| 1. |
- Ademuyiwa, Adesoji O., et al.
(författare)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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| 2. |
- Bang Madsen, Kathrine, et al.
(författare)
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Attention-Deficit Hyperactivity Disorder (ADHD) Medication Use Trajectories Among Women in the Perinatal Period
- 2024
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Ingår i: CNS Drugs. - : Adis International Ltd.. - 1172-7047 .- 1179-1934. ; 38, s. 301-314
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: An increasing number of women of reproductive age are treated with attention-deficit hyperactivity disorder (ADHD) medication; however, patterns of ADHD medication use for women in the perinatal period have not been well described.OBJECTIVE: This study aimed to describe ADHD medication use patterns from 1 year before pregnancy to 1 year after delivery, and to describe sociodemographic characteristics and clinical features by medication trajectories.METHODS: The population-based cohort study included pregnancies in Denmark between 1997 and 2020, from the Medical Birth Register, by women who filled at least one prescription for ADHD medication from 12 months before pregnancy until 12 months after delivery. We applied group-based trajectory modeling to classify women into subgroups based on the identification of heterogeneous ADHD medication treatment patterns, and described the characteristics associated with these groups.RESULTS: Overall, we included 4717 pregnancies leading to liveborn singletons by 4052 mothers with a mean (standard deviation) age of 27.5 (5.6) years. We identified four treatment trajectories across pregnancy and the postpartum period: continuers (23.3%), discontinuers (41.8%), interrupters who ceased filling prescriptions during pregnancy but resumed postpartum (17.2%), and postpartum initiators (17.7%). Continuers were older at the time of conception, gave birth in more recent years, were more likely to smoke during pregnancy, and used other psychotropic medications during pregnancy. A large proportion of continuers used methylphenidate (89.1%) compared with the other groups (75.9-84.1%) and had switched ADHD medication type during the whole period (16.4% vs. 7.4-14.8%).CONCLUSION: We found that approximately 60% of women discontinued or interrupted their ADHD medication around pregnancy, and those who continued differed in sociodemographic and clinical factors that may reflect more severe ADHD.
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| 3. |
- Bodén, Robert, 1973-, et al.
(författare)
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Psychomotor and cognitive deficits as predictors of 5-year outcome in first-episode schizophrenia
- 2014
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Ingår i: Nordic Journal of Psychiatry. - : Informa UK Limited. - 0803-9488 .- 1502-4725. ; 68:4, s. 282-288
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cognitive deficits are common in schizophrenia but the predictive value of these deficits for long-term outcome in first-episode patients is unclear. Aims: We aimed to investigate associations of performance in psychomotor and cognitive tests with a 5-year functional and symptomatic outcome. Methods: After clinical stabilization, patients with a first schizophrenia spectrum diagnosis (n = 46) were assessed for global cognitive function [Synonyms, Reasoning, and Block Design (SRB)], psychomotor speed [Trail Making Test (TMT) and finger tapping] and verbal learning (Claeson-Dahl Verbal Learning Test). The subsequent 5-year outcome regarding independent living, occupational and social function, and symptomatic remission status was assessed. Results: Low psychomotor speed was associated with poor social function 5 years later, with an odds ratio (OR) of 3.37 and a 95% confidence interval (CI) of 1.08-10.51, adjusted for antipsychotic drug use. Better performance on finger tapping with the non-dominant hand was associated with an increased risk of a 5-year symptomatic non-remission (adjusted OR = 0.42, CI 0.19-0.96). Occupational function and independent living were not significantly associated with any of the investigated tests. Conclusions: Psychomotor speed is associated with a long-term outcome regarding social function and symptom remission in patients with first-episode schizophrenia.
