Multicenter Studies as Topic

Background The use of non-steroidal anti-inflammatory drugs (NSAIDs) is often associated with upper gastrointestinal symptoms such as heartburn and acid regurgitation. Aim To assess the efficacy of esomeprazole 20 and 40 mg for resolution of heartburn and acid regurgitation in continuous NSAIDs. Methods A post hoc analysis of five clinical trials was performed. Two identically designed, placebo-controlled, 4-week studies (NASA1, SPACE1) enrolled non-ulcer, NSAIDs-treated patients with upper abdominal pain, discomfort or burning. PLUTO and VENUS were identically designed, placebo-controlled, 6-month studies that enrolled patients at risk of NSAIDs-induced ulcers. Study 285 was an 8-week comparative study with ranitidine (300 mg/day) in patients with NSAIDs-induced gastric ulcers. Resolution of investigator-assessed heartburn and acid regurgitation was defined as symptom severity of 'none' in the last 7 days. Results In NASA1/SPACE1, heartburn resolved in 61% and 62% of patients taking esomeprazole 20 and 40 mg, respectively (vs. 36% on placebo, P < 0.001), and acid regurgitation resolved in 65% and 67% (vs. 48%, P < 0.001). Resolution of both symptoms was greater with esomeprazole than with placebo in PLUTO/VENUS (P £ 0.001), and than with ranitidine in study 285 (P < 0.05 for esomeprazole 20 mg). Conclusion Heartburn and regurgitation are common in patients taking NSAIDs and esomeprazole is efficacious for resolution of these symptoms.

There is increasing importance placed on conducting clinical trials in dentistry to provide a robust evidence base for the treatment provided, and models of care delivered. However, providing the evidence upon which to base such decisions is not straightforward, as the conduct of these trials is complex. Currently, only limited information is available about the strategies to deliver successful clinical trials in primary care settings, and even less available on dental clinical trials. Considerable knowledge and experience is lost once a trial is completed as details about effective management of a trial are generally not reported or disseminated to trial managers and researchers. This leads to loss of vital knowledge that could assist with the effective delivery of new trials. The aim of this study is to examine the conduct and delivery of five dental clinical trials across both Australia and the UK and identify the various factors that impacted upon their implementation. Findings ...

Background Short-term preoperative radiotherapy and total mesorectal excision have each been shown to improve local control of disease in patients with resectable rectal cancer. We conducted a multicenter, randomized trial to determine whether the addition of preoperative radiotherapy increases the benefit of total mesorectal excision. Methods We randomly assigned 1861 patients with resectable rectal cancer either to preoperative radiotherapy (5 Gy on each of five days) followed by total mesorectal excision (924 patients) or to total mesorectal excision alone (937 patients). The trial was conducted with the use of standardization and qualitycontrol measures to ensure the consistency of the radiotherapy, surgery, and pathological techniques. Results Of the 1861 patients randomly assigned to one of the two treatment groups, 1805 were eligible to participate. The overall rate of survival at two years among the eligible patients was 82.0 percent in the group assigned to both radiotherapy and surgery and 81.8 percent in the group assigned to surgery alone (P=0.84). Among the 1748 patients who underwent a macroscopically complete local resection, the rate of local recurrence at two years was 5.3 percent. The rate of local recurrence at two years was 2.4 percent in the radiotherapy-plus-surgery group and 8.2 percent in the surgery-only group (P<0.001). Conclusions Short-term preoperative radiotherapy reduces the risk of local recurrence in patients with rectal cancer who undergo a standardized total mesorectal excision.

This series of articles for rehabilitation in practice aims to cover a knowledge element of the rehabilitation medicine curriculum. Nevertheless they are intended to be of interest to a multidisciplinary audience. The competency addressed in this article is the neuropsychologist.

