| 1. |
- 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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| 2. |
- Zannad, F., et al.
(författare)
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Clinical outcome endpoints in heart failure trials: a European Society of Cardiology Heart Failure Association consensus document
- 2013
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 15:10, s. 1082-1094
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Tidskriftsartikel (refereegranskat)abstract
- Endpoint selection is a critically important step in clinical trial design. It poses major challenges for investigators, regulators, and study sponsors, and it also has important clinical and practical implications for physicians and patients. Clinical outcomes of interest in heart failure trials include all-cause mortality, cause-specific mortality, relevant non-fatal morbidity (e.g. all-cause and cause-specific hospitalization), composites capturing both morbidity and mortality, safety, symptoms, functional capacity, and patient-reported outcomes. Each of these endpoints has strengths and weaknesses that create controversies regarding which is most appropriate in terms of clinical importance, sensitivity, reliability, and consistency. Not surprisingly, a lack of consensus exists within the scientific community regarding the optimal endpoint(s) for both acute and chronic heart failure trials. In an effort to address these issues, the Heart Failure Association of the European Society of Cardiology (HFA-ESC) convened a group of expert heart failure clinical investigators, biostatisticians, regulators, and pharmaceutical industry scientists (Nice, France, 12-13 February 2012) to evaluate the challenges of defining heart failure endpoints in clinical trials and to develop a consensus framework. This report summarizes the group's recommendations for achieving common views on heart failure endpoints in clinical trials.
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| 3. |
- Bosworth, H. B., et al.
(författare)
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Medication adherence: a call for action
- 2011
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Ingår i: American heart journal. - : Elsevier BV. - 1097-6744 .- 0002-8703. ; 162:3, s. 412-24
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Tidskriftsartikel (refereegranskat)abstract
- Poor adherence to efficacious cardiovascular-related medications has led to considerable morbidity, mortality, and avoidable health care costs. This article provides results of a recent think-tank meeting in which various stakeholder groups representing key experts from consumers, community health providers, the academic community, decision-making government officials (Food and Drug Administration, National Institutes of Health, etc), and industry scientists met to evaluate the current status of medication adherence and provide recommendations for improving outcomes. Below, we review the magnitude of the problem of medication adherence, prevalence, impact, and cost. We then summarize proven effective approaches and conclude with a discussion of recommendations to address this growing and significant public health issue of medication nonadherence.
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| 4. |
- Ekman, Inger, 1952, et al.
(författare)
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Heart rate reduction with ivabradine and health related quality of life in patients with chronic heart failure: results from the SHIFT study
- 2011
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Ingår i: European heart journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 32:19, s. 2395-2404
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Tidskriftsartikel (refereegranskat)abstract
- AimsHeart failure (HF) has a major impact on health-related quality of life (HQoL). The aim was to evaluate whether heart rate (HR) reduction with ivabradine can translate into increased HQoL in parallel to a reduction of primary outcomes in SHIFT.Methods and resultsIn symptomatic patients with systolic HF treated with recommended background therapy, HQoL was assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ) containing the following dimensions: overall summary score (OSS) and clinical summary score (CSS), analysed at baseline, and 4, 12, and 24 months, and last post-baseline visit. A total of 1944 patients (968 ivabradine, 976 placebo) were evaluated. At 12 months, incidence of clinical events (cardiovascular death or hospital admission for HF) was inversely associated with KCCQ scores. Ivabradine reduced HR by 10.1 bpm (placebo-corrected, P < 0.001) and improved KCCQ by 1.8 for CSS and 2.4 for OSS (placebo-corrected, P = 0.02 and P < 0.01, respectively); these changes were associated with the change in HR for both CSS (P < 0.001) and OSS (P < 0.001). The relationship was found in both allocation groups though the changes were more pronounced in the ivabradine group. Health-related quality of life at follow-up was better preserved in the ivabradine group compared with placebo; poorest outcomes were seen in the placebo group with lowest KCCQ scores (<50).ConclusionIn patients with systolic HF, low HQoL is associated with an increased rate of cardiovascular death or hospital admission for HF. Reduction in HR with ivabradine is associated with improved HQoL. The magnitude of HR reduction is related to the extent of improvement in HQoL.
