| 1. |
- Hibar, D. P., et al.
(författare)
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Cortical abnormalities in bipolar disorder: An MRI analysis of 6503 individuals from the ENIGMA Bipolar Disorder Working Group
- 2018
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 23:4, s. 932-942
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Tidskriftsartikel (refereegranskat)abstract
- Despite decades of research, the pathophysiology of bipolar disorder (BD) is still not well understood. Structural brain differences have been associated with BD, but results from neuroimaging studies have been inconsistent. To address this, we performed the largest study to date of cortical gray matter thickness and surface area measures from brain magnetic resonance imaging scans of 6503 individuals including 1837 unrelated adults with BD and 2582 unrelated healthy controls for group differences while also examining the effects of commonly prescribed medications, age of illness onset, history of psychosis, mood state, age and sex differences on cortical regions. In BD, cortical gray matter was thinner in frontal, temporal and parietal regions of both brain hemispheres. BD had the strongest effects on left pars opercularis (Cohen's d='0.293; P=1.71 × 10 '21), left fusiform gyrus (d='0.288; P=8.25 × 10 '21) and left rostral middle frontal cortex (d='0.276; P=2.99 × 10 '19). Longer duration of illness (after accounting for age at the time of scanning) was associated with reduced cortical thickness in frontal, medial parietal and occipital regions. We found that several commonly prescribed medications, including lithium, antiepileptic and antipsychotic treatment showed significant associations with cortical thickness and surface area, even after accounting for patients who received multiple medications. We found evidence of reduced cortical surface area associated with a history of psychosis but no associations with mood state at the time of scanning. Our analysis revealed previously undetected associations and provides an extensive analysis of potential confounding variables in neuroimaging studies of BD. © 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
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| 2. |
- Hibar, D. P., et al.
(författare)
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Subcortical volumetric abnormalities in bipolar disorder
- 2016
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 21:12, s. 1710-1716
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Tidskriftsartikel (refereegranskat)abstract
- Considerable uncertainty exists about the defining brain changes associated with bipolar disorder (BD). Understanding and quantifying the sources of uncertainty can help generate novel clinical hypotheses about etiology and assist in the development of biomarkers for indexing disease progression and prognosis. Here we were interested in quantifying case-control differences in intracranial volume (ICV) and each of eight subcortical brain measures: nucleus accumbens, amygdala, caudate, hippocampus, globus pallidus, putamen, thalamus, lateral ventricles. In a large study of 1710 BD patients and 2594 healthy controls, we found consistent volumetric reductions in BD patients for mean hippocampus (Cohen's d=-0.232; P=3.50 × 10 -7) and thalamus (d=-0.148; P=4.27 × 10 -3) and enlarged lateral ventricles (d=-0.260; P=3.93 × 10 -5) in patients. No significant effect of age at illness onset was detected. Stratifying patients based on clinical subtype (BD type I or type II) revealed that BDI patients had significantly larger lateral ventricles and smaller hippocampus and amygdala than controls. However, when comparing BDI and BDII patients directly, we did not detect any significant differences in brain volume. This likely represents similar etiology between BD subtype classifications. Exploratory analyses revealed significantly larger thalamic volumes in patients taking lithium compared with patients not taking lithium. We detected no significant differences between BDII patients and controls in the largest such comparison to date. Findings in this study should be interpreted with caution and with careful consideration of the limitations inherent to meta-analyzed neuroimaging comparisons. © 2016 Macmillan Publishers Limited, part of Springer Nature.
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| 3. |
- Thompson, Paul M., et al.
(författare)
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The ENIGMA Consortium : large-scale collaborative analyses of neuroimaging and genetic data
- 2014
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Ingår i: BRAIN IMAGING BEHAV. - : Springer Science and Business Media LLC. - 1931-7557 .- 1931-7565. ; 8:2, s. 153-182
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Tidskriftsartikel (refereegranskat)abstract
- The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
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| 4. |
- Granger, B. B., et al.
