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  1. Article ; Online: Risk of clozapine-associated agranulocytosis and mandatory white blood cell monitoring: Can the regulations be relaxed?

    Schulte, Peter F J / Veerman, Selene R T / Bakker, Bert / Bogers, Jan P A M / Jongkind, Amy / Cohen, Dan

    Schizophrenia research

    2023  

    Abstract: After the introduction of clozapine eight Finnish patients died after developing agranulocytosis. Clozapine was withdrawn from the market and only reintroduced with strict mandatory white blood cell monitoring as long as treatment lasts and thresholds at ...

    Abstract After the introduction of clozapine eight Finnish patients died after developing agranulocytosis. Clozapine was withdrawn from the market and only reintroduced with strict mandatory white blood cell monitoring as long as treatment lasts and thresholds at which clozapine must be discontinued definitively. The fear of agranulocytosis and the need for intensive blood monitoring is the single most important barrier for prescribers and patients alike and leads to underprescription of the only effective and approved medication for treatment-resistant schizophrenia. We summarize evidence that the risk of agranulocytosis is smaller than perceived at the time of reintroduction, is concentrated in the first 18 weeks of treatment, is not greater than with other antipsychotics thereafter and that frequent blood monitoring has not demonstrably decreased the rate of agranulocytosis. Therefore we propose 1) mandatory monitoring of the absolute neutrophil count (ANC) exclusively during the first 18 weeks of clozapine treatment, 2) that thereafter the prescriber and the well-informed patient decide together about further monitoring frequency, 3) that clozapine treatment must be stopped if the ANC falls below 1.0 × 10
    Language English
    Publishing date 2023-09-26
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 639422-x
    ISSN 1573-2509 ; 0920-9964
    ISSN (online) 1573-2509
    ISSN 0920-9964
    DOI 10.1016/j.schres.2023.09.024
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  2. Article ; Online: Clozapine and COVID-19 Vaccination: Effects on blood levels and leukocytes. An observational cohort study.

    Veerman, Selene R T / Moscou, Timo / Bogers, Jan P A M / Cohen, Dan / Schulte, Peter F J

    Acta psychiatrica Scandinavica

    2022  Volume 146, Issue 2, Page(s) 168–178

    Abstract: Objective: To investigate the safety of COVID-19 vaccination in patients on clozapine as regards plasma clozapine concentration and haematological parameters.: Methods: We conducted a multicentre observational cohort study from 22 February 2021 to 2 ... ...

    Abstract Objective: To investigate the safety of COVID-19 vaccination in patients on clozapine as regards plasma clozapine concentration and haematological parameters.
    Methods: We conducted a multicentre observational cohort study from 22 February 2021 to 2 September 2021. Primary outcomes were clinically relevant increase in clozapine blood levels (>100 μg/L increase compared to baseline) and clozapine alert levels (>1000 μg/L). Secondary outcomes were granulocytopenia, leukocytopenia and lymphocytopenia. Outcomes were measured approximately 5 days after the first and (where applicable) second dose of COVID-19 vaccine.
    Results: This study included 139 patients. Compared to baseline, clozapine blood levels increased significantly (ES = 0.28, p = 0.003) after the second vaccination. Clinically relevant increases in clozapine blood levels occurred in 20/92 patients (22%) and in 16/56 patients (29%) during the first and second phases, respectively. Clozapine alert levels developed in one patient (1%) following the first dose and in three patients (5%) after the second dose. In both phases, changes in white blood cells (WBC) were limited to mild granulocytopenia (3% and 5%), moderate granulocytopenia (1% and 0%) and leukocytopenia (2% and 3%) without cause for extra monitoring according to the guideline.
    Conclusion: In general, as regards WBC counts COVID-19 vaccination seems to be safe in patients with SMI. Changes in WBC had no clinical implications. Psychoeducation on the symptoms of clozapine intoxication is recommended, especially in patients with clozapine blood levels approaching the upper limit of the therapeutic range. Increase in the C-reactive protein (CRP) level can signal inflammation rapidly and help to prevent clozapine intoxication following vaccination.
    MeSH term(s) Agranulocytosis/chemically induced ; Agranulocytosis/drug therapy ; Antipsychotic Agents/adverse effects ; Antipsychotic Agents/blood ; COVID-19/prevention & control ; COVID-19 Vaccines/adverse effects ; Clozapine/adverse effects ; Clozapine/blood ; Cohort Studies ; Humans ; Leukocytes ; Leukopenia/chemically induced ; Leukopenia/drug therapy ; Vaccination
    Chemical Substances Antipsychotic Agents ; COVID-19 Vaccines ; Clozapine (J60AR2IKIC)
    Language English
    Publishing date 2022-04-01
    Publishing country United States
    Document type Journal Article ; Observational Study
    ZDB-ID 103-x
    ISSN 1600-0447 ; 0001-690X
    ISSN (online) 1600-0447
    ISSN 0001-690X
    DOI 10.1111/acps.13428
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  3. Article ; Online: COVID-19: Risks, Complications, and Monitoring in Patients on Clozapine.

    Veerman, Selene R T / Bogers, Jan P A M / Cohen, Dan / Schulte, Peter F J

    Pharmacopsychiatry

    2021  Volume 55, Issue 1, Page(s) 48–56

    Abstract: The Dutch Clozapine Collaboration Group is frequently asked for advice about the management of clozapine-treated patients when infected with or vaccinated against SARS-CoV-2. We provide state of the art information about the risks of SARS-CoV-2 infection ...

