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Patton, A.-C., Thörnblom, E., Ros, H. S. & Bodén, R. (2019). A case of bipolar disorder onset with subsequent catatonia in a 14-year-old boy treated successfully with electroconvulsive therapy [Letter to the editor]. Nordic Journal of Psychiatry, 73(8), 497-500
Open this publication in new window or tab >>A case of bipolar disorder onset with subsequent catatonia in a 14-year-old boy treated successfully with electroconvulsive therapy
2019 (English)In: Nordic Journal of Psychiatry, ISSN 0803-9488, E-ISSN 1502-4725, Vol. 73, no 8, p. 497-500Article in journal, Letter (Other academic) Published
Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD, 2019
National Category
Psychiatry
Identifiers
urn:nbn:se:uu:diva-396178 (URN)10.1080/08039488.2019.1655590 (DOI)000482501000001 ()31430220 (PubMedID)
Funder
Swedish Research Council, 2016-02362
Available from: 2019-10-31 Created: 2019-10-31 Last updated: 2019-10-31Bibliographically approved
Li, G., Fife, D., Wang, G., Sheehan, J. J., Bodén, R., Brandt, L., . . . DiBernardo, A. (2019). All-cause mortality in patients with treatment-resistant depression: a cohort study in the US population. Annals of General Psychiatry, 18(1), Article ID 23.
Open this publication in new window or tab >>All-cause mortality in patients with treatment-resistant depression: a cohort study in the US population
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2019 (English)In: Annals of General Psychiatry, ISSN 1744-859X, E-ISSN 1744-859X, Vol. 18, no 1, article id 23Article in journal (Refereed) Published
Abstract [en]

Background Treatment-resistant depression (TRD) may represent a substantial proportion of major depressive disorder (MDD); however, the risk of mortality in TRD is still incompletely assessed. Methods Data were obtained from Optum Clinformatics (TM) Extended, a US claims database. Date of the first antidepressant (AD) dispensing was designated as the index date for study entry and 6 months prior to that was considered the baseline period. Patients with MDD aged >= 18 years, index date between January 1, 2008 and September 30, 2015, no AD claims during baseline, and continuous enrollment in the database during baseline were included. Patients who started a third AD regimen after two regimens of appropriate duration were included in the TRD cohort. All-cause mortality was compared between patients with TRD and non-TRD MDD using a proportional hazards model and Kaplan-Meier estimate with TRD status being treated as a time-varying covariate. The model was adjusted for study year, age, gender, depression diagnosis, substance use disorder, psychiatric comorbidities, and Charlson comorbidity index. Results Out of 355,942 patients with MDD, 34,176 (9.6%) met the criterion for TRD. TRD was associated with a significantly higher mortality compared with non-TRD MDD (adjusted HR: 1.29; 95% CI 1.22-1.38; p < 0.0001). Survival time was significantly shorter in the TRD cohort compared with the non-TRD MDD cohort (p < 0.0001). Conclusions Patients with TRD had a higher all-cause mortality compared with non-TRD MDD patients.

Place, publisher, year, edition, pages
BMC, 2019
Keywords
Major depressive disorder, Mortality, Treatment-resistant depression
National Category
Psychiatry
Identifiers
urn:nbn:se:uu:diva-395733 (URN)10.1186/s12991-019-0248-0 (DOI)000488471800001 ()31583010 (PubMedID)
Funder
Swedish Research Council, 2016-02362
Available from: 2019-10-23 Created: 2019-10-23 Last updated: 2019-10-23Bibliographically approved
Wingård, L., Brandt, L., Bodén, R., Kieler, H., Andersen, M. & Reutfors, J. (2019). Monotherapy vs. combination therapy for post mania maintenance treatment: A population based cohort study. European Neuropsychopharmacology, 29(6), 691-700
Open this publication in new window or tab >>Monotherapy vs. combination therapy for post mania maintenance treatment: A population based cohort study
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2019 (English)In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 29, no 6, p. 691-700Article in journal (Refereed) Published
Abstract [en]

