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Prognostic relevance of apoptotic cell death in non-Hodgkin's lymphomas: a multivariate survival analysis including Ki67 and p53 oncoprotein expression.

AIMS: To evaluate the independent prognostic value of apoptotic versus proliferative fractions in a series of 92 patients with non-Hodgkin's lymphomas (NHL). METHODS AND RESULTS: Apoptotic fractions were quantified by use of the TdT (terminal deoxynucleotidyl-transferase)-mediated in-situ end-labelling technique (TUNEL), the percentage of positive cells constituting the apoptotic index (AI). Proliferative rate was expressed as percentage of Ki67 positive cells (Ki67 LI). Tissues were also stained for p53 protein with the DO-1 antibody. Patients were followed up until death (n = 33) or for an average of 63 months (n = 56). AI increased with malignancy grade and proliferative activity but was not related to location, cell of origin, clinical stage, bone marrow involvement and p53 expression. In multivariate analysis, overall survival was independently influenced by grade, stage, p53 LI and chemotherapy. The independent predictors of disease-free survival were Ki67 LI location and chemotherapy. AI turned out to be the only independent (negative) predictor of post-relapse survival. On the other hand, a low Ki67 LI increased the risk of relapse (logistic regression analysis) whereas a low p53 LI increased the probability of complete response. CONCLUSIONS: Our results suggest that the combined assessment of apoptotic fraction, proliferative rate and p53 expression may provide important prognostic information independent of other clinicopathological parameters in NHL.

Adolescent↗

UGT1A1 gene variations and irinotecan treatment in patients with metastatic colorectal cancer.

SN-38 is the active metabolite of irinotecan and it is metabolised through conjugation by uridine diphosphate glucuronosyl transferase (UGT1A1). The major toxicity of irinotecan therapy is diarrhoea, which has been related to the enzymatic activity of UGT1A1. We examined the influence of the UGT1A1 gene promoter polymorphism in the toxicity profile, in the response rate and in the overall survival (OS) in 95 patients with metastatic colorectal cancer treated with an irinotecan-containing chemotherapy. Genotypes were determined by analysing the sequence of TATA box of UGT1A1 of genomic DNA from the patients. Clinical parameters and genotypes were compared by univariate and multivariate statistical methods. The more frequent adverse effects were asthenia (34 patients), diarrhoea (29 patients) and neutropenia (20 patients). Severe diarrhoea was observed in 7/10 homozygous (70%) and 15/45 heterozygous (33%) in comparison to 7/40 (17%) wild-type patients (P=0.005). These results maintained the statistical significance in logistic regression analysis (P=0.01) after adjustment for other clinical relevant variables. The presence of severe haematological toxicity increased from wild-type patients to UGT1A1(*)28 homozygotes, but without achieving statistical significance. No relationship was found between the UGT1A1(*)28 genotypes and infection, nausea or mucositis. In univariate studies, patients with the UGT1A1(*)28 polymorphism showed a trend to a poorer OS (P=0.09). In the multivariate analysis, the genotype was not related to clinical response or to OS. The role of the UGT1A1 genotype as a predictor of toxicity in cancer patients receiving irinotecan demands the performance of a randomized trial to ascertain whether genotype-adjusted dosages of the drug can help to establish safe and effective doses not only for patients with the UGT1A1(*)28 homozygous genotype but also for those with the most common UGT1A1 6/6 or 6/7 genotype.

Adult↗

An ecologically relevant exposure assessment for a polluted river using an integrated multivariate PLS approach.

A case study is presented where an integrated, ecologically relevant exposure assessment is presented for a polluted lowland river. Using partial least squares regression of latent structures (PLS), an analysis of the impact of two effluents on physico-chemical water quality measures, macroinvertebrate and diatom communities, and in situ bioassay responses with four different test species are combined into an integrative exposure assessment. Bioassays focussed on growth and condition related endpoints, because they are key functional processes of organisms and populations. Integrating these multiple lines of evidence, we were able to discriminate among the impact of both effluents, link changes in physico-chemical water quality with bioassay endpoints and ecological quality of the ecosystem, and address the importance of integrating all information into one exposure assessment framework. The bioassays under field conditions indicated that most endpoints measured are a reflection of ecological effects rather than pollution related effects, or at least a combination of both ecological and toxicological effects. Factors such as food availability clearly influenced the outcome of in situ bioassays and ecological information was essential to explain observed discrepancies when trying to extrapolate bioassay results from the laboratory to the field.

