| 1. |
- Bridel, Claire, et al.
(författare)
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Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology : A Systematic Review and Meta-analysis
- 2019
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Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:9, s. 1035-1048
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Forskningsöversikt (refereegranskat)abstract
- Importance Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.Objectives To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.Data Sources PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.Study Selection Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.Data Extraction and Synthesis Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.Main Outcome and Measure The cNfL levels adjusted for age and sex across diagnoses.Results Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.Conclusions and Relevance These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
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| 2. |
- Dickmark, Malin, et al.
(författare)
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Risk factors for seizures in the vigorous term neonate : A population-based register study of singleton births in Sweden
- 2022
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 17:2
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Tidskriftsartikel (refereegranskat)abstract
- Background Neonatal seizures have been associated with increased mortality and impaired neurodevelopment and, knowledge about risk factors may be useful for prevention. Clear associations have been established between labor-related risk factors and seizures in asphyxiated neonates. However, there is limited information about why some vigorous term-born infants experience seizures. Objectives Our aim was to assess antepartum and intrapartum risk factors for seizures in vigorous term-born neonates. Methods This was a national cohort study of singleton infants born at term in Sweden from 2009-2015. Vigorous was defined as an Apgar score of at least 7 at 5 and 10 minutes. Data on the mothers and infants were obtained from the Swedish Medical Birth Register and the Swedish Neonatal Quality Register. A diagnosis of neonatal seizures was the main outcome measure and the exposures were pregnancy and labor variables. Logistic regression analysis was used and the results are expressed as adjusted odds ratios (aOR) with 95% confidence intervals (CI). Results The incidence of neonatal seizures was 0.81/1,000 for 656 088 births. Seizures were strongly associated with obstetric emergencies (aOR 4.0, 95% CI 2.2-7.4), intrapartum fever and/or chorioamnionitis (aOR 3.4, 95% CI 2.1-5.3), and intrapartum fetal distress (aOR 3.0, 95% CI 2.4-3.7). Other associated intrapartum factors were: labor dystocia, occiput posterior position, operative vaginal delivery, and Cesarean delivery. Some maternal factors more than doubled the risk: a body mass of more than 40 (aOR 2.6, 95% CI 1.4-4.8), hypertensive disorders (aOR 2.3, 95% CI 1.7-3.1) and diabetes mellitus (aOR 2.6, 95% CI 1.7-4.1). Conclusion A number of intrapartum factors were associated with an increased risk of seizures in vigorous term-born neonates. Obstetric emergencies, intrapartum fever and/or chorioamnionitis and fetal distress were the strongest associated risks. The presence of such factors, despite a reassuring Apgar score could prompt close surveillance.
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| 3. |
- Friedrichsen, Maria, 1966-, et al.
(författare)
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Prolonged grievers : A qualitative evaluation of a support group intervention
- 2014
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Ingår i: Palliative & Supportive Care. - : Cambridge University Press. - 1478-9515 .- 1478-9523. ; 12:4, s. 299-308
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this project was to study prolonged grievers psychosocial processes and experience during participation in a group intervention and 6–8 weeks after discontinuation. The intervention in this study was a group therapy with the aim of getting in contact with their pain and loss and confronting and working with this loss.Methods: Data was collected by using diaries and tape-recorded interviews, analyzed with grounded theory. The participants were 11 females between the ages of 33 and 71.Results: The main process that was found in the qualitative data was: Ambivalence when struggling and learning through work and rest towards a balance. Sub-processes were: To share and be confirmed in the group through sense of cohesion; To dare/venture to discover problems and solutions; To react when you get emotionally involved, and to compare and discover.Significance of results: This study gives insight into prolonged grievers' thinking, which is valuable knowledge. Rather than assuming that all individuals suffering from prolonged grief need the same treatment, we suggest that there should be a range of different therapies.
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| 4. |
- Hellberg, C, et al.
