Antecedents, psychiatric characteristics and follow-up of adolescents hospitalized for suicide attempt of overwhelming suicidal ideation.

OBJECTIVES: To evaluate the socio-demographic as well as the health and psychiatric profiles of adolescents hospitalised for suicide attempt or overwhelming suicide ideation and to assess repetition of suicide attempt over a period of 18 months. PATIENTS AND METHODS: Between April 2000 and September 2001, all patients aged 16 to 21 years admitted to the University Hospitals of Geneva and Lausanne for suicide attempt or ideation were included in the study. At this time (T0) semi-structured face to face interviews were conducted to identify socio-demographic data, mental health and antecedents regarding suicidal conducts. Current psychiatric status was assessed with the MINI (Mini International Neuropsychiatric Instrument). At T1 and T2, reassessments included psychiatric status (MINI) as well as lifestyles, socio-professional situation and suicidal behaviours. RESULTS: At T0, 269 subjects met the study criteria, among whom 83 subjects (56 girls and 27 boys) left the hospital too quickly to be involved or refused to participate in the study (final sample at T0: 149 girls; 37 boys). The participation rate at T1 and T2 was respectively 66% and 62% of the original sample. The percentage of adolescents meeting the criteria for psychiatric diagnoses (91%) was high: affective disorder (78%); anxiety disorder (64%); substance use disorder (39%); eating disorder (9%); psychotic disorder (11%); antisocial personality (7%) with most subjects (85%) having more than one disorder. Around 90% of the subjects interviewed at T1, and/or T2, had received follow-up care after their hospitalisation, either by a primary care physician or a psychotherapist or both. Two subjects died of violent death and 18% made a further suicide attempt. CONCLUSION: Most adolescents hospitalised for suicidal episodes suffer from psychiatric problems which should be addressed by a careful psychiatric assessment, followed up if needed by a structured after care plan.

Development of mental disorders one year after exposure to psychosocial stressors; a cohort study in primary care patients with a physical complaint.

BACKGROUND: Mental disorders, common in primary care, are often associated with physical complaints. While exposure to psychosocial stressors and development or presence of principal mental disorders (i.e. depression, anxiety and somatoform disorders defined as multisomatoforme disorders) is commonly correlated, temporal association remains unproven. The study explores the onset of such disorders after exposure to psychosocial stressors in a cohort of primary care patients with at least one physical symptom. METHOD: The cohort study SODA (SOmatization, Depression and Anxiety) was conducted by 21 private-practice GPs and three fellow physicians in a Swiss academic primary care centre. GPs included patients via randomized daily identifiers. Depression, anxiety or somatoform disorders were identified by the full Patient Health Questionnaire (PHQ), a validated procedure to identify mental disorders based on DSM-IV criteria. The PHQ was also used to investigate exposure to psychosocial stressors (before the index consultation and during follow up) and the onset of principal mental disorders after one year of follow up. RESULTS: From November 2004 to July 2005, 1020 patients were screened for inclusion. 627 were eligible and 482 completed the PHQ one year later and were included in the analysis (77%). At one year, prevalence of principal mental disorders was 30/153 (19.6% CI95% 13.6; 26.8) for those initially exposed to a major psychosocial stressor and 26/329 (7.9% CI95% 5.2; 11.4) for those not. Stronger association exists between psychosocial stressors and depression (RR = 2.4) or anxiety (RR = 3.5) than multisomatoforme disorders (RR = 1.8). Patients who are "bothered a lot" (subjective distress) by a stressor are therefore 2.5 times (CI95% 1.5; 4.0) more likely to experience a mental disorder at one year. A history of psychiatric comorbidities or psychological treatment was not a confounding factor for developing a principal mental disorder after exposure to psychosocial stressors. CONCLUSION: This primary care study shows that patients with physical complaints exposed to psychosocial stressors had a higher risk for developing mental disorders one year later. This temporal association opens the field for further research in preventive care for mental diseases in primary care patients.

Correlation between microtensile bond strength data and clinical outcome of Class V restorations.