In recent years, the use of atypical antipsychotics and combination therapy for relapse prevention in bipolar disorder has increased substantially. However, real-world data on the comparative effectiveness of these treatment options are largely non-existent. We conducted a population-based cohort study, using data from Swedish national registers. All patients aged 18-75 years who were hospitalized for mania 2006-2014 and filled at least one prescription of lithium, valproate, olanzapine, quetiapine, aripiprazole or any combination of these drugs were included, and followed for up to one year after hospital discharge, generating follow-up data from 5 713 hospitalizations. We used Cox proportional hazard regression models to study time to treatment failure for each individual drug and combination therapy, using lithium as comparator. Treatment failure was defined as treatment discontinuation, switch, or rehospitalization, and the results were adjusted for clinical and sociodemographic factors. We found that treatment failure occurred in 85% of cases and that the majority of combination therapies were associated with lower risks of treatment failure compared to monotherapies. Patients combining lithium + valproate + quetiapine had the lowest risk of treatment failure (adjusted HR [AHR] 0.40, 95% CI 0.30-0.54), followed by patients on lithium + valproate + olanzapine (AHR 0.55, 95% CI 0.45-0.68). In contrast, monotherapies with antipsychotics were associated with significantly higher risks of treatment failure compared to single use of lithium. In conclusion, our results support experimental findings, suggesting that combination therapy is more effective than monotherapy after a manic episode.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE BV, 2019
Keywords
Cohort studies, Bipolar disorder, Maintenance treatment, Antipsychotic agents, Lithium
National Category
Psychiatry Pharmacology and Toxicology
Identifiers
urn:nbn:se:uu:diva-390038 (URN)10.1016/j.euroneuro.2019.04.003 (DOI)000471165600001 ()31078359 (PubMedID)
Funder
Swedish Research Council, 2016-02362Stiftelsen Söderström - Königska sjukhemmet, SLS-480131Fredrik och Ingrid Thurings Stiftelse, 2015-00114Novo Nordisk, NNF15SA0018404Swedish Society of Medicine, SLS-502541Swedish Society of Medicine, SLS-587661
Available from: 2019-08-05 Created: 2019-08-05 Last updated: 2019-08-05Bibliographically approved
Persson, J., Szalisznyo, K., Antoni, G., Wall, A., Fällmar, D., Zora, H. & Bodén, R. (2019). Phosphodiesterase 10A levels are related to striatal function in schizophrenia: a combined positron emission tomography and functional magnetic resonance imaging study. European Archives of Psychiatry and Clinical Neuroscience
Open this publication in new window or tab >>Phosphodiesterase 10A levels are related to striatal function in schizophrenia: a combined positron emission tomography and functional magnetic resonance imaging study
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2019 (English)In: European Archives of Psychiatry and Clinical Neuroscience, ISSN 0940-1334, E-ISSN 1433-8491Article in journal (Refereed) Published
Abstract [en]

Pharmacological inhibition of phosphodiesterase 10A (PDE10A) is being investigated as a treatment option in schizophrenia. PDE10A acts postsynaptically on striatal dopamine signaling by regulating neuronal excitability through its inhibition of cyclic adenosine monophosphate (cAMP), and we recently found it to be reduced in schizophrenia compared to controls. Here, this finding of reduced PDE10A in schizophrenia was followed up in the same sample to investigate the effect of reduced striatal PDE10A on the neural and behavioral function of striatal and downstream basal ganglia regions. A positron emission tomography (PET) scan with the PDE10A ligand [11C]Lu AE92686 was performed, followed by a 6 min resting-state magnetic resonance imaging (MRI) scan in ten patients with schizophrenia. To assess the relationship between striatal function and neurophysiological and behavioral functioning, salience processing was assessed using a mismatch negativity paradigm, an auditory event-related electroencephalographic measure, episodic memory was assessed using the Rey auditory verbal learning test (RAVLT) and executive functioning using trail-making test B. Reduced striatal PDE10A was associated with increased amplitude of low-frequency fluctuations (ALFF) within the putamen and substantia nigra, respectively. Higher ALFF in the substantia nigra, in turn, was associated with lower episodic memory performance. The findings are in line with a role for PDE10A in striatal functioning, and suggest that reduced striatal PDE10A may contribute to cognitive symptoms in schizophrenia.

