Association between early suicidal trajectories in first-episode psychosis and 10-year follow-up: TIPS registry-linked study.

BACKGROUND: Although the risk of suicidality is high in first-episode psychosis, patterns and individual variability in suicidal thoughts and behaviours over time are under-researched. We aimed to identify early trajectories of suicidality over a 2-year follow-up, assess their baseline predictors, and explore associations between those trajectories and later suicidality. METHODS: This longitudinal follow-up study was a part of the Early Treatment and Intervention in Psychosis (TIPS)study. Participants, linked to Norwegian and Danish death registries, were recruited from four catchment areas (665 000 inhabitants) in Norway and Denmark (both inpatient and outpatient). We included participants aged 15-65 years, with an intelligence quotient of more than 70, willing to give informed consent, and with a first episode of active psychotic symptoms. Individuals with comorbid neurological or endocrinal disorders, or those with contraindications to antipsychotics, were excluded. Growth mixture modelling was used to identify trajectories of suicidal thoughts and behaviours over the first 2 years. Multinomial logistic regression was applied to examine the baseline predictors of those trajectories and their associations with suicidality at 10-year follow-up. FINDINGS: A total of 301 participants were recruited from Jan 1, 1997, to Dec 31, 2000. Of the 299 with completed suicidality data at baseline, 271 participated in 1-year follow-up, 250 in 2-year follow-up, 201 in 5-year follow-up, and 186 at 10-year follow-up. At baseline, 176 (58%) were male, 125 (42%) were female. The mean age was 27·80 years (SD 9·64; range 15-63). 280 (93%) participants were of Scandinavian origin. Four trajectories over 2 years were identified: stable non-suicidal (217 [72%]), stable suicidal ideation (45 [15%]), decreasing suicidal thoughts and behaviours (21 [7%]), and worsening suicidal thoughts and behaviours (18 [6%]). A longer duration of untreated psychosis (odds ratio [OR] 1·24, 95% CI 1·02-1·50, p=0·033), poorer premorbid childhood social adjustment (1·33, 1·01-1·73, p=0·039), more severe depression (1·10, 1·02-1·20, p=0·016), and substance use (2·33, 1·21-4·46, p=0·011) at baseline predicted a stable suicidal ideation trajectory. Individuals in the stable suicidal ideation trajectory tended to have suicidal thoughts and behaviours at 10-year follow-up (3·12, 1·33-7·25, p=0·008). Individuals with a worsening suicidal trajectory were at a higher risk of death by suicide between 2 and 10 years (7·58, 1·53-37·62, p=0·013). INTERPRETATION: Distinct suicidal trajectories in first-episode psychosis were associated with specific predictors at baseline and distinct patterns of suicidality over time. Our findings call for early and targeted interventions for at-risk individuals with persistent suicidal ideation or deteriorating patterns of suicidal thoughts and behaviours, or both. FUNDING: Health West, Norway; the Norwegian National Research Council; the Norwegian Department of Health and Social Affairs; the National Council for Mental Health and Health and Rehabilitation; the Theodore and Vada Stanley Foundation; the Regional Health Research Foundation for Eastern Region, Denmark; Roskilde County, Helsefonden, Lundbeck Pharma; Eli Lilly; Janssen-Cilag Pharmaceuticals, Denmark; a National Alliance for Research on Schizophrenia and Depression Distinguished Investigator Award and The National Institute of Mental Health grant; a National Alliance for Research on Schizophrenia & Depression Young Investigator Award from The Brain & Behavior Research Foundation; Health South East; Health West; and the Regional Centre for Clinical Research in Psychosis.

Myocardial inefficiency is an early indicator of exercise-induced myocardial fatigue.

