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Over the years, the palette of treatment options for hemophilia has grown extensively, leading to an increased life expectancy and quality of life for people living with hemophilia. Nonetheless, it is frequently emphasized that none of the current treatment modalities provides a "cure." It is therefore hoped that innovative treatments such as gene therapy may bridge this void. However, the precise definition of a "cure" for hemophilia remains unclear. In this review, we show how the concept of cure is currently used in the field of hemophilia. We then relate the discussion on cure to debates surrounding the classification of hemophilia and philosophical debates on the concepts of health and disease., (© 2024 The Author(s).)

Objective: The endovascular treatment of venous obstruction has expanded significantly in recent years. Best practices for optimal patient outcomes are not well established and the evidence base is poor. The purpose of this study was to obtain consensus on management criteria for patients with lower extremity venous outflow obstruction., Methods: The study was conducted as a two round Delphi consensus. Statements addressed imaging, symptoms and other baseline measures, differential diagnosis, treatment algorithm, indications for stenting, inflow and outflow assessment, successful procedural outcomes, post-procedure therapies and stent surveillance, and clinical success factors. Statements were prepared by six expert physicians (round 1, 40 statements) and an expanded panel of 24 physicians (round 2, 80 statements) and sent to a pre-identified group of venous experts who met qualifying criteria. A 9 point Likert scale was used and consensus was defined as ≥ 70% of respondents rating a statement between 7 and 9 (agreement) or between 1 and 3 (disagreement). Round 1 results were used to guide rewording and splitting compound statements for greater clarity in round 2., Results: In round 1, 75 of 110 (68%) experts responded, and 91 of 121 (75%) experts responded in round 2. Round 1 achieved consensus in 32/40 (80%) statements. Consensus was not reached in the treatment algorithm section. Round 2 achieved consensus in 50/80 (62.5%). Statements reaching consensus were imaging (2/3, 66%), symptoms and other baseline measures (12/24, 50%), differential diagnosis (2/8, 25%), treatment algorithm (10/17, 59%), indications for stenting (10/10, 100%), inflow and outflow assessment (2/2, 100%), procedural outcomes (2/2, 100%), post-procedure therapies and stent surveillance, (5/7, 71%), and clinical success factors (5/7, 71%)., Conclusion: This study demonstrated that considerable consensus was achieved between venous experts on the optimal management of lower extremity venous outflow obstruction. There were multiple domains where consensus is lacking, highlighting important areas for further investigation and research., (Copyright © 2023 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Background: There are great expectations for the potential role of gene therapy in the treatment of hemophilia. At the same time, developments in the field of hemophilia gene therapy have always raised ethical issues. It remains unknown how these ethical issues are perceived by stakeholders, particularly regarding the most recent developments in the field., Objectives: To obtain insight into stakeholders' morally reasoned opinions on gene therapy for hemophilia., Methods: We conducted qualitative research with Dutch people with hemophilia ( n  = 13), parents of children with hemophilia ( n  = 5), physicians ( n  = 4), nurses ( n  = 3), a regulator ( n  = 1), and a representative from a pharmaceutical company ( n  = 1). We conducted semistructured interviews based on a topic list and reported the results according to the Consolidated Criteria for Reporting Qualitative Research guidelines., Results: We identified 3 main themes. The theme freedom and independence describes the hope people with hemophilia have of increasing their freedom through gene therapy, as well as concerns that gene therapy increases their dependence on their treatment center. The theme trust and altruism describes how people with hemophilia have a high level of trust in their physician and treatment center as well as in scientific research. As a result of this trust, they are willing to participate in research to help other people with hemophilia. The theme incremental benefits describes doubts respondents have about the added value of gene therapy compared to standard treatment., Conclusion: Stakeholders embrace the theoretical potential of gene therapy, while several people with hemophilia question the added value of the current gene transfer products for themselves., (© 2023 The Authors.)

