A validated web-based tool to display individualised Crohn's disease predicted outcomes based on clinical, serologic and genetic variables.

BACKGROUND: Early treatment for Crohn's disease (CD) with immunomodulators and/or anti-TNF agents improves outcomes in comparison to a slower 'step up' algorithm. However, there remains a limited ability to identify those who would benefit most from early intensive therapy. AIM: To develop a validated, individualised, web-based tool for patients and clinicians to visualise individualised risks for developing Crohn's disease complications. METHODS: A well-characterised cohort of adult patients with CD was analysed. Available data included: demographics; clinical characteristics; serologic immune responses; NOD2 status; time from diagnosis to complication; and medication exposure. Cox proportional analyses were performed to model the probability of developing a CD complication over time. The Cox model was validated externally in two independent CD cohorts. Using system dynamics analysis (SDA), these results were transformed into a simple graphical web-based display to show patients their individualised probability of developing a complication over a 3-year period. RESULTS: Two hundered and forty three CD patients were included in the final model of which 142 experienced a complication. Significant variables in the multivariate Cox model included small bowel disease (HR 2.12, CI 1.05-4.29), left colonic disease (HR 0.73, CI 0.49-1.09), perianal disease (HR 4.12, CI 1.01-16.88), ASCA (HR 1.35, CI 1.16-1.58), Cbir (HR 1.29, CI 1.07-1.55), ANCA (HR 0.77, CI 0.62-0.95), and the NOD2 frameshift mutation/SNP13 (HR 2.13, CI 1.33-3.40). The Harrell's C (concordance index for predictive accuracy of the model) = 0.73. When applied to the two external validation cohorts (adult n = 109, pediatric n = 392), the concordance index was 0.73 and 0.75, respectively, for adult and pediatric patients. CONCLUSIONS: A validated, web-based tool has been developed to display an individualised predicted outcome for adult patients with Crohn's disease based on clinical, serologic and genetic variables. This tool can be used to help providers and patients make personalised decisions about treatment options.

[Opioids in musculoskeletal pain]. / Opioide bei muskuloskelettalen Schmerzen.

Opioids are the most potent analgesics available and are well established for the treatment of severe acute, surgical and cancer pain. Due to their high effectiveness, their use in chronic non-cancer pain (CNCP) is being propagated. However, the use of opioids is still controversial due to their side effects, such as tolerance, addiction or withdrawal, and administrative difficulties associated with their prescription. Chronic rheumatic diseases, in particular low back pain and arthritis, are the leading causes of CNCP. The present article provides a brief overview of the role of opioids in chronic rheumatic diseases, pointing out that a national guideline for opioid use in CNCP is expected at the end of 2008. Furthermore, the peripheral effects of opioids on pain and inflammation in rheumatic diseases will be outlined.

Predictors of operative time in multicenter port-access valve registry: institutional differences in learning.

BACKGROUND: The predictors of operative time and the effects of learning in isolated valve operations using port-access techniques have not been defined. METHODS: Analysis of covariance was used to examine the determinants of procedure time, pump time, and aortic clamp time. In the largest prospective, registry of patients undergoing isolated aortic valve replacement (AVR, N=199), mitral repair (MVP, N=307), or mitral replacement (MVR, N=232) using port-access techniques 1997-1999 at 27 institutions. RESULTS: Institutional case volume ranged from one to 214 (median 6). Operative time was longer in redo procedures (5.3 +/- 1.6 vs. 4.4 +/- 1.3 hr, p = 0.0001), longer with MVP or MVR vs. AVR (4.8 +/- 1.2 vs. 5.0 +/- 1.5 vs. 3.8 +/- 1.2 hr, p = 0.0001), and decreased with case number (mean decrease 1.00 +/- 0.19 min/case, p = 0.04). Operative time also varied between institutions (p = 0.001). Rate of learning (decrease in time per case) varied significantly between institutions only for MVP (p = 0.03). Similar analysis showed that pump time and clamp times did not significantly change over time (p > 0.17) but varied significantly between institutions. Institutional volume did not affect operative, pump, or clamp times or rate of learning (decrease in operative time/case). CONCLUSIONS: These prospective registry data demonstrate that, for port-access valve procedures, procedure times continue to improve (learning) even after 100 cases. Procedure time and learning are affected by institutional differences and by the type of procedure, but are little affected by institutional volume. This data provides a model to understand learning of new surgical procedures, and this data suggests that port-access valve procedures can be mastered by a variety of institutions.

