| 1. |
|
|
| 2. |
- Locke, Adam E, et al.
(författare)
-
Genetic studies of body mass index yield new insights for obesity biology.
- 2015
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
-
Tidskriftsartikel (refereegranskat)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
|
|
| 3. |
- Shungin, Dmitry, et al.
(författare)
-
New genetic loci link adipose and insulin biology to body fat distribution.
- 2015
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
-
Tidskriftsartikel (refereegranskat)abstract
- Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
|
|
| 4. |
- Ballantyne, Kaye N., et al.
(författare)
-
Toward Male Individualization with Rapidly Mutating Y-Chromosomal Short Tandem Repeats
- 2014
-
Ingår i: Human Mutation. - : John Wiley & Sons. - 1059-7794 .- 1098-1004. ; 35:8, s. 1021-1032
-
Tidskriftsartikel (refereegranskat)abstract
- Relevant for various areas of human genetics, Y-chromosomal short tandem repeats (Y-STRs) are commonly used for testing close paternal relationships among individuals and populations, and for male lineage identification. However, even the widely used 17-loci Yfiler set cannot resolve individuals and populations completely. Here, 52 centers generated quality-controlled data of 13 rapidly mutating (RM) Y-STRs in 14,644 related and unrelated males from 111 worldwide populations. Strikingly, greater than99% of the 12,272 unrelated males were completely individualized. Haplotype diversity was extremely high (global: 0.9999985, regional: 0.99836-0.9999988). Haplotype sharing between populations was almost absent except for six (0.05%) of the 12,156 haplotypes. Haplotype sharing within populations was generally rare (0.8% nonunique haplotypes), significantly lower in urban (0.9%) than rural (2.1%) and highest in endogamous groups (14.3%). Analysis of molecular variance revealed 99.98% of variation within populations, 0.018% among populations within groups, and 0.002% among groups. Of the 2,372 newly and 156 previously typed male relative pairs, 29% were differentiated including 27% of the 2,378 father-son pairs. Relative to Yfiler, haplotype diversity was increased in 86% of the populations tested and overall male relative differentiation was raised by 23.5%. Our study demonstrates the value of RMY-STRs in identifying and separating unrelated and related males and provides a reference database.
|
|
| 5. |
- Donaldson, M., et al.
(författare)
-
Optimal Pubertal Induction in Girls with Turner Syndrome Using Either Oral or Transdermal Estradiol: A Proposed Modern Strategy
- 2019
-
Ingår i: Hormone Research in Paediatrics. - : S. Karger AG. - 1663-2818 .- 1663-2826. ; 91:3, s. 153-163
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Most girls with Turner syndrome (TS) require pubertal induction with estrogen, followed by long term replacement. However, no adequately powered prospective studies comparing transdermal with oral 17 beta-estradiol administration exist. This reflects the difficulty of securing funding to study a rare condition with relatively low morbidity/mortality when competing against conditions such as cancer and vascular disease. Protocol Consensus: The TS Working Group of the European Society for Paediatric Endocrinology (ESPE) has agreed to both a 3-year oral and a 3-year transdermal regimen for pubertal induction. Prerequisites include suitable 17 beta-estradiol tablets and matrix patches to allow the delivery of incremental doses based on body weight. Study Proposal: An international prospective cohort study with single centre analysis is proposed in which clinicians and families are invited to choose either of the agreed regimens, usually starting at 11 years. We hypothesise that pubertal induction with transdermal estradiol will result in better outcomes for some key parameters. The primary outcome measure chosen is height gain during the induction period. Analysis: Assessment of the demographics and drop-out rates of patients choosing either oral or transdermal preparations; and appropriate analysis of outcomes including pubertal height gain, final height, liver enzyme and lipid profile, adherence/acceptability, cardiovascular health, including systolic and diastolic blood pressure and aortic root diameter and bone health. Conclusion: The proposed model of prospective data collection according to internationally agreed protocols aims to break the current impasse in obtaining evidence-based management for TS and could be applied to other rare paediatric endocrine conditions. (C) 2019 S. Karger AG, Basel
|
|
| 6. |
- George, Julie, et al.
(författare)
-
Comprehensive genomic profiles of small cell lung cancer
- 2015
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 524:7563, s. 47-U73
-
Tidskriftsartikel (refereegranskat)abstract
- We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis leading to overexpression of cyclin D1 (encoded by the CCND1 gene), revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumour suppressors TP53 and RB1 is obligatory in SCLC. We discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73Dex2/3. In rare cases, SCLC tumours exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signalling in a pre-clinical SCLC mouse model strikingly reduced the number of tumours and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer.
|
|
| 7. |
- Jung, Christian, et al.