Gene therapy is expected to become a promising treatment, and potentially even a cure, for hemophilia. After several years of research, the first gene therapy product has been granted conditional market authorization by the European Union in August 2022. The recent progress in the field also has implications on the ethical aspects of hemophilia gene therapy. Reviews conducted in the 2000s mainly identified questions on the ethics of conducting early-phase clinical trials. However, since then, the knowledge on safety and efficacy has improved, and the field has moved toward clinical application, a phase that has its own ethical aspects. Therefore, we conducted a narrative review to take stock of the ethical aspects of hemophilia gene therapy. Based on our analysis of the literature, we identified 3 ethical themes. The theme Living up to expectations describes the existing hopes for gene therapy and the unlikelihood of the currently approved product becoming a permanent cure. In the theme Psychosocial impacts, we discuss the fear that gene therapy will impact the identity of people with hemophilia and their need for psychosocial support. The theme Costs and access discusses the expected cost-effectiveness of gene therapy and its implications on accessibility worldwide. We conclude that it may be necessary to change the narratives surrounding gene therapy, from describing it as a cure to describing it as one of the many treatments that temporarily relieve symptoms and that there is a need to reevaluate the desirability of gene therapy for hemophilia, given the availability of other treatments., Competing Interests: Declaration of competing interests K.M. reports speaker fees from Alexion, Bayer, and CSL Behring; participation in trial steering committee for Bayer; participation in data monitoring and endpoint adjudication committee for Octapharma; all outside the scope of this review. She received consulting fees from Uniqure for participation in a writing committee for a gene therapy study, and she is investigator in a number of gene therapy trials. All fees are paid to her institution. All other authors have no conflicts of interest to declare., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To evaluate patients' experience of having served as controls without a notification at the time of randomization in the context of the trial within cohorts (TwiCs) design., Methods: Patients were asked for their opinion on having served as controls in TwiCs, before and after having been provided the trial results. Patients had provided broad consent to randomization at cohort entry and had served as controls in one of two TwiCs (an exercise program after breast cancer treatment or radiotherapy dose-escalation for rectal cancer)., Results: Two to 6 years after cohort entry, 15% (n = 16) of all patients remembered having provided broad consent to randomization. Before disclosure of trial results, 47% (n = 52) of patients thought positively, 45% (n = 50) neutrally, and 2% (n = 2) negatively of having served as controls in one of the two trials. Seventeen percent (n = 18) of patients were positive, 65% (n = 71) neutral, and 11% (n = 12) negative about not having been notified when serving as controls. The survey results were comparable after disclosure of trial results., Conclusions: These results support the use of the TwiCs design with the staged-informed consent procedure. Keeping patients engaged and aware of the consents provided might further improve patients' experience of serving as controls in TwiCs., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Treatment choices for individual patients with an inborn bleeding disorder are increasingly challenging due to increasing options and rising costs for society. We have initiated an integrated interdisciplinary national research programme., Objectives: The SYMPHONY consortium strives to orchestrate personalized treatment in patients with an inborn bleeding disorder, by unravelling the mechanisms behind inter-individual variations of bleeding phenotype., Patients: The SYMPHONY consortium will investigate patients with an inborn bleeding disorder, both diagnosed and not yet diagnosed., Results: Research questions are categorized under the themes: 1) Diagnosis; 2) Treatment; and 3) Fundamental research and consist of workpackages addressing specific domains. Importantly, collaborations between patients and talented researchers from different areas of expertise promise to augment the impact of the SYMPHONY consortium, leading to unique interactions and intellectual property., Conclusions: SYMPHONY will perform research on all aspects of care, treatment individualization in patients with inborn bleeding disorders as well as diagnostic innovations and results of molecular genetics and cellular model technology with regard to the hemostatic process. We believe that these research investments will lead to health care innovations with long-term clinical and societal impact. This consortium has been made possible by a governmental, competitive grant from the Netherlands Organization for Scientific Research (NWO) within the framework of the NWA-ORC Call grant agreement NWA.1160.18.038., (This article is protected by copyright. All rights reserved.)

Objective: This study aimed to validate trial patient eligibility screening and baseline data collection using text-mining in electronic healthcare records (EHRs), comparing the results to those of an international trial., Study Design and Setting: In three medical centers with different EHR vendors, EHR-based text-mining was used to automatically screen patients for trial eligibility and extract baseline data on nineteen characteristics. First, the yield of screening with automated EHR text-mining search was compared with manual screening by research personnel. Second, the accuracy of extracted baseline data by EHR text mining was compared to manual data entry by research personnel., Results: Of the 92,466 patients visiting the out-patient cardiology departments, 568 (0.6%) were enrolled in the trial during its recruitment period using manual screening methods. Automated EHR data screening of all patients showed that the number of patients needed to screen could be reduced by 73,863 (79.9%). The remaining 18,603 (20.1%) contained 458 of the actual participants (82.4% of participants). In trial participants, automated EHR text-mining missed a median of 2.8% (Interquartile range [IQR] across all variables 0.4-8.5%) of all data points compared to manually collected data. The overall accuracy of automatically extracted data was 88.0% (IQR 84.7-92.8%)., Conclusion: Automatically extracting data from EHRs using text-mining can be used to identify trial participants and to collect baseline information., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Objective: The Trials within Cohorts design aims to reduce recruitment difficulties and