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| 5. |
- Ekman, M., et al.
(författare)
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PMH30 The Societal Cost of Depression: Evidence from 10,000 Swedish Patients in Psychiatric Care
- 2012
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Ingår i: Value in Health. - 1098-3015. ; 15:4, s. A87-A87
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Konferensbidrag (refereegranskat)abstract
- Objectives Depression is a major health problem. Previous studies on the cost of depression have mainly taken a primary care perspective. Such studies do not include all patients with depression, and should be completed by cost estimates from psychiatric care. The objectives of this study were to estimate the annual societal cost of depression per patient in psychiatric care in Sweden, and to relate costs to disease severity, depressive episodes, hospitalization, and patient functioning. Methods Retrospective resource use data in inpatient and outpatient care for 2006-2008, as well as ICD-10 diagnoses and Global Assessment of Functioning (GAF), were obtained from Northern Stockholm psychiatric clinic with a catchment area including 47% of the adult inhabitants in Stockholm city. This data set was combined with national register data on prescription pharmaceuticals and sick leave to estimate the societal cost of depression. Results The study included 10,593 patients (63% women). The average annual societal cost per patient was around USD 21,000 in 2006-2008. The largest cost item was indirect costs due to productivity losses (89%), and the second largest was outpatient care (6%). Patients with mild, moderate or severe depression had an average cost of approximately USD 18,000, USD 21,000, and USD 29,000, respectively. Total costs were significantly higher during depressive episodes, for patients with co-morbid psychosis or anxiety, for hospitalized patients, and for patients with low GAF scores. Conclusions The largest share of societal costs for patients with depression in psychiatric care is indirect. The total costs were higher than previously reported from a primary care setting, and strongly related to hospitalization, episodes of active depression, and global functioning. This suggests that effective treatment and rehabilitation that avoid depressive episodes and hospitalization may not only improve patient health, but also reduce the societal cost of depression.
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| 6. |
- Ekman, M., et al.
(författare)
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The societal cost of bipolar disorder in Sweden
- 2013
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Ingår i: Social Psychiatry and Psychiatric Epidemiology. - : Springer Science and Business Media LLC. - 0933-7954 .- 1433-9285. ; 48:10, s. 1601-1610
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Tidskriftsartikel (refereegranskat)abstract
- There is a lack of comprehensive cost-of-illness studies in bipolar disorder, in particular studies based on patient-level data. The purpose of this study was to estimate the societal cost of bipolar disorder and to relate costs to disease severity, depressive episodes, hospitalisation and patient functioning. Retrospective resource use data in inpatient and outpatient care during 2006-2008, as well as ICD-10 diagnoses and Global Assessment of Functioning (GAF) scores, were obtained from the Northern Stockholm psychiatric clinic with a catchment area including 47 % of the adult inhabitants in Stockholm. This dataset was combined with national register data on prescription pharmaceuticals and sick leave to estimate the societal cost of bipolar disorder. The study was conducted from a societal perspective, with indirect costs valued according to the human capital method. The average annual cost per patient was a,not sign28,011 in 2008 (n = 1,846). Indirect costs due to sick leave and early retirement represented 75 %, inpatient costs 13 %, outpatient costs 8 %, pharmaceuticals 2 % and community care another 2 % of the total cost. Total costs were considerably higher during mood episodes (six times higher than in remission), for hospitalised patients (a,not sign55,500 vs. a,not sign22,200) and for patients with low GAF scores. The high cost of bipolar disorder is driven primarily by indirect costs. Costs were strongly associated with mood episodes, hospitalisations and low GAF scores. This suggests that treatment that reduces the risk for relapses and hospitalizations and improve functioning may decrease both the societal cost of bipolar disorder and patient suffering.