Phonological processing in reading Chinese among normally achieving and poor readers.

Ninety-four children in grades one to six (7 to 12 years old) in Hong Kong were individually administered a Chinese reading test consisting of 80 characters that varied in frequency (high or low) and orthographic structure (simple or complex). Phonological processing tasks, including short-term memory, pseudo-character recognition, and tone discrimination, were also administered. During reading, younger normal and poor readers made more semantic and visual errors, whereas older and normally achieving children made more phonologically related errors. Normally achieving readers also performed at a higher level than poor readers on short-term memory, pseudo-character recognition, and tone discrimination tasks. Phonological processing apparently plays a significant part in the development of reading skills in Chinese.

Short-term memory, working memory, and inhibitory control in children with difficulties in arithmetic problem solving.

The relations between short-term memory, working memory, inhibitory control, and arithmetic word problem solution were studied in children who were poor in arithmetic problem solving (n = 23). The children were compared with a group of good problem solvers (n = 26), matched for vocabulary, age, and gender. The results corroborate the hypothesis of poor problem solvers' general deficit in inhibitory processes. They had lower scores and made more intrusion errors in a series of working memory tasks requiring inhibition of irrelevant information. The results showed that problem solving performance is related to the ability of reducing the accessibility of nontarget and irrelevant information in memory. Span tasks that imply passive storage of information showed that poor problem solvers were impaired when they have to retain numerical information, but they did not differ from children who did not have difficulty with mathematics when the material included words.

Speech perception, lexicality, and reading skill.

This study examined the interaction between speech perception and lexical information among a group of 7-year-old children, of which 26 were poor readers and 36 were good readers. The children's performance was examined on tasks assessing reading skill, phonological awareness, pseudoword repetition, and phoneme identification. Although good readers showed clearly defined categorical perception in the phoneme identification task for both the /bif/-/pif/ and the /bis/-/pis/ continua, the category boundary for /bif/-/pif/ was at longer VOTs than the boundary for /bis/-/pis/, which characterizes the classic lexicality effect. Poor readers showed less sharply defined categorical perception on both continua. Although poor readers did not show the classic lexicality effect, lexicality did affect the overall rate with which phonemes were identified as /b/ or /p/ at each VOT. These findings suggest that the lexicon may operate as a compensatory mechanism for resolving ambiguities in speech perception. Furthermore, statistical correction for group differences in phoneme identification made group differences in phoneme deletion disappear, suggesting that deficits in speech perception may play a causal role in the phonological core deficit associated with reading failure.

Predictors of outcome in a multicenter port-access valve registry.

BACKGROUND: The aim of this study was to examine the predictors of outcome in patients undergoing isolated valve operation using port-access techniques. METHODS: Logistic regression analysis was performed in a prospective, multi-institutional registry of patients undergoing isolated aortic valve replacement (AVR, n = 252), mitral repair (MVP, n = 491), or mitral replacement (MVR, n = 568) using port-access techniques from 1997 to 1999. RESULTS: Endoaortic balloon occlusion was used in 2% (AVR), 93% (MVP), and 90% (MVR) of cases. Conversion to full sternotomy occurred in 3.8% of all cases. For all patients, early mortality was 50 of 1,311 (3.8%) and onset of new atrial fibrillation occurred in 140 of 1,311 (11%) patients. The determinants of 30-day mortality were redo, age, and MVR or AVR. The determinants of reoperation for bleeding were age, reoperation, and MVR. Age was a predictor for stroke, and age and low or medium volume center were predictors of new atrial fibrillation. CONCLUSIONS: Excellent short-term results can be obtained using port-access techniques in isolated mitral or aortic valve operations. Patient outcome is not related to institutional case volume, and the primary determinants of outcome after port-access valve procedures are generally patient-related factors.

Institutional variability in red blood cell conservation practices for coronary artery bypass graft surgery. Institutions of the MultiCenter Study of Perioperative Ischemia Research Group.