disappointment bias in pragmatic trials. On cohort enrollment, broad informed consent for randomization is asked, after which cohort participants can be randomized to interventions or serve as controls without further notification. We evaluated patients' recollection, understanding, and acceptance of broad consent in a clinical oncology setting., Methods: We surveyed 610 patients with cancer participating in ongoing TwiCs; 482 patients (79%) responded, of which 312 patients shortly after cohort enrollment, 108 patients after randomization to an intervention (12-18 months after cohort enrollment), and a random sample of 62 cohort participants who had not been selected for interventions (1-6 months after cohort enrollment)., Results: Shortly after providing cohort consent, 76% of patients (238/312) adequately remembered whether they had given broad consent for randomization. Of patients randomly offered interventions, 76% (82/108) remembered giving broad consent for randomization; 41% (44/108) understood they were randomly selected, 44% (48/108) were not interested in selection procedures, and 10% (11/108) did not understand selection was random. Among patients not selected for interventions, 42% (26/62) understood selection was random; 89% felt neutral regarding the scenario of "not being selected for an intervention while your data were being used in comparison with patients receiving interventions," 10% felt reassured (6/62) and 2% scared/insecure (2/62)., Conclusion: Patients adequately remember giving broad consent for randomization shortly after cohort enrollment and after being offered an intervention, but recollection is lower in those never selected for interventions. Patients are acceptant of serving as control without further notifications., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

In 2012, Weijer et al published "The Ottawa Statement on the ethical design and conduct of cluster randomized trials". In 2015, we reflected on this statement and argued that three recommendations in this statement need to be further refined. Weijer and Taljaard have responded to our comments in this issue of the journal. They agree with one of the proposed revisions but not with two others. In this commentary, we argue that the main reason why there is disagreement about two of our refinements is that we have different views on the moral and legal status of the health care workers as "research participants" in cluster randomized trials (CRTs). In this commentary, we clarify misunderstandings about our view expressed in 2015 and elaborate on the positions of health care workers in CRTs. We argue that there is sufficient reason to doubt whether the rights and interests of health care workers (HCWs) should be protected by means of ethics guidance documents and laws on human subjects research. Their interests are protected in the first place by professional codes of conduct which ensure that they cannot provide substandard care. Furthermore, protection of HCWs by ethics guidance on human subjects research will create an enormous burden for principle investigators and research ethics committees. Further debate is essential to determine how the interests of HCWs in CRTs can be protected best., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: Iliac vein compression syndrome can cause severe leg symptoms. In clinical practice, it remains a challenge to differentiate which compression is clinically relevant. The aim of the current study was to assess the general treatment indications and the prevalence of angiographic signs of iliac vein compression in a group of healthy participants., Methods: This was a prospective cohort study. A total of 20 healthy volunteers (median age 21, range 20-22 years) were recruited through advertisement and underwent angiography of the iliac veins. When no compression signs were present, a balloon occlusion was performed. Additionally, a 10 item survey regarding indications for venous stenting was developed and sent to 30 vascular specialists treating patients with deep venous obstruction., Results: In 16 (80%) participants, at least two signs indicative of May-Thurner compression were seen. In three (15%) subjects, narrowing of the common iliac vein without collaterals was shown and one (5%) did not show any signs of obstruction. In 23 (70%) of the survey responders, collaterals were found to be the most typical sign indicative of significant venous obstruction. An angiographic sign of >50% compression was found to be an indication to stent in 55% of responders., Conclusion: This study demonstrates a remarkably high percentage of generally accepted signs of significant iliac vein obstruction (May-Thurner compression) on venography in healthy young subjects. Diagnosis of true iliac vein obstruction remains a major challenge, which mostly leans on improvement of clinical symptoms rather than imaging findings. Treating the patient rather than the image seems to be a valid principle all the more., (Copyright © 2018 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Background: Although there is consensus among many that exclusion of pregnant women from clinical research should be justified, there is uncertainty as to whether and why pregnant women themselves would be willing to participate even if they were found to be eligible. The objective was to identify the reasons why pregnant women participate in clinical research and thereby to distinguish between facilitators and barriers., Methods: We conducted a systematic review of articles regarding pregnant women's reasons for participation in clinical research. We used the PubMed/MEDLINE, EMBASE, PsycINFO and CINAHL databases and retrieved additional articles through manually searching the reference lists. We included all articles that reported on pregnant women's reasons for participation in clinical research. We accumulated all reasons that were mentioned in the total of articles and collated them to themes, classifying these themes as a facilitator or a barrier., Results: The search identified thirty articles that met the inclusion criteria. Themes classified as facilitators: aspirational benefits, collateral benefits, direct benefits, third party influence and lack of inconvenience. Themes classified as barriers: inconveniences, risks, randomisation, lack of trust in research enterprise, medical reasons and third party influence., Conclusions: Pregnant women report mostly altruistic and personal reasons for their willingness to participate in clinical research, while barriers primarily relate to inconveniences. It appears that pregnant women's described reasoning is similar to the described reasoning of non-pregnant research subjects. Enhancing the facilitators and overcoming the barriers is the next step to increase the evidence-base underlying maternal and foetal health., (Copyright © 2017 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.)