Background Over the past decade, annual funding for biomedical research has more than doubled while new molecular entity approvals have declined by one third. Objective To assess the value of practices commonly employed in the conduct of large-scale clinical trials, and to identify areas where costs could be reduced without compromising scientific validity. Methods In the qualitative phase of the study, an expert panel recommended potential modifications of mega-trial designs and operations in order to maximize their value (cost versus scientific benefit tradeoff). In the quantitative phase, a mega-trial economic model was used to assess the financial implications of these recommendations. Our initial chronic disease trial design included 20,000 patients randomized at 1000 sites. Each site was assigned 24 monitoring visits and a $10,000 per patient site payment. The case report form (CRF) was 60 pages long, and trial duration was assumed to be 48 months. Results The total costs of the initial trial design were $421 million ($US 2007). Following the expert panel's recommendations, we varied study duration, CRF length, number of sites, electronic data capture (EDC), and site management components to determine their individual and combined effects upon total trial costs. The use of EDC and modified site management practices were associated with significant reductions in total trial costs. When reductions in all five trial components were combined in a streamlined pharmaceutical industry design, a 59% reduction in total trial costs resulted. When we assumed an even more streamlined trial design than has typically been considered for regulatory submissions in the past, there was a 90% reduction in total trial costs. Conclusion Our results suggest that it is possible to reduce substantially the cost of large-scale clinical trials without compromising the scientific validity of their results. If implemented, our recommendations could free billions of dollars annually for additional clinical studies. Research in the setting of clinical trials should be conducted to refine these findings. Clinical Trials 2008; 5: 75-84. http://

Haemovigilance was part of the reform of the French transfusion system. The haemovigilance network is now operational with approximately 4600 transfusion incidents reported annually. Immediate incidents observed within 8 days after transfusion account for 85 % of the reports. A cause cannot be identified in 41% of these, usually concerning minor clinical incidents with transient fever and /or shivers. An allergic reaction is described in 31% of transfusion reactions. Immunological conflicts account for 18% and bacteria associated transfusion reactions for 6%. The importance of bacteria associated transfusion reactions, the first identified cause of death associated with transfusion is one of the findings of haemovigilance. Improvement in the haemovigilance systems aims at obtaining better descriptions of transfusion incidents, standardisation of severity and imputability assessment and definitions of denominators such as the actual number of recipients. Delayed incidents will ultimately provide a true vision of post transfusion immunisation and infection The improvement of haemovigilance now considered as part of transfusion medicine practice is a continuous process. 01998 S. Karger AG, Basel 0042-9007/98/0746-044 1 S 1 5 .OO/O

PURPOSE: Report the test-retest reliability, construct validity, minimum clinically important difference (MCID), and minimal detectable change (MDC) for the Neck Disability Index (NDI). STUDY DESIGN/SETTING: Cohort study of patients presenting to outpatient physical therapy clinics. PATIENT SAMPLE: Ninety-one subjects with a primary complaint of neck pain, with or without concomitant upper extremity (UE) symptoms, who were participants in a randomized clinical trial. OUTCOME MEASURES: NDI and the 15-point Global Rating of Change (GRC) self-report measures. METHODS: All subjects completed the NDI at baseline and at a 3-week follow-up. Additionally, subjects completed the GRC scale, which was used to dichotomize patients into improved or stable groups. Changes in the NDI were used to assess test-retest reliability, construct validity, MCID, and MDC. RESULTS: Test-retest reliability was moderate for the NDI (intraclass correlation coefficient, 0.64; 95% confidence interval, 0.19-0.84). For the NDI, the MCID was 7.5 points and the MDC was 10.2 points. CONCLUSIONS: The NDI appears to demonstrate adequate responsiveness based on statistical reference criteria when used in a sample that approximates the high percentage of patients with neck pain and concomitant UE referred symptoms. Because the MCID is within the bounds of measurement error, a 10-point change (the MDC) should be used as the MCID. Ó

To summarize empirical evidence relating to stressors that may affect patients' psychosocial health following colostomy or ileostomy surgery during hospitalization and after discharge. Data Sources: An extensive search was performed on the CINAHL ® , Cochrane Library, PubMed, PsycINFO, Scopus, Science Direct, and Web of Science electronic databases. Data Synthesis: Eight articles were included with three qualitative and five quantitative research designs. Most studies were conducted in Western nations with one other in Taiwan. Following colostomy or ileostomy surgery, common stressors reported by patients during hospitalization included stoma formation, diagnosis of cancer, and preparation for self-care. After discharge, stressors that patients experienced encompassed adapting to body changes, altered sexuality, and impact on social life and activities. Conclusions: This review suggests that patients with stomas experience various stressors during hospitalization and after discharge. Additional research is needed for better understanding of patient postoperative experiences to facilitate the provision of appropriate nursing interventions to the stressors. Implications for Nursing: To help patients deal with stressors following stoma surgery, nurses may provide preand postoperative education regarding the treatment and recovery process and encourage patient self-care. Following discharge, nurses may provide long-term ongoing counseling and support, build social networks among patients with stomas, and implement home visit programs. Knowledge Translation: Stoma surgery negatively affects patients' physical, psychological, social, and sexual health. Postoperative education programs in clinical settings mostly focus on physical health and underemphasize psychological issues. More pre-and postoperative education programs are needed to help patients cope with stoma stressors.

