Correction to: Safety and efficacy of Cerebrolysin in acute brain injury and neurorecovery: CAPTAIN I-a randomized, placebo-controlled, double-blind, Asian-Pacific trial.

The above article was published online with incorrect abbreviations in Figures 2 and 3 last sentence of the legend. HDA should be corrected to HADS.

Safety and efficacy of Cerebrolysin in acute brain injury and neurorecovery: CAPTAIN I-a randomized, placebo-controlled, double-blind, Asian-Pacific trial.

OBJECTIVE: To evaluate the safety and efficacy of Cerebrolysin as an add-on therapy to local standard treatment protocol in patients after moderate-to-severe traumatic brain injury. METHODS: The patients received the study medication in addition to standard care (50 mL of Cerebrolysin or physiological saline solution daily for 10 days, followed by two additional treatment cycles with 10 mL daily for 10 days) in a prospective, randomized, double-blind, placebo-controlled, parallel-group, multi-centre phase IIIb/IV trial. The primary endpoint was a multidimensional ensemble of 14 outcome scales pooled to be analyzed by means of the multivariate, correlation-sensitive Wei-Lachin procedure. RESULTS: In 46 enrolled TBI patients (Cerebrolysin 22, placebo 24), three single outcomes showed stand-alone statistically significant superiority of Cerebrolysin [Stroop Word/Dots Interference (p = 0.0415, Mann-Whitney(MW) = 0.6816, 95% CI 0.51-0.86); Color Trails Tests 1 and 2 (p = 0.0223/0.0170, MW = 0.72/0.73, 95% CI 0.53-0.90/0.54-0.91), both effect sizes lying above the benchmark for "large" superiority (MW > 0.71)]. While for the primary multivariate ensemble, statistical significance was just missed in the intention-to-treat population (pWei-Lachin < 0.1, MWcombined = 0.63, 95% CI 0.48-0.77, derived standardized mean difference (SMD) 0.45, 95% CI -0.07 to 1.04, derived OR 2.1, 95% CI 0.89-5.95), the per-protocol analysis showed a statistical significant superiority of Cerebrolysin (pWei-Lachin = 0.0240, MWcombined = 0.69, 95% CI 0.53 to 0.85, derived SMD 0.69, 95% CI 0.09 to 1.47, derived OR 3.2, 95% CI 1.16 to 12.8), with effect sizes of six single outcomes lying above the benchmark for "large" superiority. Safety aspects were comparable to placebo. CONCLUSION: Our trial suggests beneficial effects of Cerebrolysin on outcome after TBI. Results should be confirmed by a larger RCT with a comparable multidimensional approach.

Facilitators of high-quality teaching in medical school: findings from a nation-wide survey among clinical teachers.

BACKGROUND: Clinical teachers in medical schools are faced with the challenging task of delivering high-quality patient care, producing high-impact research and contributing to undergraduate medical education all at the same time. Little is known on the gap between an 'ideal' environment supporting clinical teachers to provide high quality teaching for their students and the reality of clinical teaching during worktime in the clinical environment. Most quantitative research published so far was done in a wide range of medical educators and did not consider individual academic qualifications. In this study, we wanted to survey clinical teachers in particular and assess the potential impact of individual academic qualification on their perceptions. METHODS: Based on qualitative data of focus group discussions, we developed a questionnaire which was piloted among 189 clinical teachers. The final web-based questionnaire was completed by clinical teachers at nine German medical schools. RESULTS: A total of 833 clinical teachers (569 junior physicians, 264 assistant professors) participated in the online survey. According to participants, the most important indicator of high quality teaching was "sustained student learning outcome" followed by "stimulation of interest in the subject matter". Lack of time was the main factor impeding effective teaching (78%). Among the factors facilitating high-quality teaching, protected preparation time during working hours (48%) and more recognition of high-quality teaching within medical schools (21%) were perceived as most helpful. Three out of four teachers (76%) were interested in faculty development programmes directed at teaching skills, but 60% stated they had no time to engage in such activities. With regard to evaluation, teachers preferred individual feedback (75%) over global ratings (21%). Differences between assistant professors and junior physicians were found in that the latter group perceived their teaching conditions as more difficult. CONCLUSIONS: Lack of time is a major barrier against planning and delivering good clinical teaching in medical schools. According to our findings, the situation at German medical schools is particularly challenging for junior physicians. Creating an institutional culture in which teaching is regarded as highly as patient care and research is a prerequisite for overcoming the barriers identified in this study.