Objectives: The primary aim was to investigate whether stenting of post-thrombotic iliofemoral obstruction reduces venous hypertension. The secondary aim was to establish whether improvement in haemodynamic parameters impacts on quality of life., Methods: In this prospective observational study, 12 participants with unilateral post-thrombotic obstruction of the iliac and/or common femoral veins (CFVs) underwent a treadmill stress test with invasive pressure measurements in the CFVs and dorsal foot veins of both affected and non-affected limbs. This was performed the day before and 3 months after stenting the obstructed tract. Paired sample t-tests were used to compare the treatment effect and univariable linear regression analysis to determine the association with improvement in quality of life., Results: Before treatment, CFV pressure increased 34.8 ± 23.1 mmHg during walking in affected limbs compared with 3.9 ± 5.8 mmHg in non-affected limbs. This pressure rise decreased to 22.3 ± 24.8 mmHg after 3 months follow up compared with a 4.0 ± 6.0 mmHg increase in non-affected limbs (-26.2 mmHg difference; 95% CI -41.2 to -11.3). No such effect was found in the dorsal foot veins. The VEINES-QOL increased 25.3 ± 11.3 points after stenting and was significantly associated with a decrease in CFV pressure rise during walking (regression coefficient 0.4; 95% CI 0.1-0.6)., Conclusion: Stenting of post-thrombotic iliofemoral obstruction significantly reduces venous hypertension in the common femoral vein and correlates with an improvement in the quality of life. Larger studies with a broader range of degree of obstruction need be performed to assess whether pre-stenting pressure measurements can predict post stenting clinical success., (Copyright © 2018 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Caval aneurysms are very rare but potentially lethal. Discussion about the need for treatment rises on individual basis. Based on the underlying etiology, a well-considered treatment plan should be made. Possible complications for invasive treatment and conservative management should be carefully weighed against each other. We present a patient with a caval aneurysm due to an arteriovenous fistula which we treated with endovascular embolization. Six months after treatment the patient is asymptomatic and the aneurysm size is decreased., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective/background: Deep venous obstruction is relatively prevalent in patients with chronic venous disease. Endovascular treatments and hybrid interventions can be used to relieve venous outflow obstructions. This paper assesses mid-term clinical outcomes and patency rates in a large cohort after percutaneous and hybrid interventions., Methods: This was a prospectively analysed cohort study. Patients with symptomatic deep venous obstruction who presented at a tertiary referral hospital were divided into three groups: patients who underwent percutaneous stenting for non-thrombotic iliac vein compression syndrome (IVCS group); patients with post-thrombotic syndrome (PTS) treated by percutaneous stent placement (P-PTS group); and PTS patients with obstruction involving the veins below the saphenofemoral junction in which a hybrid procedure was performed, combining stenting with open surgical disobliteration (H-PTS group). Patency rates, complications, and clinical outcomes were analysed., Results: A total of 425 lower extremities in 369 patients were treated. At 60 months, primary patency, assisted primary patency, and secondary patency rates were 90%, 100%, and 100% for IVCS, and 64%, 81%, and 89% for the P-PTS group, respectively. The H-PTS group, showed patency rates of 37%, 62%, and 72%, respectively, at 36 months. Venous claudication subsided in 90%, 82%, and 83%, respectively. At the 24 month follow-up, mean Venous Clinical Severity Score decreased for all patients and improvement in Villalta score was seen in post-thrombotic patients. The number of complications was related to the extent of deep venous obstruction in which patients in the H-PTS group showed the highest complication rates (81%) and re-interventions (59%)., Conclusion: Percutaneous stent placement to treat non-thrombotic iliac vein lesions, and post-thrombotic ilio-femoral obstructions are safe, effective, and showed patency rates comparable with previous research. Patients with advanced disease needing a hybrid procedure showed a lower patency rate and more complications. However, when successful, the clinical outcome was favourable at mid-term follow-up and the procedure may be offered to selected patients., (Copyright © 2017 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Early onset is regarded as an important characteristic of anxiety disorders, associated with higher severity. However, previous findings diverge, as definitions of early onset vary and are often unsubstantiated. We objectively defined early onset in social phobia, panic disorder, agoraphobia, and generalised anxiety disorder, using cluster analysis with data gathered in the general population. Resulting cut-off ages for early onset were ≤22 (social phobia), ≤31 (panic disorder), ≤21 (agoraphobia), and ≤27 (generalised anxiety disorder). Comparison of psychiatric comorbidity and general wellbeing between subjects with early and late onset in the general population and an outpatient cohort, demonstrated that among outpatients anxiety comorbidity was more common in early onset agoraphobia, but also that anxiety- as well as mood comorbidity were more