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- Calvert, Clara, et al.
(författare)
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Changes in preterm birth and stillbirth during COVID-19 lockdowns in 26 countries
- 2023
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Ingår i: Nature Human Behaviour. - : Springer Nature. - 2397-3374. ; 7:4, s. 529-544
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Tidskriftsartikel (refereegranskat)abstract
- Preterm birth (PTB) is the leading cause of infant mortality worldwide. Changes in PTB rates, ranging from -90% to +30%, were reported in many countries following early COVID-19 pandemic response measures ('lockdowns'). It is unclear whether this variation reflects real differences in lockdown impacts, or perhaps differences in stillbirth rates and/or study designs. Here we present interrupted time series and meta-analyses using harmonized data from 52 million births in 26 countries, 18 of which had representative population-based data, with overall PTB rates ranging from 6% to 12% and stillbirth ranging from 2.5 to 10.5 per 1,000 births. We show small reductions in PTB in the first (odds ratio 0.96, 95% confidence interval 0.95-0.98, P value <0.0001), second (0.96, 0.92-0.99, 0.03) and third (0.97, 0.94-1.00, 0.09) months of lockdown, but not in the fourth month of lockdown (0.99, 0.96-1.01, 0.34), although there were some between-country differences after the first month. For high-income countries in this study, we did not observe an association between lockdown and stillbirths in the second (1.00, 0.88-1.14, 0.98), third (0.99, 0.88-1.12, 0.89) and fourth (1.01, 0.87-1.18, 0.86) months of lockdown, although we have imprecise estimates due to stillbirths being a relatively rare event. We did, however, find evidence of increased risk of stillbirth in the first month of lockdown in high-income countries (1.14, 1.02-1.29, 0.02) and, in Brazil, we found evidence for an association between lockdown and stillbirth in the second (1.09, 1.03-1.15, 0.002), third (1.10, 1.03-1.17, 0.003) and fourth (1.12, 1.05-1.19, <0.001) months of lockdown. With an estimated 14.8 million PTB annually worldwide, the modest reductions observed during early pandemic lockdowns translate into large numbers of PTB averted globally and warrant further research into causal pathways.
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| 4. |
- KC, Ashish, 1982-, et al.
(författare)
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Changes in preterm birth and stillbirth during COVID-19 lockdowns in 26 countries.
- 2023
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Ingår i: Nature human behaviour. - : Springer Science and Business Media LLC. - 2397-3374. ; 7:4, s. 529-544
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Tidskriftsartikel (refereegranskat)abstract
- Preterm birth (PTB) is the leading cause of infant mortality worldwide. Changes in PTB rates, ranging from -90% to +30%, were reported in many countries following early COVID-19 pandemic response measures ('lockdowns'). It is unclear whether this variation reflects real differences in lockdown impacts, or perhaps differences in stillbirth rates and/or study designs. Here we present interrupted time series and meta-analyses using harmonized data from 52 million births in 26 countries, 18 of which had representative population-based data, with overall PTB rates ranging from 6% to 12% and stillbirth ranging from 2.5 to 10.5 per 1,000 births. We show small reductions in PTB in the first (odds ratio 0.96, 95% confidence interval 0.95-0.98, P value <0.0001), second (0.96, 0.92-0.99, 0.03) and third (0.97, 0.94-1.00, 0.09) months of lockdown, but not in the fourth month of lockdown (0.99, 0.96-1.01, 0.34), although there were some between-country differences after the first month. For high-income countries in this study, we did not observe an association between lockdown and stillbirths in the second (1.00, 0.88-1.14, 0.98), third (0.99, 0.88-1.12, 0.89) and fourth (1.01, 0.87-1.18, 0.86) months of lockdown, although we have imprecise estimates due to stillbirths being a relatively rare event. We did, however, find evidence of increased risk of stillbirth in the first month of lockdown in high-income countries (1.14, 1.02-1.29, 0.02) and, in Brazil, we found evidence for an association between lockdown and stillbirth in the second (1.09, 1.03-1.15, 0.002), third (1.10, 1.03-1.17, 0.003) and fourth (1.12, 1.05-1.19, <0.001) months of lockdown. With an estimated 14.8 million PTB annually worldwide, the modest reductions observed during early pandemic lockdowns translate into large numbers of PTB averted globally and warrant further research into causal pathways.