Pregnancy and Birth Outcomes Among Immigrant Women in the US and Europe: A Systematic Review.

Human migration is not a new phenomenon, but it has changed significantly with the advance of globalization. We focus on differences in the published literature concerning migration and health (EU vs the US), centering specifically on reproductive health outcomes. We conducted a literature search in the Pubmed and Embase databases. We reviewed papers that contrast migrants to native-born populations and analyzed differences between countries as well as challenges for future research. The prevalence of low birthweight among migrants varies by the host country characteristics as well as the composition of migrants to different regions. The primary driver of migrant health is the migrant "regime" in different countries at specific periods of time. Future health outcomes of immigrants will depend on the societal characteristics (legal protections, institutions and health systems) of host countries.

[A new instrument to measure quality of life in older people: The French version of the WHOQOL-OLD]. / Un nouvel instrument destiné à mesurer la qualité de vie des personnes âgées : le WHOQOL-OLD version française.

PURPOSE: We present the validation data of the French version of a new quality of life questionnaire, specifically developed for use with older adults (>60 years old): the WHOQOL-OLD module. This questionnaire, which contains 24 items in six domains, is a complementary module of the WHOQOL-BREF quality of life questionnaire. It was internationally developed by a World Health Organization (WHO) group. METHODS: The first development and pilot studies led to a first questionnaire applied in field studies in 20 centers all over the world. They were done in 5566 subjects and allowed the validation of the final form of the WHOQOL-OLD questionnaire. For its French version, 281 subjects, with a mean age of 74 years, were recruited in three centers (Paris, Nancy and Geneva). RESULTS: The results of the psychometric properties of the questionnaire, particularly the multitrait analysis, are compatible with the assumptions underlying the construction of scores. Otherwise, scores present a sufficient accuracy to use this instrument in group comparisons. CONCLUSION: The WHOQOL-OLD questionnaire can be used in older people in health services, clinical research and epidemiologic studies.

The diagnostic spectrum in patients with suspected chronic Lyme neuroborreliosis--the experience from one year of a university hospital's Lyme neuroborreliosis outpatients clinic.

BACKGROUND AND PURPOSE: Studies addressing the diagnostic relevance of anti-Borrelia burgdorferi (BB) serum antibodies in patients with non-specific symptoms and suspected chronic Lyme neuroborreliosis (LNB) are scarce. METHODS: In this study, we enrolled within 1 year 122 patients with suspected chronic LNB. One hundred and fourteen patients had previously tested positive for BB. All patients had previously received antibiotic treatment. Each patient received a clinical examination and measurement of BB-specific antibodies. The diagnosis of neuroborreliosis was made according to the national guidelines of the German Society of Neurology. Nine patients had acute borreliosis. One of the nine met the criteria of acute LNB. Of the remaining 113 patients, 85 patients underwent a lumbar puncture. Ten seronegative subjects without lumbar puncture were also considered. In 61.8% of these 95 patients the quality of life, of sleep, mood, and anxiety were assessed. RESULTS: Of 95 patients, 25.3% had symptoms without a somatic cause or evidence of borreliosis, 38.9% had a well-defined illness unrelated to BB infection, and 29.5% suffered from symptoms without a detectable somatic cause, displaying antibodies against BB. Six patients were grouped as post-LNB syndrome. Most common symptoms in all categories were arthralgia, myalgia, dysaesthesia, depressive mood and chronic fatigue. CONCLUSION: Patients with persistent symptoms with elevated serum antibodies against BB but without signs of cerebrospinal fluid inflammation require further diagnostic examinations to exclude ongoing infection and to avoid co-infections and other treatable conditions (e.g. autoimmune diseases). One patient with acute LNB, who was treated with ceftriaxone for 3 weeks suffered from LNB with new headaches and persistent symptoms 6 months later. These data should encourage further studies with new experimental parameters.

The QOLIBRI--towards a quality of life tool after traumatic brain injury: current developments in Asia.