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| 4. |
- Borg, Jacqueline
(författare)
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Molecular imaging of the serotonin system in human behaviour
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The serotonin (5-HT) neurotransmission system has a role in essential physiological and psychological functions such as sleep, eating behaviour, sexuality, perception, emotion and cognition. Individual measures of serotonin biomarkers in the living human brain can be obtained using positron emission tomography (PET) imaging, direct measures of. The interindividual variability in these measures can then be related to human behavioural output. In combination with genotyping, this strategy provides an approach to complex chain of events linking the genetic endowment to higher brain functions. The present thesis includes a series of PET studies aimed to increase understanding of the role of serotonin in higher brain functions in man. In study I, fifteen control subjects were examined with PET and [11C]WAY100635, a radioligand that is selective for the serotonin 5-HT1A receptor. Personality traits were assessed with the Temperament and Character Inventory (TCI) self-report questionnaire. Availability of 5-HT1A receptor was found to correlate inversely with scores for self-transcendence, a personality trait covering religious behaviour and attitudes. This finding indicates that the serotonin system may serve as a biological underpinning for spiritual experiences. Interestingly, the observed several-fold variability in 5-HT1A receptor density may partly explain why people vary greatly in spiritual zeal. In study II, twenty-four control subjects were examined with [11C]WAY100635 PET and a battery of tests covering all major cognitive domains. There were no significant correlations between regional 5-HT1A binding and cognitive performance. The results do not provide support for involvement of the 5-HT1A receptor in cognitive functioning in man, thereby questioning the predictive validity of some currently used animal models in translational neuroscience. In study III, seventeen volunteers were examined with [11C]MADAM PET and a battery of cognitive tests. Serotonin transporter (5-HTT) availability in cortical regions correlated significantly with performance in sustained attention. The results support a role for the serotonin system in some but not all cognitive functions in man. In study IV, fifty-four control subjects were examined with [11C]WAY100635 PET and a battery of cognitive tests. Subjects were genotyped for the 5-HTT linked polymorphic region (5-HTTLPR), a functional polymorphism in the promoter region of the 5-HTT gene. The short (S) allele of the 5-HTTLPR has been associated with depression as well as anxiety-related personality traits. Carriers of the S allele of the 5-HTTLPR did not differ from non-carriers with respect to [11C]WAY100635 binding potential in any of the brain regions studied. S-carriers however performed significantly better in the Wisconsin Card Sorting Test. These observations suggest that functional implications of the 5-HTTLPR are not likely to be mediated by differences in 5-HT1A density and that other biomarkers must be considered for future investigations at phenotype level. The present studies of serotonergic biomarkers in man provide new evidence for a role of the serotonin system in complex human behaviour such as cognitive functions and personality traits.
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| 5. |
- Borg, Jacqueline, et al.
(författare)
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The serotonin system and spiritual experiences
- 2003
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Ingår i: American Journal of Psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 160:11, s. 1965-1969
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The serotonin system has long been of interest in biological models of human personality. The purpose of this positron emission tomography (PET) study was to search for relationships between serotonin 5-HT(1A) receptor density and personality traits. METHOD: Fifteen normal male subjects, ages 20-45 years, were examined with PET and the radioligand [(11)C]WAY100635. Personality traits were assessed with the Swedish version of the Temperament and Character Inventory self-report questionnaire. Binding potential, an index for the density of available 5-HT(1A) receptors, was calculated for the dorsal raphe nuclei, the hippocampal formation, and the neocortex. For each region, correlation coefficients between 5-HT(1A) receptor binding potential and Temperament and Character Inventory personality dimensions were calculated and analyzed in two-tailed tests for significance. RESULTS: The authors found that the binding potential correlated inversely with scores for self-transcendence, a personality trait covering religious behavior and attitudes. No correlations were found for any of the other six Temperament and Character Inventory dimensions. The self-transcendence dimension consists of three distinct subscales, and further analysis showed that the subscale for spiritual acceptance correlated significantly with binding potential but not with the other two subscales. CONCLUSIONS: This finding in normal male subjects indicated that the serotonin system may serve as a biological basis for spiritual experiences. The authors speculated that the several-fold variability in 5-HT(1A) receptor density may explain why people vary greatly in spiritual zeal.
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| 6. |
- Caravaggio, Fernando, et al.