Animals↗

Predictors of response to glimepiride in patients with type 2 diabetes mellitus.

OBJECTIVE: The purpose of DIAMETRE (DIabète et Amarel en Monothérapie. Etude de Titration pour la définition des Répondeurs) was to identify factors predictive of response to glimepiride monotherapy in type 2 diabetic patients in the setting of a prospective multicentre open study. MATERIAL AND METHODS: Patients aged 35-70 years with poorly controlled diabetes [fasting plasma glucose (FPG) > or =1,40 g/l and < 3 g/l at baseline] were treated with glimepiride for 6 months, with dosage titrated from 1-6 mg daily, depending on the monthly FPG measurement. Responders were defined as patients with a) FPG < 7.78 mmol/l (1.40 g/l) and HbA(1c) < 7.5% at endpoint, or b) decrease in FPG > or = 20% and/or HbA1c > or = 10%. Stepwise logistic regression analysis was used to identify factors predictive of response. RESULTS: Of 849 patients evaluable for efficacy, 483 (56.9%) were responders. The response was independently influenced by prior treatment with OADs [OR: 0.399 (0.290-0.549), p=0.0001] and diabetes duration [OR: 0.912 (0.877-0.948), p=0.0001]. Ninety patients (9.2%) experienced 124 episodes of symptomatic hypoglycaemia. Multivariate analysis revealed that a high level of HbA(1c) decreased the risk of symptomatic hypoglycaemia [OR: 0.734 (0.628; 0.858), p=0.0001] whereas a family history of type 2 diabetes doubled this risk [OR: 1.956 (1.246; 3.072), p=0.003]. CONCLUSION: This large-scale study, conducted under conditions approximating to current medical practice, confirms that glimepiride has a favourable risk-benefit ratio in type 2 diabetes mellitus. Diabetes duration and previous treatment with OADs reduced the likelihood of being a responder to treatment.

Adult↗

Increases in P-wave dispersion predict postoperative atrial fibrillation after coronary artery bypass graft surgery.

UNLABELLED: Atrial fibrillation (AF) is a common complication after coronary artery bypass graft (CABG) surgery. In this study we examined the effect of surgery on atrial electrophysiology as measured by P-wave characteristics and to determine the potential predictive value of P-wave characteristics on the incidences of postoperative AF in patients undergoing CABG surgery. Patients undergoing elective CABG surgery were monitored by continuous electrocardiogram (ECG) telemetry during the in-hospital period until discharge for the occurrence of postoperative AF. Differences in P-wave characteristics (P-wave duration, amplitude, axis, dispersion, PR interval, segment depression, and dispersion) were compared between the pre- and postoperative 12-lead ECG measurements, and also between patients with and without postoperative AF. The association of postoperative AF and potential clinical predictors and P-wave characteristics were determined by multivariate logistic regression. Postoperative AF occurred in 81 (27%) of 300 patients. Univariate analysis showed that patients who subsequently developed postoperative AF compared with those without AF were significantly older (mean age 68 +/- 8 versus 63 +/- 10 yr, P < 0.0001), had a larger body surface area (BSA) (2.03 +/- 0.24 versus 1.92 +/- 0.22 m(2), P = 0.0002), were more likely to have a history of AF (8 of 81 versus 1 of 219, P = 0.003), used preoperative antiarrhythmic medications more frequently (7 of 81 versus 4 of 219, P = 0.01), and had a more frequent rate of return to the operating room for postoperative complications (9 of 81 versus 9 of 219, P = 0.029). Furthermore, the postoperative P-wave duration decreased to a larger extent (mean change -11.3 +/- 0.1 ms versus -8.4 +/- 0.1 ms, P < 0.0001), and the P-wave dispersion increased postoperatively to a larger extent (3.1 +/- 15.5 ms versus -1.6 +/- 14.6 ms, P = 0.028) in those who subsequently developed AF compared with those without AF. Multivariate logistic regression showed age (odds ratio [OR] = 1.1, 95% confidence interval [CI]: 1.06-1.15, P < 0.0001), BSA (OR = 38.1, 95% CI: 8.2-176, P < 0.0001), and an increase in postoperative P-wave dispersion (OR = 1.03, 95% CI: 1.01-1.05, P = 0.01) to be independent predictors of postoperative AF. No surgical factor was identified to be responsible for this postoperative change in atrial electrophysiology. IMPLICATIONS: In addition to clinical factors, such as advanced age and body surface area, we demonstrated that electrophysiologic changes involving an increase in P-wave dispersion postoperatively independently predict atrial fibrillation after coronary artery bypass graft surgery.