common in late onset social phobia. A major limitation was the retrospective assessment of onset. Our results encourage future studies into correlates of early onset of psychiatric disorders., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Unlabelled: Essentials Little is known about the hemodynamic consequences of deep venous obstructive disease. We investigated pressure changes in 22 patients with unilateral postthrombotic obstruction. Common femoral vein pressure significantly increased after walking, compared to control limbs. Common femoral vein hypertension could explain the debilitating effect of venous claudication. Click to hear Dr Ten Cate's perspective on postthrombotic syndrome, Summary: Background Little is known about the hemodynamic consequences of deep venous obstructive disease. Objectives The aim of this study was to investigate the hemodynamic effect of postthrombotic obstruction of the iliofemoral veins and to determine what pressure parameters differentiate best between limbs with post-thrombotic obstructive disease of the iliofemoral veins and those without obstruction. Methods Twenty-two participants with unilateral obstruction of the iliac and common femoral veins underwent a standardized treadmill test with simultaneous bilateral invasive pressure measurements in the common femoral vein and dorsal foot vein. Results Mean age was 42.8 ± 11.9 years and 86.4% of participants were female. Postthrombotic limbs showed a mean common femoral vein (CFV) pressure increase of 28.1 ± 21.0 mmHg after walking, compared with 2.1 ± 6.2 mmHg in control limbs (26.0 mmHg difference; 95% confidence interval [CI], 17.1-34.9). Less difference was observed in the dorsal foot vein (net drop of 36.8 ± 22.7 mmHg in affected limbs vs. 48.7 ± 23.1 mmHg in non-affected limbs, 11.9 mmHg difference; 95% CI, -1.3 to 25.0). Change in CFV pressure after walking yielded the best discrimination between affected and non-affected limbs (area under the receiver operated characteristic curve of 0.94 [95% CI, 0.85-1.00], compared with 0.57 [95% CI, 0.37-0.76] in the dorsal foot vein, P < 0.001). Conclusions Common femoral vein pressure significantly increases during ambulation in patients with iliofemoral postthrombotic obstruction, which could explain the debilitating effects of venous claudication. This is an indication that patients with an iliofemoral obstruction may benefit from further treatment that resolves the deep vein obstruction., Clinical Trial Registration: https://clinicaltrials.gov/show/NCT01846780., (© 2016 International Society on Thrombosis and Haemostasis.)

Objective: Deep venous stenting has become the primary treatment option for chronic venous obstructive disease, both for iliac vein compression and post-thrombotic venous lesions. Until recently, only stents aimed at arterial pathology were used, because no dedicated venous stents were available. However, three such stents have now become available. These venous stents are characterized by increased length, diameter, flexibility, and radial force. This study reports an early experience with one of these devices; the sinus Venous stent (OptiMed GmbH, Ettlingen, Germany)., Methods: Between March 2012 and July 2014, 75 patients were treated with the sinus Venous stent: 35 cases of iliac vein compression syndrome and 40 cases of unilateral chronic obstruction in post-thrombotic syndrome (PTS). Diagnosis of relevant obstruction was made using clinical evaluation, duplex ultrasound, and magnetic resonance venography. Patency during follow up was assessed with duplex ultrasound. Clinical improvement was assessed by VCSS, Villalta score, rate of ulcer healing, and improvement of venous claudication., Results: The cumulative patency rates at 3, 6, and 12 months were 99%, 96%, and 92%, respectively. The cumulative assisted primary patency rates were 99% at 3, 6, and 12 months. The cumulative secondary patency rate at 12 months was 100%. Differences exist in patency rate between the subgroups of non-thrombotic and post-thrombotic, with the first showing no re-occlusions. All re-thromboses in the PTS group were treated by ancillary treatment modalities. VCSS and Villalta score decreased significantly after stenting, as did venous claudication. Morbidity was low without clinically relevant pulmonary embolism, and mortality was nil. Although two out of seven ulcers healed temporarily, no ulcer remained healed at 12 months follow up., Conclusion: Short-term clinical results using the sinus Venous stent are excellent, with significant symptom reduction, low morbidity rates, and no mortality. Loss of stent patency is seen less often compared with arterial stents described in the literature., (Copyright © 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Objectives: The Ottawa Statement is the first guidance document for the ethical and scientific conduct of cluster-randomized trials (CRTs). However, not all recommendations are straightforward to implement. In this paper we will reflect in particular on the recommendation on identifying human research subjects and the issue to what extent the randomization process should be disclosed if there is a risk of contamination., Study Design and Setting: The Ottawa Statement was thoroughly evaluated within a multidisciplinary research team, consisting amongst others of epidemiologists and ethicists., Results: Patients in a CRT may also be considered as research subjects if they are indirectly affected by the studied interventions in a CRT. Second, health care workers are