The Women, Co-occurring Disorders, and Violence Study (WCDVS) was a multi-site cooperative study to evaluate new service models for women with co-occurring mental health and substance use disorders and a history of physical and/or sexual abuse. Despite common features in the service interventions and evaluation procedures, diversity across the nine sites plus differences introduced by non-random assignment led to numerous methodological challenges. This article describes the design, measurement, and analysis decisions behind the WCDVS and lays the foundation for understanding participant-level outcomes and service costs. This article also describes the study population, as recruited and following attrition at the 6-month follow-up, in order to address the threat of selection bias to inferences drawn from this multi-site study.

are consultants and equity stock holders, and William Maixner and Dr. Luda Diatchenko are officers and equity stock holders in Algynomics, Inc., a company providing research services in personalized pain medication and diagnostics. Portions of these data were presented at the 2010 Annual Scientific Meeting of the American Pain Society in Baltimore, MD.

The newly available techniques for sensitive proteome analysis and the resulting amount of data require a new bioinformatics focus on automatic methods for spectrum reprocessing and peptide/protein validation. Manual validation of results in such studies is not feasible and objective enough for quality relevant interpretation. The necessity for tools enabling an automatic quality control is, therefore, important to produce reliable and comparable data in such big consortia as the Human Proteome Organization Brain Proteome Project. Standards and well-defined processing pipelines are important for these consortia. We show a way for choosing the right database model, through collecting data, processing these with a decoy database and end up with a quality controlled protein list merged from several search engines, including a known falsepositive rate.

Retrospective review of prospective database. To define the variability of neurologic examination and recovery after nonpenetrating complete thoracic spinal cord injuries (American Spinal Injury Association [ASIA] A). Neurologic examinations after spinal cord injury (SCI) can be difficult and inconsistent. Unlike cervical SCI patients, alterations in thoracic (below T1) complete SCI (ASIA A-based on the ASIA Impairment Scale [AIS]) patients' examinations are based only on sensory testing, thus changes in the neurologic level (NL) are determined only by sensory changes. A retrospective review of the placebo control patients in a multicenter prospective database used for the pharmacologic trial of Sygen. Patients were included if they had a complete thoracic SCI on initial evaluation, with completed ASIA examinations at follow-up weeks 4, 8, 16, 26, and 52. Specifically, pin prick (PP) and light touch (LT) were assessed and the absolute change was calculated as the number of spinal levels at a given observation time. Three thousand one hundred sixty-five patients were initially screened for the Sygen clinical trial, of which 51 were the control placebo patients used in this analysis. Alterations from the baseline examination (PP and LT) were fairly consistent and the median change/recovery in neurologic examination was 1 spinal level. Across all observations postbaseline, the average change for PP was 1.48 +/- 0.13 (mean +/- SE), and for LT, 1.40 +/- 0.13. There were equal proportions of directional changes (none, improved, lost). Changes in a thoracic complete (ASIA A) SCI patients ASIA examination as measured through sensory methods (PP/LT) are fairly uncommon. The overall examination had only 1- to 2-level variability across patients, indicating minimal change in the sensory examination over the follow-up period. Stability in the ASIA examination as measured through sensory methods has thus been demonstrated over time, making it an excellent tool to monitor changes in neurologic function.

The Women, Co-occurring Disorders, and Violence Study (WCDVS) was a multi-site cooperative study to evaluate new service models for women with co-occurring mental health and substance use disorders and a history of physical and/or sexual abuse. Despite common features in the service interventions and evaluation procedures, diversity across the nine sites plus differences introduced by non-random assignment led to numerous methodological challenges. This article describes the design, measurement, and analysis decisions behind the WCDVS and lays the foundation for understanding participant-level outcomes and service costs. This article also describes the study population, as recruited and following attrition at the 6-month follow-up, in order to address the threat of selection bias to inferences drawn from this multi-site study. D