Aged↗

Epoetin requirement does not depend on dialysis dose when Kt/N > 1.33 in patients on regular dialysis treatment with cellulosic membranes and adequate iron stores.

BACKGROUND: An inverse correlation between Kt/V and epoetin requirement has recently been demonstrated in stable hemodialysis (HD) patients with adequate iron stores, dialyzed with cellulosic membranes. However, there is no evidence as to whether or not this effect continues for Kt/V even in the adequate or higher range. METHODS: We investigated the relationship between Kt/V and the weekly epoetin dose in 85 stable HD patients (age 63 +/- 16 years) treated with bicarbonate HD and unsubstituted cellulose membranes for 6-338 months (median: 70 months). INCLUSION CRITERIA: HD for at least 6 months, subcutaneous rHuEPO for at least 4 months, transferrin saturation (TSAT) > or = 20%, serum ferritin > or = 100 ng/mL, hemoglobin (Hb) level targeted to approximately equal to 12 g/dL for at least 3 months. EXCLUSION CRITERIA: HBsAg and HIV positivity; need for blood transfusions or evidence of blood loss in the 3 months before the study, acute and chronic infections. To evaluate the effect of dialysis adequacy on the epoetin requirement, we also performed the same analysis after dividing of the patients according to Kt/V. Hematocrit (Hct) and Hb levels were evaluated weekly for 3 weeks; TSAT, serum ferritin, Kt/V, PCRn, serum albumin (sAlb), and weekly epoetin dose were evaluated at the end of observation. No change in dialysis or therapy prescription was made during the study. RESULTS: The results for all the patients were: Hct 36 +/- 2 %, Hb 12 +/- 0.7 g/dL, TSAT 28 +/- 7%, serum ferritin 234 +/- 171 ng/mL, sAlb 4.2 +/- 0.4 g/dL, Kt/V 1.33 +/- 0.17, PCRn 1.15 +/- 0.28 g/Kg/day, weekly epoetin dose 117 +/- 74 U/Kg. There was no correlation between Hb and Kt/V, whereas there was an inverse correlation between the reciprocal of the weekly epoetin dose and Kt/V (r = -0.448, p = 0.0001). Further regression line analysis showed a break-point for Kt/V at the level of 1.33. In the 52 patients with Kt/V < 1.33, the correlation was confirmed between epoetin and Kt/V (r = - 0.563, p = 0.0001), while in the 33 patients with Kt/V > or = 1.33, there was no correlation between epoetin dose and Kt/V (r = 0.021, p = NS). In these patients, multiple regression analysis, with the weekly epoetin dose as a dependent variable, confirmed Kt/V as a non-significant factor. CONCLUSIONS: In iron-replete HD patients on cellulosic membranes and stabilized epoetin therapy, inadequate dialysis was associated with higher epoetin requirement, but for Kt/V values > or = 1.33, there was no further effect on epoetin responsiveness.

Adult↗

Assessment of the surface water quality in Northern Greece.

The application of different multivariate statistical approaches for the interpretation of a large and complex data matrix obtained during a monitoring program of surface waters in Northern Greece is presented in this study. The dataset consists of analytical results from a 3-yr survey conducted in the major river systems (Aliakmon, Axios, Gallikos, Loudias and Strymon) as well as streams, tributaries and ditches. Twenty-seven parameters have been monitored on 25 key sampling sites on monthly basis (total of 22,350 observations). The dataset was treated using cluster analysis (CA), principal component analysis and multiple regression analysis on principal components. CA showed four different groups of similarity between the sampling sites reflecting the different physicochemical characteristics and pollution levels of the studied water systems. Six latent factors were identified as responsible for the data structure explaining 90% of the total variance of the dataset and are conditionally named organic, nutrient, physicochemical, weathering, soil-leaching and toxic-anthropogenic factors. A multivariate receptor model was also applied for source apportionment estimating the contribution of identified sources to the concentration of the physicochemical parameters. This study presents the necessity and usefulness of multivariate statistical assessment of large and complex databases in order to get better information about the quality of surface water, the design of sampling and analytical protocols and the effective pollution control/management of the surface waters.