Background: The effect of prolonged, high-intensity endurance exercise on myocardial function is unclear. This study aimed to determine the left ventricular (LV) response to increased exercise duration and intensity using novel echocardiographic tools to assess myocardial work and fatigue. Materials and methods: LV function was assessed by echocardiography before, immediately, and 24 h after a cardiopulmonary exercise test (CPET) and a 91-km mountain bike leisure race. Cardiac Troponin I (cTnI) was used to assess myocyte stress. Results: 59 healthy recreational athletes, 52 (43-59) years of age, 73% males, were included. The race was longer and of higher intensity generating higher cTnI levels compared with the CPET (p < 0.0001): Race/CPET: exercise duration: 230 (210, 245)/43 (40, 45) minutes, mean heart rate: 154 ± 10/132 ± 12 bpm, max cTnI: 77 (37, 128)/12 (7, 23) ng/L. Stroke volume and cardiac output were higher after the race than CPET (p < 0.005). The two exercises did not differ in post-exercise changes in LV ejection fraction (LVEF) or global longitudinal strain (GLS). There was an increase in global wasted work (p = 0.001) following the race and a persistent reduction in global constructive work 24 h after exercise (p = 0.003). Conclusion: Increased exercise intensity and duration were associated with increased myocardial wasted work post-exercise, without alterations in LVEF and GLS from baseline values. These findings suggest that markers of myocardial inefficiency may precede reduction in global LV function as markers of myocardial fatigue.

Determinants of Interindividual Variation in Exercise-Induced Cardiac Troponin I Levels.

Background Postexercise cardiac troponin levels show considerable interindividual variations. This study aimed to identify the major determinants of this postexercise variation in cardiac troponin I (cTnI) following 3 episodes of prolonged high-intensity endurance exercise. Methods and Results Study subjects were recruited among prior participants in a study of recreational cyclists completing a 91-km mountain bike race in either 2013 or 2014 (first race). In 2018, study participants completed a cardiopulmonary exercise test 2 to 3 weeks before renewed participation in the same race (second race). Blood was sampled before and at 3 and 24 hours following all exercises. Blood samples were analyzed using the same Abbot high-sensitivity cTnI STAT assay. Fifty-nine individuals (aged 50±9 years, 13 women) without cardiovascular disease were included. Troponin values were lowest before, highest at 3 hours, and declining at 24 hours. The largest cTnI difference was at 3 hours following exercise between the most (first race) (cTnI: 200 [87-300] ng/L) and the least strenuous exercise (cardiopulmonary exercise test) (cTnI: 12 [7-23] ng/L; P<0.001). The strongest correlation between troponin values at corresponding times was before exercise (r=0.92, P<0.0001). The strongest correlations at 3 hours were between the 2 races (r=0.72, P<0.001) and at 24 hours between the cardiopulmonary exercise test and the second race (r=0.83, P<0.001). Participants with the highest or lowest cTnI levels showed no differences in race performance or baseline echocardiographic parameters. Conclusions The variation in exercise-induced cTnI elevation is largely determined by a unique individual cTnI response that is dependent on the duration of high-intensity exercise and the timing of cTnI sampling. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02166216.

Endurance exercise training volume is not associated with progression of coronary artery calcification.

BACKGROUND: Recent cross-sectional studies have suggested a dose-dependent relationship between lifelong exposure to physical activity and the burden of calcified coronary artery disease (CAD). No longitudinal studies have addressed this concern. HYPOTHESIS: Exercise volume is associated with progression of coronary artery calcium (CAC), defined as ≥10 units increase in CAC score. METHODS: Sixty-one recreational athletes who were assessed by coronary computed tomography angiography (CCTA) as part of the NEEDED 2013/14 study were re-assessed 4-5 years later, in 2018. RESULTS: Subjects were 45.9 ± 9.6 years old at inclusion, and 46 (74%) were male. Between 2013 and 2018, the participants reported median 5 (range: 0-20, 25th-75th percentile: 4-6) hours of high-intensity exercise per week. None of the included subjects smoked during follow-up. At inclusion, 21 (33%) participants had coronary artery calcifications. On follow-up CCTA in 2018, 15 (25%) subjects had progressive coronary calcification (≥10 Agatston units increase in CAC). These subjects were older (53 ± 9 vs 44 ± 9 years old, P = .002) and had higher levels of low-density lipoprotein at baseline (3.5 (2.9-4.3) vs 2.9 (2.3-3.5) mmol/L, P = .031) as compared to subjects with stable condition. No relationship was found between hours of endurance training per week and progression of coronary artery calcification. In multiple regression analysis, age and baseline CAC were the only significant predictors of progressive CAC. CONCLUSION: No relationship between exercise training volume and the progression of coronary artery calcification was found in this longitudinal study of middle-aged recreational athletes.