(författare)
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Adherence to candesartan and placebo and outcomes in chronic heart failure in the CHARM programme: double-blind, randomised, controlled clinical trial
- 2005
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Ingår i: Lancet. - 1474-547X. ; 366:9502, s. 2005-11
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Chronic heart failure (CHF) is an important cause of hospital admission and death. Poor adherence to medication is common in some chronic illnesses and might reduce the population effectiveness of proven treatments. Because little is known about adherence in patients with CHF and about the consequences of non-adherence, we assessed the association between adherence and clinical outcome in the CHARM (Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity) programme. METHODS: CHARM was a double-blind, randomised, controlled clinical trial, comparing the effects of the angiotensin receptor blocker candesartan with placebo in 7599 patients with CHF. Median follow-up was 38 months. The proportion of time patients took more than 80% of their study medication was defined as good adherence and 80% or less as poor adherence. We used a Cox proportional hazards regression model, with adherence as a time-dependent covariate in the model, to examine the association between adherence and mortality in the candesartan and placebo groups. FINDINGS: We excluded 187 patients because of missing information on adherence. In the time-dependent Cox regression model, after adjustment for predictive factors (demographics, physiological and severity-of-illness variables, smoking history, and number of concomitant medications), good adherence was associated with lower all-cause mortality in all patients (hazard ratio [HR] 0.65, 95% CI 0.57-0.75, p<0.0001). The adjusted HR for good adherence was similar in the candesartan (0.66, 0.55-0.81, p<0.0001) and placebo (0.64, 0.53-0.78, p<0.0001) groups. INTERPRETATION: Good adherence to medication is associated with a lower risk of death than poor adherence in patients with CHF, irrespective of assigned treatment. This finding suggests that adherence is a marker for adherence to effective treatments other than study medications, or to other adherence behaviours that affect outcome. Understanding these factors could provide an opportunity for new interventions, including those aimed at improving adherence.
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| 5. |
- Granger, B. B., et al.
(författare)
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Adherence to medication according to sex and age in the CHARM programme
- 2009
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Ingår i: European Journal of Heart Failure. - 1879-0844. ; 11:11, s. 1092-8
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Although many patients with heart failure have incomplete adherence to prescribed medications, predisposing factors remain unclear. This analysis investigates factors associated with adherence, with particular emphasis on age and sex. METHODS AND RESULTS: A multivariable regression analysis of 7599 heart failure patients from the CHARM trial was done to evaluate factors associated with adherence. Adherence was measured as the proportion of time patients took more than 80% of study medication. The mean age was 66 years (SD 11) and 31.5% (n = 2400) were women. Women were slightly less adherent than men (87.3 vs. 89.8%, P = 0.002), even in adjusted, multivariable models (treatment, P = 0.006; placebo P = 0.004; and overall P < 0.001). However, all-cause mortality was lower in women (21.5%) than in men (25.3%) (adjusted hazard ratio, 0.77; 95% CI, 0.69-0.86; P < 0.001), but patients with a low adherence regardless of sex had a higher mortality. Age, severity of heart failure, number of medications, and smoking status were not associated with adherence. CONCLUSION: Women, particularly those <75 years of age, were less likely to be adherent in this large sample of patients with symptomatic heart failure. Understanding factors associated with adherence may provide opportunities for intervention.
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| 6. |
- Granger, B. B., et al.
(författare)
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Results of the Chronic Heart Failure Intervention to Improve MEdication Adherence study: A randomized intervention in high-risk patients
- 2015
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703. ; 169:4, s. 539-548
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Tidskriftsartikel (refereegranskat)abstract
- Background Poor adherence to evidence-based medications in heart failure (HF) is a major cause of avoidable hospitalizations, disability, and death. To test the feasibility of improving medication adherence, we performed a randomized proof-of-concept study of a self-management intervention in high-risk patients with HF. Methods Patients with HF who screened positively for poor adherence (<6 Morisky Medication Adherence Scale 8-item) were randomized to either the intervention or attention control group. In the intervention group (n = 44), a nurse conducted self-management training before discharge that focused on identification of medication goals, facilitation of medication-symptom associations, and use of a symptom response plan. The attention control group (n = 42) received usual care; both groups received follow-up calls at 1 week. However, the content of follow-up calls for the attention control group was unrelated to HF medications or symptoms. General linear mixed models were used to evaluate the magnitude of change in adherence and symptom-related events at 3-, 6-, and 12-month follow-up clinic visits. Efficacy was measured as improved medication adherence using nurse-assessed pill counts at each time point. Results Pooled over all time points, patients in the intervention group were more likely to be adherent to medications compared with patients in the attention control group (odds ratio 3.92, t = 3.51, P = .0007). Conclusions A nurse-delivered, self-care intervention improved medication adherence in patients with advanced HF. Further work is needed to examine whether this intervention can be sustained to improve clinical outcomes.