OBJECTIVE: To determine if the results of resin-dentin microtensile bond strength (µTBS) is correlated with the outcome parameters of clinical studies on non-retentive Class V restorations. METHODS: Resin-dentin µTBS data were obtained from one test center; the in vitro tests were all performed by the same operator. The µTBS testing was performed 8h after bonding and after 6 months of storing the specimens in water. Pre-test failures (PTFs) of specimens were included in the analysis, attributing them a value of 1MPa. Prospective clinical studies on cervical restorations (Class V) with an observation period of at least 18 months were searched in the literature. The clinical outcome variables were retention loss, marginal discoloration and marginal integrity. Furthermore, an index was formulated to be better able to compare the laboratory and clinical results. Estimates of adhesive effects in a linear mixed model were used to summarize the clinical performance of each adhesive between 12 and 36 months. Spearman correlations between these clinical performances and the µTBS values were calculated subsequently. RESULTS: Thirty-six clinical studies with 15 adhesive/restorative systems for which µTBS data were also available were included in the statistical analysis. In general 3-step and 2-step etch-and-rinse systems showed higher bond strength values than the 2-step/3-step self-etching systems, which, however, produced higher values than the 1-step self-etching and the resin modified glass ionomer systems. Prolonged water storage of specimens resulted in a significant decrease of the mean bond strength values in 5 adhesive systems (Wilcoxon, p<0.05). There was a significant correlation between µTBS values both after 8h and 6 months of storage and marginal discoloration (r=0.54 and r=0.67, respectively). However, the same correlation was not found between µTBS values and the retention rate, clinical index or marginal integrity. SIGNIFICANCE: As µTBS data of adhesive systems, especially after water storage for 6 months, showed a good correlation with marginal discoloration in short-term clinical Class V restorations, longitudinal clinical trials should explore whether early marginal staining is predictive for future retention loss in non-carious cervical restorations.

Patterns of pain-free response in 497 cases of classic trigeminal neuralgia treated with Gamma Knife surgery and followed up for least 1 year.

Object The goal of this study was to establish whether clear patterns of initial pain freedom could be identified when treating patients with classic trigeminal neuralgia (TN) by using Gamma Knife surgery (GKS). The authors compared hypesthesia and pain recurrence rates to see if statistically significant differences could be found. Methods Between July 1992 and November 2010, 737 patients presenting with TN underwent GKS and prospective evaluation at Timone University Hospital in Marseille, France. In this study the authors analyzed the cases of 497 of these patients, who participated in follow-up longer than 1 year, did not have megadolichobasilar artery- or multiple sclerosis-related TN, and underwent GKS only once; in other words, the focus was on cases of classic TN with a single radiosurgical treatment. Radiosurgery was performed with a Leksell Gamma Knife (model B, C, or Perfexion) using both MR and CT imaging targeting. A single 4-mm isocenter was positioned in the cisternal portion of the trigeminal nerve at a median distance of 7.8 mm (range 4.5-14 mm) anterior to the emergence of the nerve. A median maximum dose of 85 Gy (range 70-90 Gy) was delivered. Using empirical methods and assisted by a chart with clear cut-off periods of pain free distribution, the authors were able to divide patients who experienced freedom from pain into 3 separate groups: patients who became pain free within the first 48 hours post-GKS; those who became pain free between 48 hours and 30 days post-GKS; and those who became pain free more than 30 days after GKS. Results The median age in the 497 patients was 68.3 years (range 28.1-93.2 years). The median follow-up period was 43.75 months (range 12-174.41 months). Four hundred fifty-four patients (91.34%) were initially pain free within a median time of 10 days (range 1-459 days) after GKS. One hundred sixty-nine patients (37.2%) became pain free within the first 48 hours (Group PF(≤ 48 hours)), 194 patients (42.8%) between posttreatment Day 3 and Day 30 (Group PF((>48 hours, ≤ 30 days))), and 91 patients (20%) after 30 days post-GKS (Group PF(>30 days)). Differences in postoperative hypesthesia were found: in Group PF(≤ 48 hours) 18 patients (13.7%) developed postoperative hypesthesia, compared with 30 patients (19%) in Group PF((>48 hours, ≤ 30 days)) and 22 patients (30.6%) in Group PF(>30 days) (p = 0.014). One hundred fifty-seven patients (34.4%) who initially became free from pain experienced a recurrence of pain with a median delay of 24 months (range 0.62-150.06 months). There were no statistically significant differences between the patient groups with respect to pain recurrence: 66 patients (39%) in Group PF(≤ 48 hours) experienced pain recurrence, compared with 71 patients (36.6%) in Group PF((>48 hours, ≤ 30 days)) and 27 patients (29.7%) in Group PF(>30 days) (p = 0.515). Conclusions A substantial number of patients (169 cases, 37.2%) became pain free within the first 48 hours. The rate of hypesthesia was higher in patients who became pain free more than 30 days after GKS, with a statistically significant difference between patient groups (p = 0.014).