research subjects in CRTs but have a different moral status compared with ordinary research participants. This different status has implications for withdrawal and the choice of the primary objective. Third, modified informed consent for CRTs may be obtained when researchers can demonstrate that disclosure of the randomization process would affect the validity of a CRT., Conclusion: Recommendations of the Ottawa Statement on identifying the research subject and providing informed consent can and should be refined., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: The objective of this study is to investigate to what extent psychiatric history affects preabortion decision difficulty, experienced burden, and postabortion emotions and coping. Women with and without a history of mental disorders might respond differently to unwanted pregnancy and subsequent abortion., Study Design: Women who had an abortion (n=325) were classified as either with or without a history of mental disorders, using the Composite International Diagnostic Interview version 3.0. The two groups were compared on preabortion doubt, postabortion decision uncertainty, experienced pressure, experienced burden of unwanted pregnancy and abortion, and postabortion emotions, self-efficacy and coping. The study was conducted in the Netherlands. Data were collected using structured face-to-face interviews and analyzed with regression analyses., Results: Compared to women without prior mental disorders, women with a psychiatric history were more likely to report higher levels of doubt [odds ratio (OR)=2.30; confidence interval (CI)=1.29-4.09], more burden of the pregnancy (OR=2.23; CI=1.34-3.70) and the abortion (OR=1.93; CI=1.12-3.34) and more negative postabortion emotions (β=.16; CI=.05-.28). They also scored lower on abortion-specific self-efficacy (β=-.11; CI=-.22 to .00) and higher on emotion-oriented (β=.22; .11-.33) and avoidance-oriented coping (β=.12; CI=.01-.24). The two groups did not differ significantly in terms of experienced pressure, decision uncertainty and positive postabortion emotions., Conclusions: Psychiatric history strongly affects women's pre- and postabortion experiences. Women with a history of mental disorders experience a more stressful pre- and postabortion period in terms of preabortion doubt, burden of pregnancy and abortion, and postabortion emotions, self-efficacy and coping., Implications: Negative abortion experiences may, at least partially, stem from prior or underlying mental health problems., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective/background: Stent placement in the venous system is an increasingly used treatment modality in chronic venous obstruction and as additional treatment after thrombolytic therapy in ilio-femoral deep vein thrombosis (DVT). Experience in treating in-stent thrombosis with ultrasound accelerated catheter directed thrombolysis (UACDT) is reported., Methods: A retrospective analysis of patients treated for venous stent occlusion, after percutaneous transluminal angioplasty (PTA) and stent placement for either chronic venous occlusive disease or persistent vein compression in patients with acute DVT was performed. Duration of occlusion and suspected clot age were assessed using patient complaints and typical findings on duplex ultrasonography (DUS). DUS and venography were used to assess patency and to determine the cause of re-occlusion. Acute treatment of occlusion was by UACDT. Additional procedures included PTA, stent placement, and creation of an arteriovenous (AV) fistula., Results: Eighteen patients (median age 43 years; 67% male), treated for occluded stent tracts with UACDT between January 2009 and July 2014, were identified. Indications for initial stenting were treatment of chronic venous obstructive disease (12 patients) and treatment of underlying obstruction after initial thrombolysis in acute DVT (six patients). Technical success was achieved in 11/18 (61%) patients. Primary patency in 8/11 patients was 73% at last follow up (median follow up 14 months [range 0-41 months]). Additional treatments after successful lysis were re-stenting (seven patients) and creation of an AV fistula (six patients)., Conclusion: Treatment with UACDT of recently occluded stent tracts is feasible and effective. Recanalization of the stent tract can be achieved in most cases. Additional interventions were frequently used after successful UACDT treatment. Suboptimal stent positioning caused the majority of the stent occlusions., (Copyright © 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Background: Although only a few people exposed to a traumatic event (TE) develop posttraumatic stress disorder (PTSD), symptoms that do not meet full PTSD criteria are common and often clinically significant. Individuals with these symptoms sometimes have been characterized as having subthreshold PTSD, but no consensus exists on the optimal definition of this term. Data from a large cross-national epidemiologic survey are used in this study to provide a principled basis for such a definition., Methods: The World Health Organization World Mental Health Surveys administered fully structured psychiatric diagnostic interviews to community samples in 13 countries containing assessments of PTSD associated with randomly selected TEs. Focusing on the 23,936 respondents reporting lifetime TE exposure, associations of approximated DSM-5 PTSD symptom profiles with six outcomes (distress-impairment, suicidality, comorbid fear-distress disorders, PTSD