Duration of Elevated Heart Rate Is an Important Predictor of Exercise-Induced Troponin Elevation.

Background The precise mechanisms causing cardiac troponin (cTn) increase after exercise remain to be determined. The aim of this study was to investigate the impact of heart rate (HR) on exercise-induced cTn increase by using sports watch data from a large bicycle competition. Methods and Results Participants were recruited from NEEDED (North Sea Race Endurance Exercise Study). All completed a 91-km recreational mountain bike race (North Sea Race). Clinical status, ECG, blood pressure, and blood samples were obtained 24 hours before and 3 and 24 hours after the race. Participants (n=177) were, on average, 44 years old; 31 (18%) were women. Both cTnI and cTnT increased in all individuals, reaching the highest level (of the 3 time points assessed) at 3 hours after the race (P<0.001). In multiple regression models, the duration of exercise with an HR >150 beats per minute was a significant predictor of both cTnI and cTnT, at both 3 and 24 hours after exercise. Neither mean HR nor mean HR in percentage of maximum HR was a significant predictor of the cTn response at 3 and 24 hours after exercise. Conclusions The duration of elevated HR is an important predictor of physiological exercise-induced cTn elevation. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT02166216.

Occult obstructive coronary artery disease is associated with prolonged cardiac troponin elevation following strenuous exercise.

BACKGROUND: Sudden cardiac death among middle-aged recreational athletes is predominantly due to myocardial ischaemia. This study examined whether measuring cardiac troponin I and T (cTnI and cTnT) after strenuous exercise could identify occult obstructive coronary artery disease. DESIGN: Prospective observational study. METHODS: Subjects were recruited from 1002 asymptomatic recreational cyclists completing a 91-km mountain bike race (North Sea Race Endurance Exercise Study). No subject had known cardiovascular disease or took cardiovascular medication. Blood samples were collected within 24 h before and 3 h and 24 h after the race. Coronary computed tomography angiography was performed in 80 participants with the highest post-exercise cTnI and in 40 reference subjects with moderately elevated cTnI values. RESULTS: Study subjects (N = 120) were 45 (36-52) years old and 74% were male. There were similar demographics in the High-cTnI group and the Reference group. The cTn concentrations were highest at 3 h post-race: cTnI, 224 (125-304) ng/L; cTnT, 89 (55-124) ng/L. Nine subjects had obstructive coronary artery disease on coronary computed tomography angiography, eight of whom were High-cTnI responders. Two subjects had myocardial bridging, both High-cTnI responders. Troponin concentrations at 24 h post-race were higher in subjects with obstructive coronary artery disease than in the rest of the cohort (n = 109): cTnI, 151 (72-233) ng/L vs. 24 (19-82) ng/L, p = 0.005; cTnT, 39 (25-55) ng/L vs. 20 (14-31) ng/L, p = 0.002. The areas under the receiver operating characteristic curves for predicting obstructive coronary artery disease were 0.79, p = 0.005 (cTnI) and 0.82, p = 0.002 (cTnT). CONCLUSION: In subjects with occult obstructive coronary artery disease there was a prolonged elevation of cTn following strenuous exercise.

Early Substance Use Cessation Improves Cognition-10 Years Outcome in First-Episode Psychosis Patients.

Background: Cognitive impairment may be a risk factor for, as well as a consequence of, psychosis. Non-remitting symptoms, premorbid functioning, level of education, and socioeconomic background are known correlates. A possible confounder of these associations is substance use, which is common among patients with psychosis and linked to worse clinical outcomes. Studies however show mixed results for the effect of substance use on cognitive outcomes. In this study, the long-term associations of substance use with cognition in a representative sample of first-episode psychosis patients were examined. Methods: The sample consisted of 195 patients. They were assessed for symptom levels, function, and neurocognition at 1, 2, 5, and 10 years after first treatment. Test scores were grouped into factor analysis-based indices: motor speed, verbal learning, visuomotor processing, verbal fluency, and executive functioning. A standardized composite score of all tests was also used. Patients were divided into four groups based on substance-use patterns during the first 2 years of treatment: persistent users, episodic users, stop-users, and nonusers. Data were analyzed using linear mixed effects modeling. Results: Gender, premorbid academic functioning, and previous education were the strongest predictors of cognitive trajectories. However, on motor speed and verbal learning indices, patients who stopped using substances within the first 2 years of follow-up improved over time, whereas the other groups did not. For verbal fluency, the longitudinal course was parallel for all four groups, while patients who stopped using substances demonstrated superior performances compared with nonusers. Persistent users demonstrated impaired visuomotor processing speed compared with nonusers. Within the stop- and episodic use groups, patients with narrow schizophrenia diagnoses performed worse compared with patients with other diagnoses on verbal learning and on the overall composite neurocognitive index. Discussion: This study is one of very few long-term studies on cognitive impairments in first-episode psychosis focusing explicitly on substance use. Early cessation of substance use was associated with less cognitive impairment and some improvement over time on some cognitive measures, indicating a milder illness course and superior cognitive reserves to draw from in recovering from psychosis.

