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| 2. |
- Liu, Ke, et al.
(författare)
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X Chromosome Dose and Sex Bias in Autoimmune Diseases
- 2016
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Ingår i: Arthritis & Rheumatology. - : WILEY-BLACKWELL. - 2326-5191 .- 2326-5205. ; 68:5, s. 1290-1300
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Tidskriftsartikel (refereegranskat)abstract
- Objective. More than 80% of autoimmune disease predominantly affects females, but the mechanism for this female bias is poorly understood. We suspected that an X chromosome dose effect accounts for this, and we undertook this study to test our hypothesis that trisomy X (47, XXX; occurring in similar to 1 in 1,000 live female births) would be increased in patients with female-predominant diseases (systemic lupus erythematosus [SLE], primary Sjogrens syndrome [SS], primary biliary cirrhosis, and rheumatoid arthritis [RA]) compared to patients with diseases without female predominance (sarcoidosis) and compared to controls. Methods. All subjects in this study were female. We identified subjects with 47, XXX using aggregate data from single-nucleotide polymorphism arrays, and, when possible, we confirmed the presence of 47, XXX using fluorescence in situ hybridization or quantitative polymerase chain reaction. Results. We found 47, XXX in 7 of 2,826 SLE patients and in 3 of 1,033 SS patients, but in only 2 of 7,074 controls (odds ratio in the SLE and primary SS groups 8.78 [95% confidence interval 1.67-86.79], P = 0.003 and odds ratio 10.29 [95% confidence interval 1.18-123.47], P = 0.02, respectively). One in 404 women with SLE and 1 in 344 women with SS had 47, XXX. There was an excess of 47, XXX among SLE and SS patients. Conclusion. The estimated prevalence of SLE and SS in women with 47, XXX was similar to 2.5 and similar to 2.9 times higher, respectively, than that in women with 46, XX and similar to 25 and similar to 41 times higher, respectively, than that in men with 46, XY. No statistically significant increase of 47, XXX was observed in other female-biased diseases (primary biliary cirrhosis or RA), supporting the idea of multiple pathways to sex bias in autoimmunity.
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| 3. |
- Liu, Ke, et al.
(författare)
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X Chromosome Dose and Sex Bias in Autoimmune Diseases : Increased 47,XXX in Systemic Lupus Erythematosus and Sjögren's Syndrome
- 2016
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Ingår i: Arthritis & Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 68:5, s. 1290-1300
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:More than 80% of autoimmune disease is female dominant, but the mechanism for this female bias is poorly understood. We suspected an X chromosome dose effect and hypothesized that trisomy X (47,XXX, 1 in ∼1,000 live female births) would be increased in female predominant diseases (e.g. systemic lupus erythematosus [SLE], primary Sjögren's syndrome [SS], primary biliary cirrhosis [PBC] and rheumatoid arthritis [RA]) compared to diseases without female predominance (sarcoidosis) and controls.METHODS:We identified 47,XXX subjects using aggregate data from single nucleotide polymorphism (SNP) arrays and confirmed, when possible, by fluorescent in situ hybridization (FISH) or quantitative polymerase chain reaction (q-PCR).RESULTS:We found 47,XXX in seven of 2,826 SLE and three of 1,033 SS female patients, but only in two of the 7,074 female controls (p=0.003, OR=8.78, 95% CI: 1.67-86.79 and p=0.02, OR=10.29, 95% CI: 1.18-123.47; respectively). One 47,XXX subject was present for ∼404 SLE women and ∼344 SS women. 47,XXX was present in excess among SLE and SS subjects.CONCLUSION:The estimated prevalence of SLE and SS in women with 47,XXX was respectively ∼2.5 and ∼2.9 times higher than in 46,XX women and ∼25 and ∼41 times higher than in 46,XY men. No statistically significant increase of 47,XXX was observed in other female-biased diseases (PBC or RA), supporting the idea of multiple pathways to sex bias in autoimmunity. This article is protected by copyright. All rights reserved.
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| 4. |
- Anderson, P., et al.
