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| 2. |
- Franks, P. W., et al.
(författare)
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Technological readiness and implementation of genomic-driven precision medicine for complex diseases
- 2021
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 290:3, s. 602-620
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Forskningsöversikt (refereegranskat)abstract
- The fields of human genetics and genomics have generated considerable knowledge about the mechanistic basis of many diseases. Genomic approaches to diagnosis, prognostication, prevention and treatment - genomic-driven precision medicine (GDPM) - may help optimize medical practice. Here, we provide a comprehensive review of GDPM of complex diseases across major medical specialties. We focus on technological readiness: how rapidly a test can be implemented into health care. Although these areas of medicine are diverse, key similarities exist across almost all areas. Many medical areas have, within their standards of care, at least one GDPM test for a genetic variant of strong effect that aids the identification/diagnosis of a more homogeneous subset within a larger disease group or identifies a subset with different therapeutic requirements. However, for almost all complex diseases, the majority of patients do not carry established single-gene mutations with large effects. Thus, research is underway that seeks to determine the polygenic basis of many complex diseases. Nevertheless, most complex diseases are caused by the interplay of genetic, behavioural and environmental risk factors, which will likely necessitate models for prediction and diagnosis that incorporate genetic and non-genetic data.
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| 3. |
- Astuto, L. M., et al.
(författare)
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CDH23 mutation and phenotype heterogeneity : a profile of 107 diverse families with Usher syndrome and nonsyndromic deafness
- 2002
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 71:2, s. 262-275
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Tidskriftsartikel (refereegranskat)abstract
- Usher syndrome type I is characterized by congenital hearing loss, retinitis pigmentosa (RP), and variable vestibular areflexia. Usher syndrome type ID, one of seven Usher syndrome type I genetic localizations, have been mapped to a chromosomal interval that overlaps with a nonsyndromic-deafness localization, DFNB12. Mutations in CDH23, a gene that encodes a putative cell-adhesion protein with multiple cadherin-like domains, are responsible for both Usher syndrome and DFNB12 nonsyndromic deafness. Specific CDH23 mutational defects have been identified that differentiate these two phenotypes. Only missense mutations of CDH23 have been observed in families with nonsyndromic deafness, whereas nonsense, frameshift, splice-site, and missense mutations have been identified in families with Usher syndrome. In the present study, a panel of 69 probands with Usher syndrome and 38 probands with recessive nonsyndromic deafness were screened for the presence of mutations in the entire coding region of CDH23, by heteroduplex, single-strand conformation polymorphism, and direct sequence analyses. A total of 36 different CDH23 mutations were detected in 45 families; 33 of these mutations were novel, including 18 missense, 3 nonsense, 5 splicing defects, 5 microdeletions, and 2 insertions. A total of seven mutations were common to more than one family. Numerous exonic and intronic polymorphisms also were detected. Results of ophthalmologic examinations of the patients with nonsyndromic deafness have found asymptomatic RP-like manifestations, indicating that missense mutations may have a subtle effect in the retina. Furthermore, patients with mutations in CDH23 display a wide range of hearing loss and RP phenotypes, differing in severity, age at onset, type, and the presence or absence of vestibular areflexia.
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- Bratland-Sanda, S., et al.
(författare)
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Physical activity in treatment units for eating disorders : Clinical practice and attitudes
- 2009
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Ingår i: Eating and Weight Disorders. - 1124-4909 .- 1590-1262. ; 14:2-3, s. E106-E112
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Physical activity (PA) in eating disorders (ED) may be harmful, but in a therapeutic setting also beneficial. The purpose of this survey was to examine these contradictory aspects of PA in ED specialist treatment settings. We examined whether 1) PA is assessed by the unit, 2) the units have guidelines for managing excessive PA, 3) the units have staff with higher education and special competence in PA and exercise science, 4) how units regard PA in ED, 5) whether regular PA is integrated in the treatment programs, and 6) how the units rate the role of PA in the treatment of ED compared with other mental disorders. METHODS: Of the 49 units located in Scandinavia and the United Kingdom, 41 (84%) responded to a questionnaire. RESULTS: In 28 units (68%) PA was assessed regularly. Excessive PA was considered a harmful symptom in ED, and most units reported guidelines to manage excessive PA. Thirty-two units included PA in their treatment programmes. Clinicians found PA most relevant in the treatment of obesity and, except for binge eating, less for ED. CONCLUSION: PA was more commonly integrated in treatment compared to previous studies. Future research should address how to manage excessive PA, and the potential beneficial role of PA in the treatment of ED. (Eating Weight Disord. 14: e106-e112, 2009). (C) 2009, Editrice Kurtis
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| 5. |
- Christiansen, Evald H, et al.