Race duration and blood pressure are major predictors of exercise-induced cardiac troponin elevation.

BACKGROUND: The underlying mechanisms of the exercise-induced increase in cardiac troponins (cTn) are poorly understood. The aim of this study was to identify independent determinants of exercise-induced cTn increase in a large cohort of healthy recreational athletes. METHODS: A total of 1002 recreational cyclists without known cardiovascular disease or medication, participating in a 91-km mountain bike race were included. Median age was 47 years and 78% were males. Blood samples were obtained 24 h prior to, and 3 and 24 h after the race. RESULTS: Cardiac TnI concentrations increased markedly from baseline [1.9 (1.6-3.0) ng/L] to 3 h after the race [52.1 (32.4-91.8) ng/L], declining at 24 h after the race [9.9 (6.0-20.0) ng/L]. Similarly, cTnT increased from baseline [3.0 (3.0-4.2) ng/L] to 3 h after the race [35.6 (24.4-54.4) ng/L], followed by a decline at 24 h after the race [10.0 (6.9-15.6) ng/L]. The 99th percentile was exceeded at 3 h after the race in 84% (n = 842) of subjects using the cTnI assay and in 92% (n = 925) of study subjects using the cTnT assay. Shorter race duration and higher systolic blood pressure (SBP) at baseline were highly significant (p < 0.001) independent predictors of exercise-induced cTn increase both in bivariate and multivariable analysis. The age, gender, body mass index, training experience and cardiovascular risk of participants were found to be less consistent predictors. CONCLUSION: Systolic blood pressure and race duration were consistent predictors of the exercise-induced cTn increase. These variables likely reflect important mechanisms involved in the exercise-induced cTn elevation. TRIAL REGISTRATION NUMBER: NCT02166216 https://clinicaltrials.gov/ct2/show/NCT02166216.

A Longitudinal Study of Neurocognition in Dementia with Lewy Bodies Compared to Alzheimer's Disease.

INTRODUCTION: There are relatively few longitudinal studies on the differences in cognitive decline between Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), and the majority of existing studies have suboptimal designs. AIM: We investigated the differences in cognitive decline in AD compared to DLB over 4 years and cognitive domain predictors of progression. METHODS: In a longitudinal study, 266 patients with first-time diagnosis of mild dementia were included and followed annually. The patients were tested annually with neuropsychological tests and screening instruments [MMSE (Mini-Mental Status Examination), Clinical Dementia Rating (CDR), the second edition of California Verbal Learning Test (CVLT-II), Trail Making Test A & B (TMT A & B), Stroop test, Controlled Oral Word Associations Test (COWAT) animal naming, Boston Naming Test, Visual Object and Space Perception Battery (VOSP) Cubes and Silhouettes]. Longitudinal analyses were performed with linear mixed effects (LME) models and Cox regression. Both specific neuropsychological tests and cognitive domains were analyzed. RESULTS: This study sample comprised 119 AD and 67 DLB patients. In TMT A, the DLB patients had a faster decline over 4 years than patients with AD (p = 0.013). No other longitudinal differences in specific neuropsychological tests were found. Higher executive domain scores at baseline were associated with a longer time to reach severe dementia (CDR = 3) or death for the total sample (p = 0.032). High or low visuospatial function at baseline was not found to be associated with cognitive decline (MMSE) or progression of dementia severity (CDR) over time. CONCLUSION: Over 4 years, patients with DLB had a faster decline in TMT A than patients with AD, but this should be interpreted cautiously. Beyond this, there was little support for faster decline in DLB patients neuropsychologically than in AD patients.