Environmental Monitoring↗

Relationship between extent of cocaine use and dependence among adolescents and adults in the United States.

The relationships between intensity of cocaine use, route of administration and past year dependence were investigated in a nationally representative sample of past year cocaine users aged 12 and over (N = 2,349) from three aggregated surveys (1991-1993) of the National Household Survey on Drug Abuse (NHSDA). An approximate measure of DSM-IV dependence criteria was developed from self-reported symptoms of dependence and drug-related problems. The model and the data provided no basis for rejecting the hypothesis that the logit of the probability of dependence increased linearly with the logarithm of the frequency of cocaine use in the past year and with quantity of cocaine use in the past 30 days. The associations between frequency and quantity of cocaine use and cocaine dependence varied significantly by an age-by-gender interaction and race/ethnicity. African-American users, who had higher rates of cocaine dependence than whites, used cocaine more frequently, used it by more addictive routes (smoking or injection), and were more likely to use crack. Adolescent females, who reported higher rate of cocaine dependence than males, used cocaine more frequently and reported more symptoms at low doses of cocaine use. Multivariate logistic regressions indicated that frequency and quantity of use, as well as route of administration, retained unique associations with cocaine dependence. Implications of the findings for the epidemiological study of cocaine use and dependence are discussed.

Adolescent↗

FDG-PET status following chemoradiotherapy provides high management impact and powerful prognostic stratification in oesophageal cancer.

PURPOSE: The purpose of this study was to evaluate the impact of FDG-PET following chemoradiotherapy (CRT) on treatment planning and survival in patients with oesophageal cancer (OC). METHODS: Fifty-three consecutive OC patients had a post-treatment PET scan to evaluate tumour response to CRT prior to possible surgery. Baseline pre-CRT PET was performed in 33 patients. Prospectively recorded post-CRT management plans were compared with post-PET treatment. High impact was defined as a change in treatment intent or modality. Survival was analysed using the Kaplan-Meier product limit method and Cox proportional hazards regression model. RESULTS: After completion of CRT, 23/53 patients (43%) achieved complete metabolic response (CMR), as compared with only four (8%) with complete response on computed tomography. High PET impact was observed in 19 patients (36%). CMR was strongly predictive of survival (p<0.008) on multivariate analysis. CMR patients in whom resection was not performed had comparable survival to those (CMR and non-CMR) who underwent resection. CONCLUSION: The use of post-treatment FDG-PET for assessment of tumour response after CRT changed the clinical management of more than one-third of OC patients. CMR status as assessed by PET powerfully stratified prognosis. Even in the absence of a baseline study, normalisation of uptake at all sites of known tumoral involvement carries a good medium-term prognosis.

Adult↗

Perceived neighborhood social disorder and residents' attitudes toward reporting child physical abuse.

OBJECTIVE: This study aimed to explore the relationship between perceived neighborhood social disorder and attitudes toward reporting child physical abuse. METHOD: Data from a national probabilistic sample (N=9,759) were used. Responses about the perception of neighborhood social disorder, perceived frequency of child physical abuse in Spanish families, and willingness to report a case of child physical abuse to the police were collected through face-to-face interviews in respondents' homes. RESULTS: Multivariate logistic regression analysis showed that perceived neighborhood social disorder was negatively related to residents' attitudes toward reporting child physical abuse. These results take into account the potential confounding effects of gender, age, socio-economic status, educational level, size of city, and perceived frequency of child physical abuse on reporting attitudes. CONCLUSION: Results illustrate the important role that community characteristics may play in processes relevant to the prevention of child maltreatment such as residents' attitudes towards reporting child physical abuse, and suggest that especially disadvantaged communities characterized by high levels of social disorder need to be specifically targeted if the aim is to increase the capacity to prevent child maltreatment in the community.

Adolescent↗

Pupil size and quality of vision after LASIK.