INTRODUCTION: There is no disease-specific health-related quality of life (HRQoL) tool devoted to traumatic brain injury (TBI). MATERIAL AND METHODS: Over 1500 TBI patients from 10 countries filled out a preliminary version of the QOLIBRI taking TBI specificities into account. 3 successive versions and consecutive statistical analyses were necessary to get a psychometrically-reliable tool. RESULTS: The QOLIBRI final version, filled out in 15 min, consists of 2 parts. The first part assesses satisfaction with HRQoL and is composed of 6 overall items and 29 items allocated to 4 subscales: thinking, feelings, autonomy and social aspects. The second part, devoted to "bothered" questions, is composed of 12 items in 2 subscales: negative feelings and restrictions. The 6 subscales meet standard psychometric criteria. In addition, 2 items evaluate medical-oriented aspects. The questionnaire is validated in German, Finnish, Italian, French, English, Dutch. CONCLUSION: TBI patients may now be assessed, beyond more "objective" measures including handicap and recovery, with a new measure of assessing the TBI patient's own opinion on his/her HRQoL, applicable across different populations and cultures. Validations in China Mainland, Hong-Kong, Taiwan, Japan, Egypt, Poland, Norway, Indonesia, and Malaya are on the way.

Chronic posttraumatic stress symptoms after nonsevere stroke.

OBJECTIVE: To determine whether posttraumatic stress disorder (PTSD)-related symptoms were present 1 year after a nonsevere stroke and, if so, to examine the relationship between PSTD, coexisting cognitive variables, and infarct localization METHODS: The authors assessed 49 patients using standard measures of memory, trauma experience, neurologic deficit, depression, anxiety, and PTSD. RESULTS: Fifteen (31%) patients had significant PTSD symptoms on the Impact of Event Scale (IES > 30). PTSD-like syndrome was independent of neurologic impairment, peristroke amnesia, long-term memory impairment, nosognosia, hypochondriac preoccupations, and physical pain during hospitalization, but was more frequent in women, less educated patients, and patients with more negative appraisals of the stroke experience. Intrusions were increased after basal ganglia strokes, suggesting that the re-experiencing phenomena may be modulated by frontosubcortical pathways. CONCLUSIONS: Posttraumatic stress disorder symptoms seem frequent in patients with nonsevere stroke and were associated with the subjective intensity of the stroke experience and accompanied by a depressive and anxious state.

Health-related quality of life in patients with coronary artery disease treated for angina: validity and reliability of German translations of two specific questionnaires.

The German versions of two patient-perceived heart disease specific health-related quality of life (HRQL) questionnaires, the Seattle Angina Questionnaire (SAQ) and the MacNew Heart Disease questionnaire, were examined for their psychometric properties in patients with angiographically documented coronary artery disease and angina who were treated either medically or invasively and followed up for 1 year. Both HRQL questionnaires and the modified Canadian Cardiovascular Society (CCS) angina-associated disability scale were completed by 158 patients at baseline and 12 months later when they also completed a generic health status questionnaire, the SF-36. Both specific HRQL questionnaires were acceptable to patients. Three of the four MacNew scales, but none of the SAQ scales, discriminated between patients by baseline CCS disability levels I and IV. Internal consistency ranged from 0.75 to 0.94 for the SAQ and from 0.86 to 0.97 for the MacNew scales. Test-retest reliability over a 4-week period of time ranged from 0.45 to 0.81 for the SAQ scales and 0.61 to 0.68 for the MacNew scales. Over 12 months, HRQL improved (p < 0.001) on three of the five SAQ and on all four of the MacNew scales with the responsiveness statistic ranging from 0.59 to 1.55 for the SAQ and 0.86 to 1.12 for the MacNew. The 12 month scores on all SAQ and MacNew scales were significantly higher in patients who improved than those who deteriorated on the SF-36 reported health transition question. We conclude that the SAQ and the MacNew are both valid, reliable, and responsive in German, that the MacNew discriminates better between angina grades at baseline, that HRQL improves over 12 months with both measures, that the SAQ angina frequency and disease perception scales have the largest effect sizes, and that the 12-month change in HRQL with both instruments was associated with change in SF-36 reported health transition status.

Hemispheric specialisation for self-paced motor sequences.