Stress in School. Some Empirical Hints on the Circadian Cortisol Rhythm of Children in Outdoor and Indoor Classes.

This prospective longitudinal survey compared the stress levels of students taught using an outdoor curriculum in a forest, with children in a normal school setting. We were especially interested in the effect outdoor teaching might have on the children's normal diurnal cortisol rhythm. 48 children (mean age = 11.23; standard deviation (SD) = 0.46) were enrolled, with 37 in the intervention group (IG), and 11 in the control group (CG). The intervention consisted of one full school day per week in the forest over the school year. Stress levels were measured in cortisol with three samples of saliva per day. Furthermore, the data allowed for statistical control of physical activity (PA) values. For data analysis, we used a linear mixed-effects model (LMM) with random intercept and general correlation matrix for the within-unit residuals. The LMM yields that IG have expected greater decline of cortisol compared to CG; rate 0.069 µg/L vs. 0.0102 µg/L (log-units/2 h), p = 0.009. PA does not show a statistically significant interaction with cortisol (p = 0.857), despite being higher in the intervention group (p < 0.001). The main effect in our measures was that the IG had a steady decline of cortisol during the school day. This is in accordance with a healthy child's diurnal rhythm, with a significant decline of cortisol from morning to noon. This effect is constant over the school year. The CG does not show this decline during either measurement day. Further research is needed to fully explain this interesting phenomenon.

Long-Term Cognitive Decline in Dementia with Lewy Bodies in a Large Multicenter, International Cohort.

BACKGROUND/OBJECTIVE: The aim of this study was to describe the rate and clinical predictors of cognitive decline in dementia with Lewy bodies (DLB), and compare the findings with Alzheimer's disease (AD) and Parkinson's disease dementia (PDD) patients. METHODS: Longitudinal scores for the Mini-Mental State Examination (MMSE) in 1,290 patients (835 DLB, 198 PDD, and 257 AD) were available from 18 centers with up to three years longitudinal data. Linear mixed effects analyses with appropriate covariates were used to model MMSE decline over time. Several subgroup analyses were performed, defined by anti-dementia medication use, baseline MMSE score, and DLB core features. RESULTS: The mean annual decline in MMSE score was 2.1 points in DLB, compared to 1.6 in AD (p = 0.07 compared to DLB) and 1.8 in PDD (p = 0.19). Rates of decline were significantly higher in DLB compared to AD and PDD when baseline MMSE score was included as a covariate, and when only those DLB patients with an abnormal dopamine transporter SPECT scan were included. Decline was not predicted by sex, baseline MMSE score, or presence of specific DLB core features. CONCLUSIONS: The average annual decline in MMSE score in DLB is approximately two points. Although in the overall analyses there were no differences in the rate of decline between the three neurodegenerative disorders, there were indications of a more rapid decline in DLB than in AD and PDD. Further studies are needed to understand the predictors and mechanisms of cognitive decline in DLB.

The Effect of Substance Use on 10-Year Outcome in First-Episode Psychosis.

Substance use is common in first-episode psychosis (FEP) and has been linked to poorer outcomes with more severe psychopathology and higher relapse rates. Early substance discontinuation appears to improve symptoms and function. However, studies vary widely in their methodology, and few have examined patients longitudinally, making it difficult to draw conclusions for practice and treatment. We aimed to investigate the relationship between substance use and early abstinence and the long-term course of illness in a representative sample of FEP patients. Out of 301 included patients, 266 could be divided into 4 groups based on substance use patterns during the first 2 years of treatment: persistent users, episodic users, stop-users and nonusers. Differences in clinical and functional measures during the follow-up period were assessed using linear mixed effects models for the analysis of repeated measures data. Patients who stopped using substances within the first 2 years after diagnosis had outcomes similar to those who had never used with fewer symptoms than episodic or persistent users. Both episodic and persistent users had lower rates of symptom remission than nonusers, and persistent users also had more negative symptoms than those who stopped using. Our findings emerge from one of very few long-term longitudinal studies examining substance use cessation in FEP with 10-year follow-up. The results convey hope that the detrimental effects of substance abuse on mental health may be significantly reversed if one stops the abuse in time. This can help patients who struggle with addiction with their motivation to embrace abstinence.

