Biomedical subjects

Haiqun Lin

Publications and source records attributed to Haiqun Lin.

17 recordsLinked to original sources

PubMed2007

Impact of supported housing on clinical outcomes: analysis of a randomized trial using multiple imputation technique.

In 1992, the US Department of Housing and Urban Development (HUD) and the US Department of Veterans Affairs (VA) established the HUD-VA Supported Housing (HUD-VASH) Program to provide integrated clinical and housing services to homeless veterans with psychiatric and/or substance abuse disorders at 19 sites. At four sites, 460 subjects were randomly assigned to one of the three groups: (1) HUD-VASH, with both Section 8 vouchers and intensive case management; (2) case management only; and (3) standard VA care. A previous publication found HUD-VASH resulted in superior housing outcomes but yielded no benefits on clinical outcomes. Since many participants missed prescheduled visits during the follow-up period and follow-up rates were quite different across the groups, we reanalyzed these data using multiple imputation statistical methods to account for the missing observations. Significant benefits were found for HUD-VASH in drug and alcohol abuse outcomes that had not previously been identified.

Alcoholism↗

PubMed2006

Tertiary Gleason pattern 5 is a powerful predictor of biochemical relapse in patients with Gleason score 7 prostatic adenocarcinoma.

PURPOSE: In radical prostatectomy specimens Gleason score 7 is among the most commonly assigned scores for prostate carcinoma accounting for 30% to 50% of cases. Gleason score 7 is different from other more differentiated prostate carcinomas (tumors of Gleason scores 5 and 6) with a significantly worse outcome and higher rate of recurrence. Nonetheless, Gleason score 7 tumors are heterogeneous. In this study we examined the differences in clinical outcome between primary Gleason grade 3 and 4 tumors in patients who underwent radical prostatectomy, and determined the influence of tertiary Gleason pattern 5 on patient outcome. MATERIALS AND METHODS: A total of 504 patients underwent radical prostatectomy for prostate cancer and 228 of the patients (45%) had a Gleason score of 7. Cases were analyzed for a variety of clinical and pathological parameters. The influence of primary Gleason pattern and tertiary Gleason pattern 5 on patient outcome was assessed in the Cox regression model. RESULTS: Among 228 patients with Gleason score 7 prostatic adenocarcinoma, 91 (40%) had a primary Gleason pattern 4 and 137 (60%) had primary Gleason pattern 3. Patients of the former group were more likely to have a higher pathological stage (p = 0.003), more likely to have PSA recurrence (p = 0.02) and more likely to have a tertiary Gleason pattern 5 (p <0.0001). A total of 37 (41%) patients with primary Gleason 4 had a tertiary Gleason pattern 5, whereas only 13 (9%) patients with primary Gleason 3 had a tertiary Gleason pattern 5. In the Cox regression model controlling for tumor stage and surgical margin status, the primary Gleason pattern was not an independent predictor of PSA recurrence (p = 0.80), whereas the presence of tertiary Gleason pattern 5 was a significant predictor of PSA recurrence (hazard ratio 2.10, 95% CI 1.24-3.55, p = 0.006). Five-year PSA recurrence-free survival was 70% for patients without a tertiary Gleason pattern 5 compared to 19% for those patients with a tertiary Gleason pattern 5. CONCLUSIONS: Among patients with Gleason score 7, primary Gleason grade 4 indicates a likelihood of higher tumor stage and higher probability of PSA recurrence than does primary pattern 3. However, it does not independently predict a worse outcome after controlling for other known prognostic parameters associated with disease progression. Regardless of whether the primary Gleason pattern is 3 or 4, a tertiary Gleason pattern 5 is the strongest predictor of a worse outcome in patients with Gleason grade 7 prostatic adenocarcinoma. Therefore, tertiary pattern 5 should be reported in radical prostatectomy specimens.

