index, and body weight. Results At 2 years follow-up, 28 of the 82 patients (34%) had undergone staged placement of a contralateral electrode while the remainder chose to continue with unilateral stimulation. Statistically significant improvements in UPDRS total and part 3 scores were retained at the end of the 2 year follow-up period in both subsets of patients. Multivariate logistic regression showed that the most important predictors for early staged placement of a second subthalamic stimulator were low asymmetry index (odds ratio 13.4; 95% confidence interval 2.8, 64.9), high tremor subscore (OR 7.2; CI 1.5, 35.0), and low body weight (OR 5.5; CI 1.4, 22.3). Conclusions This single center study provides evidence that elements of the preoperative PD phenotype predict whether patients will require early staged bilateral subthalamic DBS. These data may aid in the management of patients with advanced PD who undergo subthalamic DBS. PMID

Age and aphasia: a review of presence, type, recovery and clinical outcomes.

PubMed

Ellis, Charles; Urban, Stephanie

2016-12-01

Each year approximately 100,000 stroke survivors are diagnosed with aphasia. Although stroke is associated with age, the relationship between age and aphasia is less clear. To complete a review of the literature to examine the relationship between age and: (a) presence or likelihood of aphasia after stroke, (b) aphasia type, (c) aphasia recovery patterns, and (d) aphasia clinical outcomes. Articles were identified by a comprehensive search of "OneSearch," PubMed, and individual journals: Aphasiology, Stroke and the Journal of Stroke and Cerebrovascular Diseases. Inclusion criteria included: age and incidence of aphasia, likelihood of aphasia, aphasia recovery, and aphasia clinical outcome. Independent searches were completed by the authors. Each author independently assessed the full text of reports meeting inclusion criteria. Differences regarding study eligibility and need to proceed with data extraction were resolved by consensus. 1617 articles were identified during the initial search. Forty studies including 14,795 study participants were included in the review. The review generally demonstrated that: (a) stroke patients with aphasia are typically older than stroke with patients without aphasia and (b) aphasia type and age are associated as younger patients with aphasia are more likely to exhibit non-fluent or Broca's type of aphasia. In contrast, studies examining aphasia recovery and aphasia clinical outcomes did not demonstrate a positive relationship between age and recovery or clinical outcomes. Stroke is a condition of the elderly. However, age appears to only influence likelihood of aphasia and aphasia type.

Dysthymic disorder: clinical characteristics in relation to age at onset.

PubMed

Barzega, G; Maina, G; Venturello, S; Bogetto, F

2001-09-01

The variability in the clinical presentation of dysthymia has given rise to a rich debate in literature, and various hypotheses have been proposed. One is that the clinical presentation differs in relation to age at onset. The aim of the study was to evaluate differences in socio-demographic and clinical characteristics in a sample of patients with dysthymia (DSM-IV), in relation to age at onset. 84 consecutive outpatients with a diagnosis of dysthymia (DSM-IV) were studied. All subjects were evaluated by a semistructured clinical interview and the following rating scales: HAM-A, HAM-D, MADRS, Paykel's Interview for Recent Life Events. 23.8% of the sample had early-onset (<21 yrs) dysthymia. Patients with early-onset disorder were significantly younger at the observation, more frequently female and single. They had a significantly longer duration of illness and in a significantly higher percentage had already received a specialist treatment before admission in the present trial. No differences in the frequency of symptoms were observed. A significantly higher percentage of patients with late-onset disease reported at least one stressful event in the year preceding the onset of dysthymia. A positive history of major depression was significantly more common among the early-onset group; social phobia, panic disorder and conversive disorder were also more frequent in this group. The late-onset patients frequently presented generalized anxiety disorder, substance abuse and somatization disorder. The study is retrospective and enrolls a limited number of cases. The present study agrees with other reports on the differences in clinical presentation of dysthymia according to age at onset. Although they are not actually related to age at onset, some interesting findings emerged in the symptomatological characterization of the disorder, referring to the diagnostic criteria proposed in DSM-IV.

Sleep Stage Transition Dynamics Reveal Specific Stage 2 Vulnerability in Insomnia.

PubMed

Wei, Yishul; Colombo, Michele A; Ramautar, Jennifer R; Blanken, Tessa F; van der Werf, Ysbrand D; Spiegelhalder, Kai; Feige, Bernd; Riemann, Dieter; Van Someren, Eus J W

2017-09-01

Objective sleep impairments in insomnia disorder (ID) are insufficiently understood. The present study evaluated whether whole-night sleep stage dynamics derived from polysomnography (PSG) differ between people with ID and matched controls and whether sleep stage dynamic features discriminate them better than conventional sleep parameters. Eighty-eight participants aged 21-70 years, including 46 with ID and 42 age- and sex-matched controls without sleep complaints, were recruited through www.sleepregistry.nl and completed two nights of laboratory PSG. Data of 100 people with ID and 100 age- and sex-matched controls from a previously reported study were used to validate the generalizability of findings. The second night was used to obtain, in addition to conventional sleep parameters, probabilities of transitions between stages and bout duration distributions of each stage. Group differences were evaluated with nonparametric tests. People with ID showed higher empirical probabilities to transition from stage N2 to the lighter sleep stage N1 or wakefulness and a faster decaying stage N2 bout survival function. The increased transition probability from stage N2 to stage N1 discriminated people with ID better than any of their deviations in conventional sleep parameters, including less total sleep time, less sleep efficiency, more stage N1, and more wake after sleep onset. Moreover, adding this transition probability significantly improved the discriminating power of a multiple logistic regression model based on conventional sleep parameters. Quantification of sleep stage dynamics revealed a particular vulnerability of stage N2 in insomnia. The feature characterizes insomnia better than-and independently of-any conventional sleep parameter. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Age determination enhanced by embryonic foot bud and foot plate measurements in relation to Carnegie stages, and the influence of maternal cigarette smoking.

PubMed

Lutterodt, M C; Rosendahl, M; Yding Andersen, C; Skouby, S O; Byskov, A G

2009-08-01

Reliable age determination of first-trimester human embryos and fetuses is an important parameter for clinical use and basic science. Age determination by ultrasound or morphometric parameters of embryos 4-6 weeks post conception (p.c.) have been questioned, and more accurate methods are required. Data on whether and how maternal smoking and alcohol consumption influence embryonic and fetal foot growth is also lacking. Embryonic tissue from 102 first-trimester legal abortions (aged 35-69 days p.c.) were collected. All women answered a questionnaire concerning smoking and drinking habits, and delivered a urine sample for cotinine analysis. Embryonic age was evaluated by vaginal ultrasound measurements and by post-termination foot length and compared with the Carnegie stages. Foot bud and foot plate were defined and measured as foot length in embryos aged 35-47 days p.c. (range 0.8-2.1 mm). In embryos and fetuses aged 41-69 days p.c., heel-toe length was measured (range 2.5-7.5 mm). We found a significant linear correlation between foot length and age. Morphology of the feet was compared visually with the Carnegie collection, and we found that the mean ages of the two collections correlated well. Foot length was independent of gender, Environmental Tobacco Smoke, maternal smoking and alcohol consumption. Foot length correlated linearly to embryonic and foetal age, and was unaffected by gender, ETS, maternal smoking and alcohol consumption.

Characterising the premonitory stage of migraine in children: a clinic-based study of 100 patients in a specialist headache service.

PubMed

Karsan, N; Prabhakar, P; Goadsby, P J

2016-12-01

The premonitory stage of migraine attacks, when symptomatology outside of pain can manifest hours to days before the onset of the headache, is well recognised. Such symptoms have been reported in adults in a number of studies, and have value in predicting an impending headache. These symptoms have not been extensively studied in children. We aimed to characterise which, if any, of these symptoms are reported in children seen within a Specialist Headache Service. We reviewed clinic letters from the initial consultation of children and adolescents seen within the Specialist Headache Service at Great Ormond Street Hospital between 1999 and 2015 with migraine in whom we had prospectively assessed clinical phenotype data. We randomly selected 100 cases with at least one premonitory symptom recorded in the letter. For these patients, the age at headache onset, presence of family history of headache, headache diagnosis, presence of episodic syndromes which may be associated with headache, developmental milestones, gestation at birth, mode of delivery and presence of premonitory symptoms occurring before or during headache were recorded. Of the 100 patients selected, 65 % were female. The age range of the patients was 18 months to 15 years at the time of headache onset. The most common diagnosis was chronic migraine in 58 %, followed by episodic migraine (29 %), New Daily Persistent Headache with migrainous features (8 %) and hemiplegic migraine (5 %). A history of infantile colic was noted in 31 % and was the most common childhood episodic syndrome associated with migraine. The most common premonitory symptoms recorded were fatigue, mood change and neck stiffness. The commonest number of reported premonitory symptoms was two. Premonitory symptoms associated with migraine are reported in children as young as 18 months, with an overall clinical phenotype comparable to adults. Better documentation of this stage will aid parents and clinicians to better understand

Non-invasive, investigative methods in skin aging.

PubMed

Longo, C; Ciardo, S; Pellacani, G

2015-12-01

A precise and noninvasive quantification of aging is of outmost importance for in vivo assessment of the skin aging "stage", and thus acts to minimize it. Several bioengineering methods have been proposed to objectively, precisely, and non-invasively measure skin aging, and to detect early skin damage, that is sub-clinically observable. In this review we have described the most relevant methods that have emerged from recently introduced technologies, aiming at quantitatively assessing the effects of aging on the skin.

Development and testing of a de novo clinical staging system for podoconiosis (endemic non-filarial elephantiasis).

PubMed

Tekola, Fasil; Ayele, Zewdu; Mariam, Dereje Haile; Fuller, Claire; Davey, Gail

2008-10-01

To develop and test a robust clinical staging system for podoconiosis, a geochemical disease in individuals exposed to red clay soil. We adapted the Dreyer system for staging filarial lymphoedema and tested it in four re-iterative field tests conducted in an area of high-podoconiosis prevalence in Southern Ethiopia. The system has five stages according to proximal spread of disease and presence of dermal nodules, ridges and bands. We measured the 1-week repeatability and the inter-observer agreement of the final staging system. The five-stage system is readily understood by community workers with little health training. Kappa for 1-week repeatability was 0.88 (95% CI 0.80-0.96), for agreement between health professionals was 0.71 (95% CI 0.60-0.82), while that between health professionals and community podoconiosis agents without formal health training averaged 0.64 (95% CI 0.52-0.78). This simple staging system with good inter-observer agreement and repeatability can assist in the management and further study of podoconiosis.

Evaluation of the reliability of clinical staging of T2 N0 esophageal cancer: a review of the Society of Thoracic Surgeons database.

PubMed

Crabtree, Traves D; Kosinski, Andrzej S; Puri, Varun; Burfeind, William; Bharat, Ankit; Patterson, G Alexander; Hofstetter, Wayne; Meyers, Bryan F

2013-08-01

Clinical staging of esophageal cancer has improved with positron-emission tomography/computed tomography and endoscopic ultrasound imaging. Despite such progress, small single-center studies have questioned the reliability of clinical staging of T2 N0 esophageal cancer. This study broadly examines the adequacy of clinical staging of T2 N0 disease using The Society of Thoracic Surgeons database. We retrospectively studied 810 clinical stage T2 N0 patients from 2002 to 2011, with 58 excluded because of incomplete pathologic staging data. Clinical stage, pathologic stage, and preoperative characteristics were recorded. Logistic regression analysis was used to identify factors associated with upstaging at the time of surgical intervention. Among 752 clinical stage T2 N0 patients, 270 (35.9%) received induction therapy before the operation. Of 482 patients who went directly to surgical intervention, 132 (27.4%) were confirmed as pathologic T2 N0, 125 (25.9%) were downstaged (ie, T0-1 N0), and 225 (46.7%) were upstaged at the operation (T3-4 N0 or Tany N1-3). Exclusive tumor upstaging (ie, pathologic T3-4 N0) accounted for 41 patients (18.2%), whereas exclusive nodal upstaging (ie, pathological T1-2 N1-3) accounted for 100 (44.5%). Combined tumor and nodal upstaging (ie, pathological T3-4 N1-3) accounted for 84 patients (37.3%). Among patients who received induction therapy, 103 (38.1%) were upstaged vs 225 (46.7%) without induction therapy (p = 0.026). Comparing the induction therapy group and the primary surgical group, postoperative 30-day mortality (3.7% vs 3.7%, p > 0.99) and morbidity (46.3% vs 45%, p = 0.76) were similar. Despite advances in staging techniques, clinical staging of T2 N0 esophageal cancer remains unreliable. Recognizing T2 N0 as a threshold for induction therapy in esophageal cancer, many surgeons have opted to treat T2 N0 disease with induction therapy, even though one-quarter of these patients will be pathologic T1 N0. Although this study

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

Correlation between clinical fetal head station and sonographic angle of progression during the second stage of labor.

PubMed

Perlman, Sharon; Kivilevitch, Zvi; Moran, Orit; Katorza, Eldad; Kees, Salim; Achiron, Reuven; Gilboa, Yinon

2017-08-04

To investigate the correlation between the angle of progression and the clinical fetal head station (FHS) during the second stage of labor, and to build reference range. A prospective, observational study was conducted. Women carrying singleton term pregnancies were enrolled during the second stage of labor. FHS was assessed manually by a senior obstetrician, while the angle of progression (AOP) was assessed by transperineal ultrasound (TPU). Both examiners were blinded to each others results. The correlation between the sonographic AOP and the clinical FHS was analyzed. Seventy patients comprised the study group. Clinical FHS demonstrated an excellent correlation with the sonographic measurement of AOP (Pearson's Correlation 0.642, p < 0.001). This correlation was best described by a cubic regression according to the formula: 123.800 + 10.290 × FHS -2.889 * FHS +0.910, (r 2  = 0.423, p < .001). After aggregation of the mean AOP per FHS, the relative predicted centiles values and standard deviation were calculated. The mean Z score between measured and predicted values of the AOP for a given FHS was 0.007 (range -0.13 to +0.006). Our results demonstrate a significant correlation between the clinical FHS and the TPU measured AOP. These standardized sonographic values may serve the obstetrician as a reliable, objective auxiliary tool for the evaluation of the FHS during the second stage of labor.