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- Breves, J. P., et al.
(författare)
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Hepatic insulin-like growth factor binding protein (igfbp) responses to food restriction in Atlantic salmon smolts
- 2016
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Ingår i: General and Comparative Endocrinology. - : Elsevier BV. - 0016-6480. ; 233, s. 79-87
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Tidskriftsartikel (refereegranskat)abstract
- The growth hormone (Gh)/insulin-like growth-factor (Igf) system plays a central role in the regulation of growth in fishes. However, the roles of Igf binding proteins (Igfbps) in coordinating responses to food availability are unresolved, especially in anadromous fishes preparing for seaward migration. We assayed plasma Gh, Igf1, thyroid hormones and cortisol along with igfbp mRNA levels in fasted and fed Atlantic salmon (Salmo solar). Fish were fasted for 3 or 10 days near the peak of smoltification (late April to early May). Fasting reduced plasma glucose by 3 days and condition factor by 10 days. Plasma Gh, cortisol, and thyroxine (T-4) were not altered in response to fasting, whereas Igf1 and 3,5,3'-triiodo-L-thyronine (T-3) were slightly higher and lower than controls, respectively. Hepatic igfbp1b1, -1b2, -2a,-2b1 and -2b2 mRNA levels were not responsive to fasting, but there were marked increases in igfbp1a1 following 3 and 10 days of fasting. Fasting did not alter hepatic igf1 or igf2; however, muscle igf1 was diminished by 10 days of fasting. There were no signs that fasting compromised branchial ionoregulatory functions, as indicated by unchanged Na+/K+-ATPase activity and ion pump/transporter mRNA levels. We conclude that dynamic hepatic igfbp1a1 and muscle igf1 expression participate in the modulation of Gh/Igf signaling in smolts undergoing catabolism.
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| 24. |
- Breves, J. P., et al.
(författare)
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Variation in branchial expression among insulin-like growth-factor binding proteins (igfbps) during Atlantic salmon smoltification and seawater exposure
- 2017
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Ingår i: BMC Physiology. - : Springer Science and Business Media LLC. - 1472-6793. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: In preparation for migration from freshwater to marine habitats, Atlantic salmon (Salmo salar L.) undergo smoltification, a transformation that includes the acquisition of hyposmoregulatory capacity. The growth hormone (Gh)/insulin-like growth-factor (Igf) axis promotes the development of branchial ionoregulatory functions that underlie ion secretion. Igfs interact with a suite of Igf binding proteins (Igfbps) that modulate hormone activity. In Atlantic salmon smolts, igfbp4,-5a,-5b1,-5b2,-6b1 and-6b2 transcripts are highly expressed in gill. We measured mRNA levels of branchial and hepatic igfbps during smoltification (March, April, and May), desmoltification (July) and following seawater (SW) exposure in March and May. We also characterized parallel changes in a broad suite of osmoregulatory (branchial Na+/K+-ATPase (Nka) activity, Na + /K + /2Cl - cotransporter 1 (nkcc1) and cystic fibrosis transmembrane regulator 1 (cftr1) transcription) and endocrine (plasma Gh and Igf1) parameters. Results: Indicative of smoltification, we observed increased branchial Nka activity, nkcc1 and cftr1 transcription in May. Branchial igfbp6b1 and -6b2 expression increased coincidentally with smoltification. Following a SW challenge in March, igfbp6b1 showed increased expression while igfbp6b2 exhibited diminished expression. igfbp5a,-5b1 and-5b2 mRNA levels did not change during smolting, but each had lower levels following a SW exposure in March. Conclusions: Salmonids express an especially large suite of igfbps. Our data suggest that dynamic expression of particular igfbps accompanies smoltification and SW challenges; thus, transcriptional control of igfbps may provide a mechanism for the local modulation of Igf activity in salmon gill. © 2017 The Author(s).