Adenocarcinoma↗

PubMed2006

Cost-effectiveness of second-generation antipsychotics and perphenazine in a randomized trial of treatment for chronic schizophrenia.

BACKGROUND: Second-generation antipsychotics have largely replaced first-generation antipsychotics for the treatment of schizophrenia, but a large-scale cost/effectiveness analysis has not been attempted. METHOD: Patients with schizophrenia (N=1,493) were assigned to treatment with a first-generation antipsychotic (perphenazine) or one of four second-generation drugs (olanzapine, quetia-pine, risperidone, or ziprasidone) and followed for up to 18 months. Patients with tardive dyskinesia were prohibited from assignment to perphenazine. Patients could be reassigned at any time to another second-generation drug, including clozapine, but not to perphenazine. The cost analysis included medications plus health services use. Quality-adjusted life year (QALY) ratings were assessed on the basis of Positive and Negative Syndrome Scale (PANSS) subscale scores and side effects. An intention-to-treat analysis included all available observations, classified by initial drug assignment, and costs of reassignment of most patients to another second-generation drug. The analysis was repeated considering only treatment on initially assigned medications. RESULTS: Although QALY ratings, PANSS scores, and other quality of life measures indicated modest improvement over 18 months, there were no significant differences between perphenazine and any second-generation medication. Average total monthly health care costs were 300 dollars-600 dollars (20%-30%) lower for perphenazine than for second-generation antipsychotics because of lower drug cost. Differences in costs remained when maximally discounted drug prices were used for all patients and when only observations during treatment with the first medication were included. CONCLUSIONS: Treatment with perphenazine was less costly than treatment with second-generation antipsychotics with no significant differences in measures of effectiveness. However, the trial was limited by a high dropout rate, and longer-term neurological and metabolic side effects require further study.

Adolescent↗

PubMed2005

Increased serum levels of interleukin-12 and tumor necrosis factor-alpha in Tourette's syndrome.

BACKGROUND: The hypothesis that common infections can modulate the onset and course of tic disorders and early-onset obsessive-compulsive disorder (OCD) in pediatric populations is longstanding. To date, most investigations have focused on the hypothesis of molecular mimicry and humoral immune responses. This study was carried out to investigate whether cytokines associated with the innate immune response or T cell activation were altered under baseline conditions and during periods of symptom exacerbation. METHODS: Forty-six patients with Tourette's syndrome and/or early-onset OCD, aged 7-17 years, and 31 age-matched control subjects participated in a prospective longitudinal study. Ratings of clinical severity and serum were collected at regular intervals, and serum concentrations of 10 cytokines were measured repeatedly. RESULTS: Interleukin-12 and tumor necrosis factor alpha concentrations at baseline were elevated in patients compared with control subjects. Both of these markers were further increased during periods of symptom exacerbation. CONCLUSIONS: These findings suggest that symptom exacerbations are associated with an inflammatory process propagated by systemic and local cytokine synthesis that might involve the central nervous system. We conclude that, in the future, longitudinal studies of children with neuropsychiatric disorders should examine the involvement of innate and T cell immunity.

Adolescent↗

PubMed2005

Thyroid transcription factor 1 expression in small cell carcinoma of the urinary bladder: an immunohistochemical profile of 44 cases.