(författare)
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Improving the delivery of brief interventions for heavy drinking in primary health care: outcome results of the Optimizing Delivery of Health Care Intervention (ODHIN) five-country cluster randomized factorial trial
- 2016
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Ingår i: Addiction. - : Wiley. - 1360-0443 .- 0965-2140. ; 111:11, s. 1935-1945
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To test if training and support, financial reimbursement and option of referring screen-positive patients to an internet-based method of giving advice (eBI) can increase primary health-care providers' delivery of Alcohol Use Disorders Identification Test (AUDIT)-C-based screening and advice to heavy drinkers. Design: Cluster randomized factorial trial with 12-week implementation and measurement period. Setting: Primary health-care units (PHCU) in different locations throughout Catalonia, England, the Netherlands, Poland and Sweden. Participants: A total of 120 PHCU, 24 in each of Catalonia, England, the Netherlands, Poland and Sweden. Interventions: PHCUs were randomized to one of eight groups: care as usual, training and support (TS), financial reimbursement (FR) and eBI; paired combinations of TS, FR and eBI, and all of FR, TS and eBI. Measurements: The primary outcome measure was the proportion of eligible adult (age 18+ years) patients screened during a 12-week implementation period. Secondary outcome measures were proportion of screen-positive patients advised; and proportion of consulting adult patients given an intervention (screening and advice to screen-positives) during the same 12-week implementation period. Findings: During a 4-week baseline measurement period, the proportion of consulting adult patients who were screened for their alcohol consumption was 0.059 per PHCU (95% CI 0.034 to 0.084). Based on the factorial design, the ratio of the logged proportion screened during the 12-week implementation period was 1.48 (95% CI = 1.13–1.95) in PHCU that received TS versus PHCU that did not receive TS; for FR, the ratio was 2.00 (95% CI = 1.56–2.56). The option of referral to eBI did not lead to a higher proportion of patients screened. The ratio for TS plus FR was 2.34 (95% CI = 1.77–3.10), and the ratio for TS plus FR plus eBI was1.68 (95% CI = 1.11–2.53). Conclusions: Providing primary health-care units with training, support and financial reimbursement for delivering Alcohol Use Disorders Identification Test-C-based screening and advice to heavy drinkers increases screening for alcohol consumption. Providing primary health-care units with the option of referring screen-positive patients to an internet-based method of giving advice does not appear to increase screening for alcohol consumption. © 2016 Society for the Study of Addiction
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| 5. |
- Keurhorst, M., et al.
(författare)
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Impact of primary healthcare providers' initial role security and therapeutic commitment on implementing brief interventions in managing risky alcohol consumption: a cluster randomised factorial trial
- 2016
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Ingår i: Implementation Science. - : Springer Science and Business Media LLC. - 1748-5908. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Brief interventions in primary healthcare are cost-effective in reducing drinking problems but poorly implemented in routine practice. Although evidence about implementing brief interventions is growing, knowledge is limited with regard to impact of initial role security and therapeutic commitment on brief intervention implementation. Methods: In a cluster randomised factorial trial, 120 primary healthcare units (PHCUs) were randomised to eight groups: care as usual, training and support, financial reimbursement, and the opportunity to refer patients to an internet-based brief intervention (e-BI); paired combinations of these three strategies, and all three strategies combined. To explore the impact of initial role security and therapeutic commitment on implementing brief interventions, we performed multilevel linear regression analyses adapted to the factorial design. Results: Data from 746 providers from 120 PHCUs were included in the analyses. Baseline role security and therapeutic commitment were found not to influence implementation of brief interventions. Furthermore, there were no significant interactions between these characteristics and allocated implementation groups. Conclusions: The extent to which providers changed their brief intervention delivery following experience of different implementation strategies was not determined by their initial attitudes towards alcohol problems. In future research, more attention is needed to unravel the causal relation between practitioners' attitudes, their actual behaviour and care improvement strategies to enhance implementation science.
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| 6. |
- Flenady, Vicki, et al.
(författare)
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Stillbirths : recall to action in high-income countries.