Fate of clinical research studies after ethical approval--follow-up of study protocols until publication.

BACKGROUND: Many clinical studies are ultimately not fully published in peer-reviewed journals. Underreporting of clinical research is wasteful and can result in biased estimates of treatment effect or harm, leading to recommendations that are inappropriate or even dangerous. METHODS: We assembled a cohort of clinical studies approved 2000-2002 by the Research Ethics Committee of the University of Freiburg, Germany. Published full articles were searched in electronic databases and investigators contacted. Data on study characteristics were extracted from protocols and corresponding publications. We characterized the cohort, quantified its publication outcome and compared protocols and publications for selected aspects. RESULTS: Of 917 approved studies, 807 were started and 110 were not, either locally or as a whole. Of the started studies, 576 (71%) were completed according to protocol, 128 (16%) discontinued and 42 (5%) are still ongoing; for 61 (8%) there was no information about their course. We identified 782 full publications corresponding to 419 of the 807 initiated studies; the publication proportion was 52% (95% CI: 0.48-0.55). Study design was not significantly associated with subsequent publication. Multicentre status, international collaboration, large sample size and commercial or non-commercial funding were positively associated with subsequent publication. Commercial funding was mentioned in 203 (48%) protocols and in 205 (49%) of the publications. In most published studies (339; 81%) this information corresponded between protocol and publication. Most studies were published in English (367; 88%); some in German (25; 6%) or both languages (27; 6%). The local investigators were listed as (co-)authors in the publications corresponding to 259 (62%) studies. CONCLUSION: Half of the clinical research conducted at a large German university medical centre remains unpublished; future research is built on an incomplete database. Research resources are likely wasted as neither health care professionals nor patients nor policy makers can use the results when making decisions.

Bond strength of orthodontic brackets using different light and self-curing cements

The purpose of the study was to evaluate the shear bond strength of stainless steel orthodontic brackets directly bonded to extracted human premolar teeth. Fifty teeth were randomly divided into ¿ve groups: (1) System One (chemically cured composite resin), (2) Light Bond (light-cured composite resin), (3) Vivaglass Cem (self-curing glass ionomer cement), (4) Fuji Ortho LC (light-cured glass ionomer cement) used after 37% orthophosphoric acid¿etching of enamel (5) Fuji Ortho LC without orthophosphoric acid¿etching. The brackets were placed on the buccal and lingual surfaces of each tooth, and the specimens were stored in distilled water (24 hours) at 378C and thermocycled. Teeth were mounted on acrylic block frames, and brackets were debonded using an Instron machine. Shear bond strength values at fracture (Nw)were recorded. ANOVA and Student-Newman-Keuls multiple comparison tests were performed (P , .05). Bonding failure site was recorded by stereomicroscope and analyzed by Chi-square test, selected specimens of each group were observed by scanning electron microscope. System One attained the highest bond strength. Light Bond and Fuji Ortho LC, when using an acid-etching technique, obtained bond strengths that were within the range of estimated bond strength values for successful clinical bonding. Fuji Ortho LC and Vivaglass Cem left an almost clean enamel surface after debracketing.

Monitoring one-year compliance to antihypertension medication in the Seychelles.