Association of serum ferritin levels with immunological status and clinical staging of HIV patients: a retrospective study

NASA Astrophysics Data System (ADS)

Saragih, R. H.; Mardia, A. I.; Purba, G. C. F.; Syahrini, H.

2018-03-01

Serum ferritin has long known as an acute phase reactant during inflammation. It works as an oxidative stress marker beside its role in the storage of intracellular iron. The increase of serum ferritin levels (SFL) has been reported found in HIV patients. It remains unclear though whether it causes, or is the cause, to the progressivity of the disease. The purpose of this study was to find the association between the SFL and the progressivity of the HIV disease. A retrospective study of 91 patients was carried out at the Haji Adam Malik Central General Hospital. All of the study population were HIV positive inpatients admitted from January to December 2016. The data needed to be all obtained from the patient’s medical records. The WHO Clinical Staging System was used to assess the HIV clinical staging. An inverse relationship was found between the SFL with the immunological status of the HIV patients (r=-0.213) based on their CD4+ count. There was no association found between the SFL with the clinical staging of the HIV patients (p=0.953). The elevated SFL is a feature found in HIV-diagnosed patients with the low CD4+ count, and it affects the progressivity of the disease.

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

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

Ward, Matthew Christopher, E-mail: wardm3@ccf.org; Pham, Yvonne D.; Kotecha, Rupesh

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 literaturemore » 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.« less

Midwives׳ clinical reasoning during second stage labour: Report on an interpretive study.

PubMed

Jefford, Elaine; Fahy, Kathleen

2015-05-01

clinical reasoning was once thought to be the exclusive domain of medicine - setting it apart from 'non-scientific' occupations like midwifery. Poor assessment, clinical reasoning and decision-making skills are well known contributors to adverse outcomes in maternity care. Midwifery decision-making models share a common deficit: they are insufficiently detailed to guide reasoning processes for midwives in practice. For these reasons we wanted to explore if midwives actively engaged in clinical reasoning processes within their clinical practice and if so to what extent. The study was conducted using post structural, feminist methodology. to what extent do midwives engage in clinical reasoning processes when making decisions in the second stage labour? twenty-six practising midwives were interviewed. Feminist interpretive analysis was conducted by two researchers guided by the steps of a model of clinical reasoning process. Six narratives were excluded from analysis because they did not sufficiently address the research question. The midwives narratives were prepared via data reduction. A theoretically informed analysis and interpretation was conducted. using a feminist, interpretive approach we created a model of midwifery clinical reasoning grounded in the literature and consistent with the data. Thirteen of the 20 participant narratives demonstrate analytical clinical reasoning abilities but only nine completed the process and implemented the decision. Seven midwives used non-analytical decision-making without adequately checking against assessment data. over half of the participants demonstrated the ability to use clinical reasoning skills. Less than half of the midwives demonstrated clinical reasoning as their way of making decisions. The new model of Midwifery Clinical Reasoning includes 'intuition' as a valued way of knowing. Using intuition, however, should not replace clinical reasoning which promotes through decision-making can be made transparent and be

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

PubMed

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

2016-12-01

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.

Clinical engineering in Romania. The coming of age.

PubMed

Naianu, B P; Negoescu, R

Biomedical engineering (BME) includes clinical engineering and bioengineering. Bioengineering is academically oriented towards theory and research in biology using the methods of exact sciences such as maths and physics, while clinical engineering (CE) has a rather practical orientation focusing on the general management of clinic/hospital equipment and providing aid to the medical staff in the use of advanced technologies for diagnosis and therapy purposes. The Romanian physiological community has been closely involved in the growth of BME that has now come of age in this country. Radu Vrâncianu's great intuition in opening the door to this science and its practical application in an institution created by Daniel Danielopolu definitely represented a good chance for Romanian public health. Recently, both clinical engineering and medical bioengineering have been introduced into the Romanian Classification of Occupations.

The Effects of Aging on Clinical Vestibular Evaluations

PubMed Central

Maheu, Maxime; Houde, Marie-Soleil; Landry, Simon P.; Champoux, François

2015-01-01

Balance disorders are common issues for aging populations due to the effects of normal aging on peripheral vestibular structures. These changes affect the results of vestibular function evaluations and make the interpretation of these results more difficult. The objective of this article is to review the current state of knowledge of clinically relevant vestibular measures. We will first focus on otolith function assessment methods cervical-VEMP (cVEMP) and ocular-VEMP (oVEMP), then the caloric and video-head impulse test (vHIT) methods for semicircular canals assessment. cVEMP and oVEMP are useful methods, though research on the effects of age for some parameters are still inconclusive. vHIT results are largely independent of age as compared to caloric stimulation and should therefore be preferred for the evaluation of the semicircular canals function. PMID:26441824

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.

[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.

Predicting distant failure in early stage NSCLC treated with SBRT using clinical parameters.

PubMed

Zhou, Zhiguo; Folkert, Michael; Cannon, Nathan; Iyengar, Puneeth; Westover, Kenneth; Zhang, Yuanyuan; Choy, Hak; Timmerman, Robert; Yan, Jingsheng; Xie, Xian-J; Jiang, Steve; Wang, Jing

2016-06-01

The aim of this study is to predict early distant failure in early stage non-small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT) using clinical parameters by machine learning algorithms. The dataset used in this work includes 81 early stage NSCLC patients with at least 6months of follow-up who underwent SBRT between 2006 and 2012 at a single institution. The clinical parameters (n=18) for each patient include demographic parameters, tumor characteristics, treatment fraction schemes, and pretreatment medications. Three predictive models were constructed based on different machine learning algorithms: (1) artificial neural network (ANN), (2) logistic regression (LR) and (3) support vector machine (SVM). Furthermore, to select an optimal clinical parameter set for the model construction, three strategies were adopted: (1) clonal selection algorithm (CSA) based selection strategy; (2) sequential forward selection (SFS) method; and (3) statistical analysis (SA) based strategy. 5-cross-validation is used to validate the performance of each predictive model. The accuracy was assessed by area under the receiver operating characteristic (ROC) curve (AUC), sensitivity and specificity of the system was also evaluated. The AUCs for ANN, LR and SVM were 0.75, 0.73, and 0.80, respectively. The sensitivity values for ANN, LR and SVM were 71.2%, 72.9% and 83.1%, while the specificity values for ANN, LR and SVM were 59.1%, 63.6% and 63.6%, respectively. Meanwhile, the CSA based strategy outperformed SFS and SA in terms of AUC, sensitivity and specificity. Based on clinical parameters, the SVM with the CSA optimal parameter set selection strategy achieves better performance than other strategies for predicting distant failure in lung SBRT patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Age differences in presentation, diagnosis pathway and management of colorectal cancer.

PubMed

Esteva, Magdalena; Ruiz, Amador; Ramos, Maria; Casamitjana, Monserrat; Sánchez-Calavera, María A; González-Luján, Luis; Pita-Fernández, Salvador; Leiva, Alfonso; Pértega-Díaz, Sonia; Costa-Alcaraz, Ana M; Macià, Francesc; Espí, Alejandro; Segura, Josep M; Lafita, Sergio; Novella, Maria T; Yus, Carmen; Oliván, Barbara; Cabeza, Elena; Seoane-Pillado, Teresa; López-Calviño, Beatriz; Llobera, Joan

2014-08-01

The gap in survival between older and younger European cancer patients is getting wider. It is possible that cancer in the elderly is being managed or treated differently than in their younger counterparts. This study aims to explore age disparities with respect to the clinical characteristics of the tumour, diagnostic pathway and treatment of colorectal cancer patients. We conducted a multicenter cross sectional study in 5 Spanish regions. Consecutive incident cases of CRC were identified from pathology services. From patient interviews, hospital and primary care clinical records, we collected data on symptoms, stage, doctors investigations, time duration to diagnosis/treatment, quality of care and treatment. 777 symptomatic cases, 154 were older than 80 years. Stage was similar by age group. General symptoms were more frequent in the eldest and abdominal symptoms in the youngest. No differences were found regarding perception of symptom seriousness and symptom disclosure between age groups as no longer duration to diagnosis or treatment was observed in the oldest groups. In primary care, only ultrasound is more frequently ordered in those <65 years. Those >80 years had a significantly higher proportion of iron testing and abdominal XR requested in hospital. We observed a high resection rate independently of age but less adjuvant chemotherapy in Stage III colon cancer, and of radiotherapy in stage II and III rectal cancer as age increases. There are no relevant age disparities in the CRC diagnosis process with similar stage, duration to diagnosis, investigations and surgery. However, further improvements have to be made with respect to adjuvant therapy. Copyright © 2014 Elsevier Ltd. All rights reserved.

Age and performance at fledging are a cause and consequence of juvenile mortality between life stages

PubMed Central

2018-01-01

Should they stay or should they leave? The age at which young transition between life stages, such as living in a nest versus leaving it, differs among species and the reasons why are unclear. We show that offspring of songbird species that leave the nest at a younger age have less developed wings that cause poorer flight performance and greater mortality after fledging. Experimentally delayed fledging verified that older age and better developed wings provide benefits of reduced juvenile mortality. Young are differentially constrained in the age that they can stay in the nest and enjoy these fitness benefits because of differences among species in opposing predation costs while in the nest. This tension between mortality in versus outside of the nest influences offspring traits and performance and creates an unrecognized conflict between parents and offspring that determines the optimal age to fledge.

Determinants of age at menopause in women attending menopause clinics in Italy.

PubMed

Parazzini, Fabio

2007-03-20

We analysed the mean age at menopause and its determinants in 31,000 women attending menopause clinics in Italy. Between 1997 and 2003 we conducted a large cross-sectional study on the characteristics of peri- and post-menopausal women attending a network of first-level outpatient menopause clinics in Italy for general counseling or treatment of menopausal symptoms. Spontaneous menopause was defined as natural cessation of menses for 12 or more months. A total of 31,834 women with spontaneous menopause entered the study. The mean age at spontaneous menopause was 51.2. The age at menopause did not markedly changed with cohort of birth. Higher education was associated with lower age at menopause (51.1 in women with low education versus 51.3 for women with high school or university degree, p<0.05). A higher body mass index (BMI) was associated with later age at menopause. Smokers reported a lower age at menopause (51.2 in nonsmokers versus 51.1 in smokers, p<0.05). A later age at menarche was associated with a later age at menopause. Likewise, lifelong irregular menstrual cycles and higher parity were related with later age at menopause. No association emerged between ever oral contraceptive use and age at menopause. Low educational level, lower BMI, smoking, early menarche, nulliparity and regular cycles are independently associated with lower age at natural menopause in a large sample of women attending menopause clinics in Italy. However, in absolute terms the effect of these factors in our sample is very small.

Routine conventional karyotyping of lymphoma staging bone marrow samples does not contribute clinically relevant information.

PubMed

Nardi, Valentina; Pulluqi, Olja; Abramson, Jeremy S; Dal Cin, Paola; Hasserjian, Robert P

2015-06-01

Bone marrow (BM) evaluation is an important part of lymphoma staging, which guides patient management. Although positive staging marrow is defined as morphologically identifiable disease, such samples often also include flow cytometric analysis and conventional karyotyping. Cytogenetic analysis is a labor-intensive and costly procedure and its utility in this setting is uncertain. We retrospectively reviewed pathological reports of 526 staging marrow specimens in which conventional karyotyping had been performed. All samples originated from a single institution from patients with previously untreated Hodgkin and non-Hodgkin lymphomas presenting in an extramedullary site. Cytogenetic analysis revealed clonal abnormalities in only eight marrow samples (1.5%), all of which were positive for lymphoma by morphologic evaluation. Flow cytometry showed a small clonal lymphoid population in three of the 443 morphologically negative marrow samples (0.7%). Conventional karyotyping is rarely positive in lymphoma staging marrow samples and, in our cohort, the BM karyotype did not contribute clinically relevant information in the vast majority of cases. Our findings suggest that karyotyping should not be performed routinely on BM samples taken to stage previously diagnosed extramedullary lymphomas unless there is pathological evidence of BM involvement by lymphoma. © 2015 Wiley Periodicals, Inc.

Biomechanical and clinical factors related to stage I posterior tibial tendon dysfunction.

PubMed

Rabbito, Melissa; Pohl, Michael B; Humble, Neil; Ferber, Reed

2011-10-01

Case control. To investigate differences in arch height, ankle muscle strength, and biomechanical factors in individuals with stage I posterior tibial tendon dysfunction (PTTD) in comparison to healthy individuals. PTTD is a progressive condition, so early recognition and treatment are essential to help delay or reverse the progression. However, no previous studies have investigated stage I PTTD, and no single study has measured static anatomical structure, muscle strength, and gait mechanics in this population. Twelve individuals with stage I PTTD and 12 healthy, age- and gender-matched control subjects, who were engaged in running-related activities, participated in this study. Measurements of arch height index, maximum voluntary ankle invertor muscle strength, and 3-dimensional rearfoot and medial longitudinal arch kinematics during walking were obtained. The runners with PTTD demonstrated significantly lower seated arch height index (P = .02) and greater (P = .03) and prolonged (P = .05) peak rearfoot eversion angle during gait, compared to the healthy runners. No differences were found in standing arch height index values (P = .28), arch rigidity index (P = .06), ankle invertor strength (P = .49), or peak medial longitudinal arch values (P = .49) between groups. The increased foot pronation is hypothesized to place greater strain on the posterior tibialis muscle, which may partially explain the progressive nature of this condition.