(författare)
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Instantaneous Wave-free Ratio versus Fractional Flow Reserve to Guide PCI.
- 2017
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Ingår i: The New England journal of medicine. - : Massachussetts Medical Society. - 1533-4406 .- 0028-4793. ; 376:19, s. 1813-1823
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Tidskriftsartikel (refereegranskat)abstract
- The instantaneous wave-free ratio (iFR) is an index used to assess the severity of coronary-artery stenosis. The index has been tested against fractional flow reserve (FFR) in small trials, and the two measures have been found to have similar diagnostic accuracy. However, studies of clinical outcomes associated with the use of iFR are lacking. We aimed to evaluate whether iFR is noninferior to FFR with respect to the rate of subsequent major adverse cardiac events.We conducted a multicenter, randomized, controlled, open-label clinical trial using the Swedish Coronary Angiography and Angioplasty Registry for enrollment. A total of 2037 participants with stable angina or an acute coronary syndrome who had an indication for physiologically guided assessment of coronary-artery stenosis were randomly assigned to undergo revascularization guided by either iFR or FFR. The primary end point was the rate of a composite of death from any cause, nonfatal myocardial infarction, or unplanned revascularization within 12 months after the procedure.A primary end-point event occurred in 68 of 1012 patients (6.7%) in the iFR group and in 61 of 1007 (6.1%) in the FFR group (difference in event rates, 0.7 percentage points; 95% confidence interval [CI], -1.5 to 2.8; P=0.007 for noninferiority; hazard ratio, 1.12; 95% CI, 0.79 to 1.58; P=0.53); the upper limit of the 95% confidence interval for the difference in event rates fell within the prespecified noninferiority margin of 3.2 percentage points. The results were similar among major subgroups. The rates of myocardial infarction, target-lesion revascularization, restenosis, and stent thrombosis did not differ significantly between the two groups. A significantly higher proportion of patients in the FFR group than in the iFR group reported chest discomfort during the procedure.Among patients with stable angina or an acute coronary syndrome, an iFR-guided revascularization strategy was noninferior to an FFR-guided revascularization strategy with respect to the rate of major adverse cardiac events at 12 months. (Funded by Philips Volcano; iFR SWEDEHEART ClinicalTrials.gov number, NCT02166736 .).
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| 7. |
- De Man Lapidoth, Joakim, 1969-, et al.
(författare)
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Psychometric properties of the Eating Disorders in Obesity questionnaire : Validating against the Eating Disorder Examination interview
- 2007
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Ingår i: Eating and Weight Disorders. - : Editrice Kurtis s.r.l.. - 1124-4909 .- 1590-1262. ; 12:4, s. 168-175
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Tidskriftsartikel (refereegranskat)abstract
- Inconclusive results of how weight-loss treatment (WLT) results are affected by participants' eating disorders and/or binge eating are partly due to the variation caused by the multitude of assessment instruments used. The objective of the present study was to evaluate the psychometric properties of a short DSM-IV-based assessment instrument designed to be used specifically in WLT settings, the Eating Disorders in Obesity (EDO) questionnaire. Participants were 97 patients seeking WLT at four surgical and one non-surgical clinics. Participants were assessed by the EDO and the Eating Disorder Examination (EDE) interview . The validity and reliability of the EDO was measured as concordance with the EDE, and test-retest agreement of the EDO, respectively. Validity as well as reliability was found to be good for both eating disorders diagnoses and binge eating as a distinct symptom. Results suggest that the EDO is a short, easily administered instrument with good psychometric properties which makes it a suitable, economical method of assessing eating disorders and binge eating in clinical WLT settings. ©2007, Editrice Kurtis.
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| 8. |
- Gyldenkerne, Christine, et al.