OBJECTIVE: To examine the compliance to medication among newly diagnosed hypertensive patients screened from the general population of the Seychelles, a rapidly developing country. METHODS: Among the 1067 participants to a population-based survey for cardiovascular risk factors, hypertension was discovered in 50 (previously unaware of having hypertension and having blood pressure > or = 160/95 mmHg over 3 visits). These 50 patients were placed on a daily one-pill regimen of medication (bendrofluazide, atenolol, or a combination of hydrochlorothiazide and atenolol) and compliance to the regimen was assessed over 12 months using electronic pill containers. Satisfactory compliance was defined as taking the medication on 6 or 7 days a week on average (which corresponds to a mean compliance level of > or = 86%). FINDINGS: In the first month, fewer than half (46%) of the new hypertension patients achieved satisfactory compliance, and only about one-quarter (26%) achieved this level by the twelfth month. Compliance was better among the 23 participants who regularly attended medical follow-up, with nearly three-quarters of these patients (74%) achieving satisfactory compliance during the first month and over one-half (55%) by the twelfth month. There was a direct association between mean 12-month compliance level and having a highly skilled occupation; having good health awareness; and regularly attending medical appointments. In contrast, there was an inverse relationship between mean compliance level and heavy drinking. CONCLUSION: The low proportion of people selected from the general population who were capable of sustaining satisfactory compliance to antihypertension medication may correspond to the maximum effectiveness of medication interventions based on a screening and treatment strategy in the general population. The results stress the need for both high-risk and population approaches to improve hypertension control.

Ebstein's anomaly: one and a half ventricular repair.

Patients with Ebstein's anomaly can present after childhood or adolescence with cyanosis, arrhythmias, severe right ventricular dysfunction and frequently with left ventricular dysfunction secondary to the prolonged cyanosis and to the right ventricular interference. At this point conventional repair is accompanied by elevated mortality and morbidity and poor functional results. We report our experience with three patients (8, 16 and 35 years of age) with Ebstein's anomaly, very dilated right atrium, severe tricuspid valve regurgitation (4/4), bi-directional shunt through an atrial septal defect and reduced left ventricular function (mean ejection fraction = 58%, mean shortening fraction = 25%). All underwent one and a half ventricular repair consisting of closure of the atrial septal defect, tricuspid repair with reduction of the atrialised portion of the right ventricle and end-to-side anastomosis of the superior vena cava to the right pulmonary artery. All patients survived, with a mean follow-up of 33 months. In all there was complete regression of the cyanosis and of the signs of heart failure. Postoperative echocardiography showed reduced degree of tricuspid regurgitation (2/4) and improvement of the left ventricular function (mean ejection fraction = 77%, mean shortening fraction = 40%). In patients with Ebstein's anomaly referred late for surgery with severely compromised right ventricular function or even with reduced biventricular function, the presence of a relatively hypoplastic and/or malfunctioning right ventricular chamber inadequate to sustain the entire systemic venous return but capable of managing part of the systemic venous return, permits a one and a half ventricular repair with good functional results.

Long-term follow-up of colorectal carcinoma patients by repeated CEA radioimmunoassay.

One of the major practical applications of carcinoembryonic antigen (CEA) assay is the monitoring of colorectal carcinoma patients after complete tumor resection. During the last 5 years, we have followed by repeated CEA assays 66 patients with histologically confirmed colon or rectum adenocarcinoma. Among 19 patients who developed a tumor recurrence, 17 had increased CEA levels preceding the clinical diagnosis by 2 to 26 months. Among the 47 patients who did not show any clinical evidence of tumor recurrence, 35 had CEA values remaining below the limit of 5 ng/ml, whereas 12 had moderate elevations of CEA level fluctuating around this limit. The majority of patients in this last group were heavy smokers or had liver enlargement, but in a few of them we did not find a satisfactory explanation for their moderately increased CEA levels. While our results confirm that repeated CEA assays can predict tumor recurrence with a lead time of several months over clinical diagnosis, they also give a word of warning concerning the interpretation of moderate elevations of CEA level. A moderate increase of CEA level can be the result of early distant metastases, local recurrence or exacerbation of an inflammatory disease. We feel that the decision of second look operations based on CEA results should be made only if increasing CEA values have been observed on three different blood samples taken within a period of 3 months and if no nonmalignant diseases known to increase CEA level are present. Ultimately only randomized clinical studies will determine if second look operations motivated by elevated CEA levels can improve the quality and length of survival of patients with colorectal carcinoma.

Detailed analysis and follow-up studies of a high-throughput screening for indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors.