The Effect of Two-Staged Warm Compress on the Pain Duration of First and Second Labor Stages and Apgar Score in Prim Gravida Women: a Randomized Clinical Trial

PubMed Central

Akbarzadeh, Marzieh; Nematollahi, Azar; Farahmand, Mahnaz; Amooee, Sedigheh

2018-01-01

Introduction: The aim of this study was to assess the effect of two-stage warm compress technique on the pain duration of the first and second labor stages and neonatal outcomes. Methods: The clinical trial was done on 150 women (75 subjects in each groups) in Shiraz-affiliated hospitals in 2012 A two-staged warm compress was done for 15-20 minutes in the first and second labor phase (cervical dilatation of 7 and 10 cm with zero status) while the control group received hospital routine care. The duration of labor and Apgar score were evaluated. Results: According to t-test, the average of labor duration was lower in the intervention group compared to the control group at the second stage. However, there was no significant difference for labor duration at the first stage and the first and fifth minute Apgar score. Conclusion: According to the result, this intervention seems a good method for decreasing labor duration at the second stage of parturition. PMID:29637053

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

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

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. Copyright © 2015 Elsevier Ltd. All rights reserved.

Ultra-wide-field scanning laser ophthalmoscopy assists in the clinical detection and evaluation of asymptomatic early-stage familial exudative vitreoretinopathy.

PubMed

Lyu, Jiao; Zhang, Qi; Wang, Shi-Yuan; Chen, Yi-Ye; Xu, Yu; Zhao, Pei-Quan

2017-01-01

This study aims to investigate the ability of the ultra-wide-field scanning laser ophthalmoscope (UWF SLO) in clinically detecting and evaluating asymptomatic early-stage familial exudative vitreoretinopathy (FEVR). We retrospectively reviewed 163 eyes of 83 asymptomatic family members of 48 patients with FEVR. UWF SLO imaging (Optos® PLC, Scotland, UK) was performed on asymptomatic family members as a preliminary screening test for fundus anomalies, and the findings were compared with subsequent examinations using indirect fundus ophthalmoscopy in full mydriasis, fluorescein angiography (FA), fundus autoflourescence, and genetic sequencing. A total of 86 eyes of 43 asymptomatic family members were clinically diagnosed with early-stage FEVR, and 17 of the affected 43 family members were also genetically diagnosed. Compared with FA as a standard, the UWF SLO was highly effective in diagnosing FEVR with a sensitivity and specificity of 93.0 % and 97.5 %, respectively. The UWF SLO was able to diagnose early-stage FEVR in 93.0 % of eyes, and guided the selection of therapies in 46.5 % of the eyes studied. UWF SLO is a valuable imaging tool for detecting fundus anomalies related to early-stage FEVR, and this tool can assist in the clinical diagnosis and evaluation of early-stage FEVR in asymptomatic family members of patients with FEVR.

Arterial spin labeling perfusion-weighted MR imaging: correlation of tumor blood flow with pathological degree of tumor differentiation, clinical stage and nodal metastasis of head and neck squamous cell carcinoma.

PubMed

Abdel Razek, Ahmed Abdel Khalek; Nada, Nadia

2018-05-01

The prognostic parameters of head and neck squamous cell carcinoma (HNSCC) include the pathological degree of tumor differentiation, clinical staging, and presence of metastatic cervical lymph nodes. To correlate tumor blood flow (TBF) acquired from arterial spin labeling (ASL) perfusion-weighted MR imaging with pathological degree of tumor differentiation, clinical stage, and nodal metastasis of HNSCC. Retrospective analysis of 43 patients (31 male, 12 female with a mean age of 65 years) with HNSCC that underwent ASL of head and neck and TBF of HNSCC was calculated. Tumor staging and metastatic lymph nodes were determined. The stages of HNSCC were stage 1 (n = 7), stage II (n = 12), stage III (n = 11) and stage IV (n = 13). Metastatic cervical lymph nodes were seen in 24 patients. The degree of tumor differentiation was determined through pathological examination. The mean TBF of poorly and undifferentiated HNSCC (157.4 ± 6.7 mL/100 g/min) was significantly different (P = 0.001) than that of well-to-moderately differentiated (142.5 ± 5.7 mL/100 g/min) HNSCC. The cut-off TBF used to differentiate well-moderately differentiated from poorly and undifferentiated HNSCC was 152 mL/100 g/min with an area under the curve of 0.658 and accuracy of 88.4%. The mean TBF of stages I, II (146.10 ± 9.1 mL/100 g/min) was significantly different (P = 0.014) than that of stages III, IV (153.33 ± 9.3 mL/100 g/min) HNSCC. The cut-off TBF used to differentiate stages I, II from stages III and IV was 148 mL/100 g/min with an area under the curve of 0.701 and accuracy of 69.8%. The TBF was higher in patients with metastatic cervical lymph nodes. The cut-off TBF suspect metastatic node was 147 mL/100 g/min with an area under the curve of 0.671 and accuracy of 67.4%. TBF is a non-invasive imaging parameter that well correlated with pathological degree of tumor differentiation, clinical stage of tumor and nodal metastasis of HNSCC.

Experience with International Neuroblastoma Staging System and Pathology Classification

PubMed Central

Ikeda, H; Iehara, T; Tsuchida, Y; Kaneko, M; Hata, J; Naito, H; Iwafuchi, M; Ohnuma, N; Mugishima, H; Toyoda, Y; Hamazaki, M; Mimaya, J; Kondo, S; Kawa, K; Okada, A; Hiyama, E; Suita, S; Takamatsu, H

2002-01-01

The International Neuroblastoma Staging System and Pathology Classification were proposed in 1988 and in 1999, respectively, but their clinical value has not yet been fully studied in new patients. Six hundred and forty-four patients with neuroblastoma treated between January 1995 and December 1999 were analysed by these classifications. The 4-year overall survival rate of patients <12 months of age with INSS stages 1, 2A, 2B, 3 and 4S disease was 98.5%, which was significantly higher than the 73.1% rate in stage 4 patients <12 months (P<0.0001). When patients were ⩾12 months, the 4-year overall survival rate of patients with neuroblastoma at 1, 2A, 2B and 3 stages was 100% and that of patients at stage 4 was 48.5% (P<0.0001). As to the International Neuroblastoma Pathology Classification histology, the 4-year overall survival rate was 98.8% in patients with favourable histology and 60.7% in those with unfavourable histology in the <12 months group (P<0.0001). In the ⩾12 months group, the 4-year oral survival of patients with favourable histology was 95.3% and that of patients with unfavourable histology was 50.6% (P<0.0001). Among biological factors, MYCN amplification, DNA diploidy and 1p deletions were significantly associated with poor prognosis in patients <12 months, as were MYCN amplification and DNA diploidy in patients ⩾12 months of age. Multivariate analysis showed that the INSS stage (stage 4 vs other stages) and International Neuroblastoma Pathology Classification histology (unfavourable vs favourable) were significantly and independently associated with the survival of patients undergoing treatment, stratified by age, stage and MYCN amplification (P=0.0002 and P=0.0051, respectively). British Journal of Cancer (2002) 86, 1110–1116. DOI: 10.1038/sj/bjc/6600231 www.bjcancer.com © 2002 Cancer Research UK PMID:11953858

Pulmonary 3 T MRI with ultrashort TEs: influence of ultrashort echo time interval on pulmonary functional and clinical stage assessments of smokers.

PubMed

Ohno, Yoshiharu; Nishio, Mizuho; Koyama, Hisanobu; Yoshikawa, Takeshi; Matsumoto, Sumiaki; Seki, Shinichiro; Obara, Makoto; van Cauteren, Marc; Takahashi, Masaya; Sugimura, Kazuro

2014-04-01

To assess the influence of ultrashort TE (UTE) intervals on pulmonary magnetic resonance imaging (MRI) with UTEs (UTE-MRI) for pulmonary functional loss assessment and clinical stage classification of smokers. A total 60 consecutive smokers (43 men and 17 women; mean age 70 years) with and without COPD underwent thin-section multidetector row computed tomography (MDCT), UTE-MRI, and pulmonary functional measurements. For each smoker, UTE-MRI was performed with three different UTE intervals (UTE-MRI A: 0.5 msec, UTE-MRI B: 1.0 msec, UTE-MRI C: 1.5 msec). By using the GOLD guidelines, the subjects were classified as: "smokers without COPD," "mild COPD," "moderate COPD," and "severe or very severe COPD." Then the mean T2* value from each UTE-MRI and CT-based functional lung volume (FLV) were correlated with pulmonary function test. Finally, Fisher's PLSD test was used to evaluate differences in each index among the four clinical stages. Each index correlated significantly with pulmonary function test results (P < 0.05). CT-based FLV and mean T2* values obtained from UTE-MRI A and B showed significant differences among all groups except between "smokers without COPD" and "mild COPD" groups (P < 0.05). UTE-MRI has a potential for management of smokers and the UTE interval is suggested as an important parameter in this setting. Copyright © 2013 Wiley Periodicals, Inc.

Is human immunodeficiency virus (HIV) stage an independent risk factor for altering the periodontal status of HIV-positive patients? A South African study.

PubMed

John, Cathy Nisha; Stephen, Lawrence Xavier; Joyce Africa, Charlene Wilma

2013-12-03

The immunosuppresion in HIV patients makes them highly susceptible to microbial infections. The aim of the study was to establish whether HIV stage (as depicted by CD4+ T lymphocyte counts) could independently be associated with periodontal status (as revealed by the measurement of clinical indices). One hundred and twenty HIV-infected patients attending an infectious diseases clinic in the Western Cape, South Africa were included in the study. The periodontal clinical indices such as plaque index, gingival index, pocket probing depth and clinical attachment levels were measured on the mesial aspect of the six Ramfjord teeth. The CD4 + T cell counts were taken from the patients' medical records and patients' HIV stage determined and grouped according to their CD4+ T cell counts into A (<200 cells /mm3), B (200-500 cells /mm3) and C (>500 cells /mm3). The mean age of 120 HIV-positive patients was 33.25 years and the mean CD4 + T cell count was 293.43 cells/mm3. The probing depth and clinical attachment loss were found to be significantly associated with the total CD4 + T cell counts but not with HIV stage. Significant correlations were found between age and all clinical indices except for clinical attachment loss. No correlation was found between age and HIV stage of the patients. The use of antiretroviral therapy was significantly associated with probing depth and clinical attachment loss, but not with plaque nor gingival index. Significant associations were observed between smoking and all of the clinical indices except for the gingival index. A significant association was observed between the use of interdental aids and all the clinical indices except for probing depth, while brushing was significantly associated with plaque index only. CD4 + T cell counts were significantly associated with brushing frequency (p = 0.0190) and the use of interdental aids (p = 0.0170). The findings of this study conclude that HIV stage, ART and age are not independent risk factors

Diffusion-weighted MR imaging in thymic epithelial tumors: correlation with World Health Organization classification and clinical staging.

PubMed

Abdel Razek, Ahmed Abdel Khalek; Khairy, Mohamed; Nada, Nadia

2014-10-01

To assess thymic epithelial tumors with diffusion-weighted magnetic resonance (MR) imaging. Informed consent from patients and institutional review board approval were obtained. Prospective study was conducted on 30 consecutive patients (21 men and nine women; age range, 35-71 years) with thymic epithelial tumors. They underwent true fast imaging with steady-state precession and single-shot echo-planar diffusion-weighted MR imaging of the mediastinum with b values of 0, 400, and 800 sec/mm(2). Apparent diffusion coefficient (ADC) of the thymic epithelial tumors was calculated by the same observer at two settings and was correlated with World Health Organization classification and clinical staging. There was significant difference in longest diameter (P = .001) and necrotic part of the tumor (P = .014) between low-risk thymoma, high-risk thymoma, and thymic carcinoma. Mean ADC value of both readings of thymic epithelial tumors (n = 30) was 1.24 × 10(-3) mm(2)/sec and 1.22 × 10(-3) mm(2)/sec, with good intraobserver agreement (κ = 0.732). There was significant difference in both readings (P = .01 and .20) of low-risk thymoma (1.30 × 10(-3) mm(2)/sec and 1.29 × 10(-3) mm(2)/sec), high-risk thymoma (1.16 × 10(-3) mm(2)/sec and 1.14 × 10(-3) mm(2)/sec), and thymic carcinoma (1.18 × 10(-3) mm(2)/sec and 1.06 × 10(-3) mm(2)/sec). Cutoff ADC values of both readings used to differentiate low-risk thymoma from high-risk thymoma and thymic carcinoma were 1.25 and 1.22 × 10(-3) mm(2)/sec with area under the curve of 0.804 and 0.851, respectively. There was significant difference in both readings of ADC value of early (stage I, II) and advanced stages (stage III, IV) of thymic epithelial tumors (P = .006 and .005, respectively). ADC value is a noninvasive, reliable, and reproducible imaging parameter that may help to assess and characterize thymic epithelial tumors. © RSNA, 2014.