Background: The measurement of spasticity as a symptom of neurologic disease is an area of growing interest. Clinician-rated measures of spasticity purport to be objective but do not measure the patient's experience and may not be sensitive to changes that are meaningful to the patient. In a patient with clinical spasticity, the best judge of the perceived severity of the symptom is the patient. Objectives: The aim of this study was to assess the validity and reliability, and determine the clinical importance, of change on a 0-10 numeric rating scale (NRS) as a patient-rated measure of the perceived severity of spasticity. Methods: Using data from a large, randomized, doubleblind, placebo-controlled study of an endocannabinoid system modulator in patients with multiple sclerosisrelated spasticity, we evaluated the test-retest reliability and comparison-based validity of a patient-reported 0-10 NRS measure of spasticity severity with the Ashworth Scale and Spasm Frequency Scale. We estimated the level of change from baseline on the 0-10 NRS spasticity scale that constituted a clinically important difference (CID) and a minimal CID (MCID) as anchored to the patient's global impression of change (PGIC). Results: Data from a total of 189 patients were included in this assessment (114 women, 75 men; mean age, 49.1 years). The test-retest reliability analysis found an interclass correlation coefficient of 0.83 (P < 0.001) between 2 measures of the 0-10 NRS spasticity scores recorded over a 7-to 14-day period before randomization. A significant correlation was found between change on 0-10 NRS and change in the Spasm Frequency Scale (r = 0.63; P < 0.001), and a moderate correlation was found between the change on 0-10 NRS and the PGIC (r = 0.47; P < 0.001). A reduction of ~30% in the spasticity 0-10 NRS score best represented the CID and a change of 18% the MCID. Conclusions: The measurement of the symptom of spasticity using a patient-rated 0-10 NRS was found to be both reliable and valid. The definitions of CID and MCID will facilitate the use of appropriate responder analyses and help clinicians interpret the significance of future results.

Objective. To determine the cumulative rate of relapse of lupus nephritis that has been treated successfully with cyclophosphamide (CYC), and to estimate the association between time to relapse and demographic, clinical, laboratory, and treatment variables.Methods. This was an observational study of 48 systemic lupus erythematosus (SLE) patients who were treated successfully with CYC between 1979 and 1993 and followed up thereafter at 3 university hospitals. Demographic and clinical variables, laboratory data during the first month of nephritis, and therapy-related variables were recorded from charts. Renal biopsy specimens were retrieved and analyzed by a pathologist. Relapse of nephritis was the outcome of interest. Descriptive analysis of patients who did and those who did not have a relapse was performed by chi-square test, Fisher's exact test, and Wilcoxon 2-sample test. The cumulative rate of relapse was computed using the actuarial method. Univariate comparisons of time to relapse were computed by log-rank test. Proportional hazards modeling was used to assess the combined effect of patient characteristics that have been hypothesized to be prognostic factors.Results. Nephritis relapsed in 11 patients. Previous hematologic disorder, arthritis or arthralgia, and the use of CYC in oral form were more frequent in patients who had a relapse. The cumulative rate of relapse was 25% and 46% at 5 years and 10 years, respectively. A significant univariate difference in time to relapse was found when patients were stratified by time from diagnosis to initiation of CYC treatment (⩽ 5 months versus >5 months; P = 0.02). By multivariate analysis, age <29 years at nephritis onset (relative risk [RR] 6.29, 95% confidence interval [95% CI] 1.13–34.94, P = 0.03) and delay of >5 months from onset of nephritis to initiation of CYC therapy (RR 3.66, 95% CI 1.06–12.63, P = 0.04) were independently associated with time to relapse.Conclusion. A selected population of SLE patients may have long-term remission of renal disease following successful CYC therapy. Patients in whom CYC treatment is delayed or who are young at the time of nephritis onset are at increased risk of relapse.

From a University of California—Los Angeles, School of Nursing, b Cedars-Sinai Medical Center, and c University of California—Los Angeles, Schools of Public Health and Medicine. ... Objective: The purpose of this study was to evaluate gender differences in quality of life ...

Achieving optimal and safe pain-management practices in the nursing home setting continues to challenge administrators, nurses, physicians, and other health care providers. Several factors in nursing home settings complicate the conduct of clinical process improvement research. The purpose of this qualitative study was to explore the perceptions of a sample of Colorado nursing home staff who participated in a study to develop and evaluate a multifaceted pain-management intervention. Semistructured interviews were conducted with 103 staff from treatment and control nursing homes, audiotaped, and content analyzed. Staff identified changes in their knowledge and attitudes about pain and their pain-assessment and management practices. Progressive solutions and suggestions for changing practice include establishing an internal pain team and incorporating nursing assistants into the care planning process. Quality improvement strategies can accommodate the special circumstances of nursing ...