(författare)
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Trait impulsivity is not related to post-commissural putamen volumes : A replication study in healthy men
- 2018
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:12
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Tidskriftsartikel (refereegranskat)abstract
- High levels of trait impulsivity are considered a risk factor for substance abuse and drug addiction. We recently found that non-planning trait impulsivity was negatively correlated with post-commissural putamen volumes in men, but not women, using the Karolinska Scales of Personality (KSP). Here, we attempted to replicate this finding in an independent sample using an updated version of the KSP: the Swedish Universities Scales of Personality (SSP). Data from 88 healthy male participants (Mean Age: 28.16 +/- 3.34), who provided structural T1-weighted magnetic resonance images (MRIs) and self-reported SSP impulsivity scores, were analyzed. Striatal sub-region volumes were acquired using the Multiple Automatically Generated Templates (MAGeT-Brain) algorithm. Contrary to our previous findings trait impulsivity measured using SSP was not a significant predictor of post-commissural putamen volumes (beta = .14, df = 84, p = .94). A replication Bayes Factors analysis strongly supported this null result. Consistent with our previous findings, secondary exploratory analyses found no relationship between ventral striatum volumes and SSP trait impulsivity (beta = -.05, df = 84, p = .28). An exploratory analysis of the other striatal compartments showed that there were no significant associations with trait impulsivity. While we could not replicate our previous findings in the current sample, we believe this work will aide future studies aimed at establishing meaningful brain biomarkers for addiction vulnerability in healthy humans.
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| 7. |
- Farde, Lars, et al.
(författare)
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Brain neuroreceptor density and personality traits : towards dimensional biomarkers for psychiatric disorders.
- 2018
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Ingår i: Philosophical Transactions of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8436 .- 1471-2970. ; 373:1744
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Forskningsöversikt (refereegranskat)abstract
- Positron emission tomography has, for 30 years, been used in numerous case-control studies searching for hypothesized differences in the density of neuroreceptor or transporter proteins in psychiatric disorders such as schizophrenia and depression. In most cases, the results have not been conclusive. One reason could be the sizeable interindividual variability in biochemical markers, which in twin studies have shown to emanate from both environmental and genetic factors, leading to low statistical power for the detection of group effects. On the other hand, the same interindividual variability has served as an opportunity for correlative studies on the biological underpinning of behaviour. Using this approach, a series of studies has linked markers for the dopamine and serotonin system to personality traits associated with psychiatric conditions. Based on increasing evidence for the view that many psychopathological states represent extremes of a continuum rather than distinct categories, this research strategy may lead to new biological insights about the vulnerability to and pathophysiology of major psychiatric disorders.This article is part of the theme issue 'Diverse perspectives on diversity: multi-disciplinary approaches to taxonomies of individual differences'.
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| 8. |
- Gaudet, Mia M., et al.
(författare)
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Common Genetic Variants and Modification of Penetrance of BRCA2-Associated Breast Cancer
- 2010
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 6:10
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Tidskriftsartikel (refereegranskat)abstract
- The considerable uncertainty regarding cancer risks associated with inherited mutations of BRCA2 is due to unknown factors. To investigate whether common genetic variants modify penetrance for BRCA2 mutation carriers, we undertook a two-staged genome-wide association study in BRCA2 mutation carriers. In stage 1 using the Affymetrix 6.0 platform, 592,163 filtered SNPs genotyped were available on 899 young (, 40 years) affected and 804 unaffected carriers of European ancestry. Associations were evaluated using a survival-based score test adjusted for familial correlations and stratified by country of the study and BRCA2*6174delT mutation status. The genomic inflation factor (lambda) was 1.011. The stage 1 association analysis revealed multiple variants associated with breast cancer risk: 3 SNPs had p-values, 10 25 and 39 SNPs had p-values<10(-4). These variants included several previously associated with sporadic breast cancer risk and two novel loci on chromosome 20 (rs311499) and chromosome 10 (rs16917302). The chromosome 10 locus was in ZNF365, which contains another variant that has recently been associated with breast cancer in an independent study of unselected cases. In stage 2, the top 85 loci from stage 1 were genotyped in 1,264 cases and 1,222 controls. Hazard ratios (HR) and 95% confidence intervals (CI) for stage 1 and 2 were combined and estimated using a retrospective likelihood approach, stratified by country of residence and the most common mutation, BRCA2*6174delT. The combined per allele HR of the minor allele for the novel loci rs16917302 was 0.75 (95% CI 0.66-0.86, p = 3: 8 x 10(-5)) and for rs311499 was 0.72 (95% CI 0.61-0.85, p = 6: 6 x 10(-5)). FGFR2 rs2981575 had the strongest association with breast cancer risk (per allele HR = 1.28, 95% CI 1.18-1.39, p = 1: 2 x 10(-8)). These results indicate that SNPs that modify BRCA2 penetrance identified by an agnostic approach thus far are limited to variants that also modify risk of sporadic BRCA2 wild-type breast cancer.