OBJECTIVE: To assess whether substantial institutional variability exists in red blood cell conservation practices associated with coronary artery bypass graft (CABG) surgery. DESIGN: Prospective, randomized patient enrollment and data collection. SETTING: Twenty-four U.S. academic institutions participating in the Multicenter Study of Perioperative Ischemia. PARTICIPANTS: A well-defined subset of primary CABG surgery patients (n = 713) expected to be at low risk for bleeding and exposure to allogeneic transfusion. INTERVENTIONS: None (observational study). MEASUREMENTS AND MAIN RESULTS: Frequency of use of red blood cell conservation techniques was determined among institutions. Correlation was determined between use of each technique and transfusion of allogeneic red blood cells and between use of each technique and median institutional blood loss. Significant variability (p < 0.01) was detected in institutional transfusion practice with respect to the use of predonated autologous whole blood, normovolemic hemodilution, red cell salvage, and reinfusion of shed mediastinal blood. The frequency of institutional use of these techniques was not associated with allogeneic transfusion (r2 < 0.15) or blood loss (r2 < 0.10) in the low-risk population of patients examined. CONCLUSIONS: Institutions vary significantly in perioperative blood conservation practices for CABG surgery. Further study to determine the appropriate use of these techniques is warranted.

Platelet-rich plasma sequestration, with therapeutic platelet yields, reduces allogeneic transfusion in complex cardiac surgery.

UNLABELLED: Platelet dysfunction is the most common cause of nonsurgical bleeding after cardiopulmonary bypass (CPB). We hypothesized that reinfusion of a therapeutic quantity of platelets sequestered before CPB would decrease the need for allogeneic platelet transfusion, as well as decrease bleeding and total allogeneic transfusion, in cardiac surgery patients at moderately high risk for bleeding. Fifty-five patients undergoing either reoperative coronary artery bypass (CABG) or combined CABG and valve replacement were randomized to control or platelet-rich plasma sequestration (pheresis) groups. All patients received intraoperative epsilon-aminocaproic acid infusions. There was no significant difference between groups with respect to preoperative characteristics, duration of CPB, or target postoperative hematocrit. Mean platelet yields were 6.2 +/- 2.1 units (3.1 x 10(11) platelets). Mean pheresis time was 44 min. Allogeneic platelets (range = 6-12 units) were transfused to 28% of control patients, compared with 0% of pheresis patients (P < 0.01). Allogeneic packed red blood cells were transfused to 45% of control patients (1.2 units per patient) versus 31% of pheresis patients (0. 7 unit per patient) (P = 0.35). Total allogeneic units transfused were significantly reduced in the pheresis group (P < 0.02). Mediastinal chest tube drainage was not significantly decreased in the pheresis group. In this prospective, randomized study, therapeutic platelet yields were obtained before CPB. In contrast with recent studies with low platelet yields, these data support the conclusion that platelet-rich plasma sequestration is effective in reducing allogeneic platelet transfusions and total allogeneic units transfused in cardiac surgery patients at moderately high risk for post-CPB coagulopathy and bleeding. IMPLICATIONS: Transfusion of allogeneic blood products, including platelets, is common during complex cardiac surgical procedures. In the present prospective, randomized study, a significant reduction in allogeneic platelet transfusion and total allogeneic units transfused was observed after the reinfusion of a therapeutic quantity of autologous platelets sequestered before cardiopulmonary bypass.

Working memory, inhibitory control, and reading disability.

The relationships among working memory, inhibitory control, and reading skills were studied in 966 individuals, 6-49 years old. In addition to a standardized measure of word recognition, they received a working memory (listening span) task in the standard, blocked format (three sets containing two-, three-, or four-item trials) or in a mixed format (three sets each containing two-, three-, and four-item trials) to determine whether scores derived from the standard format are influenced by proactive interference. Intrusion errors were investigated in order to determine whether deficits in working memory were associated with the access, deletion, or restraint functions of inhibitory control. The results indicated that deficits in working memory were characteristic of individuals with reading disabilities at all ages. These deficits may be associated with the access and restraint functions of inhibition. Working memory skills increased until the age of 19. The blocked format showed a gradual decline in adulthood whereas the mixed format did not. The different patterns suggest that the decline in working memory skills associated with aging may result from growing inefficiencies in inhibitory control, and not diminished capacity.

A replication study of obsessional followers and offenders with mental disorders.