National Category
Psychiatry Neurosciences
Identifiers
urn:nbn:se:uu:diva-392015 (URN)10.1007/s00406-019-01021-0 (DOI)
Available from: 2019-08-28 Created: 2019-08-28 Last updated: 2019-08-28Bibliographically approved
Clapham, E., Bodén, R., Brandt, L., Jonsson, E. G., Bahmanyar, S., Ekbom, A., . . . Reutfors, J. (2019). Suicide Ideation and Behavior as Risk Factors for Subsequent Suicide in Schizophrenia: A Nested Case-Control Study. Journal of Suicide and Life-threatening Behaviour, 49(4), 996-1005
Open this publication in new window or tab >>Suicide Ideation and Behavior as Risk Factors for Subsequent Suicide in Schizophrenia: A Nested Case-Control Study
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2019 (English)In: Journal of Suicide and Life-threatening Behaviour, ISSN 0363-0234, E-ISSN 1943-278X, Vol. 49, no 4, p. 996-1005Article in journal (Refereed) Published
Abstract [en]

Objective To investigate suicide ideation and behavior as risk factors for suicide in schizophrenia during varying time periods. Method Cases were 84 patients who died by suicide within 5 years from diagnosis in a source population of patients discharged for the first time from psychiatric hospitals in Stockholm County, Sweden, with a schizophrenia spectrum diagnosis. One control was individually matched with each suicide case. Data were retrieved from clinical records in a blind fashion. Thoughts of death, thoughts of suicide, suicide plan, and suicide attempt during varying time periods were investigated as risk factors for subsequent completed suicide. Results In adjusted analyses, thoughts of suicide, suicide plan, and suicide attempt were significantly associated with subsequent completed suicide in the following year. The highest suicide risk was found within a year following suicide attempt (adjusted OR 9.9, 95% confidence interval 2.5-39.0). The association between suicide ideation and behavior and subsequent suicide declined over time. Conclusions Several types of suicide ideation and behavior were associated with suicide, and the association was stronger for suicidal behavior. The clinical significance of suicidal communication appears highest during the following month or/and year. Many suicides occurred without recorded short-term suicidal communication.

Place, publisher, year, edition, pages
WILEY, 2019
National Category
Psychiatry
Identifiers
urn:nbn:se:uu:diva-393627 (URN)10.1111/sltb.12499 (DOI)000480640600007 ()30073690 (PubMedID)
Available from: 2019-09-26 Created: 2019-09-26 Last updated: 2019-09-26Bibliographically approved
Brenner, P., Brandt, L., Li, G., DiBernardo, A., Bodén, R. & Reutfors, J. (2019). Treatment-resistant depression as risk factor for substance use disorders: a nation-wide register-based cohort study. Addiction, 114(7), 1274-1282
Open this publication in new window or tab >>Treatment-resistant depression as risk factor for substance use disorders: a nation-wide register-based cohort study
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2019 (English)In: Addiction, ISSN 0965-2140, E-ISSN 1360-0443, Vol. 114, no 7, p. 1274-1282Article in journal (Refereed) Published
Abstract [en]

Background and aims Treatment-resistant depression (TRD) is common among patients with major depressive disorder (MDD). MDD may increase the risk for developing substance use disorders (SUD). The aim of this study was to investigate the risk for developing SUD among patients with TRD compared with other depressed patients.

Design Observational cohort study.

Setting Nation-wide governmental health registers in Sweden.

Participants All patients aged 18-69 years with an MDD diagnosis in specialized health care who had received at least one antidepressant prescription during 2006-14 were identified. Patients with at least three treatment trials within a single depressive episode were classified with TRD.

Measurements Patients with TRD were compared with the whole MDD cohort regarding risk for obtaining a SUD diagnosis or medication using survival analyses adjusted for socio-demographics and comorbidities.