    Abstract The Dutch Clozapine Collaboration Group is frequently asked for advice about the management of clozapine-treated patients when infected with or vaccinated against SARS-CoV-2. We provide state of the art information about the risks of SARS-CoV-2 infection for patients on clozapine and we give advice on measures to be taken, especially in regard to the monitoring of clozapine plasma levels, WBC count and differentiation during COVID-19 and after vaccination. We present an overview of relevant editorials, observational studies, and case studies, in which COVID-19 was reported in patients on clozapine. Patients using clozapine may have a higher risk of infection than patients with schizophrenia spectrum disorders (SSD) using other antipsychotics. SARS-CoV-2 infection can result in a dangerous increase of clozapine plasma levels, and granulocytopenia and lymphocytopenia (generally mild and short-term) may also occur, usually not as a result of clozapine treatment. Clozapine intoxication, pneumonia and delirium are the main complications of COVID-19 in patients on clozapine. In order to prevent clozapine intoxication, reduction of the original dose by half is generally recommended in clozapine users who contract COVID-19. When a cytokine storm is suspected in an advanced stage of COVID-19, reduction by three quarters seems more appropriate. If COVID-19 patients on clozapine develop granulocytopenia, SARS-CoV-2, rather than clozapine, should be considered as the cause. Schizophrenia patients in general and clozapine users in particular belong to a high-risk group that warrants early vaccination on a medical indication.
    MeSH term(s) Antipsychotic Agents/adverse effects ; COVID-19 ; Clozapine/adverse effects ; Humans ; SARS-CoV-2 ; Schizophrenia/drug therapy
    Chemical Substances Antipsychotic Agents ; Clozapine (J60AR2IKIC)
    Language English
    Publishing date 2021-09-01
    Publishing country Germany
    Document type Journal Article ; Review
    ZDB-ID 605670-2
    ISSN 1439-0795 ; 0720-4280 ; 0176-3679
    ISSN (online) 1439-0795
    ISSN 0720-4280 ; 0176-3679
    DOI 10.1055/a-1562-2521
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  4. Article: COVID-19: Risks, Complications, and Monitoring in Patients on Clozapine

    Veerman, Selene R. T. / Bogers, Jan P. A. M. / Cohen, Dan / Schulte, Peter F. J.

    Pharmacopsychiatry

    (Special Issue Psychotropic Drugs and COVID)

    2021  Volume 55, Issue 01, Page(s) 48–56

    Abstract: The Dutch Clozapine Collaboration Group is frequently asked for advice about the management of clozapine-treated patients when infected with or vaccinated against SARS-CoV-2. We provide state of the art information about the risks of SARS-CoV-2 infection ...

    Series title Special Issue Psychotropic Drugs and COVID
    Abstract The Dutch Clozapine Collaboration Group is frequently asked for advice about the management of clozapine-treated patients when infected with or vaccinated against SARS-CoV-2. We provide state of the art information about the risks of SARS-CoV-2 infection for patients on clozapine and we give advice on measures to be taken, especially in regard to the monitoring of clozapine plasma levels, WBC count and differentiation during COVID-19 and after vaccination. We present an overview of relevant editorials, observational studies, and case studies, in which COVID-19 was reported in patients on clozapine. Patients using clozapine may have a higher risk of infection than patients with schizophrenia spectrum disorders (SSD) using other antipsychotics. SARS-CoV-2 infection can result in a dangerous increase of clozapine plasma levels, and granulocytopenia and lymphocytopenia (generally mild and short-term) may also occur, usually not as a result of clozapine treatment. Clozapine intoxication, pneumonia and delirium are the main complications of COVID-19 in patients on clozapine. In order to prevent clozapine intoxication, reduction of the original dose by half is generally recommended in clozapine users who contract COVID-19. When a cytokine storm is suspected in an advanced stage of COVID-19, reduction by three quarters seems more appropriate. If COVID-19 patients on clozapine develop granulocytopenia, SARS-CoV-2, rather than clozapine, should be considered as the cause. Schizophrenia patients in general and clozapine users in particular belong to a high-risk group that warrants early vaccination on a medical indication.
    Keywords antipsychotic drugs ; schizophrenia ; immune system ; clozapine ; COVID-19
    Language English
    Publishing date 2021-09-01
    Publisher Georg Thieme Verlag KG
    Publishing place Stuttgart ; New York
    Document type Article
    ZDB-ID 605670-2
    ISSN 1439-0795 ; 0176-3679 ; 0720-4280
    ISSN (online) 1439-0795
    ISSN 0176-3679 ; 0720-4280
    DOI 10.1055/a-1562-2521
    Database Thieme publisher's database

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  5. Article ; Online: Treatment for Negative Symptoms in Schizophrenia: A Comprehensive Review.

    Veerman, Selene R T / Schulte, Peter F J / de Haan, Lieuwe

    Drugs

    2017  Volume 77, Issue 13, Page(s) 1423–1459

    Abstract: Negative symptoms (such as amotivation and diminished expression) associated with schizophrenia are a major health concern. Adequate treatment would mean important progress with respect to quality of life and participation in society. Distinguishing ... ...

    Abstract Negative symptoms (such as amotivation and diminished expression) associated with schizophrenia are a major health concern. Adequate treatment would mean important progress with respect to quality of life and participation in society. Distinguishing primary from secondary negative symptoms may inform treatment options. Primary negative symptoms are part of schizophrenia. Well-known sources of secondary negative symptoms are psychotic symptoms, disorganisation, anxiety, depression, chronic abuse of illicit drugs and alcohol, an overly high dosage of antipsychotic medication, social deprivation, lack of stimulation and hospitalisation. We present an overview of reviews and meta-analyses of double-blind, controlled randomised trials, in which the efficacy of pharmacological and non-pharmacological interventions for negative symptoms was assessed. Unfortunately, there have been very few clinical trials focusing on primary negative symptoms and selecting chronically ill patients with predominant persistent negative symptoms. An important limitation in many of these studies is the failure to adequately control for potential sources of secondary negative symptoms. At present, there is no convincing evidence regarding efficacy for any treatment of predominant persistent primary negative symptoms. However, for several interventions there is short-term evidence of efficacy for negative symptoms. This evidence has mainly been obtained from studies in chronically ill patients with residual symptoms and studies with a heterogeneous study population of patients in both the acute and chronic phase. Unfortunately, reliable information regarding the distinction between primary and secondary negative symptoms is lacking. Currently, early treatment of psychosis, add-on therapy with aripiprazole, antidepressants or topiramate, music therapy and exercise have been found to be useful for unspecified negative symptoms. These interventions can be considered carefully in a shared decision-making process with patients, and are promising enough to be examined in large, well-designed long-term studies focusing on primary negative symptoms. Future research should be aimed at potential therapeutic interventions for primary negative symptoms since there is a lack of research in this field.
    Language English
    Publishing date 2017-09
    Publishing country New Zealand
    Document type Journal Article ; Review
    ZDB-ID 120316-2
    ISSN 1179-1950 ; 0012-6667
    ISSN (online) 1179-1950
    ISSN 0012-6667
    DOI 10.1007/s40265-017-0789-y
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    Zs.A 762: Show issues Location:
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  6. Article ; Online: Simvastatin Augmentation for Patients With Early-Phase Schizophrenia-Spectrum Disorders: A Double-Blind, Randomized Placebo-Controlled Trial.

