| 1. |
- Boen, Rune, et al.
(författare)
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Beyond the global brain differences : intraindividual variability differences in 1q21.1 distal and 15q11.2 bp1-bp2 deletion carriers
- 2024
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Ingår i: Biological Psychiatry. - 0006-3223 .- 1873-2402. ; 95:2, s. 147-160
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Tidskriftsartikel (refereegranskat)abstract
- Background: Carriers of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants exhibit regional and global brain differences compared with noncarriers. However, interpreting regional differences is challenging if a global difference drives the regional brain differences. Intraindividual variability measures can be used to test for regional differences beyond global differences in brain structure.Methods: Magnetic resonance imaging data were used to obtain regional brain values for 1q21.1 distal deletion (n = 30) and duplication (n = 27) and 15q11.2 BP1-BP2 deletion (n = 170) and duplication (n = 243) carriers and matched noncarriers (n = 2350). Regional intra-deviation scores, i.e., the standardized difference between an individual's regional difference and global difference, were used to test for regional differences that diverge from the global difference.Results: For the 1q21.1 distal deletion carriers, cortical surface area for regions in the medial visual cortex, posterior cingulate, and temporal pole differed less and regions in the prefrontal and superior temporal cortex differed more than the global difference in cortical surface area. For the 15q11.2 BP1-BP2 deletion carriers, cortical thickness in regions in the medial visual cortex, auditory cortex, and temporal pole differed less and the prefrontal and somatosensory cortex differed more than the global difference in cortical thickness.Conclusions: We find evidence for regional effects beyond differences in global brain measures in 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants. The results provide new insight into brain profiling of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants, with the potential to increase understanding of the mechanisms involved in altered neurodevelopment.
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| 2. |
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| 3. |
- Harris, Michael, et al.
(författare)
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How European primary care practitioners think the timeliness of cancer diagnosis can be improved : a thematic analysis
- 2019
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 9:9, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- Background National European cancer survival rates vary widely. Prolonged diagnostic intervals are thought to be a key factor in explaining these variations. Primary care practitioners (PCPs) frequently play a crucial role during initial cancer diagnosis; their knowledge could be used to improve the planning of more effective approaches to earlier cancer diagnosis. Objectives This study sought the views of PCPs from across Europe on how they thought the timeliness of cancer diagnosis could be improved. Design In an online survey, a final open-ended question asked PCPs how they thought the speed of diagnosis of cancer in primary care could be improved. Thematic analysis was used to analyse the data. Setting A primary care study, with participating centres in 20 European countries. Participants A total of 1352 PCPs answered the final survey question, with a median of 48 per country. Results The main themes identified were: patient-related factors, including health education; care provider-related factors, including continuing medical education; improving communication and interprofessional partnership, particularly between primary and secondary care; factors relating to health system organisation and policies, including improving access to healthcare; easier primary care access to diagnostic tests; and use of information technology. Re-allocation of funding to support timely diagnosis was seen as an issue affecting all of these. Conclusions To achieve more timely cancer diagnosis, health systems need to facilitate earlier patient presentation through education and better access to care, have well-educated clinicians with good access to investigations and better information technology, and adequate primary care cancer diagnostic pathway funding.
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| 4. |
- Harris, Michael, et al.
(författare)
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Identifying important health system factors that influence primary care practitioners' referrals for cancer suspicion : a European cross-sectional survey.
- 2018
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 8:9, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Cancer survival and stage of disease at diagnosis and treatment vary widely across Europe. These differences may be partly due to variations in access to investigations and specialists. However, evidence to explain how different national health systems influence primary care practitioners' (PCPs') referral decisions is lacking.This study analyses health system factors potentially influencing PCPs' referral decision-making when consulting with patients who may have cancer, and how these vary between European countries.DESIGN: Based on a content-validity consensus, a list of 45 items relating to a PCP's decisions to refer patients with potential cancer symptoms for further investigation was reduced to 20 items. An online questionnaire with the 20 items was answered by PCPs on a five-point Likert scale, indicating how much each item affected their own decision-making in patients that could have cancer. An exploratory factor analysis identified the factors underlying PCPs' referral decision-making.SETTING: A primary care study; 25 participating centres in 20 European countries.PARTICIPANTS: 1830 PCPs completed the survey. The median response rate for participating centres was 20.7%.OUTCOME MEASURES: The factors derived from items related to PCPs' referral decision-making. Mean factor scores were produced for each country, allowing comparisons.RESULTS: Factor analysis identified five underlying factors: PCPs' ability to refer; degree of direct patient access to secondary care; PCPs' perceptions of being under pressure; expectations of PCPs' role; and extent to which PCPs believe that quality comes before cost in their health systems. These accounted for 47.4% of the observed variance between individual responses.CONCLUSIONS: Five healthcare system factors influencing PCPs' referral decision-making in 20 European countries were identified. The factors varied considerably between European countries. Knowledge of these factors could assist development of health service policies to produce better cancer outcomes, and inform future research to compare national cancer diagnostic pathways and outcomes.