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- Cesta, CE, et al.
(författare)
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Antidiabetic medication use during pregnancy: an international utilization study
- 2019
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Ingår i: BMJ open diabetes research & care. - : BMJ. - 2052-4897. ; 7:1, s. e000759-
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Tidskriftsartikel (refereegranskat)abstract
- Diabetes in pregnancy and consequently the need for treatment with antidiabetic medication (ADM) has become increasingly prevalent. The prevalence and patterns of use of ADM in pregnancy from 2006 onward in seven different countries was assessed.Research design and methodsData sources included individually linked data from the nationwide health registers in Denmark (2006–2016), Finland (2006–2016), Iceland (2006–2012), Norway (2006–2015), Sweden (2006–2015), state-wide administrative and claims data for New South Wales, Australia (2006–2012) and two US insurance databases: Medicaid Analytic eXtract (MAX; 2006–2012, public) and IBM MarketScan (2012–2015, private). The prevalence of ADM use was calculated as the proportion of pregnancies with at least one filled prescription of an ADM in the 90 days before pregnancy or within the three trimesters of pregnancy.ResultsPrevalence of any ADM use in 5 279 231 pregnancies was 3% (n=147 999) and varied from under 2% (Denmark, Norway, and Sweden) to above 5% (Australia and US). Insulin was the most used ADM, and metformin was the most used oral hypoglycemic agent with increasing use over time in all countries. In 11.4%–62.5% of pregnancies with prepregnancy use, ADM (primarily metformin) was discontinued. When ADM treatment was initiated in late pregnancy for treatment of gestational diabetes mellitus, insulin was most often dispensed, except in the US, where glibenclamide was most often used.ConclusionsPrevalence and patterns of use of ADM classes varied between countries and over time. While insulin remained the most common ADM used in pregnancy, metformin use increased significantly over the study period.
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- Fridner, Ann, et al.
(författare)
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The research collaboration HOUPE: Health and Organisation among University Hospital Physcians in four European countries: Sweden, Norway, Iceland and Italy
- 2008
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Ingår i: BMA – AMA – CMA International conference on Doctors Health, London, 18-20th of November 2008.
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Konferensbidrag (refereegranskat)abstract
- Background: Hospital statistics show increased pre-pensioning and sickness absence among physicians in Sweden. In addition, female physicians experience unconstructive work conditions, inequality of pay, and less career advancement than their male counterparts in university hospitals despite increased share of women in medical education. Signs of ill-health among physicians might have severe consequences for people involved, patients, hospital economy and for health service provided. HOUPE is a research collaboration between four University Hospitals in Europe; Karolinska University Hospital, Stockholm, Landspitali University Hospital, Reykjavik, St Olavs University Hospital, Trondheim and University Hospital Azienda Ospedaliera, Padova.Objective: In 2002 national research groups anchored at four University Hospitals in Sweden, Norway, Iceland and Italy started a comprehensive research program abbreviated: The HOUPE project intended to provide a systematic comparison of university hospitals in Europe and how the structure and organization of these hospitals affected the research activity, work load, work satisfaction, gender equality, career advancement, health, and wellbeing of physicians. Next phase in our longitudinal design will include the university hospital in Budapest, Hungary.Funding: Medical Association in Iceland and Sweden, SLS - Swedish Physician Society, NorFA, Vinnova, Stockholm City Council, the four University Hospitals.Method: Three level of data collection were executed: Document analysis concerning national frameworks, register data/hospital statistics and a cross sectional survey in 2005/2006 (N = 2095/3867) among permanently employed university hospital physicians in each country.Results: Numerous research projects are scheduled in each country based on these data in different national research project. Preliminary results will be presented based on these ongoing analyzes on differences in the prevalence of harassment level, suicide ideation, hospitals emphasize of clinical research, and the tension between work load and interaction between career and role as caregivers at home, inequality of pay between men and women, and between medical and academic position.Intervention and prevention: Survey feedback seminars (Fridner & Pingel, 2006) with physicians in each clinic and Occupational Stress Index (OSI) for physicians (Belkic, 2003).Conclusions: The lack of studies that address organisational and psychosocial work conditions for physicians in Iceland and Italy makes HOUPE data important for this purpose. Numerous research projects were scheduled in each country based on these data. In addition, HOUPE data will be able to identify existing practices in management systems of university hospitals and trough comparison between the university hospitals highlight best practice.