Infants with cardiac disease or infants born prematurely with or without bronchopulmonary dysplasia are at increased risk of severe respiratory syncytial virus (RSV) disease. A recently developed RSV immune globulin (R$VIG) was studied in a 3-year multicenter trial to determine safety and efficacy in the prevention of severe RSV disease in children who are at high risk of severe RSVillness. Two hundred forty-nine children were studied; 102 had bronchopulmonary dysplasia, 87 had congenital heart disease, and 60 were born prematurely. RSVIG was given on a monthly basis to 81 children at a high dose of 750 mg/kg (15 ml/ kg) and to 79 children at a low dose of 150 mg/kg (3 ml/kg). The 89 children in the control group did not receive RSVIG. There were 64 episodes of RSV infection: 19 in the high-dose group, 16 in the low-dose group, and 29 in the control group. High-dose recipients had significantly fewer RSV lower respiratory tract infections, hospitalizations, hospital days, intensive care unit days, and less use of ribavirin compared with control subjects. Only 19 adverse events were reported during the 580 infusions administered (3%). No death was attributed to RSV disease or RSVIG therapy. Treated children did not acquire exaggerated RSV illness in a subsequent year. Thus high-dose RSVIG reduced the incidence and severity of RSV lower respiratory tract infection. It is a safe and effective means of RSV prophylaxis in selected high-risk children.

Objectives: To develop a simplified Therapeutic Intervention Scoring System (TISS) based on the TISS-28 items and to validate the new score in an independent database. Design: Retrospective statistical analysis of a database and a prospective multicentre study. Setting: Development in the database of the Foundation for Research on Intensive Care in Europe with external validation in 64 intensive care units (ICUs) of 11 European countries. Measurements and results: Development of NEMS on a random sample of TISS-28 items, cross validation on another random sample of TISS-28, and external validation of NEMS in comparison with TISS-28 scored by two independent raters on the day of the visit to the ICUs participating in an international study. Multivariable regression techniques, Pearson's correlation, and paired sample t-tests were used (significance at p < 0.05 level). Intraclass correlation, rate of agreement, and kappa statistics were used for interrater reliability tests. The TISS-28 items were reduced to NEMS (9 items) in a random sample of 2000 records; the means of the two scores were no different: TISS-28 26.23 ± 10.38, NEMS 26.19 ± 9.12, NS. Cross-validation in a random sample of 996 records; mean TISS-28 26.13 ± 10.38, NEMS 26.17 ± 9.38, NS; R 2 = 0.76. External validation on 369 pairs of TISS-28 and NEMS has shown that the means of the two scores were no different: TISS-28 27.56 ± 11.03, NEMS 27.02 ± 8.98, NS; R 2 = 0.59. Reliability tests have shown an "almost perfect" interrater correlation. Similar to studies correlating TISS with Simplified Acute Physiology Score (SAPS)-I and/or Acute Physiology and Chronic Health Evaluation II scores, the value of NEMS scored on the first day accounts for 30.4 % of the variation of SAPS-II score. Conclusions: NEMS is a suitable therapeutic index to measure nursing workload at the ICU level. The use of NEMS is indicated for: (a) multicentre ICU studies; (b) management purposes in the general (macro) evaluation and comparison of workload at the ICU level; (c) the prediction of workload and planning of nursing staff allocation at the individual patient level.

on behalf of the SOHO Study Group. The Clinical Global Impression-Schizophrenia scale: a simple instrument to measure the diversity of symptoms present in schizophrenia. Acta Psychiatr Scand 2003: 107 (Suppl. 416): 16-23. ª Blackwell Munksgaard 2003

The use of Patient-reported Outcomes (PROs) as secondary endpoints in the development of new antidepressants has grown in recent years. The objective of this study was to assess the psychometric properties of the 9-item, patient-administered version of the Montgomery-Åsberg Depression Rating Scale (MADRS-S).

Randomized clinical trials analyzed by the intent-to-treat approach provide unbiased comparisons among treatment groups. To avoid dilution of treatment effect, many people also perform an analysis by treatment actually received, although this method may introduce bias into the results. This paper presents several approaches used for analyzing data of a recent trial and the difficulties encountered in interpreting the results of each approach.