(författare)
-
A comparison of very old patients admitted to intensive care unit after acute versus elective surgery or intervention
- 2019
-
Ingår i: Journal of critical care. - : W B SAUNDERS CO-ELSEVIER INC. - 0883-9441 .- 1557-8615. ; 52, s. 141-148
-
Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to evaluate differences in outcome between patients admitted to intensive care unit (ICU) after elective versus acute surgery in a multinational cohort of very old patients (80 years; VIP). Predictors of mortality, with special emphasis on frailty, were assessed.Methods: In total, 5063 VIPs were induded in this analysis, 922 were admitted after elective surgery or intervention, 4141 acutely, with 402 after acute surgery. Differences were calculated using Mann-Whitney-U test and Wilcoxon test. Univariate and multivariable logistic regression were used to assess associations with mortality.Results: Compared patients admitted after acute surgery, patients admitted after elective surgery suffered less often from frailty as defined as CFS (28% vs 46%; p < 0.001), evidenced lower SOFA scores (4 +/- 5 vs 7 +/- 7; p < 0.001). Presence of frailty (CFS >4) was associated with significantly increased mortality both in elective surgery patients (7% vs 12%; p = 0.01), in acute surgery (7% vs 12%; p = 0.02).Conclusions: VIPs admitted to ICU after elective surgery evidenced favorable outcome over patients after acute surgery even after correction for relevant confounders. Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery.
|
|
| 8. |
- Stray-Pedersen, Asbjorg, et al.
(författare)
-
Primary immunodeficiency diseases : Genomic approaches delineate heterogeneous Mendelian disorders
- 2017
-
Ingår i: Journal of Allergy and Clinical Immunology. - : MOSBY-ELSEVIER. - 0091-6749 .- 1097-6825. ; 139:1, s. 232-245
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Primary immunodeficiency diseases (PIDDs) are clinically and genetically heterogeneous disorders thus far associated with mutations in more than 300 genes. The clinical phenotypes derived from distinct genotypes can overlap. Genetic etiology can be a prognostic indicator of disease severity and can influence treatment decisions. Objective: We sought to investigate the ability of whole-exome screening methods to detect disease-causing variants in patients with PIDDs. Methods: Patients with PIDDs from 278 families from 22 countries were investigated by using whole-exome sequencing. Computational copy number variant (CNV) prediction pipelines and an exome-tiling chromosomal microarray were also applied to identify intragenic CNVs. Analytic approaches initially focused on 475 known or candidate PIDD genes but were nonexclusive and further tailored based on clinical data, family history, and immunophenotyping. Results: A likely molecular diagnosis was achieved in 110 (40%) unrelated probands. Clinical diagnosis was revised in about half (60/ 110) and management was directly altered in nearly a quarter (26/ 110) of families based on molecular findings. Twelve PIDD-causing CNVs were detected, including 7 smaller than 30 Kb that would not have been detected with conventional diagnostic CNV arrays. Conclusion: This high-throughput genomic approach enabled detection of disease-related variants in unexpected genes; permitted detection of low-grade constitutional, somatic, and revertant mosaicism; and provided evidence of a mutational burden in mixed PIDD immunophenotypes.
|
|
| 9. |
- Arheimer, Berit, et al.
(författare)
-
The IAHS Science for Solutions decade, with Hydrology Engaging Local People IN a Global world (HELPING)
- 2024
-
Ingår i: Hydrological Sciences Journal. - 0262-6667 .- 2150-3435.
-
Tidskriftsartikel (refereegranskat)abstract
- The new scientific decade (2023-2032) of the International Association of Hydrological Sciences (IAHS) aims at searching for sustainable solutions to undesired water conditions - may it be too little, too much or too polluted. Many of the current issues originate from global change, while solutions to problems must embrace local understanding and context. The decade will explore the current water crises by searching for actionable knowledge within three themes: global and local interactions, sustainable solutions and innovative cross-cutting methods. We capitalise on previous IAHS Scientific Decades shaping a trilogy; from Hydrological Predictions (PUB) to Change and Interdisciplinarity (Panta Rhei) to Solutions (HELPING). The vision is to solve fundamental water-related environmental and societal problems by engaging with other disciplines and local stakeholders. The decade endorses mutual learning and co-creation to progress towards UN sustainable development goals. Hence, HELPING is a vehicle for putting science in action, driven by scientists working on local hydrology in coordination with local, regional, and global processes.
|
|
| 10. |
- Murton, Bramley J., et al.