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- Halfdanarson, O, et al.
(författare)
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Antipsychotic use in pregnancy and risk of attention/deficit-hyperactivity disorder and autism spectrum disorder: a Nordic cohort study
- 2022
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Ingår i: Evidence-based mental health. - : BMJ. - 1468-960X .- 1362-0347. ; 25:2, s. 54-62
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Tidskriftsartikel (refereegranskat)abstract
- Antipsychotics are increasingly used among women of childbearing age and during pregnancy.ObjectiveTo determine whether children exposed to antipsychotics in utero are at increased risk of attention-deficit/hyperactivity disorder (ADHD) or autism spectrum disorder (ASD), accounting for maternal diagnoses of bipolar, psychotic and other psychiatric disorders.DesignPopulation-based cohort study, including a sibling analysis.SettingNationwide data on all pregnant women and their live-born singletons in Denmark (1997-2017), Finland (1996-2016), Iceland (2004-2017), Norway (2004-2017), and Sweden (2006-2016).Participants4 324 086 children were eligible for inclusion to the study cohort.InterventionAntipsychotic exposure in utero, assessed by pregnancy trimester, type of antipsychotic, and varying patterns of use.Main outcome measuresNon-mutually exclusive diagnoses of ADHD and ASD. We used Cox proportional hazard models to calculate hazard ratios (HRs) controlling for maternal psychiatric disorders and other potential confounding factors.FindingsAmong 4 324 086 singleton births, 15 466 (0.4%) were exposed to antipsychotics in utero. During a median follow-up of 10 years, we identified 72 257 children with ADHD and 38 674 children with ASD. Unadjusted HRs were raised for both outcomes but shifted substantially towards the null after adjustment; 1.10 (95%CI 1.00 to 1.27) for ADHD and 1.12 (0.97 to 1.29) for ASD. Adjusted HRs remained consistent by trimester of exposure and type of antipsychotic. Comparing in utero exposure with pre-pregnancy use yielded HRs of 0.74 (0.62 to 0.87) for ADHD and 0.88 (0.70 to 1.10) for ASD. Sibling analyses yielded HRs of 1.14 (0.79 to 1.64) for ADHD and 1.34 (0.75 to 2.39) for ASD.DiscussionOur findings suggest little or no increased risk of child ADHD or ASD after in utero exposure to antipsychotics.Clinical implicationsResults regarding child neurodevelopment are reassuring for women who need antipsychotics during pregnancy.
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| 40. |
- Harjama, L., et al.