Small cell carcinoma of the urinary bladder is a rare and aggressive tumor resembling small cell carcinoma of the lung. Thyroid transcription factor 1 (TTF-1) expression is common in small cell carcinomas arising in the lung. However, studies of its expression in extrapulmonary small cell carcinomas have yielded varying results. Because information concerning the immunohistochemical profile of small cell carcinoma of the urinary bladder is limited, we investigated the immunoreactivity of this tumor to a battery of antibodies in a series of 44 cases. Using 5-mum sections cut from paraffin-embedded tissue blocks, immunohistochemistry was performed to detect TTF-1, cytokeratin (CK) 7, CK20, and uroplakin antigenicity in 44 cases of small cell carcinoma of the urinary bladder. None of the patients had primary lung tumors. The TTF-1 immunohistochemical stain showed nuclear positivity in 17 cases (39%). Positive immunostaining for CK7 was observed in 26 cases (59%). There was no positive staining with either CK20 or uroplakin. There was no correlation between TTF-1 expression and survival (P = .27). In addition, TTF-1 expression did not correlate with clinicopathological characteristics, including age (P = .74), sex (P = .53), smoking history (P = .96), clinical stage (P = .10), pathological T stage (P = .50), lymph node metastasis (P = .40), and distant metastasis (P = .58). In summary, TTF-1 expression in small cell carcinoma of the urinary bladder was found in 39% of the tumors, demonstrating that this marker is expressed in small cell carcinomas other than those of pulmonary origin. Small cell carcinoma of the urinary bladder is positive for CK7 immunostaining in 59% of cases consistent with its origin from urothelium. Unlike urothelial carcinoma, expression of CK20 and uroplakin in small cell carcinoma of the urinary bladder is consistently negative, and thus, these stains do not appear to be useful in the diagnosis of this neoplasm. TTF-1 positivity is not a significant prognostic factor in small cell carcinoma of the urinary bladder.

Adult↗

PubMed2005

c-kit Expression in small cell carcinoma of the urinary bladder: prognostic and therapeutic implications.

The prognosis for small cell carcinoma of the urinary bladder is poor, and strategies for improved therapy are needed. Targeted therapy against the c-kit proto-oncogene has been successful in the management of gastrointestinal stromal tumor. We investigated the expression of c-kit in 52 cases of small cell carcinoma of the urinary bladder. Specimens with more than 10% of cells demonstrating strong membrane staining were considered to have positive immunostaining for c-kit. c-kit expression was detected in 21 of 52 specimens from these patients. Among the 21 specimens, seven had less than 10% staining, and were considered to be negative. Nine had 11-50% staining, and five had more than 50% staining. Overall, 14 of 52 (27%) small cell carcinomas of the urinary bladder were positive for c-kit expression. During a median follow-up of 11 months, 60% of the patients died of bladder cancer. No association was found between c-kit expression and survival or other clinicopathologic parameters. Five-year cancer-specific survivals for c-kit-positive and c-kit-negative tumors were 9 and 15%, respectively (P=0.36). A significant proportion (27%) of small cell carcinomas of the urinary bladder expressed c-kit, suggesting that it may prove useful as a therapeutic target in small cell carcinoma of the urinary bladder.

Adult↗

PubMed2005

Lymphovascular invasion is an independent prognostic factor in prostatic adenocarcinoma.

PURPOSE: Gleason grade and tumor stage are well established prognostic factors in prostate cancer. Histological demonstration of tumor in lymphovascular spaces has been associated with poor prognosis in many tumor types but it is not included in current prostate cancer grading and staging schemes. Whether lymphovascular invasion is an independent prognostic factor for disease progression in prostate cancer is uncertain. We retrospectively investigated lymphovascular invasion as a predictive factor for biochemical failure and cancer specific survival following radical prostatectomy. MATERIALS AND METHODS: The records of 504 patients with prostatic adenocarcinoma undergoing radical prostatectomy were reviewed for lymphovascular invasion. Clinical followup data were available on 459 cases. Mean followup was 44 months (range 1.5 to 144). Multivariate analysis was performed using the Cox model. RESULTS: Lymphovascular invasion was identified in 106 cases (21%). Univariate analysis showed a significant association between lymphovascular invasion and higher preoperative serum prostate specific antigen (PSA), advanced pathological stage, higher Gleason score, positive surgical margins, extraprostatic extension, seminal vesicle invasion, lymph node metastasis and perineural invasion (each p <0.001). No association was observed between lymphovascular invasion and patient age at surgery, prostate weight or high grade prostatic intraepithelial neoplasia. Lymphovascular invasion was an independent predictor of PSA recurrence (HR 1.6, 95% CI 1.12 to 2.38, p = 0.01) and cancer specific survival (HR 2.75, 95% CI 1.04 to 2.28, p = 0.041) after controlling for tumor stage, surgical margins and Gleason grade on multivariate analysis. Five-year cancer specific survival was 90% in men with lymphovascular invasion compared to 98% in those without lymphovascular invasion (p <0.001). CONCLUSIONS: Lymphovascular invasion can be identified in approximately 20% of prostate cancer cases. Lymphovascular invasion is an independent risk factor for PSA recurrence and cancer death in patients with prostate cancer.