(författare)
-
Geological fate of seafloor massive sulphides at the TAG hydrothermal field (Mid-Atlantic Ridge)
- 2019
-
Ingår i: Ore Geology Reviews. - : Elsevier. - 0169-1368 .- 1872-7360. ; 107, s. 903-925
-
Forskningsöversikt (refereegranskat)abstract
- Deep-sea mineral deposits potentially represent vast metal resources that could make a major contribution to future global raw material supply. Increasing demand for these metals, many of which are required to enable a low-carbon and high-technology society and to relieve pressure on land-based resources, may result in deep sea mining within the next decade. Seafloor massive sulphide (SMS) deposits, containing abundant copper, zinc, gold and silver, have been the subject of recent and ongoing commercial interest. Although many seafloor hydrothermally systems have been studied, inactive SMS deposits are likely more accessible to future mining and far more abundant, but are often obscured by pelagic sediment and hence difficult tolocate. Furthermore, SMS deposits are three dimensional. Yet, to date, very few have been explored or sampled below the seafloor. Here, we describe the most comprehensive study to date of hydrothermally extinct seafloor massive sulphide (eSMS) deposits formed at a slow spreading ridge. Our approach involved two research cruises in the summer of 2016 to the Trans-Atlantic Geotraverse (TAG) hydrothermal field at 26 N on the Mid-Atlantic Ridge. These expeditions mapped a number of hydrothermally extinct SMS deposits using an autonomous underwater vehicle and remotely operated vehicle, acquired a combination of geophysical data including sub-seafloor seismic reflection and refraction data from 25 ocean bottom instruments, and recovered core using a robotic lander-type seafloor drilling rig. Together, these results that have allowed us to construct a new generic model for extinct seafloor massive sulphide deposits indicate the presence of up to five times more massive sulphide at and below the seafloor than was previously thought.
|
|
| 11. |
- Wit, J M., et al.
(författare)
-
Personalized Approach to Growth Hormone Treatment: Clinical Use of Growth Prediction Models
- 2013
-
Ingår i: Hormone Research in Paediatrics. - : Karger. - 1663-2818 .- 1663-2826. ; 79:5, s. 257-270
-
Forskningsöversikt (refereegranskat)abstract
- The goal of growth hormone (GH) treatment in a short child is to attain a fast catch-up growth toward the target height (TH) standard deviation score (SDS), followed by a maintenance phase, a proper pubertal height gain, and an adult height close to TH. The short-term response variable of GH treatment, first-year height velocity (HV) (cm/year or change in height SDS), can either be compared with GH response charts for diagnosis, age and gender, or with predicted HV based on prediction models. Three types of prediction models have been described: the Kabi International Growth Hormone Study models, the Gothenburg models and the Cologne model. With these models, 50-80% of the variance could be explained. When used prospectively, individualized dosing reduces the variation in growth response in comparison with a fixed dose per body weight. Insulin-like growth factor-I-based dose titration also led to a decrease in the variation. It is uncertain whether adding biochemical, genetic or proteomic markers may improve the accuracy of the prediction. Prediction models may lead to a more evidence-based approach to determine the GH dose regimen and may reduce the drug costs for GH treatment. There is a need for user-friendly software programs to make prediction models easily available in the clinic.
|
|
| 12. |
- Aganovic, A., et al.
(författare)
-
Ventilation design conditions associated with airborne bacteria levels within the wound area during surgical procedures: a systematic review
- 2021
-
Ingår i: Journal of Hospital Infection. - : Elsevier BV. - 0195-6701 .- 1532-2939. ; 113, s. 85-95
-
Forskningsöversikt (refereegranskat)abstract
- Background: Without confirmation of the ventilation design conditions (typology and airflow rate), the common practice of identifying unidirectional airflow (UDAF) systems as equivalent to ultra-clean air ventilation systems may be misleading, but also any claims about the ineffectiveness of UDAF systems should be doubted. The aim of this review was to assess and compare ventilation system design conditions for which ultra-clean air (mean <10 cfu/m ) within 50 cm from the wound has been reported. Six medical databases were systematically searched to identify and select studies reporting intraoperative airborne levels expressed as cfu/m close to the wound site, and ventilation system design conditions. Available data on confounding factors such as the number of persons present in the operating room, number of door openings, and clothing material were also included. Predictors for achieving mean airborne bacteria levels within <10 cfu/m were identified using a penalized multivariate logistic regression model. Twelve studies met the eligibility criteria and were included for analysis. UDAF systems considered had significantly higher air volume flows compared with turbulent ventilation (TV) systems considered. Ultra-clean environments were reported in all UDAF-ventilated (N = 7) rooms compared with four of 11 operating rooms equipped with TV. On multivariate analysis, the total number of air exchange rates (P=0.019; odds ratio (OR) 95% confidence interval (CI): 0.66–0.96) and type of clothing material (P=0.031; OR 95% CI: 0.01–0.71) were significantly associated with achieving mean levels of airborne bacteria <10 cfu/m . High-volume UDAF systems complying with DIN 1946-4:2008 standards for the airflow rate and ceiling diffuser size unconditionally achieve ultra-clean air close to the wound site. In conclusion, the studied articles demonstrate that high-volume UDAF systems perform as ultra-clean air systems and are superior to TV systems in reducing airborne bacteria levels close to the wound site. 3 3 3 3
|
|
| 13. |
- Albertsson-Wikland, Kerstin, 1947, et al.