PURPOSE: To evaluate factors related to the quality of vision after LASIK. DESIGN: Survey study. PARTICIPANTS: One hundred consecutive patients. INTERVENTION: LASIK with a 6.0-mm elliptical ablation pattern without transition zone to treat mild to moderate myopia or astigmatism (preoperative manifest spherical equivalent [MSE], -4.79 +/- 1.33 diopters [D]; range, -2.88 to -9.25 D). The second eye was treated 1 month after the first. MAIN OUTCOME MEASURES: Completed questionnaires assessing night vision problems (glare, haze, and halo symptoms) before surgery and at 1, 3, and 6 months after surgery in 97, 75, 81, and 66 subjects, respectively. Mesopic pupil size and preoperative and postoperative variables were analyzed with questionnaire data using an analysis of variance (ANOVA) and multivariate regression analysis. RESULTS: Patients with large mesopic pupils had significantly more reports of glare, haze, and halo than did those with smaller pupils in the treated eye at 1 month after surgery (P=0.02, P=0.03, and P=0.02, respectively ANOVA) and of glare at 3 months (P=0.05). Significant predictors of symptoms at 6 months, identified through multivariate regression analysis, included preoperative MSE (for glare and haze), preoperative contrast acuity (glare), postoperative uncorrected visual acuity (UCVA; haze), and residual cylinder (haze). Together, these factors accounted for only 19% of the overall variability in glare and 37% of the variability in haze responses. No relationship between pupils and symptoms was noted at 6 months after surgery in either the ANOVA or regression analysis group. CONCLUSIONS: Patients with large pupils had more quality of vision symptoms in the early postoperative period, but no correlation was observed 6 months after surgery. Factors related to long-term symptoms include the level of treatment (preoperative myopia), preoperative contrast acuity, postoperative UCVA, and residual cylinder. Most of the variability in visual quality could not be explained by preoperative or clinical outcome measures, including pupil size.

Adult↗

Associations of lifestyle factors with quality of life (QOL) in Japanese children: a 3-year follow-up of the Toyama Birth Cohort Study.

PURPOSE: To examine the associations between lifestyle factors and quality of life (QOL) among Japanese children. METHODS: Participants were 7794 children (3869 boys and 3925 girls) aged 9-10. They completed a questionnaire regarding lifestyles at baseline survey and were followed up for 3 years. In the follow-up survey, QOL was evaluated using a Japanese version of the COOP charts. Children rated their QOL as one of five response categories. Subjects rated as 'very well' or 'pretty good' were considered to have good QOL, and the remainder was assumed to have poor QOL. Logistic regression analysis was performed to evaluate the relationship between lifestyles or changes in lifestyles and QOL. In the multivariate analysis model, age, sex, body mass index (BMI), and lifestyle factors were simultaneously entered. RESULTS: During the follow-up period, children became more sedentary. Compared to children participating in physical activity 'very often' at baseline, those who exercised 'almost never' were more likely to have poor QOL [OR (95% CI): 1.92 (1.26-2.93)]. Children who developed or maintained undesirable lifestyles had high OR for poor QOL. Compared to children taking breakfast 'often' during the follow-up period, those changing from 'often' to 'seldom' or those taking breakfast 'seldom' were more likely to have poor QOL [1.61 (1.24-2.07), 2.05 (1.03-4.09), respectively]. When compared with children maintaining their participation in physical activity 'often', those who changed from 'often' to 'seldom' and those who kept 'seldom' were more likely to have poor QOL [2.10 (1.84-2.39), 2.21 (1.88-2.59), respectively]. CONCLUSIONS: This study shows that unfavourable lifestyles in childhood are associated with poor QOL in early adolescence. Early intervention could be worth considering to keeping desirable lifestyles during childhood.

Adolescent↗

Determinants of normal coronary artery dimensions in humans.

BACKGROUND: Studies of normal human coronary dimensions have been performed primarily in postmortem hearts. We evaluated the influence of age, body habitus, and regional myocardial mass on coronary dimensions in living patients with normal coronary vessels. METHODS AND RESULTS: Arteriographically normal coronary angiograms were analyzed from the following groups of subjects: group 1 (age, 15-34 years) consisted of 30 post-cardiac transplant patients with donor hearts from male subjects aged 15-34 years, group 2 (age, 35-54 years) consisted of 12 post-cardiac transplant patients with donor hearts from male subjects aged 35-54 years and 26 male subjects investigated for atypical chest pain, and group 3 (age, 55-74 years) consisted of 26 male subjects investigated for atypical chest pain. All angiograms were performed after sublingual nitroglycerin. Measurements of the dimensions of the left main, proximal left anterior descending, proximal left circumflex, and proximal right coronary arteries were made using a computer-assisted edge-detection algorithm. The regional myocardial mass supplied by each vessel was derived from echocardiographically derived total left ventricular mass and a semiquantitative angiographic territory scoring system based primarily on the number and length of its terminal nutrient branches. CONCLUSIONS: Linear regression analysis showed that coronary vessel cross-sectional area and total coronary cross-sectional area increase with regional myocardial mass and decrease linearly with age. Multivariate regression analysis revealed that regional myocardial mass and age were independent predictors of cross-sectional area for each vessel and for the total coronary cross-sectional area. We speculate that age-related decline in physical activity, in part, may be responsible.