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| 7. |
- Ekman, M., et al.
(författare)
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The societal cost of depression: Evidence from 10,000 Swedish patients in psychiatric care
- 2013
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Ingår i: Journal of Affective Disorders. - : Elsevier BV. - 0165-0327 .- 1573-2517. ; 150:3, s. 790-797
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Depression cost studies have mainly taken a primary care perspective and should be completed with cost estimates from psychiatric care. The objectives of this study were to estimate the societal per-patient cost of depression in specialized psychiatric care in Sweden, and to relate costs to disease severity, depressive episodes, hospitalization, and patient functioning. Methods: Retrospective resource use data in inpatient and outpatient care for 2006-2008, as well as lCD-10 diagnoses and Global Assessment of Functioning (GAF), were obtained from the Northern Stockholm psychiatric clinic (covering half of Stockholm's population aged 18 years and above). As a complement, data from national registers on pharmaceuticals and sick leave were used in order to estimate the societal cost of depression. Results: Based on 10,430 patients (635, women), the mean annual per patient cost was (sic)17, 279 in 2008. The largest cost item was indirect costs due to productivity losses (88%), followed by outpatient care (6%). Patients with mild and severe depression had average costs of (sic)14,200 and (sic)21,500, respectively. Total costs were substantially higher during depressive episodes, among patients with co-morbid psychosis or anxiety, for hospitalized patients, and for patients with poor functioning. Limitations: Primary care costs and costs for reduced productivity at work were not included. Conclusions: The main cost item among depression patients in psychiatric care was indirect costs. Costs were higher than previously reported for primary care, and strongly related to hospitalization, depressive episodes, and low functioning. This suggests that effective treatment that avoids depressive episodes and hospitalization may reduce society's costs for depression.
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| 8. |
- Ekman, M., et al.
(författare)
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The Societal Cost of Schizophrenia in Sweden
- 2013
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Ingår i: Journal of Mental Health Policy and Economics. - 1091-4358. ; 16:1, s. 13-25
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Tidskriftsartikel (refereegranskat)abstract
- Background: Schizophrenia is a disabling psychiatric disorder that has severe consequences for patients and their families. Moreover, the expensive treatment of schizophrenia imposes a burden on health care providers and the wider society. Existing cost estimates for Sweden, however, are based on relatively small patient populations and need to be confirmed in a large register-based study. Aims of the Study: To investigate the health care resource utilization and cost-of-illness in patients with schizophrenia in Sweden and to relate the costs to hospitalizations and global assessment of functioning (GAF). Methods: Hospital-based registry data were combined with national registry data from a large patient population to get reliable estimates of the costs of schizophrenia in Sweden. Schizophrenia was defined by ICD-10 codes F20; F21; F23.1,2,8,9; F25.1,8,9. Registry data on socio-demographics and disease-related healthcare resource use in outpatient and inpatient care were obtained from Northern Stockholm Psychiatry. Data on pharmaceuticals were obtained from the National Board of Health and Welfare, and data on sick leave and early retirement were obtained from the Swedish Social Insurance Agency. Costs for community mental health care were not available at the individual level, but were estimated based on previous studies and aggregate cost data from Stockholm. Resource use data from the registries were combined with unit costs from publicly available sources. The study was conducted from a societal perspective, with indirect costs valued according to the human capital method. Results: The average annual psychiatric cost per patient with schizophrenia in 2008 was 42 700 (95% CI: 41 500 44 000), based on a sample of 2 161 patients. To this should be added costs for community mental health care of 12 400 per patient, giving a total cost of 55 100 per patient. The two largest cost items in the total costs were indirect costs due to lost productivity (60%) and community mental health care (22% of the total cost). Patients who were hospitalized in 2008 had greater psychiatric costs than those who were not, (sic)71 700 vs. (sic)37 700 (p<0.0001). Psychiatric costs were significantly and negatively correlated with GAF (p<0.001). Discussion: The major strengths of the study are the relatively large sample, and the linkage of patient-level clinical data on inpatient and outpatient care with national registry data on prescription pharmaceuticals, and days on social insurance. A limitation was that costs for informal care and primary care were not included in the data, but previous studies suggest that these costs items are small compared to other costs for schizophrenia. Implications for Health Policies and Future Research: Costs were strongly related to hospitalization and GAF, suggesting that attempts to improve global functioning and avoid hospitalizations by means of effective treatment and rehabilitation might not only decrease suffering for patients and relatives, but also reduce the societal cost of schizophrenia. A detailed knowledge of the societal costs can also be helpful in evaluating the cost-effectiveness of new treatment strategies to improve the care for patients with schizophrenia.