(författare)
-
Dose-dependent effect of growth hormone on final height in children with short stature without growth hormone deficiency
- 2008
-
Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 93:11, s. 4342-4350
-
Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: The effect of GH therapy in short non-GH-deficient children, especially those with idiopathic short stature (ISS), has not been clearly established owing to the lack of controlled trials continuing until final height (FH).OBJECTIVE: The aim of the study was to investigate the effect on growth to FH of two GH doses given to short children, mainly with ISS, compared with untreated controls.DESIGN AND SETTING: A randomized, controlled, long-term multicenter trial was conducted in Sweden.INTERVENTION: Two doses of GH (Genotropin) were administered, 33 or 67 microg/kg.d; control subjects were untreated.SUBJECTS: A total of 177 subjects with short stature were enrolled. Of these, 151 were included in the intent to treat (AllITT) population, and 108 in the per protocol (AllPP) population. Analysis of ISS subjects included 126 children in the ITT (ISSITT) population and 68 subjects in the PP (ISSPP) population.MAIN OUTCOME MEASURES: We measured FH sd score (SDS), difference in SDS to midparenteral height (diff MPHSDS), and gain in heightSDS.RESULTS: After 5.9+/-1.1 yr on GH therapy, the FHSDS in the AllPP population treated with GH vs. controls was -1.5+/-0.81 (33 microg/kg.d, -1.7+/-0.70; and 67 microg/kg.d, -1.4+/-0.86; P<0.032), vs. -2.4+/-0.85 (P<0.001); the diff MPHSDS was -0.2+/-1.0 vs. -1.0+/-0.74 (P<0.001); and the gain in heightSDS was 1.3+/-0.78 vs. 0.2+/-0.69 (P<0.001). GH therapy was safe and had no impact on time to onset of puberty. A dose-response relationship identified after 1 yr remained to FH for all growth outcome variables in all four populations.CONCLUSION: GH treatment significantly increased FH in ISS children in a dose-dependent manner, with a mean gain of 1.3 SDS (8 cm) and a broad range of response from no gain to 3 SDS compared to a mean gain of 0.2 SDS in the untreated controls.
|
|
| 14. |
- Carlsson, A., et al.
(författare)
-
Prevalence of coeliac disease in Turner syndrome
- 1999
-
Ingår i: Acta Pædiatrica. - 1651-2227 .- 0803-5253. ; 88, s. 933-
-
Tidskriftsartikel (refereegranskat)abstract
- This study was undertaken to investigate the prevalence of coeliac disease in children and adolescents with Turner syndrome. Eighty-seven children and adolescents with Turner syndrome were screened for IgA- antiendomysium antibodies (EMA) and IgA-antigliadin antibodies (AGA), 5% (4/87) being found to be EMA-positive, and 15% (13/87) to have AGA levels above normal. Of the 10 patients who were either AGA- or EMA-positive and further investigated with intestinal biopsy, four manifested villous atrophy (i.e. all three of the EMA-positive patients, but only one of the seven AGA- positive patients). The results suggest EMA-positivity to be a good immunological marker for use in screening for coeliac disease, and such screening to be justified in patients with Turner syndrome.
|
|
| 15. |
- Collett-Solberg, Paulo F., et al.
(författare)
-
Diagnosis, Genetics, and Therapy of Short Stature in Children : A Growth Hormone Research Society International Perspective
- 2019
-
Ingår i: Hormone Research in Paediatrics. - : S. Karger. - 1663-2818 .- 1663-2826. ; 92:1, s. 1-14
-
Tidskriftsartikel (refereegranskat)abstract
- The Growth Hormone Research Society (GRS) convened a Workshop in March 2019 to evaluate the diagnosis and therapy of short stature in children. Forty-six international experts participated at the invitation of GRS including clinicians, basic scientists, and representatives from regulatory agencies and the pharmaceutical industry. Following plenary presentations addressing the current diagnosis and therapy of short stature in children, breakout groups discussed questions produced in advance by the planning committee and reconvened to share the group reports. A writing team assembled one document that was subsequently discussed and revised by participants. Participants from regulatory agencies and pharmaceutical companies were not part of the writing process. Short stature is the most common reason for referral to the pediatric endocrinologist. History, physical examination, and auxology remain the most important methods for understanding the reasons for the short stature. While some long-standing topics of controversy continue to generate debate, including in whom, and how, to perform and interpret growth hormone stimulation tests, new research areas are changing the clinical landscape, such as the genetics of short stature, selection of patients for genetic testing, and interpretation of genetic tests in the clinical setting. What dose of growth hormone to start, how to adjust the dose, and how to identify and manage a suboptimal response are still topics to debate. Additional areas that are expected to transform the growth field include the development of long-acting growth hormone preparations and other new therapeutics and diagnostics that may increase adult height or aid in the diagnosis of growth hormone deficiency.
|
|
| 16. |
- Geelen, Inge G. P., et al.