Adenocarcinoma↗

PubMed2005

Visual estimation of tumour extent is not an independent predictor of prostate specific antigen recurrence.

OBJECTIVE: To analyse tumour extent as a predictor of cancer progression after radical prostatectomy (RP), using a multivariate Cox regression model, as several variables (e.g. Gleason grade and tumour stage) are well-established prognostic factors in prostate cancer but it is uncertain if the visual estimation of tumour extent (percentage of carcinoma) is an independent predictor for prostate cancer recurrence. PATIENTS AND METHODS: Tumour extent was estimated in the RP specimens from 504 men with clinically localized prostate cancer; clinical follow-up data were available for 459 men. The mean (range) follow-up was 44.3 (1.5-144) months. Cancer progression was defined by the development of biochemical recurrence, local recurrence, or distant metastasis. Multivariate analysis was used to assess tumour extent as a predictor of cancer progression. RESULTS: Of the 459 patients, 157 had cancer progression; the mean tumour extent was 36% and 24% in those with and without cancer progression, respectively (P < 0.001). Univariate analysis showed a significant association between the visual estimation of tumour extent and tumour stage, Gleason grade, surgical margins, extraprostatic extension, seminal vesicle invasion, lymph node metastasis, and preoperative serum prostate-specific antigen level (all P < 0.001). However, in a multivariate Cox regression model controlling for pathological stage, Gleason score, and surgical margin status, the visual estimation of tumour extent was no longer a significant predictor of cancer progression (P = 0.84). CONCLUSION: The visual estimation of tumour extent was associated with various established prognostic factors for prostate cancer, and with cancer progression in a univariate analysis, but it was not a significant predictor of cancer progression in the multivariate analysis controlling for pathological stage, Gleason score, and surgical margin status.

Adult↗

PubMed2004

Small cell carcinoma of the urinary bladder: a clinicopathologic analysis of 64 patients.

BACKGROUND: Small cell carcinoma of the urinary bladder is an uncommon tumor that has been described in case reports or small series. Herein, the authors report a series of 64 patients with small cell carcinoma of the urinary bladder. METHODS: Histologic slides and medical records from 64 patients with small cell carcinoma of the urinary bladder were reviewed for morphologic, demographic, and clinical data. All patients fulfilled the criteria established for small cell carcinoma according to the World Health Organization classification system. The 2002 tumor, lymph node, and metastasis (TNM) system was used for pathologic staging. The correlations of various clinicopathologic characteristics with survival were analyzed. RESULTS: Patients ranged in age from 36 years to 85 years (mean age, 66 years). The male-to-female ratio was 3.3:1.0. Among patients with clinical information available, 65% had a history of cigarette smoking, and 88% presented with hematuria. All but one patient had muscle-invasive disease at presentation. Thirty-eight patients (59%) underwent cystectomy. Sixty-six percent of patients had lymph node metastasis at the time of cystectomy. Twenty patients (32%) had pure small cell carcinoma, and 44 patients (68%) had small cell carcinoma with other histologic types (35 patients had urothelial carcinoma, 4 patients had adenocarcinoma, 2 patients had sarcomatoid urothelial carcinoma, and 3 patients had both adenocarcinoma and urothelial carcinoma). With a mean follow-up of 21 months, 68% of patients died of bladder carcinoma. None of the clinicopathologic parameters studied (age, gender, presenting symptoms, smoking history, the presence of a nonsmall cell carcinoma component, chemotherapy, or radiation therapy) were associated with survival. No significant survival difference was found between patients who did and did not undergo cystectomy (P = 0.65). Patients who had organ-confined disease had marginally better survival compared with patients who had nonorgan-confined disease (P = 0.06). The overall, 1-year, 18-month, 3-year, and 5-year disease-specific survival rates were 56%, 41%, 23%, and 16%, respectively. CONCLUSIONS: The prognosis for patients with small cell carcinoma of the urinary bladder remains poor, even though the overall survival for patients with bladder carcinoma has improved significantly over the last decade.