Use and Yield of Baseline Imaging and Laboratory Testing in Stage II Breast Cancer

PubMed Central

Guo, Hao; Sutton, Jazmine; Spring, Laura; Faig, Jennifer; Dagogo-Jack, Ibiayi; Battelli, Chiara; Houlihan, Mary Jane; Yeh, Tsai-Chu; Come, Steven E.; Lin, Nancy U.

2016-01-01

Background. Despite guideline recommendations, baseline laboratory testing and advanced imaging are widely ordered in clinical practice to stage asymptomatic patients with clinical stage II breast cancer (BC). Materials and Methods. A retrospective study at two academic centers in Boston, Massachusetts, between 2006 and 2007 explored the use, results, and implications of laboratory tests, tumor markers, and imaging in patients with clinical stage II BC. Results. Among 411 patients, 233 (57%) had liver function testing, 134 (33%) had tumor marker tests, and 237 (58%) had computed tomography (CT) as part of their initial diagnostic workup. Median age was 52 (range, 23–90 years). On multivariable analysis, young age, more advanced stage, and tumor subtype (human epidermal growth receptor-positive [HER2+] and triple-negative breast cancer [TNBC]) were significantly associated with baseline CT. The rate of detection of true metastatic disease with use of baseline staging imaging was 2.1% (95% confidence interval, 0.7%–5%). It was 2.2% (3 of 135) for estrogen receptor/progesterone receptor-positive disease, 1.9% (1 of 54) for HER2+ disease, and 2.1% (1 of 48) for TNBC. At 5 years of follow-up, 46 of 406 patients were diagnosed with metastatic breast cancer. Thirty-four of 46 (73.9%) who developed recurrent disease had imaging at their initial diagnosis, and of these, five had abnormalities on their initial imaging that was correlated with where they developed metastatic disease. Conclusion. In this cohort of women with stage II BC, staging imaging at diagnosis had a low yield in detecting distant metastases (2.1%). The detection rate was not higher with HER2+ disease or TNBC, despite the trend that patients with these subtypes were more likely to undergo imaging. Implications for Practice: Despite guideline recommendations, asymptomatic patients with stage II breast cancer (BC) often undergo staging imaging with computed tomography, bone scanning, or positron

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.

New idea for treatment strategies for Barcelona Clinic Liver Cancer stages based on a network meta-analysis.

PubMed

Li, Kun; Wang, Hai-Tao; He, Yu-Kun; Guo, Tao

2017-05-01

Currently, the Barcelona Clinic Liver Cancer staging (BCLC) system still remains controversies in the management of hepatocellular carcinoma. We are trying to determine the best therapeutic strategy for each BCLC stage through a network meta-analysis and provide a new treatment idea. We conducted a systematic literature search of the PubMed, EMBASE, and Cochrane Library databases and extracted data from randomized controlled trials (RCTs) that compared various strategies. Network meta-analyses were conducted in ADDIS by evaluating different overall survival of each stage. Cumulative probability was used to rank the included strategies. A node-splitting model assessed whether direct and indirect evidence on a specific node was in agreement. Of the 24 included RCTs, 3667 patients were included. Based on the probability P values, the results showed that TACE plus surgical resection (SR) was the first choice for BCLC Stage A (P = .38 and P = .52 for 3- and 5-year OS, respectively). The application of SR was the best strategy for BCLC Stage B (P = .51 and P = .95 for 1- and 3-year OS, respectively). For Stage C, whole net connections could not be established in this research, but combined therapy seemed to produce better results based on 3 separated net connections (P = .92, P = .80, and P = .69 for 1-year OS). The updated therapy strategies discussed in this study are recommended. More importantly, we deemed that the recommended strategy for each patient may be subject to adjustment due to individual clinical factors. The applicable scope of each strategy should also be evaluated before application.

MYCN-non-amplified metastatic neuroblastoma with good prognosis and spontaneous regression: a molecular portrait of stage 4S.

PubMed

Bénard, Jean; Raguénez, Gilda; Kauffmann, Audrey; Valent, Alexander; Ripoche, Hugues; Joulin, Virginie; Job, Bastien; Danglot, Gisèle; Cantais, Sabrina; Robert, Thomas; Terrier-Lacombe, Marie-José; Chassevent, Agnès; Koscielny, Serge; Fischer, Matthias; Berthold, Frank; Lipinski, Marc; Tursz, Thomas; Dessen, Philippe; Lazar, Vladimir; Valteau-Couanet, Dominique

2008-10-01

Stage 4 neuroblastoma (NB) are heterogeneous regarding their clinical presentations and behavior. Indeed infants (stage 4S and non-stage 4S of age <365days at diagnosis) show regression contrasting with progression in children (>365days). Our study aimed at: (i) identifying age-based genomic and gene expression profiles of stage 4 NB supporting this clinical stratification; and (ii) finding a stage 4S NB signature. Differential genome and transcriptome analyses of a learning set of MYCN-non amplified stage 4 NB tumors at diagnosis (n=29 tumors including 12 stage 4S) were performed using 1Mb BAC microarrays and Agilent 22K probes oligo-microarrays. mRNA chips data following filtering yielded informative genes before supervised hierarchical clustering to identify relationship among tumor samples. After confirmation by quantitative RT-PCR, a stage 4S NB's gene cluster was obtained and submitted to a validation set (n=22 tumors). Genomic abnormalities of infant's tumors (whole chromosomes gains or loss) differ radically from that of children (intra-chromosomal rearrangements) but could not discriminate infants with 4S from those without this presentation. In contrast, differential gene expression by looking at both individual genes and whole biological pathways leads to a molecular stage 4S NB portrait which provides new biological clues about this fascinating entity.

Effect of ageing on neurocognitive function by stage of HIV infection: evidence from the Multicenter AIDS Cohort Study.

PubMed

Goodkin, Karl; Miller, Eric N; Cox, Christopher; Reynolds, Sandra; Becker, James T; Martin, Eileen; Selnes, Ola A; Ostrow, David G; Sacktor, Ned C

2017-09-01

The demographics of the HIV epidemic in the USA have shifted towards older age. We aimed to establish the relationship between the processes of ageing and HIV infection in neurocognitive impairment. With longitudinal data from the Multicenter AIDS Cohort Study, a long-term prospective cohort study of the natural and treated history of HIV infection among men who have sex with men in the USA, we examined the effect of ageing, HIV infection (by disease stage), and their interaction on five neurocognitive domains: information processing speed, executive function, episodic memory, working memory, and motor function. We controlled for duration of serostatus in a subanalysis, as well as comorbidities and other factors that affect cognition. Analyses were by linear mixed models for longitudinal data. 5086 participants (47 886 visits) were included in the analytic sample (2278 HIV-seropositive participants contributed 20 477 visits and 2808 HIV-seronegative control participants contributed 27 409 visits). In an a-priori multivariate analysis with control variables including comorbidities and time since seroconversion, significant, direct negative effects of ageing were noted on all neurocognitive domains (p<0·0001 for all). Similar effects were noted for late-stage HIV disease progression on information processing speed (p=0·002), executive function (p<0·0001), motor function (p<0·0001), and working memory (p=0·001). Deleterious interaction effects were also noted in the domains of episodic memory (p=0·03) and motor function (p=0·02). A greater than expected effect of ageing on episodic memory and motor function with advanced stages of HIV infection suggests that these two domains are most susceptible to the progression of neurocognitive impairment caused by ageing in individuals with HIV. This deficit pattern suggests differential damage to the hippocampus and basal ganglia (specifically nigrostriatal pathways). Older individuals with HIV infection should be

EEG Arousal Norms by Age

PubMed Central

Bonnet, Michael H.; Arand, Donna L.

2007-01-01

Study Objectives: Brief arousals have been systematically scored during sleep for more than 20 years. Despite significant knowledge concerning the importance of arousals for the sleep process in normal subjects and patients, comprehensive age norms have not been published. Methods: Seventy-six normal subjects (40 men) without sleep apnea or periodic limb movements of sleep, aged 18 to 70 years, slept in the sleep laboratory for 1 or more nights. Sleep and arousal data were scored by the same scorer for the first night (comparable to clinical polysomnograms) and summarized by age decade. Results: There were no statistically significant differences for sex or interaction of sex by age (p > .5 for both). The mean arousal index increased as a function of age. Newman-Keuls comparisons (.05) showed arousal index in the 18- to 20-year and 21- to 30-year age groups to be significantly less than the arousal index in the other 4 age groups. Arousal index in the 31-to 40-year and 41-to 50-year groups was significantly less than the arousal index in the older groups. The arousal index was significantly negatively correlated with total sleep time and all sleep stages (positive correlation with stage 1 and wake). Conclusions: Brief arousals are an integral component of the sleep process. They increase with other electroencephalographic markers as a function of age. They are highly correlated with traditional sleep-stage amounts and are related to major demographic variables. Age-related norms may make identification of pathologic arousal easier. Citations: Bonnet M; Arand D. EEG Arousal Norms by Age. J Clin Sleep Med 2007;3(3):271–274 PMID:17561594

Clinical picture of meningitis in the adult patient and its relationship with age.

PubMed

Magazzini, Simone; Nazerian, Peiman; Vanni, Simone; Paladini, Barbara; Pepe, Giuseppe; Casanova, Barbara; Crugnola, Carolina; Grifoni, Stefano

2012-08-01

To analyze the clinical characteristics of acute meningitis and their relationship with age in adult patients presenting to the emergency department. We retrospectively investigated consecutive adult patients admitted with a diagnosis of bacterial or viral meningitis from 2002 to 2006. Data about patient's history, symptoms and signs at presentation, etiology and clinical course were collected. To investigate the relationship of clinical presentation with age, we divided patients in four age quartiles (<30 years, between 30 and 36 years, between 37 and 56 years, >56 years). Among the 202 patients considered in the study (mean age 42.8 ± 18.7 years, range 14-90), 162 (80.2%) patients had viral and 40 (19.8%) bacterial meningitis. Specific signs, such as neck stiffness or Kernig or Brudzinski signs, were more common in the first than in the fourth quartile (73.1 vs. 45.7% P = 0.041). Conversely, altered consciousness expressed as Glasgow Coma Scale (GCS) <15 was more frequent in the fourth (80.4%) than in the first (9.6%) quartile (P < 0.001). The linear regression analysis confirmed a significant decrease of GCS with the increasing of patient's age (r = -0.69, P < 0.001). At multivariate analysis, aging was associated with altered level of consciousness (OR 16.7, P < 0.001) independent of viral or bacterial etiology of the presence of comorbidities and of clinical severity (presence of severe sepsis or septic shock). Meningitis presentation largely differs with aging in adult patients. Level of consciousness is frequently altered in the older patients, when other specific signs become more rare, independent of etiology, comorbidities and clinical severity.

Clinical Value of Vestibular Evoked Myogenic Potential in Assessing the Stage and Predicting the Hearing Results in Ménière's Disease.

PubMed

Kim, Min-Beom; Choi, Jeesun; Park, Ga Young; Cho, Yang-Sun; Hong, Sung Hwa; Chung, Won-Ho

2013-06-01

Our goal was to find the clinical value of cervical vestibular evoked myogenic potential (VEMP) in Ménière's disease (MD) and to evaluate whether the VEMP results can be useful in assessing the stage of MD. Furthermore, we tried to evaluate the clinical effectiveness of VEMP in predicting hearing outcomes. The amplitude, peak latency and interaural amplitude difference (IAD) ratio were obtained using cervical VEMP. The VEMP results of MD were compared with those of normal subjects, and the MD stages were compared with the IAD ratio. Finally, the hearing changes were analyzed according to their VEMP results. In clinically definite unilateral MD (n=41), the prevalence of cervical VEMP abnormality in the IAD ratio was 34.1%. When compared with normal subjects (n=33), the VEMP profile of MD patients showed a low amplitude and a similar latency. The mean IAD ratio in MD was 23%, which was significantly different from that of normal subjects (P=0.01). As the stage increased, the IAD ratio significantly increased (P=0.09). After stratification by initial hearing level, stage I and II subjects (hearing threshold, 0-40 dB) with an abnormal IAD ratio showed a decrease in hearing over time compared to those with a normal IAD ratio (P=0.08). VEMP parameters have an important clinical role in MD. Especially, the IAD ratio can be used to assess the stage of MD. An abnormal IAD ratio may be used as a predictor of poor hearing outcomes in subjects with early stage MD.

Clinical Value of Vestibular Evoked Myogenic Potential in Assessing the Stage and Predicting the Hearing Results in Ménière's Disease

PubMed Central

Kim, Min-Beom; Choi, Jeesun; Park, Ga Young; Cho, Yang-Sun; Hong, Sung Hwa

2013-01-01

Objectives Our goal was to find the clinical value of cervical vestibular evoked myogenic potential (VEMP) in Ménière's disease (MD) and to evaluate whether the VEMP results can be useful in assessing the stage of MD. Furthermore, we tried to evaluate the clinical effectiveness of VEMP in predicting hearing outcomes. Methods The amplitude, peak latency and interaural amplitude difference (IAD) ratio were obtained using cervical VEMP. The VEMP results of MD were compared with those of normal subjects, and the MD stages were compared with the IAD ratio. Finally, the hearing changes were analyzed according to their VEMP results. Results In clinically definite unilateral MD (n=41), the prevalence of cervical VEMP abnormality in the IAD ratio was 34.1%. When compared with normal subjects (n=33), the VEMP profile of MD patients showed a low amplitude and a similar latency. The mean IAD ratio in MD was 23%, which was significantly different from that of normal subjects (P=0.01). As the stage increased, the IAD ratio significantly increased (P=0.09). After stratification by initial hearing level, stage I and II subjects (hearing threshold, 0-40 dB) with an abnormal IAD ratio showed a decrease in hearing over time compared to those with a normal IAD ratio (P=0.08). Conclusion VEMP parameters have an important clinical role in MD. Especially, the IAD ratio can be used to assess the stage of MD. An abnormal IAD ratio may be used as a predictor of poor hearing outcomes in subjects with early stage MD. PMID:23799160

Static Strain Aging Behavior of a Manganese-Silicon Steel After Single and Multi-stage Straining

NASA Astrophysics Data System (ADS)

Seraj, P.; Serajzadeh, S.