- 2016
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 387:10019, s. 691-702
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Tidskriftsartikel (refereegranskat)abstract
- Variation in stillbirth rates across high-income countries and large equity gaps within high-income countries persist. If all high-income countries achieved stillbirth rates equal to the best performing countries, 19,439 late gestation (28 weeks or more) stillbirths could have been avoided in 2015. The proportion of unexplained stillbirths is high and can be addressed through improvements in data collection, investigation, and classification, and with a better understanding of causal pathways. Substandard care contributes to 20-30% of all stillbirths and the contribution is even higher for late gestation intrapartum stillbirths. National perinatal mortality audit programmes need to be implemented in all high-income countries. The need to reduce stigma and fatalism related to stillbirth and to improve bereavement care are also clear, persisting priorities for action. In high-income countries, a woman living under adverse socioeconomic circumstances has twice the risk of having a stillborn child when compared to her more advantaged counterparts. Programmes at community and country level need to improve health in disadvantaged families to address these inequities.
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| 7. |
- Harris, Valerie M., et al.
(författare)
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Klinefelters syndrome (47,XXY) is in excess among men with Sjogrens syndrome
- 2016
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Ingår i: Clinical Immunology. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 1521-6616 .- 1521-7035. ; 168, s. 25-29
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Tidskriftsartikel (refereegranskat)abstract
- Primary Sjogrens syndrome (pSS) has a strong female bias. We evaluated an X chromosome dose effect by analyzing 47,XXY (Klinefelters syndrome, 1 in 500 live male births) among subjects with pSS. 47,XXY was determined by examination of fluorescence intensity of single nucleotide polymorphisms from the X and Y chromosomes. Among 136 pSS men there were 4 with 47,XXY. This was significantly different from healthy controls (1 of 1254 had 47)0(Y, p = 0.0012 by Fishers exact test) as well men with rheumatoid arthritis (0 of 363 with 47,XXY), but not different compared to men with systemic lupus erythematosus (SLE) (4 of 136 versus 8 of 306, Fishers exact test p = NS). These results are consistent with the hypothesis that the number of X chromosomes is critical for the female bias of pSS, a property that may be shared with SLE but not RA. Published by Elsevier Inc.
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| 8. |
- Urowitz, M. B., et al.
(författare)
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Cardiovascular events prior to or early after diagnosis of systemic lupus erythematosus in the systemic lupus international collaborating clinics cohort
- 2016
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Ingår i: Lupus Science and Medicine. - : BMJ. - 2053-8790. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective To describe the frequency of myocardial infarction (MI) prior to the diagnosis of systemic lupus erythematosus (SLE) and within the first 2 years of follow-up. Methods The systemic lupus international collaborating clinics (SLICC) atherosclerosis inception cohort enters patients within 15 months of SLE diagnosis. MIs were reported and attributed on a specialised vascular event form. MIs were confirmed by one or more of the following: abnormal ECG, typical or atypical symptoms with ECG abnormalities and elevated enzymes (≥2 times upper limit of normal), or abnormal stress test, echocardiogram, nuclear scan or angiogram. Descriptive statistics were used. Results 31 of 1848 patients who entered the cohort had an MI. Of those, 23 patients had an MI prior to SLE diagnosis or within the first 2 years of disease. Of the 23 patients studied, 60.9% were female, 78.3% were Caucasian, 8.7% black, 8.7% Hispanic and 4.3% other. The mean age at SLE diagnosis was 52.5±15.0 years. Of the 23 MIs that occurred, 16 MIs occurred at a mean of 6.1±7.0 years prior to diagnosis and 7 occurred within the first 2 years of follow-up. Risk factors associated with early MI in univariate analysis are male sex, Caucasian, older age at diagnosis, hypertension, hypercholesterolaemia, family history of MI and smoking. In multivariate analysis only age (OR=1.06 95% CI 1.03 to 1.09), hypertension (OR=5.01, 95% CI 1.38 to 18.23), hypercholesterolaemia (OR=4.43, 95% CI 1.51 to 12.99) and smoking (OR=7.50, 95% CI 2.38 to 23.57) remained significant risk factors. Conclusions In some patients with lupus, MI may develop even before the diagnosis of SLE or shortly thereafter, suggesting that there may be a link between autoimmune inflammation and atherosclerosis.
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