The purpose of this study was to compare certain demographic, clinical, and criminal variables within subgroups of obsessional followers, and compare them to a group of offenders with mental disorders to attempt to replicate earlier findings. A static group archival design utilized a non-random group of convenience and a randomly selected comparison group. Sixty-five obsessional followers and 65 offenders with mental disorders were evaluated by psychiatrists and psychologists for court ordered reasons during their criminal proceedings. Both groups were evaluated during the same period, in the same court diagnostic clinic, and generally for sentencing determinations. The obsessional followers were measured on demographic, diagnostic, pursuit, victim, threat, violence, emotional, motivational, and defense variables. Inferential comparisons that used parametric and nonparametric statistics were done within and between groups on select variables. The obsessional followers had significantly greater estimated IQ than the offenders with mental disorders, but were neither older nor better educated. There were no significant differences in the high prevalence of both DSM-IV Axis I and II diagnoses. Obsessional followers who stalked prior sexual intimates were significantly more likely to have a substance abuse or dependence diagnosis. Obsessional followers who stalked strangers or acquaintances were more likely to be delusional. The majority of the obsessional followers, primarily motivated by anger, both threatened and were violent toward person or property. The modal obsessional follower is an average or above IQ, unemployed, unmarried male in his fourth decade of life. chronically pursuing a prior sexually intimate female. He is diagnosed with substance abuse or dependence and a personality disorder NOS, and has a prior psychiatric, criminal and substance abuse history. He is angry, likely to threaten her, and assault her person or property without causing serious injury.

Gemcitabine and vinorelbine in advanced nonsmall cell lung carcinoma: a phase II study.

BACKGROUND: The authors conducted a Phase II study to evaluate the activity of the combination of gemcitabine and vinorelbine in patients with advanced nonsmall cell lung carcinoma (NSCLC). METHODS: Patients were eligible if they had Stage IIIB (malignant pleural effusion) or Stage IV NSCLC, no prior chemotherapy, and Cancer and Leukemia Group B performance status (PS) 0-2. Patients with brain metastases were eligible if they were neurologically stable after brain irradiation. Thirty-three patients from participating institutions were enrolled. One patient was ineligible due to untreated brain metastases. Patients were treated with gemcitabine 1250 mg/m(2) over 30 minutes (1000 mg/m(2) for the first 6 patients) and vinorelbine 25 mg/m(2) over 6 minutes, both administered intravenously on Days 1 and 8 every 21 days. Treatment was planned for a total of six cycles or more if the patient had persistent benefit. Growth factors were not allowed. RESULTS: Among all 32 eligible patients, there were 8 partial responses, for an overall response rate of 25% (95% confidence interval [CI], 11.5-43. 4%). The median survival time was 8.3 months and the 1-year survival rate was 38% (95% CI, 24-59%). Patients with PS 0-1 had a median survival of 11.7 months and a 1-year survival rate of 48%. Grade 3 and 4 neutropenia was observed in 13% and 25% of the 148 treatment cycles, respectively. One patient died of neutropenic sepsis. Only 2 episodes of Grade 3 and 4 thrombocytopenia were observed. Nonhematologic toxicity was minimal. CONCLUSIONS: Gemcitabine and vinorelbine is an active and well-tolerated regimen in patients with advanced NSCLC, with response and survival rates at least comparable to those achieved with standard platinum-based regimens. This combination may be particularly suitable for the elderly or for patients who cannot tolerate more toxic platinum-based regimens.

Posttraumatic stress disorder in children and adolescents: a review and analysis.

Only recently has the mental health community recognized the applicability of diagnostic criteria for posttraumatic stress disorder (PTSD) in children and adolescents, including a consideration of specific age-related features. This paper provides a current review of the literature on PTSD pertaining to children and adolescents. Following a discussion of issues on diagnostic criteria and assessment of this affective disorder in this population, there is an overview of the existing literature on prevalence, comorbidity, risk factors, parental and family factors, and issues of gender and age of onset. The remainder of the paper focuses on the range of traumatic stressors in children and adolescents that can result in PTSD, including natural or human disasters, war and violence, chronic or life-threatening medical conditions, community violence and the witnessing of traumatic events, and physical and/ or sexual abuse and other forms of interpersonal violence. Throughout the paper, there is an emphasis on the importance of considering developmental factors. Finally, implications of the existing literature for future areas of research are addressed.