Adenocarcinoma↗

PubMed2004

Molecular genetic evidence for different clonal origins of epithelial and stromal components of phyllodes tumor of the prostate.

Phyllodes tumor of the prostate is a rare neoplasm, composed of epithelium-lined cysts and channels embedded in a variably cellular stroma. The pathogenetic relationship of the epithelium and stroma is unknown and whether each is a clonal neoplastic element is uncertain. We studied the clonality of phyllodes tumors from six patients who underwent either enucleation or transurethral resection as their initial treatment. This was followed by total prostatectomy in three of the patients. Laser-assisted microdissection was performed to extract epithelial and stromal components of phyllodes tumor from formalin-fixed, paraffin-embedded tissue. Polymerase chain reaction was used to amplify genomic DNA at specific loci on chromosome 7q31 (D7S522), 8p21.3-q11.1 (D8S133, D8S137), 8p22 (D8S261), 10q23 (D10S168, D10S571), 17p13 (TP53), 16q23.2 (D16S507), 12q11-12 (D12S264), 17q (D17S855), 18p11.22-p11 (D18S53), and 22q11.2 (D22S264). In each tumor, stroma and epithelium were analyzed separately. Gel electrophoresis with autoradiography was used to detect loss of heterozygosity. All tumors showed allelic loss in one or more loci of both the epithelial and stromal components. The frequency of allelic loss in the epithelial component was 2 of 5 (40%) at D7S522, 2 of 6 (33%) at D8S133, 1 of 5 (20%) at D8S137, 3 of 6 (50%) at D8S261, 4 of 4 (100%) at D10S168, 4 of 6 (67%) at TP53, 2 of 6 (33%) at D10S571, 6 of 6 (100%) at D16S507, 1 of 5 (20%) at D12S264, 1 of 6 (17%) at D17S855, 2 of 6 (33%) at D18S53, and 2 of 5 (40%) at D22S264. The frequency of allelic loss in the stromal component was 2 of 5 (40%) at D7S522, 1 of 6 (17%) at D8S133, 2 of 5 (40%) at D8S137, 3 of 6 (50%) at D8S261, 1 of 4 (25%) at D10S168, 3 of 6 (50%) at TP53, 2 of 6 (33%) at D10S571, 3 of 6 (50%) at D16S507, 1 of 5 (20%) at D12S264, 0 of 6 (0%) at D17S855, 1 of 6 (17%) at D18S53, and 0 of 5 (0%) at D22S264. The pattern of allelic loss is significantly different in both stroma and epithelium statistically; completely concordant allelic loss patterns were not seen in any tumor examined. Our data demonstrate that both epithelial and stromal components of phyllodes tumor of the prostate are clonal, supporting the hypothesis that both elements are neoplastic. While both epithelium and stroma are clonal proliferations, they appear to have different clonal origins.

Clone Cells↗

PubMed2004

Low plasma lycopene concentration is associated with increased mortality in a cohort of patients with prior oral, pharynx or larynx cancers.