(författare)
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Important research outcomes for treatment studies of perinatal depression: systematic overview and development of a core outcome set
- 2021
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Ingår i: British Journal of Obstetrics and Gynecology. - : John Wiley & Sons. - 1470-0328 .- 1471-0528. ; 128:13, s. 2141-2149
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Tidskriftsartikel (refereegranskat)abstract
- Objective To develop a Core Outcome Set (COS) for treatment of perinatal depression.Design Systematic overview of outcomes reported in the literature and consensus development study.SettingInternational.Population Two hundred and twenty-two participants, mainly patients, healthcare professionals and researchers, representing 13 countries.Methods A systematic overview of outcomes reported in recently published research, a two-round Delphi survey and a consensus meeting at which the final COS was decided using modified nominal group technique.Main results In the literature search, 1772 abstracts were identified and evaluated, and 165 studies were finally included in the review. In all, 106 outcomes were identified and included in the Delphi survey. In all, 222 participants registered for the first round of the Delphi survey and 151 (68%) responded. In the second round, 123 (55%) participants responded. Thirteen participants attended the consensus meeting, where the following nine outcomes were agreed upon for inclusion in the final COS: self-assessed symptoms of depression, diagnosis of depression by a clinician, parent to infant bonding, self-assessed symptoms of anxiety, quality of life, satisfaction with intervention, suicidal thoughts, attempted or committed suicide, thoughts of harming the baby, and adverse events.Conclusions The relevant stakeholders prioritised outcomes and reached consensus on a COS comprising nine outcomes. We expect that this COS will contribute to the consistency and uniformity of outcome selection and reporting in future clinical trials involving treatment of perinatal depression.
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| 5. |
- Hellström, Sara, et al.
(författare)
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A follow up on the feasibility after national implementation of magnesium sulfate for neuroprotection prior to preterm birth.
- 2023
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Ingår i: Acta obstetricia et gynecologica Scandinavica. - : John Wiley & Sons. - 1600-0412 .- 0001-6349. ; 102:12, s. 1741-1748
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Tidskriftsartikel (refereegranskat)abstract
- The risk for brain injury manifested as cerebral palsy is higher in very preterm born children than in term. Prenatal administration of magnesium sulfate (MgSO4 ) has been shown to be neuroprotective and reduces the proportion of very preterm born children later diagnosed with cerebral palsy. A Swedish national clinical practice guideline was implemented in March 2020, stipulating the administration of a single intravenous dose of 6g MgSO4 1-24h prior to delivery before gestational age 32+0, aiming for 90% treatment coverage. The aim of this study was to evaluate the feasibility of this new clinical practice guideline in the first year of its implementation.Data on MgSO4 treatment were collected by reviewing the medical charts of women who gave birth to live born children in gestational age 22+0-31+6 during the period of March 1, 2020 to February 28, 2021, at five Swedish university hospitals. Women with pre-eclampsia, eclampsia, or high elevated liver enzymes low platelets (HELLP) were excluded.A total of 388 women were eligible and 79% received treatment with MgSO4 . Of the 21% not receiving treatment, 9% did not receive treatment due to lack of knowledge about the clinical practice guideline, 9% were not possible to treat and 3% had missing data. The proportion treated increased from 72% to 87% from the first to the last 3months. Of those treated, 81% received the drug within the stipulated timeframe (mean 8.7h, median 3.4h).There was a positive trend over time in the proportion of women receiving MgSO4 treatment, but the a priori target of 90% was not reached during the first year of implementation. Our findings indicate that this target could be reached with additional information to clinicians.
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| 6. |
- Henningsson, Susanne, 1977, et al.
(författare)
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Possible association between the androgen receptor gene and autism spectrum disorder.