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| 5. |
- Harris, Michael, et al.
(författare)
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Primary care practitioners' diagnostic action when the patient may have cancer : an exploratory vignette study in 20 European countries
- 2020
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 10:10, s. 035678-035678
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Cancer survival rates vary widely between European countries, with differences in timeliness of diagnosis thought to be one key reason. There is little evidence on the way in which different healthcare systems influence primary care practitioners' (PCPs) referral decisions in patients who could have cancer.This study aimed to explore PCPs' diagnostic actions (whether or not they perform a key diagnostic test and/or refer to a specialist) in patients with symptoms that could be due to cancer and how they vary across European countries. DESIGN: A primary care survey. PCPs were given vignettes describing patients with symptoms that could indicate cancer and asked how they would manage these patients. The likelihood of taking immediate diagnostic action (a diagnostic test and/or referral) in the different participating countries was analysed. Comparisons between the likelihood of taking immediate diagnostic action and physician characteristics were calculated. SETTING: Centres in 20 European countries with widely varying cancer survival rates. PARTICIPANTS: A total of 2086 PCPs answered the survey question, with a median of 72 PCPs per country. RESULTS: PCPs' likelihood of immediate diagnostic action at the first consultation varied from 50% to 82% between countries. PCPs who were more experienced were more likely to take immediate diagnostic action than their peers. CONCLUSION: When given vignettes of patients with a low but significant possibility of cancer, more than half of PCPs across Europe would take diagnostic action, most often by ordering diagnostic tests. However, there are substantial between-country variations.
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| 6. |
- Herrera-Rivero, Marisol, et al.
(författare)
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Exploring the genetics of lithium response in bipolar disorders.
- 2023
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Ingår i: Research square.
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N=2,064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II.We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism.Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II.
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| 7. |
- Herrera-Rivero, Marisol, et al.
(författare)
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Immunogenetics of lithium response and psychiatric phenotypes in patients with bipolar disorder.
- 2023
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Ingår i: Research square.
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The link between bipolar disorder (BP) and immune dysfunction remains controversial. While epidemiological studies have long suggested an association, recent research has found only limited evidence of such a relationship. To clarify this, we investigated the contributions of immune-relevant genetic factors to the response to lithium (Li) treatment and the clinical presentation of BP. First, we assessed the association of a large collection of immune-related genes (4,925) with Li response, defined by the Retrospective Assessment of the Lithium Response Phenotype Scale (Alda scale), and clinical characteristics in patients with BP from the International Consortium on Lithium Genetics (ConLi+Gen, N = 2,374). Second, we calculated here previously published polygenic scores (PGSs) for immune-related traits and evaluated their associations with Li response and clinical features. We found several genes associated with Li response at p < 1×10- 4 values, including HAS3, CNTNAP5 and NFIB. Network and functional enrichment analyses uncovered an overrepresentation of pathways involved in cell adhesion and intercellular communication, which appear to converge on the well-known Li-induced inhibition of GSK-3β. We also found various genes associated with BP's age-at-onset, number of mood episodes, and presence of psychosis, substance abuse and/or suicidal ideation at the exploratory threshold. These included RTN4, XKR4, NRXN1, NRG1/3 and GRK5. Additionally, PGS analyses suggested serum FAS, ECP, TRANCE and cytokine ligands, amongst others, might represent potential circulating biomarkers of Li response and clinical presentation. Taken together, our results support the notion of a relatively weak association between immunity and clinically relevant features of BP at the genetic level.
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| 8. |
- Hou, Liping, et al.
(författare)
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Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder.
- 2016
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 25:15, s. 3383-94
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Tidskriftsartikel (refereegranskat)abstract
- Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behavior. Genome-wide association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability. To identify additional risk loci, we performed a two-stage meta-analysis of >9 million genetic variants in 9,784 bipolar disorder patients and 30,471 controls, the largest GWAS of BD to date. In this study, to increase power we used ∼2,000 lithium-treated cases with a long-term diagnosis of BD from the Consortium on Lithium Genetics, excess controls, and analytic methods optimized for markers on the X-chromosome. In addition to four known loci, results revealed genome-wide significant associations at two novel loci: an intergenic region on 9p21.3 (rs12553324, p = 5.87 × 10(-9); odds ratio = 1.12) and markers within ERBB2 (rs2517959, p = 4.53 × 10(-9); odds ratio = 1.13). No significant X-chromosome associations were detected and X-linked markers explained very little BD heritability. The results add to a growing list of common autosomal variants involved in BD and illustrate the power of comparing well-characterized cases to an excess of controls in GWAS.