symptom duration) were examined to investigate implications of different subthreshold definitions., Results: Although consistently highest outcomes for distress-impairment, suicidality, comorbidity, and PTSD symptom duration were observed among the 3.0% of respondents with DSM-5 PTSD rather than other symptom profiles, the additional 3.6% of respondents meeting two or three of DSM-5 criteria B-E also had significantly elevated scores for most outcomes. The proportion of cases with threshold versus subthreshold PTSD varied depending on TE type, with threshold PTSD more common following interpersonal violence and subthreshold PTSD more common following events happening to loved ones., Conclusions: Subthreshold DSM-5 PTSD is most usefully defined as meeting two or three of DSM-5 criteria B-E. Use of a consistent definition is critical to advance understanding of the prevalence, predictors, and clinical significance of subthreshold PTSD., (Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: The link between leisure and cannabis use has been widely studied, but less so for young adults, and rarely with a focus on frequent cannabis use. Also, little is known about how changes in leisure develop over time and how they are related to transitions in cannabis use and dependence., Method: As part of a 3-year longitudinal project, in a qualitative study 47 frequent male and female young adult cannabis users with (n=23) and without (n=24) dependence at baseline were interviewed in-depth after 1.5 and 3 years., Results: Frequent cannabis users (at baseline ≥3 days per week in the past 12 months) are involved in similar leisure activities as the general young adult population and live rather conventional lives, generally away from a delinquent subculture. They mostly regulate their cannabis use to leisure time, to enhance other leisure activities, including socialising and video gaming. While they often give precedence to responsibilities (e.g. work and study), dependent and non-dependent users differed in whether they actively adapted their leisure activities to their cannabis use, or their cannabis use to their leisure time. Both types of and time spent on leisure activities were associated with transitions in use and dependence., Conclusions: While our findings generally support the normalisation thesis, it is questionable whether frequent but non-problematic cannabis use is socially accepted in wider society. This study also questions the diagnostic dependence vs. non-dependence dichotomy, and adds finer distinctions to the concept of cannabis dependence. Implications for prevention and treatment include facilitating structured spending of leisure time (e.g. sports), and targeting frequent users who spent much leisure time video gaming at home., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Alcohol consumption levels and alcohol use disorder (AUD) symptoms may serve as easily quantifiable markers for AUD relapse after remission and might help prevention workers identify at-risk individuals. We investigated the predictive value of alcohol consumption and AUD symptoms on relapse., Methods: Data are from the Netherlands Mental Health Survey and Incidence Study-2 (NEMESIS-2). We selected 506 people in ≥12-month DSM-5 AUD remission at baseline and assessed their status at 3-year follow-up. AUD symptoms and drinking patterns were assessed using the Composite International Diagnostic Interview 3.0. Time since remission was assessed retrospectively at baseline and ranged from 1 to 48 years. Predictors for relapse were examined using Cox regression analysis., Results: Cumulative AUD relapse rate was 5.6% at 5 years, 9.1% at 10 years and 12.0% at 20 years. Relapse was predicted by both medium (15-28/22-42 drinks weekly for women/men) and high (≥29/43) past alcohol intake, 6+ lifetime AUD symptoms, 'impaired control over use', and at-risk (≥8/15) current intake. The risk of relapse was especially high when medium or high past intake or 6+ lifetime symptoms coincided with current at-risk drinking., Conclusions: Only a minority of people in DSM-5 AUD remission relapsed, but the risk of relapse increased substantially with the presence of at least one of the risk factors. Moreover, at-risk current drinking coupled with other risk factors substantially increased the likelihood of relapse. Therefore, current drinking may provide an adequate reference point for relapse prevention., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objectives: Ethical guidelines for human subject research require that the burdens and benefits of participation be equally distributed. This study aimed to provide empirical data on exclusion of trial participants and reasons for this exclusion. As a secondary objective, we assessed to what extent exclusion affects generalizability of study results., Study Design and Setting: Review of trials on secondary prevention of cardiovascular events., Results: One hundred thirteen trials were identified, of which 112 reported exclusion criteria. One study justified the exclusion criteria applied. Ambiguous exclusion criteria due to the opinion of the physician (28 of 112 = 25%) or physical disability (12 of 112 = 11%) were reported. Within groups of trials that studied similar treatments (ie, beta-blocker, clopidogrel, or statin therapy), baseline characteristics differed among trials. For example, the proportion of women ranged between 23.1-47.4%, 2.1-38.9%, and 10.6-50.6% for the clopidogrel, beta-blocker, and statin trials, respectively. Nevertheless, no