    Sommer, Iris E / Gangadin, Shiral S / de Witte, Lot D / Koops, Sanne / van Baal, C / Bahn, Sabine / Drexhage, Hemmo / van Haren, N E M / Veling, Wim / Bruggeman, R / Martens, Peter / Wiersma, Sybren / Veerman, Selene R T / Grootens, Koen P / van Beveren, Nico / Kahn, Rene S / Begemann, Marieke J H

    Schizophrenia bulletin

    2021  Volume 47, Issue 4, Page(s) 1108–1115

    Abstract: Schizophrenia-spectrum disorders (SSD) are associated with increased inflammatory markers, both in brain and periphery. Augmentation with drugs that lower this pro-inflammatory status may improve clinical presentation. Simvastatin crosses the blood-brain ...

    Abstract Schizophrenia-spectrum disorders (SSD) are associated with increased inflammatory markers, both in brain and periphery. Augmentation with drugs that lower this pro-inflammatory status may improve clinical presentation. Simvastatin crosses the blood-brain barrier, has anti- inflammatory and neuroprotective effects and reduces metabolic syndrome. In this study, we investigated if 12 months of simvastatin augmentation can improve symptoms and cognition in patients with early SSD. This double-blind placebo-controlled trial included 127 SSD patients across the Netherlands, <3 years after their diagnosis. From these, 119 were randomly assigned 1:1 to simvastatin 40 mg (n = 61) or placebo (n = 58), stratified for sex and study site. Primary outcomes were symptom severity and cognition after 12 months of treatment. Depression, symptom subscores, general functioning, metabolic syndrome, movement disorders, and safety were secondary outcomes. Intention to treat analyses were performed using linear mixed models and ANCOVA. No main effect of simvastatin treatment was found on total symptom severity after 12 months of treatment as compared to placebo (X2(1) = 0.01, P = .90). Group differences varied over time (treatment*time X2(4) = 11.2; P = .025), with significantly lower symptom severity in the simvastatin group after 6 months (mean difference = -4.8; P = .021; 95% CI: -8.8 to -0.7) and at 24 months follow-up (mean difference = -4.7; P = .040; 95% CI: -9.3 to -0.2). No main treatment effect was found for cognition (F(1,0.1) = 0.37, P = .55) or secondary outcomes. SAEs occurred more frequently with placebo (19%) than with simvastatin (6.6%). This negative finding corroborates other large scale studies on aspirin, minocycline, and celecoxib that could not replicate positive findings of smaller studies, and suggests that anti-inflammatory augmentation does not improve the clinical presentation of SSD.
    MeSH term(s) Adolescent ; Adult ; Cognition/physiology ; Double-Blind Method ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Netherlands ; Schizophrenia/drug therapy ; Schizophrenia/physiopathology ; Simvastatin/therapeutic use ; Treatment Outcome ; Young Adult
    Chemical Substances Simvastatin (AGG2FN16EV)
    Language English
    Publishing date 2021-02-19
    Publishing country United States
    Document type Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
    ZDB-ID 439173-1
    ISSN 1745-1701 ; 0586-7614
    ISSN (online) 1745-1701
    ISSN 0586-7614
    DOI 10.1093/schbul/sbab010
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  7. Article ; Online: To continue or not to continue? Antipsychotic medication maintenance versus dose-reduction/discontinuation in first episode psychosis: HAMLETT, a pragmatic multicenter single-blind randomized controlled trial.

    Begemann, Marieke J H / Thompson, Ilse A / Veling, Wim / Gangadin, Shiral S / Geraets, Chris N W / van 't Hag, Erna / Müller-Kuperus, Sanne J / Oomen, Priscilla P / Voppel, Alban E / van der Gaag, Mark / Kikkert, Martijn J / Van Os, Jim / Smit, H Filip E / Knegtering, Rikus H / Wiersma, Sybren / Stouten, Luyken H / Gijsman, Harm J / Wunderink, Lex / Staring, Anton B P /
    Veerman, Selene R T / Mahabir, Amrita G S / Kurkamp, Jörg / Pijnenborg, Gerdina H M / Veen, Natalie D / Marcelis, Machteld / Grootens, Koen P / Faber, Gunnar / van Beveren, Nico J / Been, Agaath / van den Brink, Truus / Bak, Maarten / van Amelsvoort, Therese A M J / Ruissen, Andrea / Blanke, Christine / Groen, Karin / de Haan, Lieuwe / Sommer, Iris E C

    Trials

    2020  Volume 21, Issue 1, Page(s) 147

    Abstract: Background: Antipsychotic medication is effective for symptomatic treatment in schizophrenia-spectrum disorders. After symptom remission, continuation of antipsychotic treatment is associated with lower relapse rates and lower symptom severity compared ... ...