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| 9. |
- Karlsson, S. L., et al.
(författare)
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Development of stable vibrio cholerae O1 Hikojima type vaccine strains co-expressing the Inaba and Ogawa lipopolysaccharide antigens
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 9:11
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Tidskriftsartikel (refereegranskat)abstract
- We describe here the development of stable classical and El Tor V. cholerae O1 strains of the Hikojima serotype that co-express the Inaba and Ogawa antigens of O1 lipopolysaccharide (LPS). Mutation of the wbeTgene reduced LPS perosamine methylation and thereby gave only partial transformation into Ogawa LPS on the cell surface. The strains express approximately equal amounts of Inaba-and Ogawa-LPS antigens which are preserved after formalin-inactivation of the bacteria. Oral immunizations of both inbred and outbred mice with formalin-inactivated whole-cell vaccine preparations of these strains elicited strong intestinal IgA anti-LPS as well as serum vibriocidal antibody responses against both Inaba and Ogawa that were fully comparable to the responses induced by the licensed Dukoral vaccine. Passive protection studies in infant mice showed that immune sera raised against either of the novel Hikojima vaccine strains protected baby mice against infection with virulent strains of both serotypes. This study illustrates the power of using genetic manipulation to improve the properties of bacteria strains for use in killed whole-cell vaccines.
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| 10. |
- Lebens, Michael, 1956, et al.
(författare)
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Construction of novel vaccine strains of Vibrio cholerae co-expressing the Inaba and Ogawa serotype antigens
- 2011
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 29:43, s. 7505-7513
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Tidskriftsartikel (refereegranskat)abstract
- The approach of inducing protective immunity against cholera by oral vaccination with killed whole Vibrio cholerae cells is effective, but the complexity of current cholera vaccines makes them difficult and relatively expensive to manufacture, especially if recombinant cholera toxin B subunit is included in the formulation. In an effort to simplify the composition of a new generation of oral cholera vaccines we have generated a novel non-toxigenic candidate vaccine strain of V. cholerae O1 that stably expresses both the Ogawa and Inaba serotype antigens on its surface. This was done by introducing a functional wbeT gene without a functional promoter into the chromosome of an O1 Inaba strain. The resulting low levels of expression of the wbeT gene product allowed for the desired partial serotype switching. This strain (MS1342) can potentially replace the three virulent strains used in currently manufactured cholera vaccines. Oral immunization of mice with formalin-killed MS1342 bacteria gave rise to Ogawa-specific, Inaba-specific and cross-reactive serum antibodies that were detectable both by lipopolysaccharide (LPS)-specific ELISAs and as vibriocidal antibodies that are considered to predict protective efficacy. These responses as well as intestinal mucosal IgA anti-LPS antibody responses were fully comparable with those obtained by immunization with the internationally licensed oral cholera vaccine Dukoral ®. We propose that such a strain may form the basis of a single strain killed whole cell cholera vaccine protecting against cholera caused by either the Inaba or Ogawa serotype of V. cholerae O1.
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