(författare)
-
Switching from imatinib to nilotinib plus pegylated interferon-α2b in chronic phase CML failing to achieve deep molecular response : clinical and immunological effects
- 2023
-
Ingår i: Annals of Hematology. - : Springer. - 0939-5555 .- 1432-0584. ; 102:6, s. 1395-1408
-
Tidskriftsartikel (refereegranskat)abstract
- In order to improve molecular response for a discontinuation attempt in chronic myeloid leukemia (CML) patients in chronic phase, who had not achieved at least a molecular response <0.01% BCR-ABL1IS (MR4.0) after at least 2 years of imatinib therapy, we prospectively evaluated whether they could attain MR4.0 after a switch to a combination of nilotinib and 9 months of pegylated interferon-α2b (PegIFN). The primary endpoint of confirmed MR4.0 at month 12 (a BCR-ABL1IS level ≤ 0.01% both at 12 and 15 months) was reached by 44% (7/16 patients, 95% confidence interval (CI): 23- 67%) of patients, with 81% (13/16 patients, 95% CI: 57-93%) of patients achieving an unconfirmed MR4.0. The scheduled combination was completed by 56% of the patients, with premature discontinuations, mainly due to mood disturbances after the introduction of PegIFN, questioning the feasibility of the combination of nilotinib and PegIFN for this patient population and treatment goal. A comprehensive clinical substudy program was implemented to characterize the impact of the treatment changes on the immunological profile.
|
|
| 17. |
- Hagell, Peter, et al.
(författare)
-
Apomorphine formulation may influence subcutaneous complications from continuous subcutaneous apomorphine infusion in Parkinson's disease
- 2020
-
Ingår i: Journal of Neurology. - 0340-5354 .- 1432-1459. ; 267:11, s. 3411-3417
-
Tidskriftsartikel (refereegranskat)abstract
- Continuous subcutaneous (s.c.) apomorphine infusion is an effective therapy for Parkinson's disease (PD), but a limitation is the formation of troublesome s.c. nodules. Various chemically non-identical apomorphine formulations are available. Anecdotal experiences have suggested that shifting from one of these (Apo-Go PumpFill®; apoGPF) to another (Apomorphine PharmSwed®; apoPS) may influence the occurrence and severity of s.c. nodules. We, therefore, followed 15 people with advanced PD (median PD-duration, 15 years; median "off"-phase Hoehn and Yahr, IV) on apoGPF and with troublesome s.c. nodules who were switched to apoPS. Data were collected at baseline, at the time of switching, and at a median of 1, 2.5, and 7.3 months post-switch. Total nodule numbers (P < 0.001), size (P < 0.001), consistency (P < 0.001), skin changes (P = 0.058), and pain (P ≤ 0.032) improved over the observation period. PD severity and dyskinesias tended to improve and increase, respectively. Apomorphine doses were stable, but levodopa doses increased by 100 mg/day. Patient-reported apomorphine efficacy tended to increase and all participants remained on apoPS throughout the observation period; with the main patient-reported reason being improved nodules. These observations suggest that patients with s.c. nodules caused by apoGPF may benefit from switching to apoPS in terms of s.c. nodule occurrence and severity. Alternatively, observed benefits may have been due to the switch itself. As nodule formation is a limiting factor in apomorphine treatment, a controlled prospective study comparing local tolerance with different formulations is warranted.
|
|
| 18. |
- Hartman, Catharina A, et al.
(författare)
-
Anxiety, mood, and substance use disorders in adult men and women with and without Attention-Deficit/Hyperactivity Disorder : a substantive and methodological overview
- 2023
-
Ingår i: Neuroscience and Biobehavioral Reviews. - : Pergamon Press. - 0149-7634 .- 1873-7528. ; 151
-
Forskningsöversikt (refereegranskat)abstract
- Knowledge on psychiatric comorbidity in adult ADHD is essential for prevention, detection, and treatment of these conditions. This review (1) focuses on large studies (n> 10,000; surveys, claims data, population registries) to identify (a) overall, (b) sex- and (c) age-specific patterns of comorbidity of anxiety disorders (ADs), major depressive disorder (MDD), bipolar disorder (BD) and substance use disorders (SUDs) in adults with ADHD relative to adults without ADHD; and (2) describes methodological challenges relating to establishing comorbidity in ADHD in adults as well as priorities for future research. Meta-analyses (ADHD: n=550,748; no ADHD n=14,546,814) yielded pooled odds ratios of 5.0(CI:3.29-7.46) for AD, 4.5(CI:2.44-8.34) for MDD, 8.7(CI:5.47-13.89) for BD and 4.6(CI:2.72-7.80) for SUDs, indicating strong differences in adults with compared to adults without ADHD. Moderation by sex was not found: high comorbidity held for both men and women with sex-specific patterns as in the general population: higher prevalences of ADs, MDD and BD in women and a higher prevalence of SUDs in men. Insufficient data on different phases of the adult lifespan prevented conclusions on developmental changes in comorbidity. We discuss methodological challenges, knowledge gaps, and future research priorities.
|
|
| 19. |
- Johansson, A. K., et al.