Indoleamine 2,3-dioxygenase 1 (IDO1) is a key regulator of immune responses and therefore an important therapeutic target for the treatment of diseases that involve pathological immune escape, such as cancer. Here, we describe a robust and sensitive high-throughput screen (HTS) for IDO1 inhibitors using the Prestwick Chemical Library of 1200 FDA-approved drugs and the Maybridge HitFinder Collection of 14,000 small molecules. Of the 60 hits selected for follow-up studies, 14 displayed IC50 values below 20 μM under the secondary assay conditions, and 4 showed an activity in cellular tests. In view of the high attrition rate we used both experimental and computational techniques to identify and to characterize compounds inhibiting IDO1 through unspecific inhibition mechanisms such as chemical reactivity, redox cycling, or aggregation. One specific IDO1 inhibitor scaffold, the imidazole antifungal agents, was chosen for rational structure-based lead optimization, which led to more soluble and smaller compounds with micromolar activity.

A randomised controlled clinical trial and gait analysis of fixed- and mobile-bearing total knee replacements with a five-year follow-up.

This study compared the outcome of total knee replacement (TKR) in adult patients with fixed- and mobile-bearing prostheses during the first post-operative year and at five years' follow-up, using gait parameters as a new objective measure. This double-blind randomised controlled clinical trial included 55 patients with mobile-bearing (n = 26) and fixed-bearing (n = 29) prostheses of the same design, evaluated pre-operatively and post-operatively at six weeks, three months, six months, one year and five years. Each participant undertook two walking trials of 30 m and completed the EuroQol questionnaire, Western Ontario and McMaster Universities osteoarthritis index, Knee Society score, and visual analogue scales for pain and stiffness. Gait analysis was performed using five miniature angular rate sensors mounted on the trunk (sacrum), each thigh and calf. The study population was divided into two groups according to age (≤ 70 years versus > 70 years). Improvements in most gait parameters at five years' follow-up were greater for fixed-bearing TKRs in older patients (> 70 years), and greater for mobile-bearing TKRs in younger patients (≤ 70 years). These findings should be confirmed by an extended age controlled study, as the ideal choice of prosthesis might depend on the age of the patient at the time of surgery.

Long-term follow-up of high-dose chemotherapy with autologous stem-cell transplantation and response-adapted whole-brain radiotherapy for newly diagnosed primary CNS lymphoma: results of the multicenter Ostdeutsche Studiengruppe Hamatologie und Onkologie OSHO-53 phase II study.

Background We previously reported the results of a phase II study for patients with newly diagnosed primary central nervous system lymphoma treated with autologous peripheral blood stem-cell transplantation (aPBSCT) and response-adapted whole-brain radiotherapy (WBRT). Now, we update the initial results. Patients and methods From 1999 to 2004, 23 patients received high-dose methotrexate. In case of at least partial remission, high-dose busulfan/thiotepa (HD-BuTT) followed by aPBSCT was carried out. Patients refractory to induction or without complete remission after HD-BuTT received WBRT. Eight patients still alive in 2011 were contacted and Mini-Mental State Examination (MMSE) and the European Organisation for Research and Treatment of Cancer quality-of-life questionnaire (QLQ)-C30 were carried out. Results Of eight patients still alive, median follow-up is 116.9 months. Only one of nine irradiated patients is still alive with a severe neurologic deficit. In seven of eight patients treated with HD-BuTT, health condition and quality of life are excellent. MMSE and QLQ-C30 showed remarkably good results in patients who did not receive WBRT. All of them have a Karnofsky score of 90%-100%. Conclusions Follow-up shows an overall survival of 35%. In six of seven patients where WBRT could be avoided, no long-term neurotoxicity has been observed and all patients have an excellent quality of life.

One-step nucleic acid amplification (OSNA): a new road to better staging in colon cancer patients?