Temporal aspects of motor control were investigated in patients with infarction to the brain with two finger-tapping tests. In the self-paced tapping task patients with cortical left-hemispheric lesions were slowed down and patients with left-hemispheric subcortical injuries were consistently faster as compared with control subjects and patients with right hemispheric cortical lesions. The results point to the dominant control of the left-hemisphere in voluntarily timed action and to a special time range of 250-300 ms involved in motor behaviour.

Assessment of health-related quality-of-life in patients after heart transplantation under therapy with tacrolimus or cyclosporine.

Reduction of allograft rejections remains a primary goal for patients after orthotopic heart transplantation. In an open, multicentre, prospectively randomised, parallel group study, patients with primary orthotopic heart transplantation under oral immunosuppressive treatments with tacrolimus (FK506) or cyclosporine (sandimmun) were compared with respect to medical outcome data. As health-related quality-of-life (HRQOL) is also supposed to be an important outcome parameter, it was assessed as a secondary variable in these two patient groups. Patients' self-rated generic HRQOL was assessed 6 weeks, 3 months, 6 months and 12 months after surgery with the SF-36 questionnaire, a generic HRQOL instrument. For 70 patients (46 under tacrolimus, 24 under cyclosporine), intent-to-treat analyses were carried out. The tacrolimus group showed improvements in the different HRQOL subscales of the SF-36 compared to the cyclosporine group. Especially the SF-36 subscales 'vitality' and 'mental health' showed statistically higher scores for the tacrolimus group. Aggregating psychological and cognitive subscales in the 'mental component score', patients treated with tacrolimus showed a statistically significant improvement compared to the cyclosporine group. The assessment of HRQOL variables in the evaluation of treatment effects proved to be an outcome parameter in this study. The results demonstrate the benefit of tacrolimus with respect to the HRQOL of patients, especially in the psychological dimension.

Auditory temporal-order judgement is impaired in patients with cortical lesions in posterior regions of the left hemisphere.

Auditory temporal-order judgement was investigated in patients suffering from unilateral focal brain lesions, localized in anterior or posterior regions of the left hemisphere (LH) (resulting in non-fluent or fluent aphasia, respectively), or in predominantly subcortical regions of this hemisphere (without aphasic syndromes) and in anterior or posterior regions of the right hemisphere. The temporal order threshold was measured as the minimum time interval between two clicks presented consecutively and binaurally via headphones (one to each ear) that was necessary for a subject to indicate the temporal order of the two stimuli. Only the patient group with fluent aphasia showed a significantly increased mean temporal-order threshold as compared to the controls. Our results indicate that fine temporal resolution for auditory stimuli is predominantly associated with posterior regions of the LH.

Daily rhythm of temporal resolution in the auditory system.

Over a period of 24 hours, fusion thresholds (click durations 100 micros) were assessed in 7 subjects. Over the same period, order thresholds (click duration of 1 ms) were measured in 10 subjects (12 independent sessions). Auditory fusion thresholds showed a diurnal rhythm with a maximum performance (shortest intervals) around midnight. In contrast, order thresholds appear to be independent on the time of day. Sex specific differences in threshold levels were only observed in order thresholds but not in fusion thresholds.

Temporal constraints of perceiving, generating, and integrating information: Clinical indications.

Neuropsychological research on temporal constraints of perception and motor performance can add important information to research on human behavior. Without considering temporal mechanisms of perceiving, generating, and updating information, brain mechanisms can never be fully understood. In this study temporal aspects of performance in psychophysical experiments on three different temporal levels (around 30 ms, 300 ms, and 3000 ms) were investigated in patients with acquired brain lesions and a control group without neurological deficits. The patients had acquired focal brain lesions in: anterior (pre-central) regions of the left hemisphere (with non-fluent aphasia), posterior (post-central) regions of the left hemisphere (with fluent aphasia), the left hemipshere in predominantly subcortical regions (without aphasia), or anterior (pre-central) or posterior (post-central) regions of the right hemipshere. Perception of temporal order (20 to 60 ms) was impaired in patients with left-hemispheric post-central lesions; repetitive voluntary action (300 to 500 ms) was affected mostly in patients with left hemi-spheric lesions, both pre-central and post-central; and a deficit in integrating (2000 ms to 3000 ms) information was most pronounced in patients with left and right pre-central lesions. These findings provide insight into the associations between different levels of temporal organisation and circumscribed regions of the neocortex.