(författare)
-
Changes in conditions related to reported oral and general health over a ten-year period as reflected in two cohorts of 75-year-old subjects examined in 2007 and 2017
- 2020
-
Ingår i: Journal of Oral Rehabilitation. - : Wiley. - 0305-182X .- 1365-2842. ; 47:11, s. 1382-1393
-
Tidskriftsartikel (refereegranskat)abstract
- Background The rapidly ageing and increasingly dentate population puts great demands on society regarding the provision of adequate medical and dental care facilities. Objectives To present changes in reported demographic, general and oral health factors in two cohorts of 75 year olds in 2007 and 2017, and to analyse factors associated with self-reported number of remaining teeth and chewing efficiency. Material and methods All 75-year-old people living in two Swedish counties received a questionnaire in 2007 and in 2017. The response rates in 2007 and in 2017 were 71.9% (n = 3735) and 70.7% (n = 5091), respectively. Reported number of teeth was clinically validated in a selected subgroup. Results The 2017 cohort reported significantly better general health and dental state. Edentulousness was 7.8% in 2007 and 2.3% in 2017, while 'very good' chewing efficiency was 55.2% and 60.5%, respectively. Born outside Sweden, single living, not feeling healthy and smoking predicted reduced number of teeth in both cohorts. Impaired chewing efficiency in both cohorts was predicted by being born outside Sweden, lower education, not feeling healthy, reduced number of teeth and denture wearing. Conclusions Seventy-five-year-old people in Sweden reported much better oral and general health in 2017 compared to 2007. In 2017, 75% had practically all natural teeth present and only 2% were edentulous. This development of an increasingly dentate and partially dentate ageing population will put high demands on the oral healthcare system and will need adapting undergraduate/postgraduate education and management strategies to meet the requirements of the elderly.
|
|
| 20. |
- Johansson, A. K., et al.
(författare)
-
Xerostomia in 75-85-year-olds: A longitudinal population study
- 2023
-
Ingår i: Journal of Oral Rehabilitation. - : Blackwell Scientific Publications.. - 0305-182X. ; 50:9, s. 812-821
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundXerostomia can pose significant problems for many elderly people. ObjectivesTo investigate longitudinal changes in prevalence, persistence, progression, remission and incidence of xerostomia from age 75 to 85 years. MethodsAll 75-year-olds (born 1932) from two Swedish counties, Sweden were mailed a questionnaire in 2007 (N = 5195), and again in 2017 when they were aged 85 (N = 3323). The total response rates at ages 75 and 85 years were 71.9% and 60.8%, respectively. A 'panel', those who participated in both surveys, comprised 1701 individuals (response rate 51.2%). ResultsAt age 85, there was almost a doubling of self-reported 'yes often' xerostomia compared with age 75 (from 6.2% to 11.3%) and was almost twice as common in women than men (p < .001). When combining 'yes often'/'yes sometimes', xerostomia increased from 33.4% to 49.0%, and was more so among women (p < .001). Xerostomia was commoner at night than daytime, with 23.4% reporting 'yes often' night-time xerostomia at 85 compared with 18.5% at 75, and was also higher in women (p < .001). Progression rates for daytime and night-time xerostomia were 34.2% and 38.1%, for persistence 67.4% and 68.6%, and for remission 24.4% and 16.5%. Average yearly incidence was higher in women than men for both daytime (3.6% vs. 3.2%) and night-time (3.9% vs. 3.7%). Regression analyses predicted protective factors for developing xerostomia reported at age 75 as good general and oral health, absence of medications/intraoral symptom/s, good chewing function and social interaction. ConclusionsXerostomia increases markedly from age 75 to 85 years.
|
|
| 21. |
- Kasina, P., et al.