Highly increased Troponin I levels following high-intensity endurance cycling may detect subclinical coronary artery disease in presumably healthy leisure sport cyclists: The North Sea Race Endurance Exercise Study (NEEDED) 2013.

Background Circulating cardiac troponin levels increase following prolonged intense physical exercise. The aim of this study was to identify participants with highly elevated cardiac troponins after prolonged, high intensity exercise, and to evaluate these for subclinical coronary artery disease. Methods and results Ninety-seven recreational cyclists without known cardiovascular disease or diabetes, participating in a 91 km mountain bike race were included, 74 (76%) were males, age: 43 ± 10 years, race duration: 4.2 (3.6-4.7) h. Blood samples, rest electrocardiogram and physical examination were obtained 24 h prior to, and at 0, 3 and 24 h following the race. Median cardiac troponin I level at baseline: 3.4 (2.1-4.9) ng/l (upper limit of normal: 30.0 ng/l). There was a highly significant ( p < 0.0001) increase in circulating cardiac troponin I in all participants: immediately following the race; 50.5 (28.5-71.9) ng/l, peaking at 3 h 69.3 (42.3-97.7) ng/l and declining at 24 h: 14.2 (8.5-27.9) ng/l. No cyclist had symptoms or rest electrocardiogram changes compatible with coronary artery disease during or following the race. Coronary artery disease was detected by coronary angiography in the three cyclists with the three of the four highest cardiac troponin values (>370 ng/l) at 3 and 24 h following the race. Computed tomographic coronary angiography was performed in an additional 10 riders with the subsequently highest cardiac troponin I values, without identifying underlying coronary artery disease. Conclusions This study suggests that there is a pathologic cardiac troponin I response following exercise in individuals with subclinical coronary artery disease. This response may be associated with an excessive cardiac troponin I increase at 3 and 24 h following prolonged high-intensity exercise.

Alzheimer's disease cerebrospinal fluid biomarkers predict cognitive decline in lewy body dementia.

INTRODUCTION: Alzheimer's disease pathologies are common in dementia with Lewy bodies, but their clinical relevance is not clear. CSF biomarkers amyloid beta 1-42, total tau, and tau phosphorylated at threonine 181 reflect Alzheimer's disease neuropathology antemortem. In PD, low CSF amyloid beta 1-42 predict long-term cognitive decline, but little is known about these biomarkers as predictors for cognitive decline in Lewy body dementia. The aim of this study was to assess whether Alzheimer's disease CSF biomarkers predict cognitive decline in Lewy body dementia. METHODS: From a large European dementia with Lewy bodies multicenter study, we analyzed baseline Alzheimer's disease CSF biomarkers and serial MMSE (baseline and 1- and 2-year follow-up) in 100 patients with Lewy body dementia. Linear mixed-effects analyses, adjusted for sex, age, baseline MMSE, and education, were performed to model the association between CSF biomarkers and rate of cognitive decline measured with MMSE. An Alzheimer's disease CSF profile was defined as pathological amyloid beta 1-42 plus pathological total tau or phosphorylated tau. RESULTS: The Alzheimer's disease CSF profile, and pathological levels of amyloid beta 1-42, were associated with a more rapid decline in MMSE (2.2 [P < 0.05] and 2.9 points difference [P < 0.01], respectively). Higher total tau values showed a trend toward association without statistical significance (2.0 points difference; P = 0.064), whereas phosphorylated tau was not associated with decline. CONCLUSIONS: Reduced levels of CSF amyloid beta 1-42 were associated with more rapid cognitive decline in Lewy body dementia patients. Future prospective studies should include larger samples, centralized CSF analyses, longer follow-up, and biomarker-pathology correlation. © 2016 International Parkinson and Movement Disorder Society.

A longitudinal study of anxiety and cognitive decline in dementia with Lewy bodies and Alzheimer's disease.