Introduction: Approximately one fifth of stage I and II colon cancer patients will suffer from recurrent disease. This is partly due to the presence of small nodal tumour infiltrates, which are undetected by standard histopathology using Haematoxylin & Eosin (H&E) staining on one slice and thus may not receive beneficial adjuvant therapy. A new diagnostic, semi-automatic system, called one-step nucleic acid amplification (OSNA), was recently designed for the detection of cytokeratin 19 (CK19) mRNA as a surrogate for lymph node metastases. The objective of the present investigation was to compare the performance of OSNA with both standard H&E as well as intensive histopathologic analyses in the detection of colon cancer lymph node micro- and macro-metastases.Methods: In this prospective study 313 lymph nodes from 22 consecutive stage I - III colon cancer patients were assessed. Half of each lymph node was analysed initially based on one slice of H&E followed by an intensive histologic work-up (5 levels of H&E and immuno-histochemistry staining for each slice), the other half was analysed using OSNA.Results: All OSNA results were available after less than 40 minutes. Fifty-one lymph nodes were positive and 246 lymph nodes negative with both OSNA and standard H&E. OSNA was more sensitive to detect small nodal tumor infiltrates compared to H&E (11 OSNA pos. /H&E neg.). Compared to intensive histopathologic analyses, OSNA had a sensitivity of 94.5% and a specificity of 97.6% to detect lymph node micro- and macro-metastases with a concordance rate of 97.1%. An upstaging due to OSNA was found in 2/13 (15.3%) initially node negative colon cancer patients.Conclusion: OSNA appears to be a powerful and promising molecular tool for the detection of lymph node macro- and micro-metastases in colon cancer patients. OSNA has a similar performance in the detection of micro- and macro-metastases compared to intensive histopathologic investigations and appears to be superior to standard histology with H&E. Since the use of OSNA allows the analysis of the whole lymph node, the problem of sampling bias and undetected tumor deposits due to uninvestigated material will be overcome in the future and OSNA may thus improve staging in colon cancer patients. It is hoped that this improved staging will lead to better patient selection for adjuvant therapy and consecutively improved local and distant control as well as better overall survival.

Total hip replacement with a collarless polished cemented anatomic stem: clinical and gait analysis results at ten years follow-up.

PURPOSE: The aim of this study was to determine outcomes of total hip replacement (THR) with the Lemania cemented femoral stem. METHODS: A total of 78 THR patients were followed and compared to 17 "fit", healthy, elderly and 72 "frail" elderly subjects without THR, using clinical outcome measures and a portable, in-field gait analysis device at five and ten years follow-up. RESULTS: Forty-one patients (53%), mean age 83.4 years, available at ten years follow-up, reported very good to excellent satisfaction. Mean Harris Hip and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores were 81.2 and 10.5 points, respectively, with excellent radiological preservation of proximal femur bone stock. Spatial and temporal gait parameters were close to the fit group and better than the frail group. CONCLUSIONS: Lemania THR demonstrated very good, stable clinical and radiological results at ten years in an older patient group, comparable to other cemented systems for primary THR. Gait analysis confirmed good walking performance in a real-life environment.

Sporadic late-onset nemaline myopathy with MGUS: Long-term follow-up after melphalan and SCT.

OBJECTIVE: Sporadic late-onset nemaline myopathy (SLONM) is a rare, late-onset myopathy that progresses subacutely. If associated with a monoclonal gammopathy of unknown significance (MGUS), the outcome is unfavorable: the majority of these patients die within 1 to 5 years of respiratory failure. This study aims to qualitatively assess the long-term treatment effect of high-dose melphalan (HDM) followed by autologous stem cell transplantation (SCT) in a series of 8 patients with SLONM-MGUS. METHODS: We performed a retrospective case series study (n = 8) on the long-term (1-8 years) treatment effect of HDM followed by autologous SCT (HDM-SCT) on survival, muscle strength, and functional capacities. RESULTS: Seven patients showed a lasting moderate-good clinical response, 2 of them after the second HDM-SCT. All of them had a complete, a very good partial, or a partial hematologic response. One patient showed no clinical or hematologic response and died. CONCLUSIONS: This case series shows the positive effect of HDM-SCT in this rare disorder. Factors that may portend an unfavorable outcome are a long disease course before the hematologic treatment and a poor hematologic response. Age at onset, level and type of M protein (κ vs λ), and severity of muscle weakness were not associated with a specific outcome. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with SLONM-MGUS, HDM-SCT increases the probability of survival and functional improvement.