Iodine supplementation during pregnancy is a common practice in developed countries. However, scant evidence is available regarding the safety and effectiveness of maternal iodine supplementation with regard to child neuropsychological development. We previously reported an inverse association between iodine supplementation and the psychomotor development of infants in a birth cohort from Valencia, Spain. In the present study, we assessed this association in a wider sample of mother and child pairs from 3 other regions in Spain. Neuropsychological development was assessed using the Bayley Scales of Infant Development in 1,519 infants (median age, 16 months) between 2006 and 2009. In multivariate analyses, maternal consumption of 150 μg/day or more of iodine from supplements was related to a 1.5-fold increase in the odds of a psychomotor score less than 85 (95% confidence interval: 0.8, 2.9) and to a 1.7-fold increase in the odds of a mental score less than 85 (95% confidence interval: 0.9, 3.0). Findings previously reported in the Valencia cohort were only partially verified. The results of the present study suggest that, at least in these regions, iodine supplementation does not improve infant neuropsychological development at 1 year of age. Further research is needed on the risks and benefits of supplementary iodine for both maternal thyroid function and child neurodevelopment. child development; dietary supplements; fetal development; iodine; prenatal nutritional physiological phenomena Abbreviations: CI, confidence interval; INMA, Infancia y Medio Ambiente-Childhood and Environment; MS, mental scale; PS, psychomotor scale; UIC, urinary iodine concentration. 944 Am J Epidemiol. 2013;177(9):944-953 American Journal of Epidemiology Iodine Supplementation and Infant Neurodevelopment 945 Am J Epidemiol. 2013;177(9):944-953 by guest on November 8, 2016 http://aje.oxfordjournals.org/ Downloaded from Iodine Supplementation and Infant Neurodevelopment 947 Am J Epidemiol. 2013;177(9):944-953 by guest on November 8, 2016 http://aje.oxfordjournals.org/ Downloaded from Iodine Supplementation and Infant Neurodevelopment 949 Am J Epidemiol. 2013;177(9):944-953 by guest on November 8, 2016 http://aje.oxfordjournals.org/ Downloaded from Iodine Supplementation and Infant Neurodevelopment 951 Am J Epidemiol. 2013;177(9):944-953 by guest on November 8, 2016 http://aje.oxfordjournals.org/ Downloaded from Iodine Supplementation and Infant Neurodevelopment 953 Am J Epidemiol. 2013;177(9):944-953 by guest on

Background Despite the wide use of the Excited Component of the Positive and Negative Syndrome Scale (PANSS-EC) in a clinical setting to assess agitated patients, a validation study to evaluate its psychometric properties was missing. Methods Data from the observational NATURA study were used. This research describes trends in the use of treatments in patients with acute psychotic episodes and agitation seen in emergency departments. Exploratory principal component factor analysis was performed. Spearman's correlation and regression analyses (linear regression model) as well as equipercentile linking of Clinical Global Impression of Severity (CGI-S), Agitation and Calmness Evaluation Scale (ACES) and PANSS-EC items were conducted to examine the scale's diagnostic validity. Furthermore, reliability (Cronbach's alpha) and responsiveness were evaluated. Results Factor analysis resulted in one factor being retained according to eigenvalue ≥1. At admission, the PANSS-EC and CGI-S were found to be linearly related, with an average increase of 3.4 points (p PANSS-EC for each additional CGI-S point. The PANSS-EC and ACES were found to be linearly and inversely related, with an average decrease of 5.5 points (p PANSS-EC for each additional point. The equipercentile method shows the poor sensitivity of the ACES scale. Cronbach's alpha was 0.86 and effect size was 1.44. Conclusions The factorial analyses confirm the unifactorial structure of the PANSS-EC subscale. The PANSS-EC showed a strong linear correlation with rating scales such as CGI-S and ACES. PANSS-EC has also shown an excellent capacity to detect real changes in agitated patients.