Findings Of 121 669 MDD patients, 13% were classified with TRD. Among the patients without any history of SUD, patients with TRD had a risk increase for any SUD both ≤ 1 and > 1 year after antidepressant initiation [> 1 year hazard ratio (HR) = 1.4; 95% confidence interval (CI) = 1.3-1.5]. Risks were elevated for the subcategories of opioid (HR = 1.9, 95% CI = 1.4-2.5) and sedative SUD (HR = 2.7, 95% CI = 2.2-3.2). Patients with a history of SUD had a risk increase for any SUD ≤ 1 year after start of treatment (HR = 1.2, 95% CI = 1.1-1.4), and both ≤ 1 year and > 1 year for sedative (> 1 year HR = 2.0, 95% CI = 1.3-3.0) and multiple substance SUD (HR = 1.9, 95% CI = 1.4-2.5).

Conclusions Patients with treatment-resistant depression may be at greater risk for substance use disorders compared with other patients with major depressive disorder. Patterns may differ for patients with and without a history of substance use disorders, and for different categories of substance use disorder.

Keywords
Addiction, alcoholism, antidepressants, depressive disorder, epidemiology, opioid-related disorders, treatment-resistant
National Category
Psychiatry Substance Abuse
Identifiers
urn:nbn:se:uu:diva-388768 (URN)10.1111/add.14596 (DOI)000470903900012 ()30938020 (PubMedID)
Funder
Swedish Research Council, 2016-02362Stiftelsen Söderström - Königska sjukhemmet, SLS-759771Fredrik och Ingrid Thurings Stiftelse, 2017-00302
Available from: 2019-07-05 Created: 2019-07-05 Last updated: 2019-07-05Bibliographically approved
DiBernardo, A., Lin, X., Zhang, Q., Xiang, J., Lu, L., Jamieson, C., . . . Li, G. (2018). Humanistic outcomes in treatment resistant depression: a secondary analysis of the STAR*D study. BMC Psychiatry, 18, Article ID 352.
Open this publication in new window or tab >>Humanistic outcomes in treatment resistant depression: a secondary analysis of the STAR*D study
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2018 (English)In: BMC Psychiatry, ISSN 1471-244X, E-ISSN 1471-244X, Vol. 18, article id 352Article in journal (Refereed) Published
Abstract [en]

BackgroundIn the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, a third of patients did not achieve remission or adequate response after two treatment trials, fulfilling requirements for treatment resistant depression (TRD). The present study is a secondary analysis of the STAR*D data conducted to compare the humanistic outcomes in patients with TRD and non-TRD MDD.MethodsPatients with major depressive disorder who entered level 3 of the STAR*D were included in the TRD group, while patients who responded to treatment and entered follow-up from level 1 or 2 were included in the non-TRD group. The first visit in level 1 was used for baseline assessments. The time-point of assessments for comparison was the first visit in level 3 for TRD patients (median day: 141), and the visit closest to 14160days from baseline for non-TRD patients. Outcomes were assessed by the 12-item Short Form Health Survey (SF12), 16-item Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), Work and Social Adjustment Scale (WSAS), and Work Productivity and Activity Impairment scale (WPAI). Scores were compared in a linear model with adjustment for covariates including age, gender, and depression severity measured by the 17-item Hamilton Rating Scale for Depression (HDRS17) and Quick Inventory of Depressive Symptomatology (QIDS).ResultsA total of 2467 (TRD: 377; non-TRD: 2090) patients were studied. TRD patients were slightly older (mean age 44 vs 42years), had a higher proportion of men (49% vs 37%, p<.0001), and baseline depression severity (HDRS17: 24.4 vs 22.0, p<.0001) vs non-TRD patients. During follow-up, TRD patients had lower health-related quality of life (HRQOL) scores on mental (30 vs 45.7) and physical components (47.7 vs 48.9) of the SF12, and lower Q-LES-Q scores (43.6 vs 63.7), greater functional and work impairments and productivity loss vs non-TRD patients (all p<0.05).Conclusion Patients with TRD had worse HRQOL, work productivity, and social functioning than the non-TRD patients.