    Abstract Background: Antipsychotic medication is effective for symptomatic treatment in schizophrenia-spectrum disorders. After symptom remission, continuation of antipsychotic treatment is associated with lower relapse rates and lower symptom severity compared to dose reduction/discontinuation. Therefore, most guidelines recommend continuation of treatment with antipsychotic medication for at least 1 year. Recently, however, these guidelines have been questioned as one study has shown that more patients achieved long-term functional remission in an early discontinuation condition-a finding that was not replicated in another recently published long-term study.
    Methods/design: The HAMLETT (Handling Antipsychotic Medication Long-term Evaluation of Targeted Treatment) study is a multicenter pragmatic single-blind randomized controlled trial in two parallel conditions (1:1) investigating the effects of continuation versus dose-reduction/discontinuation of antipsychotic medication after remission of a first episode of psychosis (FEP) on personal and social functioning, psychotic symptom severity, and health-related quality of life. In total 512 participants will be included, aged between 16 and 60 years, in symptomatic remission from a FEP for 3-6 months, and for whom psychosis was not associated with severe or life-threatening self-harm or violence. Recruitment will take place at 24 Dutch sites. Patients are randomized (1:1) to: continuation of antipsychotic medication until at least 1 year after remission (original dose allowing a maximum reduction of 25%, or another antipsychotic drug in similar dose range); or gradual dose reduction till eventual discontinuation of antipsychotics according to a tapering schedule. If signs of relapse occur in this arm, medication dose can be increased again. Measurements are conducted at baseline, at 3, and 6 months post-baseline, and yearly during a follow-up period of 4 years.
    Discussion: The HAMLETT study will offer evidence to guide patients and clinicians regarding questions concerning optimal treatment duration and when to taper off medication after remission of a FEP. Moreover, it may provide patient characteristics associated with safe dose reduction with a minimal risk of relapse.
    Trial status: Protocol version 1.3, October 2018. The study is active and currently recruiting patients (since September 2017), with the first 200 participants by the end of 2019. We anticipate completing recruitment in 2022 and final assessments (including follow-up 3.5 years after phase one) in 2026.
    Trial registration: European Clinical Trials Database, EudraCT number 2017-002406-12. Registered 7 June 2017.
    MeSH term(s) Adolescent ; Adult ; Antipsychotic Agents/administration & dosage ; Antipsychotic Agents/standards ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Multicenter Studies as Topic ; Practice Guidelines as Topic ; Pragmatic Clinical Trials as Topic ; Psychotic Disorders/diagnosis ; Psychotic Disorders/drug therapy ; Quality of Life ; Remission Induction/methods ; Severity of Illness Index ; Single-Blind Method ; Treatment Outcome ; Young Adult
    Chemical Substances Antipsychotic Agents
    Language English
    Publishing date 2020-02-07
    Publishing country England
    Document type Clinical Trial Protocol ; Journal Article
    ZDB-ID 2040523-6
    ISSN 1745-6215 ; 1468-6694 ; 1745-6215
    ISSN (online) 1745-6215
    ISSN 1468-6694 ; 1745-6215
    DOI 10.1186/s13063-019-3822-5
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  8. Article ; Online: To continue or not to continue? Antipsychotic medication maintenance versus dose-reduction/discontinuation in first episode psychosis

    Marieke J. H. Begemann / Ilse A. Thompson / Wim Veling / Shiral S. Gangadin / Chris N. W. Geraets / Erna van ‘t Hag / Sanne J. Müller-Kuperus / Priscilla P. Oomen / Alban E. Voppel / Mark van der Gaag / Martijn J. Kikkert / Jim Van Os / H. Filip E. Smit / Rikus H. Knegtering / Sybren Wiersma / Luyken H. Stouten / Harm J. Gijsman / Lex Wunderink / Anton B. P. Staring /
    Selene R. T. Veerman / Amrita G. S. Mahabir / Jörg Kurkamp / Gerdina H. M. Pijnenborg / Natalie D. Veen / Machteld Marcelis / Koen P. Grootens / Gunnar Faber / Nico J. van Beveren / Agaath Been / Truus van den Brink / Maarten Bak / Therese A. M. J. van Amelsvoort / Andrea Ruissen / Christine Blanke / Karin Groen / Lieuwe de Haan / Iris E. C. Sommer

    Trials, Vol 21, Iss 1, Pp 1-

    HAMLETT, a pragmatic multicenter single-blind randomized controlled trial

    2020  Volume 19

    Abstract: Abstract Background Antipsychotic medication is effective for symptomatic treatment in schizophrenia-spectrum disorders. After symptom remission, continuation of antipsychotic treatment is associated with lower relapse rates and lower symptom severity ... ...

    Abstract Abstract Background Antipsychotic medication is effective for symptomatic treatment in schizophrenia-spectrum disorders. After symptom remission, continuation of antipsychotic treatment is associated with lower relapse rates and lower symptom severity compared to dose reduction/discontinuation. Therefore, most guidelines recommend continuation of treatment with antipsychotic medication for at least 1 year. Recently, however, these guidelines have been questioned as one study has shown that more patients achieved long-term functional remission in an early discontinuation condition—a finding that was not replicated in another recently published long-term study. Methods/design The HAMLETT (Handling Antipsychotic Medication Long-term Evaluation of Targeted Treatment) study is a multicenter pragmatic single-blind randomized controlled trial in two parallel conditions (1:1) investigating the effects of continuation versus dose-reduction/discontinuation of antipsychotic medication after remission of a first episode of psychosis (FEP) on personal and social functioning, psychotic symptom severity, and health-related quality of life. In total 512 participants will be included, aged between 16 and 60 years, in symptomatic remission from a FEP for 3–6 months, and for whom psychosis was not associated with severe or life-threatening self-harm or violence. Recruitment will take place at 24 Dutch sites. Patients are randomized (1:1) to: continuation of antipsychotic medication until at least 1 year after remission (original dose allowing a maximum reduction of 25%, or another antipsychotic drug in similar dose range); or gradual dose reduction till eventual discontinuation of antipsychotics according to a tapering schedule. If signs of relapse occur in this arm, medication dose can be increased again. Measurements are conducted at baseline, at 3, and 6 months post-baseline, and yearly during a follow-up period of 4 years. Discussion The HAMLETT study will offer evidence to guide patients and clinicians regarding questions ...
    Keywords Antipsychotic medication ; first episode psychosis ; Maintenance ; Treatment ; Discontinuation ; Tapering ; global functioning ; Randomized controlled trial ; Medicine (General) ; R5-920
    Subject code 150
    Language English
    Publishing date 2020-02-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Longitudinal clinical and functional outcome in distinct cognitive subgroups of first-episode psychosis: a cluster analysis.