(författare)
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Coronary Artery Lesion Lipid Content and Plaque Burden in Diabetic and Nondiabetic Patients : PROSPECT II
- 2023
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Ingår i: Circulation. - : Lippincott Williams & Wilkins. - 0009-7322 .- 1524-4539. ; 147:6, s. 469-481
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Patients with diabetes have increased rates of major adverse cardiac events (MACEs). We hypothesized that this is explained by diabetes-associated differences in coronary plaque morphology and lipid content.METHODS: In PROSPECT II (Providing Regional Observations to Study Predictors of Events in the Coronary Tree), 898 patients with acute myocardial infarction with or without ST-segment elevation underwent 3-vessel quantitative coronary angiography and coregistered near-infrared spectroscopy and intravascular ultrasound imaging after successful percutaneous coronary intervention. Subsequent MACEs were adjudicated to either treated culprit lesions or untreated nonculprit lesions. This substudy stratified patients by diabetes status and assessed baseline culprit and nonculprit prevalence of high-risk plaque characteristics defined as maximum plaque burden ≥70% and maximum lipid core burden index ≥324.7. Separate covariate-adjusted multivariable models were performed to identify whether diabetes was associated with nonculprit lesion-related MACEs and high-risk plaque characteristics.RESULTS: Diabetes was present in 109 of 898 patients (12.1%). During a median 3.7-year follow-up, MACEs occurred more frequently in patients with versus without diabetes (20.1% versus 13.5% [odds ratio (OR), 1.94 (95% CI, 1.14-3.30)]), primarily attributable to increased risk of myocardial infarction related to culprit lesion restenosis (4.3% versus 1.1% [OR, 3.78 (95% CI, 1.12-12.77)]) and nonculprit lesion-related spontaneous myocardial infarction (9.3% versus 3.8% [OR, 2.74 (95% CI, 1.25-6.04)]). However, baseline prevalence of high-risk plaque characteristics was similar for patients with versus without diabetes concerning culprit (maximum plaque burden ≥70%: 90% versus 93%, P=0.34; maximum lipid core burden index ≥324.7: 66% versus 70%, P=0.49) and nonculprit lesions (maximum plaque burden ≥70%: 23% versus 22%, P=0.37; maximum lipid core burden index ≥324.7: 26% versus 24%, P=0.47). In multivariable models, diabetes was associated with MACEs in nonculprit lesions (adjusted OR, 2.47 [95% CI, 1.21-5.04]) but not with prevalence of high-risk plaque characteristics (adjusted OR, 1.21 [95% CI, 0.86-1.69]).CONCLUSIONS: Among patients with recent myocardial infarction, both treated and untreated lesions contributed to the diabetes-associated ≈2-fold increased MACE rate during the 3.7-year follow-up. Diabetes-related plaque characteristics that might underlie this increased risk were not identified by multimodality imaging.
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| 9. |
- Hammar, M. L., et al.
(författare)
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Effects of hormonal replacement therapy on the postural balance among postmenopausal women
- 1996
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Ingår i: Obstetrics and Gynecology. - 0029-7844 .- 1873-233X. ; 88:6, s. 955-960
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To establish whether hormone replacement therapy affects postural balance in postmenopausal women. METHODS: Nineteen healthy postmenopausal women with vasomotor symptoms were included. Median age was 54 years, median time since menopause was 3 years. They underwent dynamic posturography before and after 4 and 12 weeks of transdermal estrogen treatment (17 beta-estradiol 50 micrograms/day) as well as after 2 additional weeks of combined estrogen-progestagen treatment. The dynamic posturography method quantifies the amplitude, frequency, and pattern of body sway and tests the visual, vestibular, and somatosensory systems, which together maintain balance. The two most difficult tests either cancel visual and distort somatosensory inputs or give distorted information from both the visual and somatosensory systems. RESULTS: Hormone replacement therapy increased static balance performance assessed by dynamic posturography. A highly significant improvement was seen in the two most difficult tests between the pretreatment test and the test performed after 4 weeks of estrogen therapy (P < .01, P < .001, respectively). This improvement was sustained after 12 weeks and also during the 14th week, with the women on combined estrogen-progestagen treatment. CONCLUSION: Estrogen treatment increased balance performance measured by dynamic posturography, indicating that the beneficial effects from estrogens on postmenopausal fracture risk may include central nervous system effects on balance. Two weeks' addition of gestagen to the treatment regimen did not counteract the estrogen effects.
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| 10. |
- Malm, Eva, et al.
(författare)
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Full-field electroretinography and marked variability in clinical phenotype of Alström syndrome
- 2008
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Ingår i: Archives of ophthalmology (1960). - Chicago : American medical association. - 0003-9950. ; 126:1, s. 51-57
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To characterize the clinical phenotype and to study the course of disease in patients with Alström syndrome, with an emphasis on retinal function assessed with full-field electroretinography (ERG). METHODS: Three age- and sex-matched patients with Alström syndrome were selected from our retinitis pigmentosa register for repeated ophthalmologic examinations that included tests for color vision and visual fields using Goldmann perimetry and for repeated assessment of full-field ERGs. RESULTS: Electroretinography demonstrated cone-rod degeneration in all 3 patients. A concomitant impairment of color vision and visual fields was also observed as well as marked variation in retinal function and in disease severity. CONCLUSIONS: Full-field ERGs confirmed that Alström syndrome is associated with a cone-rod type of retinal degeneration. In this study, we have shown a striking variability in retinal function and disease onset and severity, which has, to our knowledge, not been described previously in Alström syndrome.
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