2016-03-01

In this work, static strain aging behavior of an alloy steel containing high amounts of silicon and manganese was examined while the influences of initial microstructure and pre-strain on the aging kinetics were evaluated as well. The rate of strain aging in a low carbon steel was also determined and compared with that occurred in the alloy steel. The rates of static strain aging in the steels were defined at room temperature and at 95 °C by means of double-hit tensile testing and hardness measurements. In addition, three-stage aging experiments at 80 °C were carried out to estimate aging behavior under multi-pass deformation processing. The results showed that in-solution manganese and silicon atoms could significantly affect the aging behavior of the steel and reduce the kinetics of static strain aging as compared to the low carbon steel. The initial microstructure also played an important role on the aging behavior. The rapidly cooled steel having mean ferrite grain size of 9.7 μm showed the least aging susceptibility index during the aging experiments. Accordingly, the activation energies for static strain aging were calculated as 93.2 and 85.7 kJ/mole for the alloy steel having fine and coarse ferrite-pearlite structures, respectively while it was computed as 79.1 kJ/mole for the low carbon steel with ferrite mean grain size of about 16.2 μm.

Clinical Outcomes and Prognostic Factors of High-Dose Proton Beam Therapy for Peripheral Stage I Non-Small-Cell Lung Cancer.

PubMed

Hatayama, Yoshiomi; Nakamura, Tatsuya; Suzuki, Motohisa; Azami, Yusuke; Ono, Takashi; Yabuuchi, Tomonori; Hayashi, Yuichiro; Kimura, Kanako; Hirose, Katsumi; Wada, Hitoshi; Hareyama, Masato; Kikuchi, Yasuhiro; Takai, Yoshihiro

2016-09-01

The efficacy, toxicity, and prognostic factors of high-dose proton beam therapy (PBT) for peripheral stage I non-small-cell lung cancer were assessed in this retrospective study. Fifty patients with peripheral stage I non-small-cell lung cancer, two of whom had heterochronic multiple lung cancers, underwent high-dose PBT between January 2009 and September 2014. The relative biological effectiveness of the proton beam was defined as 1.1. The beam energy and spread-out Bragg peak were fine-tuned for the 90% isodose volume of the prescribed dosage to encompass the planning target volume. The cumulative survival curves were calculated using the Kaplan-Meier method. Treatment toxicities were evaluated using version 4 of the Common Terminology Criteria for Adverse Events, version 4. The study included 35 males and 15 females with a median age of 72.5 years. The median follow-up period was 22.8 months. The clinical stage was IA in 44 (85%) and IB in eight (15%) tumors. The total dose of PBT was 66 GyE in 10 fractions in all tumors. Three-year overall survival rate among all patients was 87.9% (95% confidence interval [CI], 94.8%-73.2%). Forty-five patients were alive, and 5 were dead. Three-year local control and progression-free survival rates were 95.7% (95% CI, 98.9%-83.8%) and 76.3% (95% CI, 86.9%-59.3%), respectively. Only one patient experienced Grade 2 pneumonitis. High-dose PBT may be an effective and safe treatment option for patients with stage I non-small-cell lung cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

Evolution in Stage-Structured Populations

PubMed Central

Barfield, Michael; Holt, Robert D.; Gomulkiewicz, Richard

2016-01-01

For many organisms, stage is a better predictor of demographic rates than age. Yet no general theoretical framework exists for understanding or predicting evolution in stage-structured populations. Here, we provide a general modeling approach that can be used to predict evolution and demography of stage-structured populations. This advances our ability to understand evolution in stage-structured populations to a level previously available only for populations structured by age. We use this framework to provide the first rigorous proof that Lande’s theorem, which relates adaptive evolution to population growth, applies to stage-classified populations, assuming only normality and that evolution is slow relative to population dynamics. We extend this theorem to allow for different means or variances among stages. Our next major result is the formulation of Price’s theorem, a fundamental law of evolution, for stage-structured populations. In addition, we use data from Trillium grandiflorum to demonstrate how our models can be applied to a real-world population and thereby show their practical potential to generate accurate projections of evolutionary and population dynamics. Finally, we use our framework to compare rates of evolution in age- versus stage-structured populations, which shows how our methods can yield biological insights about evolution in stage-structured populations. PMID:21460563

A stage is a stage is a stage: a direct comparison of two scoring systems.

PubMed

Dawson, Theo L

2003-09-01

L. Kohlberg (1969) argued that his moral stages captured a developmental sequence specific to the moral domain. To explore that contention, the author compared stage assignments obtained with the Standard Issue Scoring System (A. Colby & L. Kohlberg, 1987a, 1987b) and those obtained with a generalized content-independent stage-scoring system called the Hierarchical Complexity Scoring System (T. L. Dawson, 2002a), on 637 moral judgment interviews (participants' ages ranged from 5 to 86 years). The correlation between stage scores produced with the 2 systems was .88. Although standard issue scoring and hierarchical complexity scoring often awarded different scores up to Kohlberg's Moral Stage 2/3, from his Moral Stage 3 onward, scores awarded with the two systems predominantly agreed. The author explores the implications for developmental research.

Detection and differentiation of early acute and following age stages of myocardial infarction with quantitative post-mortem cardiac 1.5T MR.

PubMed

Schwendener, Nicole; Jackowski, Christian; Persson, Anders; Warntjes, Marcel J; Schuster, Frederick; Riva, Fabiano; Zech, Wolf-Dieter

2017-01-01

Recently, quantitative MR sequences have started being used in post-mortem imaging. The goal of the present study was to evaluate if early acute and following age stages of myocardial infarction can be detected and discerned by quantitative 1.5T post-mortem cardiac magnetic resonance (PMCMR) based on quantitative T1, T2 and PD values. In 80 deceased individuals (25 female, 55 male), a cardiac MR quantification sequence was performed prior to cardiac dissection at autopsy in a prospective study. Focal myocardial signal alterations detected in synthetically generated MR images were MR quantified for their T1, T2 and PD values. The locations of signal alteration measurements in PMCMR were targeted at autopsy heart dissection and cardiac tissue specimens were taken for histologic examinations. Quantified signal alterations in PMCMR were correlated to their according histologic age stage of myocardial infarction. In PMCMR seventy-three focal myocardial signal alterations were detected in 49 of 80 investigated hearts. These signal alterations were diagnosed histologically as early acute (n=39), acute (n=14), subacute (n=10) and chronic (n=10) age stages of myocardial infarction. Statistical analysis revealed that based on their quantitative T1, T2 and PD values, a significant difference between all defined age groups of myocardial infarction can be determined. It can be concluded that quantitative 1.5T PMCMR quantification based on quantitative T1, T2 and PD values is feasible for characterization and differentiation of early acute and following age stages of myocardial infarction. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Markers of Oxidant Stress that are Clinically Relevant in Aging and Age-related Disease

PubMed Central

Jacob, Kimberly D.; Hooten, Nicole Noren; Trzeciak, Andrzej R.; Evans, Michele K.

2013-01-01

Despite the long held hypothesis that oxidant stress results in accumulated oxidative damage to cellular macromolecules and subsequently to aging and age-related chronic disease, it has been difficult to consistently define and specifically identify markers of oxidant stress that are consistently and directly linked to age and disease status. Inflammation because it is also linked to oxidant stress, aging, and chronic disease also plays an important role in understanding the clinical implications of oxidant stress and relevant markers. Much attention has focused on identifying specific markers of oxidative stress and inflammation that could be measured in easily accessible tissues and fluids (lymphocytes, plasma, serum). The purpose of this review is to discuss markers of oxidant stress used in the field as biomarkers of aging and age-related diseases, highlighting differences observed by race when data is available. We highlight DNA, RNA, protein, and lipid oxidation as measures of oxidative stress, as well as other well-characterized markers of oxidative damage and inflammation and discuss their strengths and limitations. We present the current state of the literature reporting use of these markers in studies of human cohorts in relation to age and age-related disease and also with a special emphasis on differences observed by race when relevant. PMID:23428415

Linear Combinations of Multiple Outcome Measures to Improve the Power of Efficacy Analysis ---Application to Clinical Trials on Early Stage Alzheimer Disease

PubMed Central

Xiong, Chengjie; Luo, Jingqin; Morris, John C; Bateman, Randall

2018-01-01

Modern clinical trials on Alzheimer disease (AD) focus on the early symptomatic stage or even the preclinical stage. Subtle disease progression at the early stages, however, poses a major challenge in designing such clinical trials. We propose a multivariate mixed model on repeated measures to model the disease progression over time on multiple efficacy outcomes, and derive the optimum weights to combine multiple outcome measures by minimizing the sample sizes to adequately power the clinical trials. A cross-validation simulation study is conducted to assess the accuracy for the estimated weights as well as the improvement in reducing the sample sizes for such trials. The proposed methodology is applied to the multiple cognitive tests from the ongoing observational study of the Dominantly Inherited Alzheimer Network (DIAN) to power future clinical trials in the DIAN with a cognitive endpoint. Our results show that the optimum weights to combine multiple outcome measures can be accurately estimated, and that compared to the individual outcomes, the combined efficacy outcome with these weights significantly reduces the sample size required to adequately power clinical trials. When applied to the clinical trial in the DIAN, the estimated linear combination of six cognitive tests can adequately power the clinical trial. PMID:29546251

326 Lung Age/Chronological Age Index as Indicator of Clinical Improvement or Severity in Asthma Patients

PubMed Central

Castrejon-Vázquez, Isabel; Vargas, Maria Eugenia; Sabido, Raúl Cicero; Tapía, Jorge Galicia

2012-01-01

Background Spirometry is a very useful clinical test to evaluate pulmonary function in asthma. However pulmonary function could be affected by the sex, time of clinical evolution, lung age (LA) and chronological age (CA). The aim of this study was to evaluate LA/CA as index of clinical improvement or severity in asthma patients. Methods The tenets of the Declaration of Helsinki were followed, and all patients gave their informed consent to participate in this study. Asthma severity was evaluated according with GINA classification. Spirometry was performed at the beginning of this study, at 46 days, 96 days, 192 days and after 8 months. Statistical analysis was performed using t test, 2-way ANOVA test, correlation and multiple regression models as well as ROC curves were also performed, a P < 0.05 was considered as significant. Results 70 asthma patients were included (22 male and 48 female), mean CA was 35-years old; mean LA was 48-years with a LA/CA index = 1.4, time of clinical evolution was 13 years. A LA/CA index = 1 (range 0.5 to 0.9) was observed in asymptomatic patients. LA/CA index over 1 were related with airway inflammation, and a LA/CA index more than 2 correlated with GINA step 3. Interestingly when we analyzed CA and LA, we observed that in female group more than 10 years of difference between CA and LA, (GINA Step2 and 3); while in male we observed (GINA Step1, Step2 and Step3). LA/CA index ≤ 1 was considered as normal. Conclusions LA/CA index is a good as clinical indicator of clinical improvement or severity in asthma patients in with excellent correlation of pulmonary function and age.

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

Risk factors contributing to a poor prognosis of papillary thyroid carcinoma: validity of UICC/AJCC TNM classification and stage grouping.

PubMed

Ito, Yasuhiro; Miyauchi, Akira; Jikuzono, Tomoo; Higashiyama, Takuya; Takamura, Yuuki; Miya, Akihiro; Kobayashi, Kaoru; Matsuzuka, Fumio; Ichihara, Kiyoshi; Kuma, Kanji

2007-04-01

In 2002, the UICC/AJCC TNM classification for papillary thyroid carcinoma was revised. In this study, we examined the validity of this classification system by investigating the predictors of disease-free survival (DFS) and cause-specific survival (CSS) in patients. We examined various clinicopathological features, including the component of the TNM classification, for 1,740 patients who underwent initial and curative surgery for papillary carcinoma between 1987 and 1995. Clinical and pathological T4a, clinical N1b in the TNM classification, and patient age were recognized as independent predictors of not only DFS, but also CSS of patients. Tumor size, male gender, and central node metastasis independently affected DFS only. There were 1,005 pathological N1b patients, but pathological N1b did not independently affect either DFS or CSS. Regarding the stage grouping, clinical stage IVA including clinical N1b more clearly affected DFS and CSS than pathological stage IVA including pathological N1b. Clinical stage grouping was more useful than pathological stage grouping for predicting the prognosis of papillary carcinoma patients possibly because pathological stage overestimates the biological characteristics of many pathological N1b tumors.

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.

Dynamic Risk Stratification in Stage I Papillary Thyroid Cancer Patients Younger Than 45 Years of Age.