    Oomen, Priscilla P / Begemann, Marieke J H / Brand, Bodyl A / de Haan, Lieuwe / Veling, Wim / Koops, Sanne / van Os, Jim / Smit, Filip / Bakker, P Roberto / van Beveren, Nico / Boonstra, Nynke / Gülöksüz, Sinan / Kikkert, Martijn / Lokkerbol, Joran / Marcelis, Machteld / Rosema, Bram-Sieben / de Beer, Franciska / Gangadin, Shiral S / Geraets, Chris N W /
    van 't Hag, Erna / Haveman, Yudith / van der Heijden, Inge / Voppel, Alban E / Willemse, Elske / van Amelsvoort, Therese / Bak, Maarten / Batalla, Albert / Been, Agaath / van den Bosch, Marinte / van den Brink, Truus / Faber, Gunnar / Grootens, Koen P / de Jonge, Martin / Knegtering, Rikus / Kurkamp, Jörg / Mahabir, Amrita / Pijnenborg, Gerdina H M / Staring, Tonnie / Veen, Natalie / Veerman, Selene / Wiersma, Sybren / Graveland, Ellen / Hoornaar, Joelle / Sommer, Iris E C

    Psychological medicine

    2021  Volume 53, Issue 6, Page(s) 2317–2327

    Abstract: Background: Cognitive deficits may be characteristic for only a subgroup of first-episode psychosis (FEP) and the link with clinical and functional outcomes is less profound than previously thought. This study aimed to identify cognitive subgroups in a ... ...

    Abstract Background: Cognitive deficits may be characteristic for only a subgroup of first-episode psychosis (FEP) and the link with clinical and functional outcomes is less profound than previously thought. This study aimed to identify cognitive subgroups in a large sample of FEP using a clustering approach with healthy controls as a reference group, subsequently linking cognitive subgroups to clinical and functional outcomes.
    Methods: 204 FEP patients were included. Hierarchical cluster analysis was performed using baseline brief assessment of cognition in schizophrenia (BACS). Cognitive subgroups were compared to 40 controls and linked to longitudinal clinical and functional outcomes (PANSS, GAF, self-reported WHODAS 2.0) up to 12-month follow-up.
    Results: Three distinct cognitive clusters emerged: relative to controls, we found one cluster with preserved cognition (
    Conclusions: Current results demonstrate the existence of three distinct cognitive subgroups, corresponding with clinical outcome at baseline, 6- and 12-month follow-up. Importantly, the cognitively preserved subgroup was larger than the severely impaired group. Early identification of discrete cognitive profiles can offer valuable information about the clinical outcome but may not be relevant in predicting self-reported functional outcomes.
    MeSH term(s) Humans ; Psychotic Disorders/psychology ; Schizophrenia ; Cognitive Dysfunction/etiology ; Cognition ; Cluster Analysis ; Neuropsychological Tests
    Language English
    Publishing date 2021-10-19
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 217420-0
    ISSN 1469-8978 ; 0033-2917
    ISSN (online) 1469-8978
    ISSN 0033-2917
    DOI 10.1017/S0033291721004153
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.