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| 9. |
- Griffioen, Gina, et al.
(författare)
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Serotonin 5-HT1A receptor binding and self-transcendence in healthy control subjects : a replication study using Bayesian hypothesis testing
- 2018
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Ingår i: PeerJ. - : PeerJ. - 2167-8359. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Objective. A putative relationship between markers for the serotonin system and the personality scale self-transcendence (ST) and its subscale spiritual acceptance (SA) has been demonstrated in a previous PET study of 5-HT1A receptor binding in healthy control subjects. The results could however not be replicated in a subsequent PET study at an independent centre. In this study, we performed a replication of our original study in a larger sample using Bayesian hypothesis testing to evaluate relative evidence both for and against this hypothesis. Methods. Regional 5-HT1A receptor binding potential (BPND) was examined in 50 healthy male subjects using PET with the radioligand [C-11]WAY100635. 5-HT1A availability was calculated using the simplified reference tissue model (SRTM) yielding regional BPND. ST and SA were measured using the Temperament and Character Inventory (TCI) questionnaire. Correlations between ST/SA scores and 5-HT1A BPND in frontal cortex, hippocampus and raphe nuclei were examined by calculation of default correlation Bayes factors (BFs) and replication BFs. Results. There were no significant correlations between 5-HT1A receptor binding and ST/SA scores. Rather, five of six replication BFs provided moderate to strong evidence for no association between 5-HT1A availability and ST/SA, while the remaining BF provided only weak evidence. Conclusion. We could not replicate our previous findings of an association between 5-HT1A availability and the personality trait ST/SA. Rather, the Bayesian analysis provided evidence for a lack of correlation. Further research should focus on whether other components of the serotonin system may be related to ST or SA. This study also illustrates how Bayesian hypothesis testing allows for greater flexibility and more informative conclusions than traditional p-values, suggesting that this approach may be advantageous for analysis of molecular imaging data.
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| 10. |
- Gustavsson, Peter, et al.
(författare)
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Duplication 16q12.1-q22.1 characterized by array CGH in a girl with spina bifida
- 2007
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Ingår i: European Journal of Medical Genetics. - : Elsevier BV. - 1769-7212 .- 1878-0849. ; 50:3, s. 237-241
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Tidskriftsartikel (refereegranskat)abstract
- We report a 7-year-old girl with spina bifida carrying a complex chromosome abnormality resulting in duplication 16q12.1–q22.1. An abnormal karyotype was identified involving the long arm of chromosome 11 and fluorescent in situ hybridization (FISH) to metaphase chromosomes revealed an insertion of part of chromosome 16 on chromosome 11. A detailed mapping of the chromosome abnormality using whole genome array based comparative genomic hybridization (CGH) of the patient DNA revealed a duplication 16q12.1–q22.1 corresponding to gain of 19.8 Mb of DNA without any detectable loss of genetic material on chromosome 11. The karyotype is defined as 46,XX,der(11)ins(11;16)(q13;q12.1q22.1). We present here the clinical findings and a fine mapping of the associated structural chromosome abnormalities. We suggest that a gene dosage imbalance of 16q12.1–q22.1 is associated with spina bifida in the patient.
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