- 2009
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 34:5, s. 752-761
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Tidskriftsartikel (refereegranskat)abstract
- Autism is a highly heritable disorder but the specific genes involved remain largely unknown. The higher prevalence of autism in men than in women, in conjunction with a number of other observations, has led to the suggestion that prenatal brain exposure to androgens may be of importance for the development of this condition. Prompted by this hypothesis, we investigated the potential influence of variation in the androgen receptor (AR) gene on the susceptibility for autism. To this end, 267 subjects with autism spectrum disorder and 617 controls were genotyped for three polymorphisms in exon 1 of the AR gene: the CAG repeat, the GGN repeat and the rs6152 SNP. In addition, parents and affected siblings were genotyped for 118 and 32 of the cases, respectively. Case-control comparisons revealed higher prevalence of short CAG alleles as well as of the A allele of the rs6152 SNP in female cases than in controls, but revealed no significant differences with respect to the GGN repeat. Analysis of the 118 families using transmission disequilibrium test, on the other hand, suggested an association with the GGN polymorphism, the rare 20-repeat allele being undertransmitted to male cases and the 23-repeat allele being overtransmitted to female cases. Sequencing of the AR gene in 46 patients revealed no mutations or rare variants. The results lend some support for an influence of the studied polymorphisms on the susceptibility for autism, but argue against the possibility that mutations in the AR gene are common in subjects with this condition.
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| 7. |
- Jonsson, Maria, 1966-, et al.
(författare)
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Neonatal encephalopathy and the association to asphyxia in labor
- 2014
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Ingår i: American Journal of Obstetrics and Gynecology. - : Elsevier. - 0002-9378 .- 1097-6868. ; 211:6, s. 667.e1-667.e8
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: In cases with moderate and severe neonatal encephalopathy, we aimed to determine the proportion that was attributable to asphyxia during labor and to investigate the association between cardiotocographic (CTG) patterns and neonatal outcome.STUDY DESIGN: In a study population of 71,189 births from 2 Swedish university hospitals, 80 cases of neonatal encephalopathy were identified. Cases were categorized by admission CTG patterns (normal or abnormal) and by the presence of asphyxia (cord pH, <7.00; base deficit, ≥12 mmol/L). Cases with normal admission CTG patterns and asphyxia at birth were considered to experience asphyxia related to labor. CTG patterns were assessed for the 2 hours preceding delivery.RESULTS: Admission CTG patterns were normal in 51 cases (64%) and abnormal in 29 cases (36%). The rate of cases attributable to asphyxia (ie, hypoxic ischemic encephalopathy) was 48 of 80 cases (60%), most of which evolved during labor (43/80 cases; 54%). Both severe neonatal encephalopathy and neonatal death were more frequent with an abnormal, rather than with a normal, admission CTG pattern (13 [45%] vs 11 [22%]; P = .03), and 6 [21%] vs 3 [6%]; P = .04), respectively. Comparison of cases with an abnormal and a normal admission CTG pattern also revealed more frequently observed decreased variability (12 [60%] and 8 [22%], respectively) and more late decelerations (8 [40%] and 1 [3%], respectively).CONCLUSION: Moderate and severe encephalopathy is attributable to asphyxia in 60% of cases, most of which evolve during labor. An abnormal admission CTG pattern indicates a poorer neonatal outcome and more often is associated with pathologic CTG patterns preceding delivery.
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| 8. |
- Liljeström, Lena, 1977-, et al.