    Forouzanfar, Mohammad H / Alexander, Lily / Anderson, H Ross / Bachman, Victoria F / Biryukov, Stan / Brauer, Michael / Burnett, Richard / Casey, Daniel / Coates, Matthew M / Cohen, Aaron / Delwiche, Kristen / Estep, Kara / Frostad, Joseph J / Astha, K C / Kyu, Hmwe H / Moradi-Lakeh, Maziar / Ng, Marie / Slepak, Erica Leigh / Thomas, Bernadette A /
    Wagner, Joseph / Aasvang, Gunn Marit / Abbafati, Cristiana / Abbasoglu Ozgoren, Ayse / Abd-Allah, Foad / Abera, Semaw F / Aboyans, Victor / Abraham, Biju / Abraham, Jerry Puthenpurakal / Abubakar, Ibrahim / Abu-Rmeileh, Niveen M E / Aburto, Tania C / Achoki, Tom / Adelekan, Ademola / Adofo, Koranteng / Adou, Arsène K / Adsuar, José C / Afshin, Ashkan / Agardh, Emilie E / Al Khabouri, Mazin J / Al Lami, Faris H / Alam, Sayed Saidul / Alasfoor, Deena / Albittar, Mohammed I / Alegretti, Miguel A / Aleman, Alicia V / Alemu, Zewdie A / Alfonso-Cristancho, Rafael / Alhabib, Samia / Ali, Raghib / Ali, Mohammed K / Alla, François / Allebeck, Peter / Allen, Peter J / Alsharif, Ubai / Alvarez, Elena / Alvis-Guzman, Nelson / Amankwaa, Adansi A / Amare, Azmeraw T / Ameh, Emmanuel A / Ameli, Omid / Amini, Heresh / Ammar, Walid / Anderson, Benjamin O / Antonio, Carl Abelardo T / Anwari, Palwasha / Argeseanu Cunningham, Solveig / Arnlöv, Johan / Arsenijevic, Valentina S Arsic / Artaman, Al / Asghar, Rana J / Assadi, Reza / Atkins, Lydia S / Atkinson, Charles / Avila, Marco A / Awuah, Baffour / Badawi, Alaa / Bahit, Maria C / Bakfalouni, Talal / Balakrishnan, Kalpana / Balalla, Shivanthi / Balu, Ravi Kumar / Banerjee, Amitava / Barber, Ryan M / Barker-Collo, Suzanne L / Barquera, Simon / Barregard, Lars / Barrero, Lope H / Barrientos-Gutierrez, Tonatiuh / Basto-Abreu, Ana C / Basu, Arindam / Basu, Sanjay / Basulaiman, Mohammed O / Batis Ruvalcaba, Carolina / Beardsley, Justin / Bedi, Neeraj / Bekele, Tolesa / Bell, Michelle L / Benjet, Corina / Bennett, Derrick A / Benzian, Habib / Bernabé, Eduardo / Beyene, Tariku J / Bhala, Neeraj / Bhalla, Ashish / Bhutta, Zulfiqar A / Bikbov, Boris / Bin Abdulhak, Aref A / Blore, Jed D / Blyth, Fiona M / Bohensky, Megan A / Bora Başara, Berrak / Borges, Guilherme / Bornstein, Natan M / Bose, Dipan / Boufous, Soufiane / Bourne, Rupert R / Brainin, Michael / Brazinova, Alexandra / Breitborde, Nicholas J / Brenner, Hermann / Briggs, Adam D M / Broday, David M / Brooks, Peter M / Bruce, Nigel G / Brugha, Traolach S / Brunekreef, Bert / Buchbinder, Rachelle / Bui, Linh N / Bukhman, Gene / Bulloch, Andrew G / Burch, Michael / Burney, Peter G J / Campos-Nonato, Ismael R / Campuzano, Julio C / Cantoral, Alejandra J / Caravanos, Jack / Cárdenas, Rosario / Cardis, Elisabeth / Carpenter, David O / Caso, Valeria / Castañeda-Orjuela, Carlos A / Castro, Ruben E / Catalá-López, Ferrán / Cavalleri, Fiorella / Çavlin, Alanur / Chadha, Vineet K / Chang, Jung-Chen / Charlson, Fiona J / Chen, Honglei / Chen, Wanqing / Chen, Zhengming / Chiang, Peggy P / Chimed-Ochir, Odgerel / Chowdhury, Rajiv / Christophi, Costas A / Chuang, Ting-Wu / Chugh, Sumeet S / Cirillo, Massimo / Claßen, Thomas K D / Colistro, Valentina / Colomar, Mercedes / Colquhoun, Samantha M / Contreras, Alejandra G / Cooper, Cyrus / Cooperrider, Kimberly / Cooper, Leslie T / Coresh, Josef / Courville, Karen J / Criqui, Michael H / Cuevas-Nasu, Lucia / Damsere-Derry, James / Danawi, Hadi / Dandona, Lalit / Dandona, Rakhi / Dargan, Paul I / Davis, Adrian / Davitoiu, Dragos V / Dayama, Anand / de Castro, E Filipa / De la Cruz-Góngora, Vanessa / De Leo, Diego / de Lima, Graça / Degenhardt, Louisa / del Pozo-Cruz, Borja / Dellavalle, Robert P / Deribe, Kebede / Derrett, Sarah / Des Jarlais, Don C / Dessalegn, Muluken / deVeber, Gabrielle A / Devries, Karen M / Dharmaratne, Samath D / Dherani, Mukesh K / Dicker, Daniel / Ding, Eric L / Dokova, Klara / Dorsey, E Ray / Driscoll, Tim R / Duan, Leilei / Durrani, Adnan M / Ebel, Beth E / Ellenbogen, Richard G / Elshrek, Yousef M / Endres, Matthias / Ermakov, Sergey P / Erskine, Holly E / Eshrati, Babak / Esteghamati, Alireza / Fahimi, Saman / Faraon, Emerito Jose A / Farzadfar, Farshad / Fay, Derek F J / Feigin, Valery L / Feigl, Andrea B / Fereshtehnejad, Seyed-Mohammad / Ferrari, Alize J / Ferri, Cleusa P / Flaxman, Abraham D / Fleming, Thomas D / Foigt, Nataliya / Foreman, Kyle J / Paleo, Urbano Fra / Franklin, Richard C / Gabbe, Belinda / Gaffikin, Lynne / Gakidou, Emmanuela / Gamkrelidze, Amiran / Gankpé, Fortuné G / Gansevoort, Ron T / García-Guerra, Francisco A / Gasana, Evariste / Geleijnse, Johanna M / Gessner, Bradford D / Gething, Pete / Gibney, Katherine B / Gillum, Richard F / Ginawi, Ibrahim A M / Giroud, Maurice / Giussani, Giorgia / Goenka, Shifalika / Goginashvili, Ketevan / Gomez Dantes, Hector / Gona, Philimon / Gonzalez de Cosio, Teresita / González-Castell, Dinorah / Gotay, Carolyn C / Goto, Atsushi / Gouda, Hebe N / Guerrant, Richard L / Gugnani, Harish C / Guillemin, Francis / Gunnell, David / Gupta, Rahul / Gupta, Rajeev / Gutiérrez, Reyna A / Hafezi-Nejad, Nima / Hagan, Holly / Hagstromer, Maria / Halasa, Yara A / Hamadeh, Randah R / Hammami, Mouhanad / Hankey, Graeme