Adolescent↗

Simple clinical criteria to determine the prognosis of heart failure.

OBJECTIVE: To determine whether easily obtained clinical parameters serve as predictors of survival in patients with congestive heart failure. Several scoring systems to predict heart failure survival have been developed; however, many of these deal principally with transplant recipients or do not account for a patient's response to therapy. METHODS: A total of 680 patients with an ejection fraction of less than 40% were included in the analysis. Baseline assessments were performed and treatment regimens were identified; patients were then followed for up to 5 years. Univariate and multivariate Cox regression models were used to determine clinically important predictors of survival. Kaplan-Meier survival functions for patients with and without the prognostic variable were constructed and mortality was calculated at 1 year and 5 years. RESULTS: Ejection fraction improvement at 6 months, diabetes mellitus, age, serum creatinine, and blood urea nitrogen (BUN) were significant predictors for survival in the univariate model. Ejection fraction improvement, age, and BUN were significant predictors in the multivariate model. These findings were used to construct a model for predicting patient mortality. Improved ejection fraction (>15 ejection fraction units) gave a 1-year mortality of 2% and a 5-year mortality of 11%. Mortality rates according to patient age and BUN levels were also calculated. CONCLUSION: Ejection fraction improvement was the most important predictor for survival in patients with systolic dysfunction; monitoring ejection fraction changes through repeat echocardiograms has important prognostic value. In patients without ejection fraction improvement, age and renal function are important survival determinants.

Adult↗

War-related psychological sequelae among emergency department patients in the former Republic of Yugoslavia.

BACKGROUND: Residents of the Republic of Serbia faced civil war and a NATO-led bombing campaign in 1999. We sought to assess the burden of metal health dysfunction among emergency department (ED) patients presenting for care three years post-war in Serbia. METHODS: This study was conducted during July and August 2002 at two sites: a university hospital ED in Belgrade, Serbia and an ED in a remote district hospital serving a Serbian enclave in Laplje Selo, Kosovo. Investigators collected data on a systematic sample of non-acute patients presenting to the ED. All respondents completed a structured questionnaire assessing demographics and symptoms of post-traumatic stress disorder (PTSD) (using the Harvard Trauma Questionnaire), and major depression (using the Center for Epidemiologic Studies Depression Scale). RESULTS: A total of 562 respondents participated (310 in Belgrade, 252 in Laplje Selo); the response rate was 83.8%, 43% were female, and mean age was 37.6 years (SD = 13.4). Overall, 73 (13.0%) participants had symptoms consistent with PTSD, and 272 (49.2%) had symptoms consistent with depression. Sixty-six respondents had both disorders (11.9%). In separate multivariable logistic regression models, predictors of PTSD were refugee status and residence in Laplje Selo, and predictors of depression were older age, current unemployment, and lower social support. CONCLUSIONS: Three years post-war, symptoms of PTSD and major depression in Serbia remained a significant public health concern, particularly among refugees, those suffering subsequent economic instability, and persons living in rural, remote areas.

Adult↗

Physicians' reasons for not entering their patients in a randomized controlled trial in Japan.

Physicians' not entering their patients can jeopardize the success of a randomized controlled trial (RCT). We used a survey to investigate the possible reasons why physicians who initially agreed to collaborate did not recruit any patients for an RCT being conducted in Japan. A total of 167 questionnaires were sent out and 122 responses were received. Main reasons for not entering patients were: concern about the detrimental effects on the doctor-patient relationship (51.8%), patients' refusal (47.5%), complicated registration and follow-up procedures (34.9%), and not feeling comfortable recruiting their own patients (32.4%). Multivariate logistic regression made it clear that physicians who thought that registering their own patients would damage the doctor-patient relationship and who expected the RCT would fail were more likely to be uncomfortable entering their own patients. Moreover, physicians aged 50 years or older, who felt uncomfortable recruiting their own patients, and saw no advantage in participating in the trial, were more likely to view the enrolment and follow-up procedures as cumbersome. We conclude that training and a manual for obtaining informed consent and a face-to-face demonstration of patient registration/follow-up procedures for the potential participants are prerequisites for increasing physician participation in RCTs in Japan.