OBJECTIVE: This analysis was conducted to evaluate the association between plasma beta-carotene, alpha-carotene, lycopene, lutein/zeaxanthin, total carotenoids, retinol, alpha-tocopherol and subsequent mortality. METHODS: Blood samples collected longitudinally from 259 participants in a chemoprevention trial aimed at the prevention of second cancers of the oral cavity, pharynx, or larynx were analyzed by high performance liquid chromatography for selected micronutrients. All-cause mortality (primary outcome) and cause-specific mortality (secondary outcomes) were evaluated in relation to plasma micronutrient concentrations at baseline and longitudinally. RESULTS: A total of 61 deaths occurred over a follow-up time of up to 90 months. Cox proportional hazards models with time-dependent covariates were used for data analyses. In models adjusted for age, plasma cholesterol, time-dependent smoking, treatment arm, study site and gender, only plasma lycopene was significantly inversely associated with total mortality [hazard ratio (HR) above versus below median = 0.53, 95% confidence interval (CI) 0.30-0.93]. Plasma alpha-carotene was inversely associated (HR 0.24, 95% CI 0.08-0.75) while plasma retinol was positively associated (HR 5.12, 95% CI 1.54-17.05) with cardiovascular death. Smoking status modified plasma nutrient associations with total mortality. Lycopene (HR 0.08, 95% CI 0.02-0.36), alpha-carotene (HR 0.25, 95% CI 0.09-0.73) and total carotenoids (HR 0.22, 95% CI 0.07-0.70) were inversely associated with mortality in non-smokers, while plasma retinol (HR = 3.56, 95% CI 1.40-9.09) and alpha-tocopherol (HR = 2.47, 95% CI 1.02-5.98) were positively associated with mortality in smokers. CONCLUSIONS: Only plasma lycopene was significantly associated (inversely) with total mortality in the full study population. Smoking modifies associations between nutrients and mortality.

Antioxidants↗

PubMed2004

Latent pattern mixture models for informative intermittent missing data in longitudinal studies.

A frequently encountered problem in longitudinal studies is data that are missing due to missed visits or dropouts. In the statistical literature, interest has primarily focused on monotone missing data (dropout) with much less work on intermittent missing data in which a subject may return after one or more missed visits. Intermittent missing data have broader applicability that can include the frequent situation in which subjects do not have common sets of visit times or they visit at nonprescheduled times. In this article, we propose a latent pattern mixture model (LPMM), where the mixture patterns are formed from latent classes that link the longitudinal response and the missingness process. This allows us to handle arbitrary patterns of missing data embodied by subjects' visit process, and avoids the need to specify the mixture patterns a priori. One assumption of our model is that the missingness process is assumed to be conditionally independent of the longitudinal outcomes given the latent classes. We propose a noniterative approach to assess this key assumption. The LPMM is illustrated with a data set from a health service research study in which homeless people with mental illness were randomized to three different service packages and measures of homelessness were recorded at multiple time points. Our model suggests the presence of four latent classes linking subject visit patterns to homeless outcomes.

Biometry↗

PubMed2003

The interacting binding domains of the beta(4) integrin and calcium-activated chloride channels (CLCAs) in metastasis.