PubMed

Sung, Tae-Yon; Cho, Jae Won; Lee, Yu-Mi; Lee, Yi Ho; Kwon, Hyemi; Jeon, Min Ji; Kim, Won Gu; Choi, Young Jun; Song, Dong Eun; Chung, Ki-Wook; Yoon, Jong Ho; Hong, Suck Joon

2017-11-01

This study validated the dynamic risk stratification (DRS) system with regard to its association with structural recurrence and risk factors associated with non-excellent responses in patients <45 years with stage I classical papillary thyroid cancer (PTC). This historical cohort study included 598 patients with stage I classical PTC <45 years of age treated with total thyroidectomy followed by radioactive iodine remnant ablation (n = 440), total thyroidectomy without radioactive iodine remnant ablation (n = 23), and thyroid lobectomy alone (n = 135). The median follow-up period was 123 months. Structural recurrence occurred in 4.2% (n = 18/432) of the patients with an excellent response, 17.1% (18/105) of patients with an indeterminate response, 44.7% (17/38) of patients with a biochemically incomplete response, and 82.6% (19/23) of patients with a structurally incomplete response (p < 0.001) during the follow-up. The disease-free survival curves of each response showed significant differences (p < 0.001). Extensive extrathyroidal extension and extranodal extension were the independent risk factors associated with non-excellent response (p < 0.05). DRS may reduce unnecessary additional treatments by reclassifying initial risk estimates of structural recurrence. Furthermore, applying the risk factors associated with non-excellent response to initial therapy may be a more useful and viable surrogate of the risk for structural recurrence in stage I PTC patients <45 years of age.

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. © The Author(s) 2015.

Axillary Ultrasound Accurately Excludes Clinically Significant Lymph Node Disease in Patients with Early Stage Breast Cancer

PubMed Central

Tucker, Natalia S.; Cyr, Amy E.; Ademuyiwa, Foluso O.; Tabchy, Adel; George, Krystl; Sharma, Piyush; Jin, Linda X.; Sanati, Souzan; Aft, Rebecca; Gao, Feng; Margenthaler, Julie A.; Gillanders, William E.

2016-01-01

Objective Assess the performance characteristics of axillary ultrasound (AUS) for accurate exclusion of clinically significant axillary lymph node (ALN) disease. Background Sentinel lymph node biopsy (SLNB) is currently the standard of care for staging the axilla in patients with clinical T1–T2, N0 breast cancer. AUS is a noninvasive alternative to SLNB for staging the axilla. Methods Patients were identified using a prospectively maintained database. Sensitivity, specificity, and negative predictive value (NPV) were calculated by comparing AUS findings to pathology results. Multivariate analyses were performed to identify patient and/or tumor characteristics associated with false negative (FN) AUS. A blinded review of FN and matched true negative cases was performed by two independent medical oncologists to compare treatment recommendations and actual treatment received. Recurrence-free survival was described using Kaplan-Meier product limit methods. Results 647 patients with clinical T1–T2, N0 breast cancer underwent AUS between January, 2008 and March, 2013. AUS had a sensitivity of 70%, NPV of 84% and PPV of 56% for the detection of ALN disease. For detection of clinically significant disease (> 2.0 mm), AUS had a sensitivity of 76% and NPV of 89%. FN AUS did not significantly impact adjuvant medical decision making. Patients with FN AUS had recurrence-free survival equivalent to patients with pathologic N0 disease. Conclusions AUS accurately excludes clinically significant ALN disease in patients with clinical T1–T2, N0 breast cancer. AUS may be an alternative to SLNB in these patients where axillary surgery is no longer considered therapeutic, and predictors of tumor biology are increasingly used to make adjuvant therapy decisions. PMID:26779976

Dysregulated sleep-wake cycles in young people are associated with emerging stages of major mental disorders.

PubMed

Scott, Elizabeth M; Robillard, Rébecca; Hermens, Daniel F; Naismith, Sharon L; Rogers, Naomi L; Ip, Tony K C; White, Django; Guastella, Adam; Whitwell, Bradley; Smith, Kristie Leigh; Hickie, Ian B

2016-02-01

To determine if disturbed sleep-wake cycle patterns in young people with evolving mental disorder are associated with stages of illness. The sleep-wake cycle was monitored using actigraphy across 4 to 22 days. Participants (21 healthy controls and 154 persons seeking help for mental health problems) were aged between 12 and 30 years. Those persons seeking mental health care were categorized as having mild symptoms (stage 1a), an 'attenuated syndrome' (stage 1b) or an 'established mental disorder' (stage 2+). The proportions of individuals with a delayed weekdays sleep schedule increased progressively across illness stages: 9.5% of controls, 11.1% of stage 1a, 25.6% of stage 1b, and 50.0% of stage 2+ (χ(2) (3 d.f.) = 18.4, P < 0.001). A similar pattern was found for weekends (χ(2) (3 d.f.) = 7.6, P = 0.048). Compared with controls, stage 1b participants had later sleep onset on weekends (P = 0.015), and participants at stages 1b and 2+ had later sleep offset on both weekdays and weekends (P < 0.020). Compared with controls, all participants with mental disorders had more wake after sleep onset (P < 0.029) and those at stages 1a and 2+ had lower sleep efficiency (P < 0.040). Older age, medicated status and later weekdays sleep offset were found to be the three strongest correlates of later versus earlier clinical stages. In relation to clinical staging of common mental disorders in young people, the extent of delayed sleep phase is associated with more severe or persistent phases of illness. © 2014 Wiley Publishing Asia Pty Ltd.

Epilutein for Early-Stage Age-Related Macular Degeneration: A Randomized and Prospective Study.

PubMed

Forte, Raimondo; Panzella, Lucia; Cesarano, Ida; Cennamo, Gilda; Eidenberger, Thomas; Napolitano, Alessandra

2017-01-01

The hypothesis that oral supplementation of the epilutein/lutein combination could augment the macular pigment optical density (MPOD) in patients with age-related macular degeneration (AMD) was tested. In a prospective randomized interventional study, 40 consecutive patients with early-stage AMD were recruited. After a 2-week run-in period, patients were randomly treated with a daily oral administration of 8 mg epilutein and 2 mg lutein (group 1) or 10 mg lutein (group 2) for 2 months. At baseline (BL) and 1-month (M1) and 2-month visits (M2), all patients underwent a complete ophthalmological examination, including measurement of MPOD in a 7° area (Visucam 200; Carl Zeiss Meditec, Milan, Italy). Xanthophylls were quantified in plasma, as well as the HDL, non-HDL, and erythrocyte fractions at each study visit. Twenty-one patients (mean age 69.4 ± 6.7 years, 35 eyes) were included in group 1. Mean MPOD was 0.203 ± 0.02 optical density units (ODU) at BL, and increased to 0.214 ± 0.04 ODU at M1 (p = 0.008) and 0.206 ± 0.03 ODU at M2 (p = 0.04). Sixteen patients (mean age 72.0 ± 6.3 years, 29 eyes) were included in group 2. Mean MPOD was 0.215 ± 0.03 at BL, which reduced to 0.202 ± 0.03 ODU at M1 (p = 0.003) and 0.207 ± 0.02 ODU at M2 (p < 0.001). A rise in the systemic level of total xanthophylls was observed at M1 for both groups. At M2, total xanthophylls were significantly increased only in group 1 and decreased in group 2. In patients with early-stage AMD, the administration of lutein in combination with epilutein was associated with an increased MPOD compared to the administration of lutein alone. © 2017 S. Karger AG, Basel.

Electroconvulsive therapy and age: Age-related clinical features and effectiveness in treatment resistant major depressive episode.

PubMed

Socci, Chiara; Medda, Pierpaolo; Toni, Cristina; Lattanzi, Lorenzo; Tripodi, Beniamino; Vannucchi, Giulia; Perugi, Giulio

2018-02-01

This study was aimed to compare clinical features, treatments outcomes and tolerability between young (18-45 years), middle age (46-64 years) and old (≥ 65 years) patients treated with bilateral ECT for treatment resistant major depressive episode. 402 patients were evaluated 1 day prior to ECT and a week after the treatment termination using the Clinical Global Impression Scale (CGI), the Hamilton Rating Scale for Depression-17 items (HAM-D-17), the Brief Psychiatric Rating Scale (BPRS), the Young Mania Rating Scale (YMRS) and the Mini Mental State Examination (MMSE). Response was defined as a reduction of at least 50% from baseline on the HAM-D-17 score. Remission was defined as a score ≤ 7 on the HAM-D-17 at the final evaluation. Rates of response were not statistically different in the three groups (69.6% in old versus 63.5% in young and 55.5% in middle age groups). No significant differences were also observed in the proportions of remitters between the age groups (31.4% in young group, 27.7% in middle age group and 29.3% in old group). One week after the end of the ECT course the middle and old age groups showed a statistically significant increase in the MMSE score compared to baseline. We did not find significant differences between the three age groups in rates of premature drops-out due to ECT-related side effects. Our data support the use of ECT in elderly patients with treatment-resistant major depressive episode, with rates of response around 70% and effectiveness being independent from age. In the old age group the baseline cognitive impairment improved after ECT and no life-threatening adverse event was detected. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

Sequential stages and distribution patterns of aging-related tau astrogliopathy (ARTAG) in the human brain.

PubMed

Kovacs, Gabor G; Xie, Sharon X; Robinson, John L; Lee, Edward B; Smith, Douglas H; Schuck, Theresa; Lee, Virginia M-Y; Trojanowski, John Q

2018-06-11

Aging-related tau astrogliopathy (ARTAG) describes tau pathology in astrocytes in different locations and anatomical regions. In the present study we addressed the question of whether sequential distribution patterns can be recognized for ARTAG or astroglial tau pathologies in both primary FTLD-tauopathies and non-FTLD-tauopathy cases. By evaluating 687 postmortem brains with diverse disorders we identified ARTAG in 455. We evaluated frequencies and hierarchical clustering of anatomical involvement and used conditional probability and logistic regression to model the sequential distribution of ARTAG and astroglial tau pathologies across different brain regions. For subpial and white matter ARTAG we recognize three and two patterns, respectively, each with three stages initiated or ending in the amygdala. Subependymal ARTAG does not show a clear sequential pattern. For grey matter (GM) ARTAG we recognize four stages including a striatal pathway of spreading towards the cortex and/or amygdala, and the brainstem, and an amygdala pathway, which precedes the involvement of the striatum and/or cortex and proceeds towards the brainstem. GM ARTAG and astrocytic plaque pathology in corticobasal degeneration follows a predominantly frontal-parietal cortical to temporal-occipital cortical, to subcortical, to brainstem pathway (four stages). GM ARTAG and tufted astrocyte pathology in progressive supranuclear palsy shows a striatum to frontal-parietal cortical to temporal to occipital, to amygdala, and to brainstem sequence (four stages). In Pick's disease cases with astroglial tau pathology an overlapping pattern with PSP can be appreciated. We conclude that tau-astrogliopathy type-specific sequential patterns cannot be simplified as neuron-based staging systems. The proposed cytopathological and hierarchical stages provide a conceptual approach to identify the initial steps of the pathogenesis of tau pathologies in ARTAG and primary FTLD-tauopathies.

Clinical characteristics of early-stage osteonecrosis of the ankle and treatment outcomes.

PubMed

Issa, Kimona; Naziri, Qais; Kapadia, Bhaveen H; Lamm, Bradley M; Jones, Lynne C; Mont, Michael A

2014-05-07

The purposes of this study were to describe the clinical manifestations of osteonecrosis involving the distal tibia and talus, to identify risk factors associated with the disease, and to evaluate the efficacy of percutaneous drilling for the treatment of ankles with early-stage symptomatic osteonecrosis. One hundred and one ankles in seventy-three patients with symptomatic osteonecrosis of the talus and/or distal tibia treated with percutaneous drilling were identified. There were eighty-one ankles in fifty-nine patients treated only at our institution and twenty ankles in fourteen patients with a failed prior core decompression at outside institutions. The parameters evaluated included demographics, disease characteristics, clinical outcomes including the American Orthopaedic Foot & Ankle Society score, Short-Form-36 scores, University of California Los Angeles activity scores, and visual analog scale pain scores, and radiographic outcomes at a mean follow-up duration of five years (range, two to nine years). Eighty-five ankles had isolated talus osteonecrosis, eleven ankles had involvement of the distal tibia and talus, and five ankles had isolated distal tibial disease. Twenty-nine patients (40%) had initially presented with symptomatic osteonecrosis of another joint, most commonly the knee (37%), the hip (29%), and the shoulder (25%). The most common identifiable risk factors included chronic corticosteroid use (49.3%), alcohol abuse (35.6%), tobacco use (29%), and hypertension (20.5%). Overall, 83% of ankles did not demonstrate further disease progression after the procedure. There were significant improvements (p < 0.05) in clinical and patient-reported outcomes after surgical treatment. The presence of human immunodeficiency virus and sickle cell disease was associated with a higher odds ratio of disease progression to joint collapse. Osteonecrosis of the distal tibia and talus was usually part of multifocal disease, and concurrent knee osteonecrosis was

Comparison of clinical probability-adjusted D-dimer and age-adjusted D-dimer interpretation to exclude venous thromboembolism.

PubMed

Takach Lapner, Sarah; Julian, Jim A; Linkins, Lori-Ann; Bates, Shannon; Kearon, Clive

2017-10-05

Two new strategies for interpreting D-dimer results have been proposed: i) using a progressively higher D-dimer threshold with increasing age (age-adjusted strategy) and ii) using a D-dimer threshold in patients with low clinical probability that is twice the threshold used in patients with moderate clinical probability (clinical probability-adjusted strategy). Our objective was to compare the diagnostic accuracy of age-adjusted and clinical probability-adjusted D-dimer interpretation in patients with a low or moderate clinical probability of venous thromboembolism (VTE). We performed a retrospective analysis of clinical data and blood samples from two prospective studies. We compared the negative predictive value (NPV) for VTE, and the proportion of patients with a negative D-dimer result, using two D-dimer interpretation strategies: the age-adjusted strategy, which uses a progressively higher D-dimer threshold with increasing age over 50 years (age in years × 10 µg/L FEU); and the clinical probability-adjusted strategy which uses a D-dimer threshold of 1000 µg/L FEU in patients with low clinical probability and 500 µg/L FEU in patients with moderate clinical probability. A total of 1649 outpatients with low or moderate clinical probability for a first suspected deep vein thrombosis or pulmonary embolism were included. The NPV of both the clinical probability-adjusted strategy (99.7 %) and the age-adjusted strategy (99.6 %) were similar. However, the proportion of patients with a negative result was greater with the clinical probability-adjusted strategy (56.1 % vs, 50.9 %; difference 5.2 %; 95 % CI 3.5 % to 6.8 %). These findings suggest that clinical probability-adjusted D-dimer interpretation is a better way of interpreting D-dimer results compared to age-adjusted interpretation.