Adult↗

Integrative analysis identifies a glycosylation-related lncRNA signature associated with prognosis in kidney renal clear cell carcinoma.

BACKGROUND: Glycosylation and long non-coding RNAs (lncRNAs) play critical roles in tumor progression. However, the prognostic significance of glycosylation-related lncRNAs (GRLncs) in kidney renal clear cell carcinoma (KIRC) remains largely unclear. This study aimed to identify prognostic GRLncs and construct a predictive model for KIRC prognosis. METHODS: Transcriptomic and clinical data of KIRC patients were analyzed to identify GRLncs associated with overall survival (OS). A prognostic model was constructed based on selected GRLncs, and its predictive performance was evaluated using Kaplan-Meier (KM) survival analysis, receiver operating characteristic (ROC) curves, and univariate and multivariate Cox regression analyses. Patients were stratified into high- and low-risk groups according to the median risk score, and internal validation was performed using training and testing cohorts to assess the stability of the model. Tumor microenvironment characteristics, immune checkpoint expression, immunotherapy response, and drug sensitivity were further analyzed. In addition, the expression of three signature lncRNAs was validated by real-time quantitative polymerase chain reaction (RT-qPCR) in 10 paired KIRC tumor and adjacent normal tissues. Functional roles of selected lncRNAs were investigated using antisense oligonucleotides (ASOs)-mediated knockdown in KIRC cell lines, followed by Cell Counting Kit 8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU) incorporation, colony formation, and migration assays. RESULTS: Five GRLncs (AC093278.2, EPB41L4A-DT, DLGAP1-AS2, AC084876.1, and AC005261.3) were identified and used to construct a prognostic model. AC093278.2 and EPB41L4A-DT were protective factors, whereas DLGAP1-AS2, AC084876.1, and AC005261.3 were risk factors. KM analysis on GRLncs-based risk score stratification revealed patients in the high-risk group had significantly poorer OS than those in the low-risk group. ROC analysis and Cox regression demonstrated that the GRLnc-based risk score served as an independent predictor of KIRC prognosis and exhibited favorable predictive performance compared with conventional clinical variables. High- and low-risk groups also exhibited distinct immune microenvironment characteristics, immune checkpoint expression patterns, and predicted drug sensitivities. RT-qPCR detected significant downregulation of protective factor-EPB41L4A-DT in KIRC tissues, while risk factors-DLGAP1-AS2 and AC084876.1 showed expression trends consistent with their predicted risk attributes. Functional experiments further revealed that knockdown of DLGAP1-AS2 and AC084876.1 suppressed proliferation and migration of KIRC cells, whereas knockdown of EPB41L4A-DT promoted these processes, supporting the biological relevance of these three signature lncRNAs. CONCLUSIONS: This study establishes a novel prognostic model based on five GRLncs that showed promising performance in The Cancer Genome Atlas (TCGA)-based analyses of KIRC. The combined clinical expression analysis and functional validation of three constituent GRLncs (DLGAP1-AS2, EPB41L4A-DT, and AC084876.1) supports the biological plausibility of the model and suggest that GRLncs may serve as potential prognostic biomarkers and therapeutic targets for KIRC.

Kidney renal clear cell carcinoma (KIRC)↗

Curriculum emphasis and resident preparation in postgraduate general dentistry programs.

In 1999 HRSA contracted with the UCLA School of Dentistry to evaluate the impact of federal funding on postgraduate general dentistry programs. Part of that evaluation analyzed curriculum emphasis and preparation of incoming residents in advanced general dentistry programs over a five-year period. Directors of 208 civilian AEGD and GPR programs were surveyed about the curriculum content of their programs, increased or decreased emphasis in thirty subject areas, and resident preparation and quality (GPA and National Board scores). Results indicate that curriculum changes in AEGD and GPR programs over the time period have been responsive to the changing nature of general practice. At least half of all program directors reported that their residents were less than adequately prepared in fourteen curriculum areas. Sub-analyses were conducted for AEGD/GPR programs and HRSA-funded versus nonfunded programs. Multivariate regression identified lower student quality as the most important program variable in predicting a perceived need for resident remediation. Logistic regression showed that programs with higher resident GPA and National Board Part I scores had less difficulty filling resident positions.

Adolescent↗