(författare)
-
Comparison of three distinct clean air suits to decrease the bacterial load in the operating room: An observational study
- 2016
-
Ingår i: Patient Safety in Surgery. - : Springer Science and Business Media LLC. - 1754-9493. ; 10:1
-
Tidskriftsartikel (refereegranskat)abstract
- © 2016 Kasina et al. Background: Lowering air-borne bacteria counts in the operating room is essential in prevention of surgical site infections in orthopaedic joint replacement surgery. This is mainly achieved by decreasing bacteria counts through dilution, with appropriate ventilation and by limiting the bacteria carrying skin particles, predominantly shed by the personnel. The aim of this study was to investigate if a single use polypropylene clothing system or a reusable polyester clothing system could offer similar air quality in the operating room as a mobile laminar airflow device-assisted reusable cotton/polyester clothing system. Methods: Prospective observational study design, comparing the performance of three Clean Air Suits by measuring Colony Forming Units (CFU)/m3 of air during elective hip and knee arthroplasties, performed at a large university-affiliated hospital. The amount of CFU/m3 of air was measured during 37 operations of which 13 were performed with staff dressed in scrub suits made of a reusable mixed material (69 % cotton, 30 % polyester, 1 % carbon fibre) accompanied by two mobile laminar airflow units. During 24 procedures no mobile laminar airflow units were used, 13 with staff using a reusable olefin fabric clothing (woven polypropylene) and 11 with staff dressed in single-use suits (non-woven spunbonded polypropylene). Air from the operating field was sampled through a filter, by a Sartorius MD8, and bacterial colonies were counted after incubation. There were 6-8 measurements from each procedure, in total 244 measurements. Statistical analysis was performed by Mann-Whitney U-test. Results: The single-use polypropylene suit reduced the amount of CFU/m3 to a significantly lower level than both other clothing systems. Conclusion: Single-use polypropylene clothing systems can replace mobile laminar airflow unit-assisted reusable mixed material-clothing systems. Measurements in standardized laboratory settings can only serve as guidelines as environments in real operation settings present a much more difficult challenge.
|
|
| 22. |
- Larsson, Berit A M, et al.
(författare)
-
One leg standing time predicts fracture risk in older women independent of clinical risk factors and BMD
- 2022
-
Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 33, s. 185-194
-
Tidskriftsartikel (refereegranskat)abstract
- In women of ages 75-80 years, a low one leg standing time (OLST) was associated with an increased risk of incident fractures, independently of bone mineral density and clinical risk factors. OLST contributed substantially to fracture probability, indicating that the test should be considered when evaluating fracture risk in older women. Introduction Physical function and risk of falls are important risk factors for fracture. A few previous studies have suggested that a one leg standing time (OLST) less than 10 s predicts fracture risk, but the impact of OLST, in addition to known clinical risk factors, for fracture probability is unknown. The aim of this study was to determine the independent contribution of OLST to fracture probability in older women. Methods The Sahlgrenska University Hospital Prospective Evaluation of Risk of Bone Fractures (SUPERB) is a prospective population-based study of 3028 women 75-80 years old, recruited from the greater Gothenburg area in Sweden. At baseline, information on risk factors was collected using questionnaires, bone mineral density was measured with dual-energy X-ray absorptiometry (DXA), and OLST was performed. Results During a median follow-up of 3.6 years (IQR 1.5 years), X-ray-verified incident fractures were identified using health records. OLST was available in 2405 women. OLST less than 10 s was associated with an increased risk for incident hip fracture (Hazard Ratio (HR) 3.02, 95% Confidence Interval (CI) [1.49-6.10]), major osteoporotic fracture (HR 95% CI 1.76 [1.34-1.46]), and nonvertebral fracture (HR 95% CI 1.61 [1.26-2.05]) in Cox regression analyses adjusted for age, height, and weight. Depending on BMD, the 4-year fracture probability increased by a factor of 1.3 to 1.5 in a 75-year-old woman with a low OLST (<10 s). Conclusion A low OLST has a substantial impact on fracture probability and should be considered when evaluating fracture risk in older women.
|
|
| 23. |
- Nilsson, K O, et al.
(författare)
-
Improved final height in girls with Turner's syndrome treated with growth hormone and oxandrolone.
- 1996
-
Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 81, s. 635-
-
Tidskriftsartikel (refereegranskat)abstract
- The spontaneous growth process in Turner's syndrome is characterized by a progressive decline in height velocity during childhood and no pubertal growth spurt. Therefore, therapy aimed at improving height during childhood as well as increasing final height is desirable for most girls with Turner's syndrome. Forty-five girls with Turner's syndrome, 9-16 yr of age (mean age, 12.2 yr), were allocated to three study groups. Group 1 (n = 13) was initially treated with oxandrolone alone; after 1 yr of treatment, GH without (group 1a; n = 6) or with (group 1b; n = 7) ethinyl estradiol was added. Group 2 (n = 17) was treated with GH plus oxandrolone. Group 3 (n = 15) was treated with GH, oxandrolone, and ethinyl estradiol. The dosage were: GH, 0.1 IU/kg.day; oxandrolone, 0.05 mg/kg.day; and ethinyl estradiol, 100 ng/kg.day. A height of 150 cm or more was achieved in 61%, 75%, and 60% of the girls in groups 1, 2, and 3, respectively. The most impressive increase in height was seen in group 2. In this group the mean final height was 154.2 cm (SD = 6.6), which is equivalent to a mean net gain of 8.5 cm (SD = 4.6) over the projected final height. In group 3, in which ethinyl estradiol was included from the start of therapy, the initially good height velocity decelerated after 1-2 yr of treatment. Their mean final height was 151.1 (SD = 4.6) cm, equivalent to a mean net gain of 3.0 cm (SD = 3.8). A similar growth-decelerating effect of ethinyl estradiol was seen in group 1b. We conclude that in girls with Turner's syndrome who are older than 9 yr of age, treatment with GH in combination with oxandrolone results in significant growth acceleration, imitating that in normal puberty, leading to a more favorable height during childhood. This mode of treatment also results in a significantly increased final height, permitting a great number of the girls to attain a final height of more than 150 cm. However, early addition of estrogen decelerates the height velocity and reduces the gain in height.