(författare)
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Antepartum risk factors for moderate to severe neonatal hypoxic ischemic encephalopathy : a Swedish national cohort study
- 2018
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 97:5, s. 615-623
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionOur aim was to identify antepartum risk factors for neonatal hypoxic ischemic encephalopathy, with a focus on maternal body mass index and height.Material and methodsNational population-based cohort study of 692 428 live-born infants 36 gestational weeks in Sweden, 2009-2015. Data from the Swedish Medical Birth Register and the Swedish Neonatal Quality Register were linked. Short maternal stature was defined as 155 cm, and overweight as body mass index 25 kg/m(2). Therapeutic hypothermia served as surrogate marker of moderate to severe hypoxic ischemic encephalopathy. Associations between maternal and infant characteristics and hypoxic ischemic encephalopathy were calculated with logistic regression analyses, and risks were presented as odds ratios with 95% confidence intervals.ResultsModerate to severe hypoxic ischemic encephalopathy occurred in 0.67/1000 infants. Nulliparity, previous cesarean delivery, short stature, overweight, gestational age, occiput posterior presentation and birthweight were all independently associated with hypoxic ischemic encephalopathy. The risk of hypoxic ischemic encephalopathy increased with decreasing maternal height and increasing body mass index. Compared with non-short women (156 cm) with normal weight (body mass index <25 kg/m(2)), those with both short stature and overweight had increased risk of hypoxic ischemic encephalopathy (odds ratio 3.66; 95% confidence intervals 2.41-5.55). Among parous women with both short stature and overweight, the risk was almost sixfold (odds ratio 5.74; 95% confidence intervals 3.41-9.66).ConclusionsAntepartum risk factors for moderate to severe hypoxic ischemic encephalopathy included nulliparity, previous cesarean delivery, short stature, overweight, gestational age, occiput posterior presentation and birthweight. The combination of maternal short stature and overweight was associated with a more than threefold risk of subsequent hypoxic ischemic encephalopathy.
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| 9. |
- Malmqvist, Olle, et al.
(författare)
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Seizures in newborn infants without hypoxic ischemic encephalopathy - antenatal and labor-related risk factors : a case-control study
- 2020
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Ingår i: The Journal of Maternal-Fetal & Neonatal Medicine. - : Informa Healthcare. - 1476-7058 .- 1476-4954. ; 33:5, s. 799-805
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To identify antepartum and intrapartum risk factors for neonatal seizures in the absence of hypoxic ischemic encephalopathy (HIE).METHODS: Population-based case-control study. Of 98 484 births, 40 newborns at 34 gestational weeks or later had seizures within the first 7 days of life. Cases (n = 40) and controls (n = 160) were retrieved from the University hospitals of Örebro for 1994-2013 and Uppsala for 2003-2013. Demographics and characteristics of pregnancy, labor, delivery, and neonatal data were analyzed. Crude odds ratio (OR) and adjusted odds ratios (AOR) with 95% confidence intervals (CIs) for antenatal and intrapartum factors were calculated using logistic regression analysis. Main outcome measure was neonatal seizures within the first 7 days of life.RESULTS: The incidence of neonatal seizures without HIE was 0.41/1000 live births. Antenatal risk factors for neonatal seizures were as follows: short maternal stature (AOR: 5.4; 1.8-16.5); previous caesarean section (AOR: 4.8; 1.5-15.0); and assisted fertilization (AOR: 6.8; 1.3-35.2). Intrapartum risk factors were as follows: induction of labor (AOR: 5.7; 1.8-17.7); preterm birth (AOR: 13.5; 3.7-48.9); and head circumference >37 cm (AOR: 6.9; 1.4-34.8).CONCLUSIONS: Preterm birth was the strongest risk factor for neonatal seizures in the absence of HIE. The results also indicate that feto-pelvic disproportion is associated with the occurrence of seizures.RATIONALE: Antepartum and intrapartum risk factors for newborn seizures in the absence of HIE were investigated in a case-control study. Out of 98 484 births at 34 gestational weeks or more, 40 newborns had seizures without HIE. All had a normal Apgar score although they later presented with seizures. Preterm birth was the strongest risk factor (OR: 13.5; 95% CI: 3.7-48.9). Our results also indicate that feto-pelvic disproportion is of importance. Furthermore, a history of prior caesarean was associated with seizures. This is the first study to assess obstetric risk factors for newborn seizures separate from those with seizures and concomitant HIE. The distinction is of importance due to different etiologies, treatments, and preventive strategies.
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| 10. |
- Mullins, Niamh, et al.
(författare)
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Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 91:3, s. 313-327
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders.METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors.RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged.CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.
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