Objectives: To develop a simplified Therapeutic Intervention Scoring System (TISS) based on the TISS-28 items and to validate the new score in an independent database. Design: Retrospective statistical analysis of a database and a prospective multicentre study. Setting: Development in the database of the Foundation for Research on Intensive Care in Europe with external validation in 64 intensive care units (ICUs) of 11 European countries. Measurements and results: Development of NEMS on a random sample of TISS-28 items, cross validation on another random sample of TISS-28, and external validation of NEMS in comparison with TISS-28 scored by two independent raters on the day of the visit to the ICUs participating in an international study. Multivariable regression techniques, Pearson's correlation, and paired sample t-tests were used (significance at p Intraclass correlation, rate of agreement, and kappa statistics were used for interrater reliability tests. The TISS-28 items were reduced to NEMS (9 items) in a random sample of 2000 records; the means of the two scores were no different: TISS-28 26.23 ± 10.38, NEMS 26.19 ± 9.12, NS. Cross-validation in a random sample of 996 records; mean TISS-28 26.13 ± 10.38, NEMS 26.17 ± 9.38, NS; R 2 = 0.76. External validation on 369 pairs of TISS-28 and NEMS has shown that the means of the two scores were no different: TISS-28 27.56 ± 11.03, NEMS 27.02 ± 8.98, NS; R 2 = 0.59. Reliability tests have shown an “almost perfect” interrater correlation. Similar to studies correlating TISS with Simplified Acute Physiology Score (SAPS)-I and/or Acute Physiology and Chronic Health Evaluation II scores, the value of NEMS scored on the first day accounts for 30.4 % of the variation of SAPS-II score. Conclusions: NEMS is a suitable therapeutic index to measure nursing workload at the ICU level. The use of NEMS is indicated for: (a) multicentre ICU studies; (b) management purposes in the general (macro) evaluation and comparison of workload at the ICU level; (c) the prediction of workload and planning of nursing staff allocation at the individual patient level.

Cognitive deficits constitute a core symptom in schizophrenia, are difficult to treat, and have special relevance regarding prognosis and functional outcome. The search for pharmacological strategies for improving cognition in schizophrenic patients has been hindered by the lack of a consensus regarding instruments for cognitive assessment. The &#39;Measurement and Treatment Research to Improve Cognition in Schizophrenia&#39; (MATRICS) initiative of the U.S. National Institute of Mental Health (NIMH) set the development of a consensus cognitive battery as one of its objectives. In a first phase, the seven cognitive domains which have been shown to be impaired in schizophrenia and that were to be assessed were identified: Speed of processing, Attention/Vigilance, Working memory, Verbal learning, Visual learning, Reasoning and problem solving, and Social cognition. In a second phase, the MATRICS Consensus Cognitive Battery (MCCB) was developed. This is a cognitive assessment battery c...

The Diabetes Control and Complications Trial (DCCT) taught us to set target blood glucose (BG) and glycohaemoglobin (GHb) goals, to ensure safety regarding hypoglycaemia, to be flexible with insulin and meal planning and to offer frequent contact with diabetes educators, dieticians, psychologists and social workers as well as with diabetologists skilled in intensified management. Insulin dosage should be individualized based upon frequent BG monitoring results. Co-ordinated multidisciplinary health care teams provide optimum problem-solving rather than disaster control working with children, adolescents and their families. The patient and the family should form the central core of the diabetes team with outpatient follow-up every month and frequent telephone contact between visits. GHb should be obtained at least every 1-2 months to provide feedback as based on the DCCT intensified treatment cohort. Insulin lispro helps minimize hypoglycaemia and makes insulin administration more convenient and timely. Barriers to improvement should be identified: learning problems, concomitant significant illnesses (epilepsy, coeliac and thyroid disease, asthma) and family problems. Ensure age-appropriate transfer of self-care but continue adult supervision. Educate, motivate and re-educate. Meal planning includes not only carbohydrate counting but also maintaining normal lipids and energy needs for growth and development as well as strategies for activity compensation and hypoglycaemia prevention. Consideration of protein restriction may be required in adolescents with microalbuminuria. Individualized multidose insulin algorithms allow reactive (corrective) decisions based upon capillary BG results plus proactive (anticipatory) decisions to compensate for expected BG changes from changes in activity, food and/or illness using a multidose insulin schedule. The number of insulin injections does not define an intensified insulin treatment programme but rather the ability to target and achieve near-normal BG values as often as possible -without severe episodes of hypoglycaemia. Self BG monitoring is a key to success. Long-term monitoring should include not only frequent GHb but also at least annual fasting lipids, thyroid functions and microalbuminuria as well as dilated retinal exams, blood pressure, growth charting and Tanner staging.