Revised Tubiana’s Staging System for Assessment of Disease Severity in Dupuytren’s Disease—Preliminary Clinical Findings

PubMed Central

Hindocha, Sandip; Stanley, John K.; Watson, James Stewart

2007-01-01

There are few objective staging systems to assess severity of Dupuytren’s disease (DD). Previous methods to assess severity of DD were based primarily on the degree of contracture of an affected digit measured using a goniometer. Nonetheless, this method of assessment alone may be incomplete, and other factors should be considered. White (n = 92) patients diagnosed with DD from northwest of England were assessed for DD. Objective criteria for evaluating severity incorporated quantified variables. The revised severity stage was correlated to a known staging system of DD (Tubiana’s staging system) which measures total flexion deformity for a single affected digit. Total revised severity staging scores ranged between 4 and 53 (mean = 18.7) and revealed significant positive correlation to Tubiana’s original staging system (r2 = 0.8, p < 0.001). There was significant difference between severity staging scores in those with a positive family history compared to those without (p < 0.01). In current practice, often, the degree of contracture in an affected digit is used solely as a measure of disease severity. Additional objective clinical information may provide useful prognostic indices for disease progression as well as postoperative outcome. PMID:18780081

Third molar mineralization in relation to chronologic age estimation of the Han in central southern China.

PubMed

Liu, Ying; Geng, Kun; Chu, Yanhao; Xu, Mindi; Zha, Lagabaiyila

2018-03-03

The purpose of this study is to provide a forensic reference data about estimating chronologic age by evaluating the third molar mineralization of Han in central southern China. The mineralization degree of third molars was assessed by Demirjian's classification with modification for 2519 digital orthopantomograms (1190 males, 1329 females; age 8-23 years). The mean ages of the initial mineralization and the crown completion of third molars were around 9.66 and 13.88 years old in males and 9.52 and 14.09 years old in females. The minimum ages of apical closure were around 16 years in both sexes. Twenty-eight at stage C and stage G and 38 and 48 at stage F occurred earlier in males than in females. There was no significant difference between maxillary and mandibular teeth in males and females except that stage C in males. Two formulas were devised to estimate age based on mineralization stages and sexes. In Hunan Province, the person will probably be over age 14, when a third molar reaches the stage G. The results of the study could provide reference for age estimation in forensic cases and clinical dentistry.

Prognosis of canine patients with nasal tumors according to modified clinical stages based on computed tomography: a retrospective study.

PubMed

Kondo, Yumi; Matsunaga, Satoru; Mochizuki, Manabu; Kadosawa, Tsuyoshi; Nakagawa, Takayuki; Nishimura, Ryohei; Sasaki, Nobuo

2008-03-01

To evaluate the efficacy of clinical staging based on computed tomography (CT) imaging over the World Health Organization (WHO) staging system based on radiography for nasal tumors in dogs, a retrospective study was conducted. This study used 112 dogs that had nasal tumors; they had undergone radiography and CT and had been histologically confirmed as having nasal tumors. Among 112 dogs, 85 (75.9%) were diagnosed as adenocarcinoma. Then they were analyzed for survival time according to each staging system. More than 70% of the patients with adenocarcinoma were classified as having WHO stage III. The patients classified under WHO stage II tended to survive longer than those classified under WHO stage III. Dogs classified under WHO stage III were further grouped into CT stages III and IV, and CT stage III patients had a significantly longer survival time than CT stage IV patients. In addition, patients treated with a combination of surgery and radiation had a significantly longer survival time than the patients who did not receive any treatment in CT stage III. On the other hand, different treatment modalities did not show a significant difference in the survival time of CT stage IV dogs. The results suggest that WHO stage III dogs may have various levels of tumor progression, indicating that the CT staging system may be more accurate than the WHO staging system.

Clinical outcomes of stage I and IIA non-small cell lung cancer patients treated with stereotactic body radiotherapy using a real-time tumor-tracking radiotherapy system.

PubMed

Katoh, Norio; Soda, Itaru; Tamamura, Hiroyasu; Takahashi, Shotaro; Uchinami, Yusuke; Ishiyama, Hiromichi; Ota, Kiyotaka; Inoue, Tetsuya; Onimaru, Rikiya; Shibuya, Keiko; Hayakawa, Kazushige; Shirato, Hiroki

2017-01-05

To investigate the clinical outcomes of stage I and IIA non-small cell lung cancer (NSCLC) patients treated with stereotactic body radiotherapy (SBRT) using a real-time tumor-tracking radiotherapy (RTRT) system. Patterns-of-care in SBRT using RTRT for histologically proven, peripherally located, stage I and IIA NSCLC was retrospectively investigated in four institutions by an identical clinical report format. Patterns-of-outcomes was also investigated in the same manner. From September 2000 to April 2012, 283 patients with 286 tumors were identified. The median age was 78 years (52-90) and the maximum tumor diameters were 9 to 65 mm with a median of 24 mm. The calculated biologically effective dose (10) at the isocenter using the linear-quadratic model was from 66 Gy to 126 Gy with a median of 106 Gy. With a median follow-up period of 28 months (range 0-127), the overall survival rate for the entire group, for stage IA, and for stage IB + IIA was 75%, 79%, and 65% at 2 years, and 64%, 70%, and 50% at 3 years, respectively. In the multivariate analysis, the favorable predictive factor was female for overall survival. There were no differences between the clinical outcomes at the four institutions. Grade 2, 3, 4, and 5 radiation pneumonitis was experienced by 29 (10.2%), 9 (3.2%), 0, and 0 patients. The subgroup analyses revealed that compared to margins from gross tumor volume (GTV) to planning target volume (PTV) ≥ 10 mm, margins < 10 mm did not worsen the overall survival and local control rates, while reducing the risk of radiation pneumonitis. This multi-institutional retrospective study showed that the results were consistent with the recent patterns-of-care and patterns-of-outcome analysis of SBRT. A prospective study will be required to evaluate SBRT using a RTRT system with margins from GTV to PTV < 10mm.

Toward defining the preclinical stages of Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease

PubMed Central

Sperling, Reisa A.; Aisen, Paul S.; Beckett, Laurel A.; Bennett, David A.; Craft, Suzanne; Fagan, Anne M.; Iwatsubo, Takeshi; Jack, Clifford R.; Kaye, Jeffrey; Montine, Thomas J.; Park, Denise C.; Reiman, Eric M.; Rowe, Christopher C.; Siemers, Eric; Stern, Yaakov; Yaffe, Kristine; Carrillo, Maria C.; Thies, Bill; Morrison-Bogorad, Marcelle; Wagster, Molly V.; Phelps, Creighton H.

2011-01-01

The pathophysiological process of Alzheimer's disease (AD) is thought to begin many years before the diagnosis of AD dementia. This long “preclinical” phase of AD would provide a critical opportunity for therapeutic intervention; however, we need to further elucidate the link between the pathological cascade of AD and the emergence of clinical symptoms. The National Institute on Aging and the Alzheimer's Association convened an international workgroup to review the biomarker, epidemiological, and neuropsychological evidence, and to develop recommendations to determine the factors which best predict the risk of progression from “normal” cognition to mild cognitive impairment and AD dementia. We propose a conceptual framework and operational research criteria, based on the prevailing scientific evidence to date, to test and refine these models with longitudinal clinical research studies. These recommendations are solely intended for research purposes and do not have any clinical implications at this time. It is hoped that these recommendations will provide a common rubric to advance the study of preclinical AD, and ultimately, aid the field in moving toward earlier intervention at a stage of AD when some disease-modifying therapies may be most efficacious. PMID:21514248

Arthroscopic repair of the rotator cuff: prospective study of tendon healing after 70 years of age in 145 patients.

PubMed

Flurin, P-H; Hardy, P; Abadie, P; Boileau, P; Collin, P; Deranlot, J; Desmoineaux, P; Duport, M; Essig, J; Godenèche, A; Joudet, T; Kany, J; Sommaire, C; Thelu, C-E; Valenti, P

2013-12-01

The level of activity of patients older than 70 years is tending to increase, as are their expectations in terms of joint function recuperation. It has not been proven that rotator cuff repair healing is satisfactory in the elderly. The main hypothesis of this study was: repair of supraspinous lesions in patients older than 70 years is reliable in terms of both clinical results and healing. The secondary hypothesis was: tendon healing is significantly correlated with the Constant, ASES, and SST scores as well as with age, tendon retraction, and fatty infiltration. Multicenter prospective study on 145 patients older than 70 years, with 135 patients reviewed at 1 year (93%). The mean age was 73.9 years. Full-thickness tears of the supraspinatus extended at most to the upper third of the infraspinatus and retraction limited to Patte stages 1 and 2 were included. Clinical assessment was carried out in accordance with the Constant, ASES, and SST scores. Healing was evaluated with ultrasound. A significant improvement was noted in the Constant (44/76)+31.5 (P<0.0001), ASES (35/90)+54.4 (P<0.0001), and SST (3.5/10)+6.6 (P>0.0001) scores at 1 year of follow-up. The healing rate was 89% with 15 re-tears, nine of which were stage 1 and six stage 2. The clinical result was not correlated with patient age (Constant, P=0.24; ASES, P=0.38; SST, P=0.83) nor with the retraction stage (Constant, P=0.71; ASES, P=0.35; SST, P=0.69) or the stage of fatty infiltration (P>0.7). Healing was correlated with the quality of the clinical result (Constant, P=0.02; ASES, P=0.03) and age (P=0.01) but was not correlated with retraction or the fatty infiltration stage (P>0.3). Arthroscopic repair significantly improves the clinical results, even in patients older than 70 years. The clinical results are not correlated with age (but deterioration of the result was not noted after 75 years) or frontal retraction (but the study only included retractions limited to stages 1 and 2). The healing rate is

Preoperative Prolapse Stage as Predictor of Failure of Sacrocolpopexy.

PubMed

Aslam, Muhammad F; Osmundsen, Blake; Edwards, Sharon R; Matthews, Catherine; Gregory, William T

2016-01-01

Our aim was to determine if there was a correlation between the preoperative prolapse stage and postoperative recurrence of prolapse 1 year after sacrocolpopexy. Our null hypothesis is that the preoperative stage of prolapse does not increase the risk of recurrence. This is a multicenter cohort study from 3 centers. We included subjects who underwent robotic-assisted sacrocolpopexy and completed a standardized 1-year follow-up from 2009-2014. All subjects underwent a complete preoperative evaluation and completed 12 months of follow-up with the pelvic organ prolapse quantification examination. We compared those subjects who met the definition of recurrence with those who did not, analyzing the following covariates: stage of prolapse using International Continence Society (ICS) definitions, individual pelvic organ prolapse quantification points, age, body mass index, race, exogenous estrogen use, menopause, smoking, vaginal parity, cesarean section, and performance of concomitant procedures. We defined recurrence as any prolapse beyond the hymen. We had 125 women from 3 centers who met our criteria, with 23.2% of them having recurrence at 1 year. We found that recurrence increased as the preoperative ICS stage of prolapse increased (P = <0.001 in the univariate model). In the multivariate model, using logistic regression, we found that the risk of recurrence of pelvic organ prolapse increased as the presurgery clinical stage increased with an odds ratio of 3.8 (95% confidence interval, 1.5-9) when controlling for age, menopausal status, and genital hiatus (P = 0.004). Much like a higher stage of disease in oncology, we found that increasing stage of prolapse preoperatively increased the risk of recurrence at 1 year after sacrocolpopexy.

Epidemiology of cutaneous melanoma and non-melanoma skin cancer in Schleswig-Holstein, Germany: incidence, clinical subtypes, tumour stages and localization (epidemiology of skin cancer).

PubMed

Katalinic, A; Kunze, U; Schäfer, T

2003-12-01

Population-based figures on skin cancer are essential for a realistic assessment of the personal disease burden, prevention modes and the need for caring. The Robert Koch Institute in Germany estimates the incidence of melanoma skin cancer as seven cases in 100 000 persons (age-standardized by the European standard rate). Population-based studies presumably show higher incidence rates of 10-16 cases in 100 000 persons. Few data exist for non-melanoma skin cancer (NMSC) as this is not systematically registered in Germany. To present the first population-based results from the Schleswig-Holstein (Germany) Cancer Registry on incidence, stage distribution, clinical types and localization of skin cancer and to compare the results with other studies. The Cancer Registry of the Bundesland Schleswig-Holstein with 3500 registering institutions, 100 of which are dermatological institutions, investigates all notifiable incident cancer cases according to international standards. From the recorded data all melanoma and NMSC cases were identified and evaluated. Between 1998 and 2001, 1784 malignant melanoma (MM) and 12 956 NMSC cases underwent diagnostic and analytical evaluation. For MM, age-standardized incidence rates were 12.3 and 14.8 in 100 000 men and women, respectively, and the mean age of men was greater than that of women (56.6 vs. 54.9 years, P < 0.05). Superficial spreading melanoma was the most frequent clinical type (39.1%). The tumours were predominantly located on the trunk in men (46.8%) in contrast to leg and hip in women (39.5%). For NMSC, the age-standardized incidence rates were 100.2 and 72.6 in 100 000 men and women, respectively. More than 80% of all tumours were basal cell carcinoma. The first population-based data from Schleswig-Holstein on the characteristics (age, sex, histological subtypes, localization and stage) of skin tumours agree well with the existing literature and may thus be regarded as representative. However, markedly higher incidences

Clinical Features Associated With Nascent Left Ventricular Diastolic Dysfunction in a Population Aged 40 to 55 Years.