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| 9. |
- Jungo, Katharina Tabea, et al.
(författare)
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General practitioners' deprescribing decisions in older adults with polypharmacy : a case vignette study in 31 countries
- 2021
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Ingår i: BMC Geriatrics. - : BioMed Central (BMC). - 1471-2318 .- 1471-2318. ; 21:1, s. 1-12
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Tidskriftsartikel (refereegranskat)abstract
- Background General practitioners (GPs) should regularly review patients' medications and, if necessary, deprescribe, as inappropriate polypharmacy may harm patients' health. However, deprescribing can be challenging for physicians. This study investigates GPs' deprescribing decisions in 31 countries. Methods In this case vignette study, GPs were invited to participate in an online survey containing three clinical cases of oldest-old multimorbid patients with potentially inappropriate polypharmacy. Patients differed in terms of dependency in activities of daily living (ADL) and were presented with and without history of cardiovascular disease (CVD). For each case, we asked GPs if they would deprescribe in their usual practice. We calculated proportions of GPs who reported they would deprescribe and performed a multilevel logistic regression to examine the association between history of CVD and level of dependency on GPs' deprescribing decisions. Results Of 3,175 invited GPs, 54% responded (N = 1,706). The mean age was 50 years and 60% of respondents were female. Despite differences across GP characteristics, such as age (with older GPs being more likely to take deprescribing decisions), and across countries, overall more than 80% of GPs reported they would deprescribe the dosage of at least one medication in oldest-old patients (> 80 years) with polypharmacy irrespective of history of CVD. The odds of deprescribing was higher in patients with a higher level of dependency in ADL (OR =1.5, 95%CI 1.25 to 1.80) and absence of CVD (OR =3.04, 95%CI 2.58 to 3.57). Interpretation The majority of GPs in this study were willing to deprescribe one or more medications in oldest-old multimorbid patients with polypharmacy. Willingness was higher in patients with increased dependency in ADL and lower in patients with CVD.
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| 10. |
- Luethold, Renata Vidonscky, et al.
(författare)
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Understanding older patients' willingness to have medications deprescribed in primary care : a protocol for a cross-sectional survey study in nine European countries
- 2022
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Ingår i: BMC Geriatrics. - : BioMed Central (BMC). - 1471-2318 .- 1471-2318. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: To reduce inappropriate polypharmacy, deprescribing should be part of patients' regular care. Yet deprescribing is difficult to implement, as shown in several studies. Understanding patients' attitudes towards deprescribing at the individual and country level may reveal effective ways to involve older adults in decisions about medications and help to implement deprescribing in primary care settings. In this study we aim to investigate older adults' perceptions and views on deprescribing in different European countries. Specific objectives are to investigate the patients' willingness to have medications deprescribed by medication type and to have herbal or dietary supplements reduced or stopped, the role of the Patient Typology (on medication perspectives), and the impact of the patient-GP relationship in these decisions. Methods and analysis: This cross-sectional survey study has two parts: Part A and Part B. Data collection for Part A will take place in nine countries, in which per country 10 GPs will recruit 10 older patients (>= 65 years old) each (n = 900). Part B will be conducted in Switzerland only, in which an additional 35 GPs will recruit five patients each and respond to a questionnaire themselves, with questions about the patients' medications, their willingness to deprescribe those, and their patient-provider relationship. For both Part A and part B, a questionnaire will be used to assess the willingness of older patients with polypharmacy to have medications deprescribed and other relevant information. For Part B, this same questionnaire will have additional questions on the use of herbal and dietary supplements. Discussion: The international study design will allow comparisons of patient perspectives on deprescribing from different countries. We will collect information about willingness to have medications deprescribed by medication type and regarding herbal and dietary supplements, which adds important information to the literature on patients' preferences. In addition, GPs in Switzerland will also be surveyed, allowing us to compare GPs' and patients' views and preferences on stopping or reducing specific medications. Our findings will help to understand patients' attitudes towards deprescribing, contributing to improvements in the design and implementation of deprescribing interventions that are better tailored to patients' preferences.
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