CLCA (chloride channel, calcium-activated) proteins are novel pulmonary vascular addresses for blood-borne, lung-metastatic cancer cells. They facilitate vascular arrest of cancer cells via adhesion to beta4 integrin and promote early, intravascular, metastatic growth. Here we identify the interacting binding domains of endothelial CLCA proteins (e.g. hCLCA2, mCLCA5, mCLCA1, and bCLCA2) and beta4 integrin. Endothelial CLCAs share a common beta4-binding motif (beta4BM) in their 90- and 35-kDa subunits of the sequence F(S/N)R(I/L/V)(S/T)S, which is located in the second extracellular domain of the 90-kDa CLCA and near the N terminus of the 35-kDa CLCA, respectively. Using enzyme-linked immunosorbent, pull-down, and adhesion assays, we showed that glutathione S-transferase fusion proteins of beta4BMs from the 90- and 35-kDa CLCA subunits bind to the beta4 integrin in a metal ion-dependent manner. Fusion proteins from fibronectin and the integrins beta1 and beta3 served as negative controls. beta4BM fusion proteins competitively blocked the beta4/CLCA adhesion and prevented lung colonization of MDA-MB-231 breast cancer cells. A disrupted beta4BM in hCLCA1, which is not expressed in endothelia, failed to interact with beta4 integrin. The corresponding CLCA-binding domain of the beta4 integrin is localized to the specific determining loop (SDL). Again enzyme-linked immunosorbent, pull-down, and adhesion assays were used to confirm the interaction with CLCA proteins using a glutathione S-transferase fusion protein representing the C-terminal two-thirds of beta4 SDL (amino acids 184-203). A chimeric beta4 integrin in which the indicated SDL sequence had been replaced with the corresponding sequence from the beta1 integrin failed to bind hCLCA2. The dominance of the CLCA ligand in beta4 activation and outside-in signaling is discussed in reference to our previous report that beta4/CLCA ligation elicits selective signaling via focal adhesion kinase to promote metastatic growth.

Amino Acid Motifs↗

PubMed2003

Development of the Yale Children's Global Stress Index (YCGSI) and its application in children and adolescents ith Tourette's syndrome and obsessive-compulsive disorder.

OBJECTIVE: The Yale Children's Global Stress Index (YCGSI) is a new clinical rating instrument designed to provide objective global clinician ratings of psychosocial stress in studies of children and adolescents. This study was designed to evaluate the psychometric properties of the YCGSI. METHOD: Independent ratings of clinical severity and psychosocial stress were obtained at two time points separated by 4 months from 33 subjects with Tourette's syndrome (TS) and/or early-onset obsessive-compulsive disorder (OCD), aged 7 to 17 years, and 25 age-matched control subjects. Parents and children were interviewed separately. Multiple measures of stress were obtained including the YCGSI and the Daily Life Stressors Scale (DLSS). RESULTS: Data support the interrater reliability and convergent and divergent validity of the YCGSI. At both time points, children and adolescents with TS and OCD had, on average, experienced significantly more psychosocial stress than did the controls. Cross-sectional ratings of tic and obsessive-compulsive symptom severity did not correlate with the YCGSI, but did correlate with self-report ratings of stress on the DLSS. In contrast, ratings on the YCGSI were associated with clinician ratings of depression. CONCLUSIONS: The YCGSI has acceptable psychometric properties. Children and adolescents with TS and OCD appear to be at increased risk of experiencing higher levels of psychosocial stress and adversities compared with their peers in the community. Future studies need to examine the possible differential contributions of distinctive forms of stress on the intramorbid course of these disorders.

Adolescent↗

PubMed2002

Maximum likelihood estimation in the joint analysis of time-to-event and multiple longitudinal variables.

Joint modelling of longitudinal and survival data has received much attention in recent years. Most have concentrated on a single longitudinal variable. This paper considers joint modelling in the presence of multiple longitudinal variables. We explore direct association of time-to-event and multiple longitudinal processes through a frailty model and use a mixed effects model for each of the longitudinal variables. Correlations among the longitudinal variables are induced through correlated random effects. We allow effects of categorical and continuous covariates on both longitudinal and time-to-event responses and explore interactions between the longitudinal variables and other covariates on time-to-event. Estimates of the parameters are obtained by maximizing the joint likelihood for the longitudinal variable processes and the event process. We use a one-step-late EM algorithm to handle the direct dependence of the event process on the modelled longitudinal variables along with the presence of other fixed covariates in both processes. We argue that such a joint analysis with multiple longitudinal variables is advantageous to one with only a single longitudinal variable in revealing interplay among multiple longitudinal variables and the time-to-event.

Head and Neck Neoplasms↗

PubMed2002

Assessment of symptom exacerbations in a longitudinal study of children with Tourette's syndrome or obsessive-compulsive disorder.