Temporal ranges of central nervous processing: clinical evidence.

The organization of the time frames for perceiving, generating, and updating information in the CNS has as of yet received little attention despite its elementary character for human behavior. We investigated temporal epochs in perceiving, acting, and updating in patients with anterior and posterior lesions of the left and right hemisphere, in patients with lesions in the left hemisphere without aphasia, and in healthy controls. Three temporal ranges, 30, 300, and 3000 ms, were assessed with different psychophysical paradigms. Prolongation of the temporal perception of order (30 ms) was most pronounced with left posterior lesions, of repetitive action (300 ms) with left anterior lesions, and updating (3000 ms) with left and right anterior lesions. Temporal deficits are group as well as parameter specific. Our results support the notion of coordinated coexistence of different temporal mechanisms.

Temporal processing disorders in patients with Broca's aphasia.

We report an association between a language deficit following brain lesion and a new strategy in temporal integration. Patients with different brain lesions mentally grouped sequences of identical acoustic stimuli generated at various frequencies. They were asked while listening to the stimuli to accentuate every second, third or other stimulus to create an individual rhythmic pattern. After each sequence patients reported how many stimuli they had united into a perceptual unit. The integration interval was defined as the number of reported stimuli multiplied by the temporal interval between two successive stimuli. Results indicate different integration strategies depending on the lesion site, i.e. Broca's aphasics behaving differently than all other patient groups. At lower frequencies they showed longer, at higher frequencies they displayed shorter integration. From this observation we conclude that the Broca's patients acquired a new strategy because of the lesion; they relied on mental counting and less on automatic temporal integration, which is usually the case.

Temporal constraints in processing of nonverbal rhythmic patterns.

This study investigates the effect of a mental content of presented stimuli, normal aging and individual differences in cognitive abilities on temporal limits of an integration mechanism. Younger and older subject grouped together the beats generated by a metronome. Subjects were asked to listen to the beats of a metronome and to accentuate mentally every second, third, fourth...etc. beat, to create a subjective rhythm. This rhythm exists, in fact, only in subjects' mind and not objectively. Subjects reported verbally how many clicks they were able to integrate into a perceptual unit. On this basis, the time interval during which subjects were able to integrate temporally separated stimuli was calculated (number of beats reported as being integrated x time distance between beats) for different metronome frequencies. The results show, firstly, that the length of integration periods significantly depends on the frequency of presented metronome beats. When the frequency of metronome beats is high, the time interval during which the subjects integrate beats into a single perceptual unit is shorter. Secondly, older adults integrate information during a longer time interval than younger ones. Thirdly, the length of an integration period is related to a subjects' level of cognitive ability. These results suggest that the length of an integration period is not a constant, stable feature, but varies across the life span depending on the mental content of the information presented and individual factors.

Domains of rehabilitation: a theoretical perspective.

On the basis of a taxonomy of functions an outline is given on potential deficits after brain lesions. The taxonomy distinguishes between "what"- and "how"-functions. Whereas for what-functions the localizing principle may apply, the how-functions being responsible for the logistics of the brain are non-locally represented. After brain injury the what- and how-functions may be differentially effected. On this basis 4 domains of functional rehabilitation can be distinguished, namely restitution and substitution of function after partly or complete losses of what-functions, activation and integration of function after alterations of activation or a disruption of functional coordination. Different strategies of functional rehabilitation are related to basic neurobiological principles which have been made responsible for restitution of function. Neuropsychological rehabilitation remains a challenge for neurobiology.

Multistable states in intrahemispheric learning of a sensorimotor task.

We have obtained evidence from an intrahemispheric learning task using a choice-reaction-time paradigm that the acquisition of a sensorimotor skill can be discontinuous. Subjects had to react as fast as possible to either a visual or an auditory stimulus. In several successive sessions, reaction times improved markedly, however in a discontinuous way. Different levels of performance were characterized by discrete functional states, each state being associated with a particular temporal window. After sufficient learning, reactions were confined to the earlier of two such windows.