Place, publisher, year, edition, pages
BMC, 2018
Keywords
Health-related quality of life, Humanistic outcomes, Social functioning, Star*d, Treatment resistant depression
National Category
Psychiatry
Identifiers
urn:nbn:se:uu:diva-369888 (URN)10.1186/s12888-018-1920-7 (DOI)000448750800001 ()30373547 (PubMedID)
Funder
Swedish Research Council, 2016-02362
Available from: 2018-12-19 Created: 2018-12-19 Last updated: 2018-12-19Bibliographically approved
Wingard, L., Taipale, H., Reutfors, J., Westerlund, A., Bodén, R., Tiihonen, J., . . . Andersen, M. (2018). Initiation and long-term use of benzodiazepines and Z-drugs in bipolar disorder. Bipolar Disorders, 20(7), 634-646
Open this publication in new window or tab >>Initiation and long-term use of benzodiazepines and Z-drugs in bipolar disorder
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2018 (English)In: Bipolar Disorders, ISSN 1398-5647, E-ISSN 1399-5618, Vol. 20, no 7, p. 634-646Article in journal (Refereed) Published
Abstract [en]

Objectives

Increasing evidence points to the harmful effects of long‐term benzodiazepine treatment. Our objective was to study the incidence of, and predictors for, long‐term use of benzodiazepines and Z‐drugs in bipolar disorder.

Methods

We conducted a population‐based cohort study, using data from Swedish national registers. Swedish residents aged 18‐75 years with a recorded diagnosis of bipolar disorder or mania between July 2006 and December 2012, and no history of benzodiazepine/Z‐drug use in the past year, were included. Patients were followed for 1 year with regard to prescription fills of benzodiazepines/Z‐drugs. Initiators were followed for another year during which continuous use for >6 months was defined as “long‐term”. Patient and prescription characteristics were investigated as potential predictors for long‐term use in multivariate logistic regression models.

Results

Out of the 21 883 patients included, 29% started benzodiazepine/Z‐drug treatment, of whom one in five became long‐term users. Patients who were prescribed clonazepam or alprazolam had high odds for subsequent long‐term use (adjusted odds ratios [aORs] 3.78 [95% confidence interval (CI) 2.24‐6.38] and 2.03 [95% CI 1.30‐3.18], respectively), compared to those prescribed diazepam. Polytherapy with benzodiazepines/Z‐drugs also predicted long‐term use (aOR 2.46, 95% CI 1.79‐3.38), as did age ≥60 years (aOR 1.93, 95% CI 1.46‐2.53, compared to age <30 years), and concomitant treatment with psychostimulants (aOR 1.78, 95% CI 1.33‐2.39).

Conclusions

The incidence of subsequent long‐term use among bipolar benzodiazepine initiators is high. Patients on clonazepam, alprazolam or benzodiazepine/Z‐drug polytherapy have the highest risk of becoming long‐term users, suggesting that these treatments should be used restrictively.

Keywords
benzodiazepines, bipolar disorder, cohort study, drug utilization study, prescription drug misuse, zaleplon, zolpidem, zopiclone
National Category
Psychiatry
Identifiers
urn:nbn:se:uu:diva-369593 (URN)10.1111/bdi.12626 (DOI)000448841100008 ()29450954 (PubMedID)
Funder
Swedish Research Council, 2016-02362Novo Nordisk, NNF15SA0018404Swedish Society of Medicine, SLS-502541Swedish Society of Medicine, SLS-587661The Karolinska Institutet's Research Foundation, 2013-37903Fredrik och Ingrid Thurings Stiftelse, 2015-00114
Available from: 2018-12-19 Created: 2018-12-19 Last updated: 2018-12-19Bibliographically approved
Reutfors, J., Andersson, T.-L. M., Brenner, P., Brandt, L., DiBernardo, A., Li, G., . . . Bodén, R. (2018). Mortality in treatment-resistant unipolar depression: A register-based cohort study in Sweden. Journal of Affective Disorders, 238, 674-679
Open this publication in new window or tab >>Mortality in treatment-resistant unipolar depression: A register-based cohort study in Sweden
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2018 (English)In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 238, p. 674-679Article in journal (Refereed) Published
Abstract [en]