BACKGROUND: Anxiety in dementia is common but not well studied. We studied the associations of anxiety longitudinally in Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). METHODS: In total, 194 patients with a first-time diagnosis of dementia were included (n = 122 patients with AD, n = 72 patients with DLB). Caregivers rated the patients' anxiety using the Neuropsychiatric Inventory, and self-reported anxiety was assessed with the anxiety and tension items on the Montgomery-Åsberg Depression Rating Scale. The Mini Mental State Examination was used to assess cognitive outcome, and the Clinical Dementia Rating (CDR)-Global and CDR boxes were used for dementia severity. Linear mixed effects models were used for longitudinal analysis. RESULTS: Neither in the total sample nor in AD or DLB was caregiver-rated anxiety significantly associated with cognitive decline or dementia severity over a 4-year period. However, in patients with DLB, self-reported anxiety was associated with a slower cognitive decline than in patients with AD. No support was found for patients with DLB with clinical anxiety having a faster decline than patients with DLB without clinical anxiety. Over the course of 4 years, the level of anxiety declined in DLB and increased in AD. CONCLUSIONS: Anxiety does not seem to be an important factor for the rate of cognitive decline or dementia severity over time in patients with a first-time diagnosis of dementia. Further research into anxiety in dementia is needed.

Association of Butyrylcholinesterase-K Allele and Apolipoprotein E ɛ4 Allele with Cognitive Decline in Dementia with Lewy Bodies and Alzheimer's Disease.

BACKGROUND: A common polymorphism of the butyrylcholinesterase gene, the K-variant (BCHE-K) is associated with reduced butyrylcholinesterase (BuChE) activity. Insufficient studies exist regarding the frequency and role of BCHE-K in dementias. OBJECTIVE: To determine the association of BCHE-K and APOEɛ4 with diagnosis and rate of cognitive decline in dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) patients. METHODS: Genomic DNA from 368 subjects (108 AD, 174 DLB, and 86 controls) from two routine clinical cohort studies in Norway; DemVest and TrønderBrain, were genotyped for BCHE-K and APOEɛ4. The mild dementia DemVest subjects received annual Mini-Mental State Examination assessments for five years. RESULTS: BCHE-K frequency was lower in DLB (33.9% ; p <  0.01) than in control subjects (51.2%), and was numerically lower in AD as well (38.9% ; p = 0.11). More rapid cognitive decline was associated with the APOEɛ4 genotype, but not with the BCHE-K genotype. In an exploratory analysis of patients who completed all five follow-up visits, there was greater cognitive decline in BCHE-K carriers in the presence of the APOEɛ4 allele than in the absence of these polymorphisms. CONCLUSION: BCHE-K is associated with a reduced risk for AD and DLB whereas APOEɛ4 is associated with more rapid cognitive decline. The greater cognitive decline in individuals with both APOEɛ4 and BCHE-K alleles require prospective confirmation in well-controlled trials.

Frequent brief on-site simulation training and reduction in 24-h neonatal mortality--an educational intervention study.

AIM OF THE STUDY: "Helping Babies Breathe" (HBB) is a simulation-based educational program developed to help reduce perinatal mortality worldwide. A one-day HBB training course did not improve clinical management of neonates. The objective was to assess the impact of frequent brief (3-5 min weekly) on-site HBB simulation training on newborn resuscitation practices in the delivery room and the potential impact on 24-h neonatal mortality. METHODS: Before/after educational intervention study in a rural referral hospital in Northern Tanzania. Baseline data was collected from 01.02.2010 to 31.01.2011 and post-intervention data from 01.02.2011 to 31.01.2012. All deliveries were observed by research assistants who recorded information about labor, newborn delivery room management, perinatal characteristics, and neonatal outcomes. A newborn simulator was placed in the labor ward and frequent brief HBB simulation training was implemented on-site; 3-min of weekly paired practice, assisted by local-trainers. Local-trainers also facilitated 40-min monthly re-trainings. Outcome measures were; delivery room management of newborns and 24-h neonatal outcomes (normal, admitted to a neonatal area, death, or stillbirths). RESULTS: There were 4894 deliveries pre and 4814 post-implementation of frequent brief simulation training. The number of stimulated neonates increased from 712(14.5%) to 785(16.3%) (p = 0.016), those suctioned increased from 634(13.0%) to 762(15.8%) (p ≤ 0.0005). Neonates receiving bag mask ventilation decreased from 357(7.3%) to 283(5.9%) (p = 0.005). Mortality at 24-h decreased from 11.1/1000 to 7.2/1000 (p = 0.040). CONCLUSION: On-site, brief and frequent HBB simulation training appears to facilitate transfer of new knowledge and skills into clinical practice and to be accompanied by a decrease in neonatal mortality.