J / Hao, Yuantao / Harb, Hilda L / Haregu, Tilahun Nigatu / Haro, Josep Maria / Havmoeller, Rasmus / Hay, Simon I / Hedayati, Mohammad T / Heredia-Pi, Ileana B / Hernandez, Lucia / Heuton, Kyle R / Heydarpour, Pouria / Hijar, Martha / Hoek, Hans W / Hoffman, Howard J / Hornberger, John C / Hosgood, H Dean / Hoy, Damian G / Hsairi, Mohamed / Hu, Guoqing / Hu, Howard / Huang, Cheng / Huang, John J / Hubbell, Bryan J / Huiart, Laetitia / Husseini, Abdullatif / Iannarone, Marissa L / Iburg, Kim M / Idrisov, Bulat T / Ikeda, Nayu / Innos, Kaire / Inoue, Manami / Islami, Farhad / Ismayilova, Samaya / Jacobsen, Kathryn H / Jansen, Henrica A / Jarvis, Deborah L / Jassal, Simerjot K / Jauregui, Alejandra / Jayaraman, Sudha / Jeemon, Panniyammakal / Jensen, Paul N / Jha, Vivekanand / Jiang, Fan / Jiang, Guohong / Jiang, Ying / Jonas, Jost B / Juel, Knud / Kan, Haidong / Kany Roseline, Sidibe S / Karam, Nadim E / Karch, André / Karema, Corine K / Karthikeyan, Ganesan / Kaul, Anil / Kawakami, Norito / Kazi, Dhruv S / Kemp, Andrew H / Kengne, Andre P / Keren, Andre / Khader, Yousef S / Khalifa, Shams Eldin Ali Hassan / Khan, Ejaz A / Khang, Young-Ho / Khatibzadeh, Shahab / Khonelidze, Irma / Kieling, Christian / Kim, Daniel / Kim, Sungroul / Kim, Yunjin / Kimokoti, Ruth W / Kinfu, Yohannes / Kinge, Jonas M / Kissela, Brett M / Kivipelto, Miia / Knibbs, Luke D / Knudsen, Ann Kristin / Kokubo, Yoshihiro / Kose, M Rifat / Kosen, Soewarta / Kraemer, Alexander / Kravchenko, Michael / Krishnaswami, Sanjay / Kromhout, Hans / Ku, Tiffany / Kuate Defo, Barthelemy / Kucuk Bicer, Burcu / Kuipers, Ernst J / Kulkarni, Chanda / Kulkarni, Veena S / Kumar, G Anil / Kwan, Gene F / Lai, Taavi / Lakshmana Balaji, Arjun / Lalloo, Ratilal / Lallukka, Tea / Lam, Hilton / Lan, Qing / Lansingh, Van C / Larson, Heidi J / Larsson, Anders / Laryea, Dennis O / Lavados, Pablo M / Lawrynowicz, Alicia E / Leasher, Janet L / Lee, Jong-Tae / Leigh, James / Leung, Ricky / Levi, Miriam / Li, Yichong / Li, Yongmei / Liang, Juan / Liang, Xiaofeng / Lim, Stephen S / Lindsay, M Patrice / Lipshultz, Steven E / Liu, Shiwei / Liu, Yang / Lloyd, Belinda K / Logroscino, Giancarlo / London, Stephanie J / Lopez, Nancy / Lortet-Tieulent, Joannie / Lotufo, Paulo A / Lozano, Rafael / Lunevicius, Raimundas / Ma, Jixiang / Ma, Stefan / Machado, Vasco M P / MacIntyre, Michael F / Magis-Rodriguez, Carlos / Mahdi, Abbas A / Majdan, Marek / Malekzadeh, Reza / Mangalam, Srikanth / Mapoma, Christopher C / Marape, Marape / Marcenes, Wagner / Margolis, David J / Margono, Christopher / Marks, Guy B / Martin, Randall V / Marzan, Melvin B / Mashal, Mohammad T / Masiye, Felix / Mason-Jones, Amanda J / Matsushita, Kunihiro / Matzopoulos, Richard / Mayosi, Bongani M / Mazorodze, Tasara T / McKay, Abigail C / McKee, Martin / McLain, Abigail / Meaney, Peter A / Medina, Catalina / Mehndiratta, Man Mohan / Mejia-Rodriguez, Fabiola / Mekonnen, Wubegzier / Melaku, Yohannes A / Meltzer, Michele / Memish, Ziad A / Mendoza, Walter / Mensah, George A / Meretoja, Atte / Mhimbira, Francis Apolinary / Micha, Renata / Miller, Ted R / Mills, Edward J / Misganaw, Awoke / Mishra, Santosh / Mohamed Ibrahim, Norlinah / Mohammad, Karzan A / Mokdad, Ali H / Mola, Glen L / Monasta, Lorenzo / Montañez Hernandez, Julio C / Montico, Marcella / Moore, Ami R / Morawska, Lidia / Mori, Rintaro / Moschandreas, Joanna / Moturi, Wilkister N / Mozaffarian, Dariush / Mueller, Ulrich O / Mukaigawara, Mitsuru / Mullany, Erin C / Murthy, Kinnari S / Naghavi, Mohsen / Nahas, Ziad / Naheed, Aliya / Naidoo, Kovin S / Naldi, Luigi / Nand, Devina / Nangia, Vinay / Narayan, K M Venkat / Nash, Denis / Neal, Bruce / Nejjari, Chakib / Neupane, Sudan P / Newton, Charles R / Ngalesoni, Frida N / Ngirabega, Jean de Dieu / Nguyen, Grant / Nguyen, Nhung T / Nieuwenhuijsen, Mark J / Nisar, Muhammad I / Nogueira, José R / Nolla, Joan M / Nolte, Sandra / Norheim, Ole F / Norman, Rosana E / Norrving, Bo / Nyakarahuka, Luke / Oh, In-Hwan / Ohkubo, Takayoshi / Olusanya, Bolajoko O / Omer, Saad B / Opio, John Nelson / Orozco, Ricardo / Pagcatipunan, Rodolfo S / Pain, Amanda W / Pandian, Jeyaraj D / Panelo, Carlo Irwin A / Papachristou, Christina / Park, Eun-Kee / Parry, Charles D / Paternina Caicedo, Angel J / Patten, Scott B / Paul, Vinod K / Pavlin, Boris I / Pearce, Neil / Pedraza, Lilia S / Pedroza, Andrea / Pejin Stokic, Ljiljana / Pekericli, Ayfer / Pereira, David M / Perez-Padilla, Rogelio / Perez-Ruiz, Fernando / Perico, Norberto / Perry, Samuel A L / Pervaiz, Aslam / Pesudovs, Konrad / Peterson, Carrie B / Petzold, Max / Phillips, Michael R / Phua, Hwee Pin / Plass, Dietrich / Poenaru, Dan / Polanczyk, Guilherme V / Polinder, Suzanne / Pond, Constance D / Pope, C Arden / Pope, Daniel / Popova, Svetlana / Pourmalek, Farshad / Powles, John / Prabhakaran, Dorairaj / Prasad, Noela M / Qato, Dima M / Quezada, Amado D / Quistberg, D Alex A / Racapé, Lionel / Rafay, Anwar / Rahimi, Kazem / Rahimi-Movaghar, Vafa / Rahman, Sajjad Ur / Raju, Murugesan / Rakovac, Ivo / Rana, Saleem M / Rao, Mayuree / Razavi, Homie / Reddy, K Srinath / Refaat, Amany H / Rehm, Jürgen / Remuzzi, Giuseppe / Ribeiro, Antonio L / Riccio, Patricia M / Richardson, Lee / Riederer, Anne / Robinson, Margaret / Roca, Anna / Rodriguez, Alina / Rojas-Rueda, David / Romieu, Isabelle / Ronfani, Luca / Room, Robin / Roy, Nobhojit / Ruhago, George M / Rushton, Lesley / Sabin, Nsanzimana / Sacco, Ralph L / Saha, Sukanta / Sahathevan, Ramesh / Sahraian, Mohammad Ali / Salomon, Joshua A / Salvo, Deborah / Sampson, Uchechukwu K / Sanabria, Juan R / Sanchez, Luz Maria / Sánchez-Pimienta, Tania G / Sanchez-Riera, Lidia / Sandar, Logan / Santos, Itamar S / Sapkota, Amir / Satpathy, Maheswar / Saunders, James E / Sawhney, Monika / Saylan, Mete I / Scarborough, Peter / Schmidt, Jürgen C / Schneider, Ione J C / Schöttker, Ben / Schwebel, David C / Scott, James G / Seedat, Soraya / Sepanlou, Sadaf G / Serdar, Berrin / Servan-Mori, Edson E / Shaddick, Gavin / Shahraz, Saeid / Levy, Teresa Shamah / Shangguan, Siyi / She, Jun / Sheikhbahaei, Sara / Shibuya, Kenji / Shin, Hwashin H / Shinohara, Yukito / Shiri, Rahman / Shishani, Kawkab / Shiue, Ivy / Sigfusdottir, Inga D / Silberberg, Donald H / Simard, Edgar P / Sindi, Shireen / Singh, Abhishek / Singh, Gitanjali M / Singh, Jasvinder A / Skirbekk, Vegard / Sliwa, Karen / Soljak, Michael / Soneji, Samir / Søreide, Kjetil / Soshnikov, Sergey / Sposato, Luciano A / Sreeramareddy, Chandrashekhar T / Stapelberg, Nicolas J C / Stathopoulou, Vasiliki / Steckling, Nadine / Stein, Dan J / Stein, Murray B / Stephens, Natalie / Stöckl, Heidi / Straif, Kurt / Stroumpoulis, Konstantinos / Sturua, Lela / Sunguya, Bruno F / Swaminathan, Soumya / Swaroop, Mamta / Sykes, Bryan L / Tabb, Karen M / Takahashi, Ken / Talongwa, Roberto T / Tandon, Nikhil / Tanne, David / Tanner, Marcel / Tavakkoli, Mohammad / Te Ao, Braden J / Teixeira, Carolina M / Téllez Rojo, Martha M / Terkawi, Abdullah S / Texcalac-Sangrador, José Luis / Thackway, Sarah V / Thomson, Blake / Thorne-Lyman, Andrew L / Thrift, Amanda G / Thurston, George D / Tillmann, Taavi / Tobollik, Myriam / Tonelli, Marcello / Topouzis, Fotis / Towbin, Jeffrey A / Toyoshima, Hideaki / Traebert, Jefferson / Tran, Bach X / Trasande, Leonardo / Trillini, Matias / Trujillo, Ulises / Dimbuene, Zacharie Tsala / Tsilimbaris, Miltiadis / Tuzcu, Emin Murat / Uchendu, Uche S / Ukwaja, Kingsley N / Uzun, Selen B / van de Vijver, Steven / Van Dingenen, Rita / van Gool, Coen H / van Os, Jim / Varakin, Yuri Y / Vasankari, Tommi J / Vasconcelos, Ana Maria N / Vavilala, Monica S / Veerman, Lennert J / Velasquez-Melendez, Gustavo / Venketasubramanian, N / Vijayakumar, Lakshmi / Villalpando, Salvador / Violante, Francesco S / Vlassov, Vasiliy Victorovich / Vollset, Stein Emil / Wagner, Gregory R / Waller, Stephen G / Wallin, Mitchell T / Wan, Xia / Wang, Haidong / Wang, JianLi / Wang, Linhong / Wang, Wenzhi / Wang, Yanping / Warouw, Tati S / Watts, Charlotte H / Weichenthal, Scott / Weiderpass, Elisabete / Weintraub, Robert G / Werdecker, Andrea / Wessells, K Ryan / Westerman, Ronny / Whiteford, Harvey A / Wilkinson, James D / Williams, Hywel C / Williams, Thomas N / Woldeyohannes, Solomon M / Wolfe, Charles D A / Wong, John Q / Woolf, Anthony D / Wright, Jonathan L / Wurtz, Brittany / Xu, Gelin / Yan, Lijing L / Yang, Gonghuan / Yano, Yuichiro / Ye, Pengpeng / Yenesew, Muluken / Yentür, Gökalp K / Yip, Paul / Yonemoto, Naohiro / Yoon, Seok-Jun / Younis, Mustafa Z / Younoussi, Zourkaleini / Yu, Chuanhua / Zaki, Maysaa E / Zhao, Yong / Zheng, Yingfeng / Zhou, Maigeng / Zhu, Jun / Zhu, Shankuan / Zou, Xiaonong / Zunt, Joseph R / Lopez, Alan D / Vos, Theo / Murray, Christopher J

    Lancet (London, England)

    2015  Volume 386, Issue 10010, Page(s) 2287–2323

    Abstract: Background: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats ... ...

    Abstract Background: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.
    Methods: Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk-outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990-2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol.
    Findings: All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8-58·5) of deaths and 41·6% (40·1-43·0) of DALYs. Risks quantified account for 87·9% (86·5-89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa.
    Interpretation: Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.
    Funding: Bill & Melinda Gates Foundation.
    MeSH term(s) Environmental Exposure/adverse effects ; Female ; Global Health/statistics & numerical data ; Global Health/trends ; Health Behavior ; Humans ; Male ; Metabolic Diseases/epidemiology ; Nutritional Status ; Occupational Diseases/epidemiology ; Occupational Exposure/adverse effects ; Risk Assessment/methods ; Risk Factors ; Sanitation/trends
    Language English
    Publishing date 2015-09-11
    Publishing country England
    Document type Comparative Study ; Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 3306-6
    ISSN 1474-547X ; 0023-7507 ; 0140-6736
    ISSN (online) 1474-547X
    ISSN 0023-7507 ; 0140-6736
    DOI 10.1016/S0140-6736(15)00128-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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