Since 1997 the National Center for Documentation and Evaluation of Alternative Methods to Animal Experiments, ZEBET, in Berlin, has been coordinating a validation study aimed at prevalidation and validation of three in vitro embryotoxicity tests, funded by the European Center for the Validation of Alternative Methods (ECVAM) at the Joint Research Center (JRC, Ispra, Italy). The tests use the cultivation of postimplantation rat whole embryos (WEC test), cultures of primary limb bud cells of rat embryos (micromass or, MM, test), and cultures of a pluripotent mouse embryonic stem cell line (embryonic stem cell test or EST). Each of the tests was performed in four laboratories under blind conditions. In the preliminary phase of the validation study 6 out of 20 test chemicals comprising different embryotoxic potential (non, weakly, and strongly embryotoxic) were tested. The results were used to define biostatistically based prediction models (PMs) to identify the embryotoxic potential of...

Treatment with the neuroprotective drug riluzole has previously been shown to increase the probability of survival in patients with amyotrophic lateral sclerosis. This report describes a placebo-controlled, double-blind randomised clinical trial of riluzole carried out in ALS patients with advanced stage disease or aged over 75 years. The primary objective was to enable access to treatment to patients excluded from the pivotal trial which was run in parallel. Another goal was to assess the safety of riluzole in patients with advanced-stage disease. One hundred and sixty-eight patients were included, randomised to either riluzole 50 mg b. i. d. or to placebo, and treated for eighteen months. Riluzole was well-tolerated in this patient population, and the adverse events observed were similar in nature and frequency to those observed in previously published clinical trials in patients included in pivotal trials. The study could not include enough patients to reach adequate power to detect differences in survival between the two treatment groups, and no such difference was in fact observed. In conclusion, riluzole is well-tolerated in ALS patients with advanced stage disease.

Objectives: To review current understanding of the knowledge and information needs of informal caregivers in palliative settings. Data sources: Seven electronic databases were searched for the period January 1994–November 2006: Medline, CINAHL, PsychINFO, Embase, Ovid, Zetoc and Pubmed using a meta-search engine (Metalib®). Key journals and reference lists of selected papers were hand searched. Review methods: Included studies were peer-reviewed journal articles presenting original research. Given a variety of ...

Objective: To describe the clinical course of attention-deficit/hyperactivity disorder (ADHD) symptom severity and diagnosis from ages 3 to 5 up to 9 to 12 years during a 6-year follow-up after the original Preschool ADHD Treatment Study (PATS). Method: A total of 207 participants (75% male) from the original PATS, assessed at baseline (mean age, 4.4 years, when all met criteria for ADHD) and 3 months later (before medication treatment), were re-evaluated in three follow-up assessment visits (year 3, mean age 7.4 years; year 4, 8.3 years; and year 6, 10.4 years). Parents and teachers rated symptom severity, and clinicians established psychiatric diagnoses. Analyses examined longitudinal changes in symptom severity and ADHD diagnosis. Results: Parent-and teacher-rated symptom severity decreased from baseline to year 3 but remained relatively stable and in the moderate-to-severe clinical range through year 6. Girls showed generally steeper decreases in symptom T-scores. At year 6, 89% (160/180) of remaining participants met ADHD symptom and impairment diagnostic criteria. Comorbidity of oppositional defiant disorder and/or conduct disorder was associated with a 30% higher risk of having an ADHD diagnosis at year 6 in the multiple logistic model. Medication status during follow-up, on versus off, did not predict symptom severity change from year 3 to year 6 after adjustment for other variables. Conclusions: ADHD in preschoolers is a relatively stable diagnosis over a 6-year period. The course is generally chronic, with high symptom severity and impairment, in very young children with moderate-to-severe ADHD, despite treatment with medication. Development of more effective ADHD intervention strategies is needed for this age group. J. Am. Acad. Child Adolesc. Psychiatry; 2013;52(3):264-278.

Severe mitral regurgitation due to prolapse of the valve demands early surgical intervention. Recently artificial chord implantation is the prefered solution, which requires cardioplegia and application of cardiopulmonary bypass using the left atrial approach. Transoesophageal echocardiography guided transapical neochord implantation is an emerging new technique for the treatment of mitral regurgitation. It enables the operation through left minithoracotomy on beating heart using a special instrument introduced into the left ventricle. Acute procedural success rates in different centres vary between 86 and 100%. According to reports, 92% of the patients do not require additional intervention at the 3-month follow-up. Continuous integration of data resulting improved outcomes supports the hope that this novel, less-invasive technique will be applied widely for the treatment of mitral regurgitation. Orv. Hetil., 2016, 157(18), 700–705.