Background: The impact of treatment resistant depression (TRD) on mortality is not established. Methods: Using Swedish national registers, 118,774 patients between 18-69 years of age who had been prescribed an antidepressant and been diagnosed with depression in specialized care were identified. Patients with at least two additional treatment trials during the same depressive episode were classified as having TRD. Data on the covariates of sex, age, history of depression, self-harm, substance use disorders, and other psychiatric and somatic comorbidities was also used. Relative risks comparing TRD patients with other depressed patients were calculated as hazard ratios (HR) for all-cause mortality and for external and non-external causes of death, as well as excess mortality rate ratios (EMRR), with 95% confidence intervals (CI). Results: In total 15,013 patients (13%) were classified with TRD. Adjusted HR for all-cause mortality was 1.35 (95% CI 1.21-1.50). Mortality from external causes (including suicides and accidents) was markedly higher in TRD patients than in other depressed patients (HR 1.97; 1.69-2.29), while mortality from non-external causes was similar. The adjusted EMRR was 1.52 (1.31-1.76), highest among patients 18-29 years old (EMRR 2.03; 1.31-1.76) and patients without somatic comorbidity (EMRR 1.99; 1.63-2.43). Limitations: Severity of depression and adherence to treatment were not available in the data. Conclusions: Patients with TRD may have an increased all-cause mortality compared to other depressed patients, mainly for external causes of death. The relative mortality is highest among young and physically healthy patients.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE BV, 2018
Keywords
Depression, Major depressive disorder, Epidemiology, Mortality, Antidepressants, Treatment-resistant
National Category
Psychiatry
Identifiers
urn:nbn:se:uu:diva-387261 (URN)10.1016/j.jad.2018.06.030 (DOI)000439557000092 ()29966932 (PubMedID)
Available from: 2019-06-27 Created: 2019-06-27 Last updated: 2019-06-27Bibliographically approved
Nilsson, B. M., Lindström, L., Mohsen, I., Holmlöv, K. & Bodén, R. (2018). Persistent tachycardia in clozapine treated patients: A 24-hour ambulatory electrocardiogram study. Schizophrenia Research, 199, 403-406
Open this publication in new window or tab >>Persistent tachycardia in clozapine treated patients: A 24-hour ambulatory electrocardiogram study
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2018 (English)In: Schizophrenia Research, ISSN 0920-9964, E-ISSN 1573-2509, Vol. 199, p. 403-406Article in journal (Refereed) Published
Abstract [en]

Tachycardia is associated with cardiovascular mortality. Tachycardia is also a known clozapine adverse effect. However, whether clozapine-associated tachycardia is persistent is not known. Thirty clozapine-treated patients with clinical tachycardia were investigated with 24-hour ambulatory electrocardiography (ECG). Baseline peripheral heart rate (HR) was 106.7 +/- 7.8. The ambulatory ECG 24-hour-HR was 98.7 +/- 9.7. Baseline HR and 24-hour-HR correlated strongly (r = 0.74, p = 0.000003). Daytime HR was 106.4 +/- 9.9 and nighttime HR 89.2 +/- 12.0. Low dose bisoprolol reduced HR significantly. The high 24-hour-HR indicates a persistent tachycardia. Tachycardia should not discourage from clozapine use but the findings indicate a need of guidelines for detection and treatment of clozapine-associated tachycardia.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE BV, 2018
Keywords
Schizophrenia, Clozapine, Tachycardia, Heart rate, Cardiovascular health, Holter ECG
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-363629 (URN)10.1016/j.schres.2018.03.017 (DOI)000444845900060 ()29602642 (PubMedID)
Funder
Swedish Research Council, 2016-02362
Available from: 2018-10-25 Created: 2018-10-25 Last updated: 2018-10-25Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-2198-8842

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