|
|
| 24. |
- Pedersen, Marie, et al.
(författare)
-
Birth Weight, Head Circumference, and Prenatal Exposure to Acrylamide from Maternal Diet : The European Prospective Mother-Child Study (NewGeneris)
- 2012
-
Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 120:12, s. 1739-1745
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Acrylamide is a common dietary exposure that crosses the human placenta. It is classified as a probable human carcinogen, and developmental toxicity has been observed in rodents. OBJECTIVES: We examined the associations between prenatal exposure to acrylamide and birth outcomes in a prospective European mother child study. METHODS: Hemoglobin (Hb) adducts of acrylamide and its metabolite glycidamide were measured in cord blood (reflecting cumulated exposure in the last months of pregnancy) from 1,101 singleton pregnant women recruited in Denmark, England, Greece, Norway, and Spain during 2006-2010. Maternal diet was estimated through food-frequency questionnaires. RESULTS: Both acrylamide and glycidamide Hb adducts were associated with a statistically significant reduction in birth weight and head circumference. The estimated difference in birth weight for infants in the highest versus lowest quartile of acrylamide Hb adduct levels after adjusting for gestational age and country was -132 g (95% CI: -207, -56); the corresponding difference for head circumference was -0.33 cm (95% CI: -0.61, -0.06). Findings were similar in infants of nonsmokers, were consistent across countries, and remained after adjustment for Factors associated with reduced birth weight. Maternal consumption of foods rich in acrylamide, such as fried potatoes, was associated with cord blood acrylamide adduct levels and with reduced birth weight. CONCLUSIONS: Dietary exposure to acrylamide was associated with reduced birth weight and head circumference. Consumption of specific foods during pregnancy was associated with higher acrylamide exposure in utero. IF confirmed, these findings suggest that dietary intake of acrylamide should be reduced among pregnant women.
|
|
| 25. |
- Solberg, Berit Skretting, et al.
(författare)
-
Maternal fiber intake during pregnancy and development of Attention-Deficit/Hyperactivity Disorder Symptoms Across Childhood : The Norwegian Mother, Father and Child Cohort Study (MoBa)
- 2024
-
Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 95:9, s. 839-848
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Epidemiological studies suggest that the maternal diet quality during pregnancy may influence the risk of neurodevelopmental disorders in the offspring. Here we investigated the associations between maternal intake of dietary fiber and ADHD symptoms in early childhood.METHODS: We used longitudinal data of up to 21,852 mother-father-child trios (49.2% females) from the Norwegian Mother, Father, and Child Cohort Study. The relationships between maternal fiber intake during pregnancy and offspring ADHD symptoms at ages three, five, and eight years were examined using: a) multivariate regression (overall levels of ADHD symptoms), b) latent class analysis (subclasses of ADHD symptoms by sex at each age), and c) latent growth curves (longitudinal change in offspring ADHD symptoms). Covariates were ADHD polygenic scores in child and parents, total energy intake and energy-adjusted sugar intake, parental ages at birth of the child, and socio-demographic factors.RESULTS: a) Higher maternal prenatal fiber intake was associated with lower offspring ADHD symptom scores at all examined ages (βage3=-0.14(95%CI -0.18, -0.10); βage5=-0.14(-0.19, -0.09); βage8=-0.14(-0.20, -0.09)). b) Of the derived low/middle/high subclasses of ADHD symptoms, fiber was associated with lower risk of belonging to middle subclass for boys and girls, and to high subclass for girls only (middle: ORboys 0.91(0.86-0.97)/ORgirls 0.86 (0.81-0.91); high ORgirls 0.82 (0.72-0.94)). c) Maternal fiber intake and rate of change in child ADHD symptoms across ages were not associated.CONCLUSIONS: A low prenatal maternal fiber intake may increase symptom levels of ADHD in childhood, independently of genetic predisposition to ADHD, unhealthy dietary exposures, and socio-demographic factors.
|
|