(författare)
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Hereditary palmoplantar keratoderma – phenotypes and mutations in 64 patients
- 2021
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Ingår i: Journal of the European Academy of Dermatology and Venereology. - : Wiley. - 0926-9959 .- 1468-3083. ; 35:9, s. 1874-1880
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Tidskriftsartikel (refereegranskat)abstract
- Background: Hereditary palmoplantar keratodermas (PPK) represent a heterogeneous group of rare skin disorders with epidermal hyperkeratosis of the palms and soles, with occasional additional manifestations in other tissues. Mutations in at least 69 genes have been implicated in PPK, but further novel candidate genes and mutations are still to be found. Objectives: To identify mutations underlying PPK in a cohort of 64 patients. Methods: DNA of 48 patients was analysed on a custom-designed in-house panel for 35 PPK genes, and 16 patients were investigated by a diagnostic genetic laboratory either by whole-exome sequencing, gene panels or targeted single-gene sequencing. Results: Of the 64 PPK patients, 32 had diffuse (50%), 19 focal (30%) and 13 punctate (20%) PPK. None had striate PPK. Pathogenic mutations in altogether five genes were identified in 31 of 64 (48%) patients, the majority (22/31) with diffuse PPK. Of them, 11 had a mutation in AQP5, five in SERPINB7, four in KRT9 and two in SLURP1. AAGAB mutations were found in nine punctate PPK patients. New mutations were identified in KRT9 and AAGAB. No pathogenic mutations were detected in focal PPK. Variants of uncertain significance (VUS) in PPK-associated and other genes were observed in 21 patients that might explain their PPK. No suggestive pathogenic variants were found for 12 patients. Conclusions: Diffuse PPK was the most common (50%) and striate PPK was not observed. We identified pathogenic mutations in 48% of our PPK patients, mainly in five genes: AQP5, AAGAB, KRT9, SERPINB7 and SLURP1.
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- Katayama, S., et al.
(författare)
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Acute wheeze-specific gene module shows correlation with vitamin D and asthma medication
- 2020
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Ingår i: European Respiratory Journal. - : NLM (Medline). - 0903-1936 .- 1399-3003. ; 55:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Airway obstruction and wheezing in preschool children with recurrent viral infections are a major clinical problem, and are recognised as a risk factor for the development of chronic asthma. We aimed to analyse whether gene expression profiling provides evidence for pathways that delineate distinct groups of children with wheeze, and in combination with clinical information could contribute to diagnosis and prognosis of disease development. METHODS: We analysed leukocyte transcriptomes from preschool children (6 months-3 years) at acute wheeze (n=107), and at a revisit 2-3 months later, comparing them to age-matched healthy controls (n=66). RNA-sequencing applying GlobinLock was used. The cases were followed clinically until age 7 years. Differential expression tests, weighted correlation network analysis and logistic regression were applied and correlations to 76 clinical traits evaluated. FINDINGS: Significant enrichment of genes involved in the innate immune responses was observed in children with wheeze. We identified a unique acute wheeze-specific gene-module, which was associated with vitamin D levels (p<0.005) in infancy, and asthma medication and FEV1%/FVC (forced expiratory volume in 1 s/forced vital capacity) ratio several years later, at age 7 years (p<0.005). A model that predicts leukotriene receptor antagonist medication at 7 years of age with high accuracy was developed (area under the curve 0.815, 95% CI 0.668-0.962). INTERPRETATION: Gene expression profiles in blood from preschool wheezers predict asthma symptoms at school age, and therefore serve as biomarkers. The acute wheeze-specific gene module suggests that molecular phenotyping in combination with clinical information already at an early episode of wheeze may help to distinguish children who will outgrow their wheeze from those who will develop chronic asthma.
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- Kou, I, et al.
(författare)
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A multi-ethnic meta-analysis confirms the association of rs6570507 with adolescent idiopathic scoliosis
- 2018
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 11575-
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Tidskriftsartikel (refereegranskat)abstract
- Adolescent idiopathic scoliosis (AIS) is the most common type of spinal deformity and has a significant genetic background. Genome-wide association studies (GWASs) identified several susceptibility loci associated with AIS. Among them is a locus on chromosome 6q24.1 that we identified by a GWAS in a Japanese cohort. The locus is represented by rs6570507 located within GPR126. To ensure the association of rs6570507 with AIS, we conducted a meta-analysis using eight cohorts from East Asia, Northern Europe and USA. The analysis included a total of 6,873 cases and 38,916 controls and yielded significant association (combined P = 2.95 × 10−20; odds ratio = 1.22), providing convincing evidence of the worldwide association between rs6570507 and AIS susceptibility. In silico analyses strongly suggested that GPR126 is a susceptibility gene at this locus.
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