PubMed

Mosley, Jonathan D; Levinson, Rebecca T; Brittain, Evan L; Gupta, Deepak K; Farber-Eger, Eric; Shaffer, Christian M; Denny, Josh C; Roden, Dan M; Wells, Quinn S

2018-06-15

Diastolic dysfunction (DD), an abnormality in cardiac left ventricular (LV) chamber compliance, is associated with increased morbidity and mortality. Although DD has been extensively studied in older populations, co-morbidity patterns are less well characterized in middle-aged subjects. We screened 156,434 subjects with transthoracic echocardiogram reports available through Vanderbilt's electronic heath record and identified 6,612 subjects 40 to 55 years old with an LV ejection fraction ≥50% and diastolic function staging. We tested 452 incident and prevalent clinical diagnoses for associations with early-stage DD (n = 1,676) versus normal function. There were 44 co-morbid diagnoses associated with grade 1 DD including hypertension (odds ratio [OR] = 2.02, 95% confidence interval [CI] 1.78 to 2.28, p <5.3 × 10-29), type 2 diabetes (OR 1.96, 95% CI 1.68 to 2.29, p = 2.1 × 10-17), tachycardia (OR 1.38, 95% CI 0.53 to 2.19, p = 2.9 × 10-6), obesity (OR 1.76, 95% CI 1.51 to 2.06, p = 1.7 × 10-12), and clinical end points, including end-stage renal disease (OR 3.29, 95% CI 2.19 to 4.96, p = 1.2 × 10-8) and stroke (OR 1.5, 95% CI 1.12 to 2.02, p = 6.9 × 10-3). Among the 60 incident diagnoses associated with DD, heart failure with preserved ejection fraction (OR 4.63, 95% CI 3.39 to 6.32, p = 6.3 × 10-22) had the most significant association. Among subjects with normal diastolic function and blood pressure at baseline, a blood pressure measurement in the hypertensive range at the time of the second echocardiogram was associated with progression to stage 1 DD (p = 0.04). In conclusion, DD was common among subjects 40 to 55 years old and was associated with a heavy burden of co-morbid disease. Copyright © 2018 Elsevier Inc. All rights reserved.

Natural History of Wild-Type Transthyretin Cardiac Amyloidosis and Risk Stratification Using a Novel Staging System.

PubMed

Grogan, Martha; Scott, Christopher G; Kyle, Robert A; Zeldenrust, Steven R; Gertz, Morie A; Lin, Grace; Klarich, Kyle W; Miller, Wayne L; Maleszewski, Joseph J; Dispenzieri, Angela

2016-09-06

Wild-type transthyretin cardiac amyloidosis (ATTRwt) is increasingly recognized as an important cause of heart failure. The purpose of this study was to determine the natural history of ATTRwt and the predictors of survival. We retrospectively reviewed patients diagnosed with ATTRwt at the Mayo Clinic through 2013 and recorded clinical data and survival data. Factors affecting overall survival (OS) were identified, and a prognostic staging system was developed. The median age of the 360 patients diagnosed before death was 75 years (range: 47 to 94 years), and 91% were male. Presenting signs and symptoms included dyspnea or heart failure in 67% and atrial arrhythmias in 62%. Median OS from diagnosis was 3.6 years and did not change over time. Multivariate predictors of mortality included age, ejection fraction, pericardial effusion, N-terminal pro-B-type natriuretic peptide, and troponin T. A staging system was developed that used thresholds of troponin T (0.05 ng/ml) and N-terminal pro-B-type natriuretic peptide (3,000 pg/ml). The respective 4-year OS estimates were 57%, 42%, and 18% for stage I (both values below cutoff), stage II (one above), and stage III (both above), respectively. Stage III patients were at an increased risk of mortality after adjustment for age and sex compared with stage I patients (hazard ratio: 3.6; p < 0.001). The natural history of ATTRwt is poor. We report a novel cardiac biomarker staging system that enables risk stratification in an era of emerging treatment strategies. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

MicroRNA‑133b inhibits connective tissue growth factor in colorectal cancer and correlates with the clinical stage of the disease.

PubMed

Guo, Yihang; Li, Xiaorong; Lin, Changwei; Zhang, Yi; Hu, Gui; Zhou, Jianyu; Du, Juan; Gao, Kai; Gan, Yi; Deng, Hao

2015-04-01

Accumulating evidence indicates that dysregulation of microRNA‑133b (miR‑133b) is an important step in the development of certain types of human cancer and contributes to tumorigenesis. Altered expression of miR‑133b has been reported in colon carcinoma, but its association with clinical stage in colorectal cancer (CRC) has remained elusive. Connective tissue growth factor (CTGF), a potentially promising candidate gene for interaction with miR‑133b, was screened using microarray analysis. The expression of miR‑133b and CTGF was evaluated using reverse transcription‑quantitative polymerase chain reaction and western blot analysis. The regulatory effects of miR‑133b on CTGF were evaluated using a dual‑luciferase reporter assay. CTGF was identified as a functional target of miR‑133b. The results demonstrated low expression of miR‑133b in CRC specimens with poor cell differentiation (P=0.011), lymph node metastasis (P=0.037) and advanced clinical stages (stage III or IV vs. I or II; P=0.036). Furthermore, there was a significant association between a high level of expression of CTGF mRNA and an advanced clinical stage (stage III or IV vs. I or II; P=0.015) and lymph node metastasis (P=0.034). CTGF expression was negatively regulated by miR‑133b in the human colorectum, suggesting that miR‑133b and CTGF may be candidate therapeutic targets in colorectal cancer.

Malignant ovarian germ cell tumor - role of surgical staging and gonadal dysgenesis.

PubMed

Lin, Ken Y; Bryant, Stefanie; Miller, David S; Kehoe, Siobhan M; Richardson, Debra L; Lea, Jayanthi S

2014-07-01

To evaluate the effect of comprehensive surgical staging and gonadal dysgenesis on the outcomes of patients with malignant ovarian germ cell tumor. We performed a retrospective review of patients with ovarian germ cell tumors who were treated at our institution between 1976 and 2012. Malignant ovarian germ cell tumors (MOGCTs) were identified in 50 females. The median age was 24 years (range 13 to 49). Of all MOGCT patients, 42% had dysgerminoma, 20% immature teratoma, 16% endodermal sinus tumor, and 22% mixed germ cell tumor. Univariate analyses revealed that the lack of surgical staging (p=0.048) and endodermal sinus tumor (p=0.0085) were associated with disease recurrence, while age at diagnosis, ethnicity, and stage of the disease were not. Multivariate analyses revealed that the lack of surgical staging (p=0.029) and endodermal sinus tumor (p=0.016) were independently associated with disease recurrence. In addition, 7 patients (14%) had 46 XY karyotype, including 6 with pure dysgerminoma and 1 with mixed germ cell tumor. Five had Swyer syndrome and 2 had complete androgen insensitivity syndrome. Concurrent gonadoblastoma was found in 5 of the patients. No difference was found in the mean age at presentation, stage distribution, or recurrence rate for MOGCT patients with or without XY phenotype. Comprehensive surgical staging was associated with a lower rate of recurrence. Fourteen percent of phenotypic females with MOGCT and 29% of those with dysgerminoma had XY karyotype. The clinical outcome of these patients is similar to that of MOGCT patients with XX karyotype. Published by Elsevier Inc.

Prognostic Effect of Ultra-Staging Node Negative Colon Cancer without Adjuvant Chemotherapy: A Prospective National Cancer Institute Clinical Trial

PubMed Central

Protic, Mladjan; Stojadinovic, Alexander; Nissan, Aviram; Wainberg, Zev; Steele, Scott R.; Chen, David; Avital, Itzhak; Bilchik, Anton J.

2015-01-01

BACKGROUND We recently reported in a prospective randomized trial that ultra-staging of patients with colon cancer is associated with significantly improved disease-free survival (DFS) compared with conventional staging. That trial did not control for lymph node (LN) number or adjuvant chemotherapy use. STUDY DESIGN The current international prospective multi-center cooperative group trial (NCI Clinical Trial NCT00949312), “Ultra-staging in Early Colon Cancer” (UECC), evaluates whether the 12-LN quality measure and nodal ultra-staging impact DFS in patients not receiving adjuvant chemotherapy. Eligibility criteria include: a) biopsy-proven colon adenocarcinoma; b) absence of metastatic disease; c) > 12 LNs staged pathologically; d) pan-cytokeratin immunohistochemistry (IHC) of H&E-negative LNs; e) no adjuvant chemotherapy. RESULTS Of 442 patients screened, 203 patients were eligible. The majority of patients had intermediate grade (57.7%) and T3 tumors (64.9%). At a mean follow-up of 36.8±22.1 months (range 0–97 months), 94.3% remain disease-free. Recurrence was least likely in patients with ≥12, H&E negative, and IHC negative LNs (pN0i−): 2.6% vs.16.7% in the pN0i+ group (p<0.0001). CONCLUSIONS This is the first prospective report to demonstrate that patients with optimally staged node-negative colon cancer (≥12 LNs, pN0i−) are unlikely to benefit from adjuvant chemotherapy, as 97% remain disease free after primary tumor resection. Both surgical and pathological quality measures are imperative in the planning of clinical trials in non-metastatic colon cancer. PMID:26213360

Lung cancer diagnosis and staging in the minimally invasive age with increasing demands for tissue analysis

PubMed Central

Costa, Daniel B.; Wright, Jeffrey; VanderLaan, Paul A.

2015-01-01

The diagnosis and staging of patients with lung cancer in recent decades has increasingly relied on minimally invasive tissue sampling techniques, such as endobronchial ultrasound (EBUS) or endoscopic ultrasound (EUS) needle aspiration, transbronchial biopsy, and transthoracic image guided core needle biopsy. These modalities have been shown to have low complication rates, and provide adequate cellular material for pathologic diagnosis and necessary ancillary molecular testing. As an important component to a multidisciplinary team approach in the care of patients with lung cancer, these minimally invasive modalities have proven invaluable for the rapid and safe acquisition of tissue used for the diagnosis, staging, and molecular testing of tumors to identify the best evidence-based treatment plan. The continuous evolution of the field of lung cancer staging and treatment has translated into improvements in survival and quality of life for patients. Although differences in clinical practice between academic and community hospital settings still exist, improvements in physician education and training as well as adoption of technological advancements should help narrow this gap going forward. PMID:26380180

The clinical implications of ageing for rational drug therapy.

PubMed

Shi, Shaojun; Mörike, Klaus; Klotz, Ulrich

2008-02-01

The proportion of the elderly is constantly increasing and by the year 2025 20% of the population will be above 65 years of age. With advanced age, subjects will develop multiple diseases and often need to take several drugs. This polypharmacy increases the risk for drug interactions and adverse effects. In addition, age-related physiological changes affect different biological systems and can contribute to alterations in pharmacokinetics and pharmacodynamics in older patients, which are more often seen in the frail than in the fit elderly. These features will complicate drug therapy in the elderly, and a careful dose titration is advisable. Furthermore, inappropriate drug prescription and non-adherence to medication represent common therapeutic challenges in elderly subjects. To date, there is no evidence of any effective antiageing agent. This review summarizes present knowledge of age-related problems in drug action and their clinical implications for an increasingly important population.

Testing the Right Target and the Right Drug at the Right Stage

PubMed Central

Sperling, Reisa A.; Jack, Clifford R.; Aisen, Paul S.

2013-01-01

Alzheimer’s disease (AD) is the only leading cause of death for which no disease-modifying therapy is currently available. Recent disappointing trial results at the dementia stage of AD have raised multiple questions about our current approaches to the development of disease-modifying agents. Converging evidence suggests that the pathophysiological process of AD begins many years before the onset of dementia. So why do we keep testing drugs aimed at the initial stages of the disease process in patients at the end-stage of the illness? Alzheimer’s disease (AD) remains one of the most feared consequences of aging, affecting more than one out of every ten individuals over the age of 65. With more than 10,000 baby boomers turning 65 every day in the United States alone, we are truly facing an AD epidemic. Over the past decade, a string of disappointing clinical trial results have raised concerns about our current strategy for development of AD-modifying therapies. Three hypotheses can explain these recent AD trial failures: (i) We are targeting the wrong pathophysiological mechanisms; (ii) The drugs do not engage the intended targets in patients; and (iii) The drugs are hitting the right targets, but are doing so at the wrong stage of the disease. Here, we address the third supposition and suggest that specific amyloid-based therapies be directed at much earlier stages of ADperhaps even prior to the emergence of clinical symptoms. Furthermore, we argue that the field has sufficient tools to begin “secondary prevention” trials in asymptomatic individuals whoare at high risk for progression to cognitive impairment and AD dementia. PMID:22133718

Tau PET binding distinguishes patients with early-stage posterior cortical atrophy from amnestic Alzheimer disease dementia

PubMed Central