OBJECTIVES: The severity of tic and obsessive-compulsive (OC) symptoms varies over time. Consequently, how do we, as clinicians, know when a change in symptom severity occurs that falls outside of the normal range of fluctuation? The goal of this study was to describe the level of symptom severity fluctuation over time and to establish an objective, prospective, and quantitative method for identifying symptom exacerbations in children with Tourette's syndrome, obsessive-compulsive disorder (OCD), or both. A second major aim was to assess whether fluctuations in tic and OC symptom severity covaried with one another. METHOD: Monthly consecutive Yale Global Tic Severity Scale and Children's Yale-Brown Obsessive Compulsive Scale scores were prospectively obtained in 64 children diagnosed with Tourette's syndrome and/or OCD for periods ranging from 3 to 39 months. Exacerbation thresholds were estimated by using state-of-the-art bootstrap methods. These thresholds were then independently evaluated by asking two expert clinicians to identify, retrospectively, clinically significant exacerbations based on a review of all available clinical and research records. RESULTS: The severity of tic and OC symptoms displayed a high degree of intrasubject variability. Exacerbation thresholds, which incorporated the change score from the previous month and the current symptom score, provided the best agreement with those of expert clinicians. When both tic and OC symptoms were present, they showed a significant degree of covariation. CONCLUSIONS: Evidence-based treatments are coming of age. The use of valid, clinician-rated severity scales will likely become a standard part of clinical practice. Bootstrapping methods may provide a quantitative and convenient way to obtain clinically valid thresholds to assess tic and OC symptom exacerbations. This method has the potential to be applied to other symptom domains where exacerbation thresholds are needed.

Adolescent↗

PubMedDate not supplied

P53 expression in small cell carcinoma of the urinary bladder: biological and prognostic implications.

Small cell carcinoma of the urinary bladder is a rare and highly aggressive tumor. P53 expression has been shown to be associated with poor prognosis in a variety of tumors. This study was undertaken to investigate p53 expression in a large series of small cell carcinomas of the urinary bladder and to correlate the findings with clinicopathologic parameters and clinical outcome. Pathologic findings were reviewed and were correlated with clinical findings and follow-up information. Immunohistochemical staining for p53 was performed on paraffin-embedded tissue sections using the avidin-biotin-peroxidase method. Results were recorded as positive expression (> or =10% of cells with nuclear staining) or negative expression (<10% of cells with nuclear staining). The series included 40 males and 10 females. All 50 patients except one had advanced disease (T2 or above) at presentation. Pathologic stages were as follows: T1 in 1, T2 in 25, T3 in 21, and T4 in 3 patients. During a median follow-up of 12 months (range: 1 month to 122 months), 38 patients died of cancer. Two-year and 5-year cancer-specific survival rates were 45% and 16%, respectively. P53 overexpression was present in 27 out of 50 (54%) cases (7 with 10-25% staining, 4 with 25-50% staining, 11 with 50-75% staining and 5 with 75-100% staining); conversely, negative staining for p53 was observed in 23 out of 50 (46%) cases (19 with no staining and 4 with <10% staining). No correlation was demonstrated between the level of p53 expression and survival (p =0. 16). The 5-year cancer-specific survival was 16.6% for patients with tumors expressing p53 in greater than or equal to 10% of cells and was 14.7% for patients with tumors expressing p53 in less than 10% of tumor cells. There was no correlation between p53 expression and other clinicopathologic characteristics, including age (p =0.20), gender (p=0.84), history of smoking (p=0.25), pathologic Tstage (p=0.38), clinical stage (p=0.60), lymph node metastasis (p=0.17), and distant metastasis (p=0.88). Our data indicate that p53 is frequently expressed in small cell carcinoma of the urinary bladder. However, no correlation is found between p53 expression and clinicopathologic parameters, including long-term survival.

Adult↗