Neonatal outcome following cord clamping after onset of spontaneous respiration.

BACKGROUND AND OBJECTIVE: Evolving data indicate that cord clamping (CC) beyond 30 to 60 seconds after birth is of benefit for all infants. Recent experimental data demonstrated that ventilation before CC improved cardiovascular stability by increasing pulmonary blood flow. The objective was to describe the relationship between time to CC, onset of spontaneous respirations (SR), and 24-hour neonatal outcome. METHODS: In a rural Tanzanian hospital, trained research assistants, working in shifts, have observed every delivery (November 2009-February 2013) and recorded data including time interval from birth to SR and CC, fetal heart rate, perinatal characteristics and outcome (normal, death, admission). RESULTS: Of 15,563 infants born, 12,780 (84.3%) initiated SR at 10.8 ± 16.7 seconds, and CC occurred at 63 ± 45 seconds after birth. Outcomes included 12,730 (99.7%) normal, 31 deaths, and 19 admitted; 11,967 were of birth weight (BW) ≥2500 g and 813 <2500 g. By logistic modeling, the risk of death/admission was consistently higher if CC occurred before SR. Infants of BW <2500 g were more likely to die or be admitted. The risk of death/admission decreased by 20% for every 10-second delay in CC after SR; this risk declined at the same rate in both BW groups. CONCLUSIONS: Healthy self-breathing neonates are more likely to die or be admitted if CC occurs before or immediately after onset of SR. These clinical observations support the experimental findings of a smoother cardiovascular transition when CC is performed after initiation of ventilation.

Galantamine versus risperidone for agitation in people with dementia: a randomized, twelve-week, single-center study.

AIMS: To examine the effects of galantamine and risperidone on agitation in patients with dementia. METHODS: A total of 100 patients with dementia and neuropsychiatric symptoms (mean age ± SD: 78.6 ± 7.5 years; 67% female) were included in this 12-week, randomized, parallel-group, controlled, single-center trial. The participants received galantamine (n = 50; target dose: 24 mg) or risperidone (n = 50; target dose: 1.5 mg) for 12 weeks. RESULTS: Both galantamine and risperidone treatment resulted in reduced agitation. However, risperidone showed a significant advantage over galantamine both at week 3 (mean difference in total Cohen-Mansfield Agitation Inventory score: 3.7 points; p = 0.03) and at week 12 (4.3 points; p = 0.01). CONCLUSIONS: Agitation improved in both groups, even if the treatment effects were more pronounced in the risperidone group; however, the effects on cognition and other aspects of tolerability were stronger with galantamine.

Treatment and violent behavior in persons with first episode psychosis during a 10-year prospective follow-up study.

BACKGROUND: First episode psychosis (FEP) patients have an increased risk for violence and criminal activity prior to initial treatment. However, little is known about the prevalence of criminality and acts of violence many years after implementation of treatment for a first episode psychosis. AIM: To assess the prevalence of criminal and violent behaviors during a 10-year follow-up period after the debut of a first psychosis episode, and to identify early predictors and concomitant risk factors of violent behavior. METHOD: A prospective design was used with comprehensive assessments of criminal behavior, drug abuse, clinical, social and treatment variables at baseline, five, and 10-year follow-up. Additionally, threatening and violent behavior was assessed at 10-year follow-up. A clinical epidemiological sample of first-episode psychosis patients (n=178) was studied. RESULTS: During the 10-year follow-up period, 20% of subjects had been apprehended or incarcerated. At 10-year follow-up, 15% of subjects had exposed others to threats or violence during the year before assessment. Illegal drug use at baseline and five-year follow-up, and a longer duration of psychotic symptoms were found to be predictive of violent behavior during the year preceding the 10-year follow-up. CONCLUSION: After treatment initiation, the overall prevalence of violence in psychotic patients drops gradually to rates close to those of the general population. However, persistent illicit drug abuse is a serious risk factor for violent behavior, even long after the start of treatment. Achieving remission early and reducing substance abuse may contribute to a lower long-term risk for violent behavior in FEP patients.