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| 7. |
- Granger, B. B., et al.
(författare)
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The meanings associated with medicines in heart failure patients
- 2013
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Ingår i: European journal of cardiovascular nursing : journal of the Working Group on Cardiovascular Nursing of the European Society of Cardiology. - : Oxford University Press (OUP). - 1873-1953. ; 2:3, s. 276-283
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The purpose of this study was to explore the theoretical linkages between symptom experiences and meaning associated with medication adherence. The specific objectives were to evaluate the key constructs of Meaning-Response theory for understanding medication adherence in patients with chronic heart failure; to assess the influence of symptom persistence on the meaning associated with prescribed medicines; and to explore the extent to which meaningful associations improve medication adherence. Among patients with heart failure, poor medication adherence occurs in over half of the population, resulting in high rates of symptom exacerbation, avoidable hospitalization, and death. Nurses play a key role in facilitating self-management skills, but patients' perceptions of the relationship between symptoms and medicines is not clear. METHODS: Using a prospective mixed methods design, the study assessed patients' (n=10) perception of chronic heart failure symptoms and medication adherence. Patients completed guided interviews related to six concepts of meaning ascribed to medication use and four standardized measures of medication-related beliefs, behaviours, symptoms, and satisfaction. RESULTS: This study suggests that patients' perception of meaning associated with medication taking was categorized as positive, negative, or absent. Symptom persistence influenced a majority of patient beliefs in the efficacy medicines, and patients with more positive meaningful associations with their medicines were more likely to remain adherent during the course of this study. CONCLUSIONS: Development of meaningful associations with medicines may improve long-term adherence with prescribed medication in heart failure.
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| 8. |
- Ekman, Inger, et al.
(författare)
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Outpatient care programmes for the elderly
- 1999
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Ingår i: European Heart Journal. - London, United Kingdom : W. B. Saunders Co. Ltd.. - 0195-668X .- 1522-9645. ; 20:5, s. 393-4
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Tidskriftsartikel (refereegranskat)
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| 9. |
- Sobocki, P, et al.
(författare)
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Resource use and costs associated with patients treated for depression in primary care.
- 2006
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Ingår i: The European journal of health economics : HEPAC : health economics in prevention and care. - : Springer Science and Business Media LLC. - 1618-7598.
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Tidskriftsartikel (refereegranskat)abstract
- We investigated medical resource consumption, productivity loss and costs associated with patients treated with antidepressants for depression in primary care in Sweden. Patients on treatment for depression were followed naturalistically for six months, and data on patients' characteristics, daily activity and resource-use were collected. The total cost per patient was estimated at 5,500 (95%CI 5,000-6,100) over six months in 2005 prices. Direct costs were estimated at 1,900 ( 1,700-2,200), 35% of total costs, and indirect costs at 3,600 ( 3,100-4,100), 65% of total costs. The cost for antidepressants represented only 4% of the total costs. We conclude that the burden of depression is high, both to the individual as well as to wider society, and there seems to be a particular need for therapies that have the potential to improve productivity in depressed patients.
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| 10. |
- Flam, B, et al.
(författare)
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Authors' Response
- 2015
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Ingår i: Journal of intensive care medicine. - : SAGE Publications. - 1525-1489 .- 0885-0666. ; 52:1, s. 493-4
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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