Conceptualizing mental disorders in children: where have we been and where are we going?

Conceptions of mental illness in children are bound by cultural and social conventions of what constitutes healthy and unhealthy development. To understand current conceptualizations of disorders in children, we review the history of these conceptualizations from three intertwined perspectives: a sociopolitical history of American children and families, the history of the mental health fields and scientific disciplines involved in diagnosing children, and the evolution of children's role in the Diagnostic and Statistical Manual of Mental Disorders. We review where the field has been in its conception of childhood mental illness throughout the past century, where we believe it is now, and raise questions about the direction in which child diagnosis may be headed as we enter the new millennium. We conclude with social policy recommendations based on theory and research regarding mental disorders in children.

Safety and efficacy of shed mediastinal blood transfusion after cardiac surgery: a multicenter observational study. Multicenter Study of Perioperative Ischemia Research Group.

OBJECTIVE: To examine the efficacy and safety of shed mediastinal blood (SMB) transfusion in preventing allogenic red blood cell (RBC) transfusion. DESIGN: An observational clinical study. SETTING: Twelve US academic medical centers. PARTICIPANTS: Six hundred seventeen patients undergoing elective primary coronary artery bypass grafting. INTERVENTIONS: Patients were administered SMB transfusion or not, according to institutional and individual practice, without random assignment. MEASUREMENTS AND RESULTS: The independent effect of SMB transfusion on postoperative RBC transfusion was examined by multivariable modeling. Potential complications of SMB transfusion, such as bleeding and infection, were examined. Three hundred twelve of the study patients (51%) received postoperative SMB transfusion (mean volume, 554 +/- 359 mL). Patients transfused with SMB had significantly lower volumes of RBC transfusion than those not receiving SMB (0.86 +/- 1.50 v 1.08 +/- 1.65 units; p < 0.05). However, multivariable analysis showed that SMB transfusion was not predictive of postoperative RBC transfusion. Demographic factors (older age, female sex), institution, and postoperative events (greater chest tube drainage, lower hemoglobin level on arrival to the intensive care unit, and use of inotropes) were significant predictors of RBC transfusion. The volume of chest tube drainage on the operative day (707 +/- 392 v 673 +/- 460 mL; p = 0.30), reoperation for hemorrhage (3.1% v2.5%; p = 0.68), and overall frequency of infection (5.8% v 6.6%; p = 0.81) were similar between patients receiving and not receiving SMB, respectively. However, in patients who did not receive allogenic RBC transfusion, there was a significantly greater frequency of wound infection in the SMB group (3.6% v0%; p = 0.02). CONCLUSION: These data suggest that SMB is ineffective as a blood conservation method and may be associated with a greater frequency of wound infection.

Noninvasive positive-pressure ventilation facilitates tracheal extubation after laryngotracheal reconstruction in children.

Tracheal extubation after laryngotracheal reconstruction in children may be complicated by postoperative tracheal edema and pulmonary dysfunction. The replacement of a tracheal tube in this situation may exacerbate the existing injury to the tracheal mucosa, complicating subsequent attempts at tracheal extubation. We present two cases where noninvasive positive-pressure ventilation was employed to treat partial airway obstruction and respiratory failure in two children following laryngotracheal reconstruction. Noninvasive positive-pressure ventilation served as a bridge between mechanical ventilation via a tracheal tube and spontaneous breathing, providing airway stenting and ventilatory support while tracheal edema and pulmonary dysfunction were resolved. Under appropriate conditions, noninvasive positive-pressure ventilation may be useful in the management of these patients.

Adhesive capsulitis: a sticky issue.

The shoulder is a very complex joint that is crucial to many activities of daily living. Decreased shoulder mobility is a serious clinical finding. A global decrease in shoulder range of motion is called adhesive capsulitis, referring to the actual adherence of the shoulder capsule to the humeral head. Adhesive capsulitis is a syndrome defined as idiopathic restriction of shoulder movement that is usually painful at onset. Secondary causes include alteration of the supporting structures of and around the shoulder, and autoimmune, endocrine or other systemic diseases. The three defined stages of this condition are the painful stage, the adhesive stage and the recovery stage. Although recovery is usually spontaneous, treatment with intra-articular corticosteroids and gentle but persistent physical therapy may provide a better outcome, resulting in little functional compromise.