evidence was found for heterogeneity of treatment effects., Conclusion: Almost none of the articles justified the applied exclusion criteria. No evidence was found that inclusion of dissimilar participants affected generalizability. To allow for a normative discussion on equitable selection of study populations, researchers should not only report exclusion criteria but also the reasons for using these criteria., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Anxiety has been linked to onset of cardiovascular disease. This study examines the differential impact of types of anxiety (panic, phobia and worry) on 3-year onset of non-fatal cardiovascular disease (CVD). By investigating anxiety disorders as opposed to anxiety symptoms and by using a reliable diagnostic instrument to assess anxiety, limitations of previous studies are considered. 5149 persons at risk for CVD were interviewed using the Composite International Diagnostic Interview. The panic-type included panic disorder and panic attacks; the phobic-type included agoraphobia and social phobia, and the worry-type included generalized anxiety disorder. CVD was self-reported and required treatment or monitoring by a doctor. Analyses were adjusted for sociodemographics, behavioral variables, and comorbid somatic and psychiatric disorders. During follow-up, 62 persons (1.2%) developed CVD. Baseline generalized anxiety disorder was strongly associated with onset of CVD (adjusted OR: 3.39). Further research should replicate findings and focus on biological underpinnings of this association., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Relatively few cannabis dependent people seek treatment and little is known about determinants of treatment seeking., Methods: Treatment determinants were compared among 70 DSM-IV cannabis dependent patients and 241 non-treatment seeking DSM-IV cannabis dependent community subjects. In addition, perceived facilitators for treatment seeking were assessed in patients, whereas perceived barriers were assessed in 160/241 cannabis dependent community subjects not prepared to seek treatment (precluders), of whom 63/160 showed an objective treatment need, and 30/241 showed a subjective treatment need., Results: Compared to non-treatment seekers, patients reported more cannabis use (176.9 versus 82.8 joints monthly), more symptoms of dependence (5.6 versus 4.5), higher perceived lack of social support (70.0% versus 41.1%), more pressure to seek treatment (58.6% versus 21.6%), a more positive attitude to treatment, and more previous treatments. In addition, patients reported more mental health problems (internalising disorders 57.1% versus 24.5%; externalising disorders 52.9% versus 35.3%) and more functional impairments (8.4 versus 4.8 monthly days out of role). Cannabis dependent 'precluders' reported desire for self-reliance (50.0%), preference for informal help (22.5%), and absent treatment need (16.9%) as their main reasons not to seek treatment, whereas cannabis dependent community subjects with a subjective treatment need mainly expressed desire for self-reliance (36.7%), treatment ineffectiveness (16.7%), and avoiding stigma (13.3%)., Conclusions: Functional impairment, mental health problems and social pressure are important reasons to seek treatment in people with cannabis dependence. Treatment participation might improve if desire for self-reliance and the preference for informal help are considered, and perceived ineffectiveness of treatment and stigmatisation are publicly addressed., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: Frequent cannabis users are at high risk of dependence, still most (near) daily users are not dependent. It is unknown why some frequent users develop dependence, whereas others do not. This study aims to identify predictors of first-incidence DSM-IV cannabis dependence in frequent cannabis users., Methods: A prospective cohort of frequent cannabis users (aged 18-30, n=600) with baseline and two follow-up assessments (18 and 36 months) was used. Only participants without lifetime diagnosis of DSM-IV cannabis dependence at baseline (n=269) were selected. Incidence of DSM-IV cannabis dependence was established using the Composite International Diagnostic Interview version 3.0. Variables assessed as potential predictors of the development of cannabis dependence included sociodemographic factors, cannabis use variables (e.g., motives, consumption habits, cannabis exposure), vulnerability factors (e.g., childhood adversity, family history of mental disorders or substance use problems, personality, mental disorders), and stress factors (e.g., life events, social support)., Results: Three-year cumulative incidence of cannabis dependence was 37.2% (95% CI=30.7-43.8%). Independent predictors of the first incidence of cannabis dependence included: living alone, coping motives for cannabis use, number and type of recent negative life events (major financial problems), and number and type of cannabis use disorder symptoms (impaired control over use). Cannabis exposure variables and stable vulnerability factors did not independently predict first incidence of cannabis dependence., Conclusions: In a high risk population of young adult frequent cannabis users, current problems are more important predictors of first incidence cannabis dependence than the level and type of cannabis exposure and stable vulnerability factors., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objectives: To evaluate the performance of the Mental Component of the Short-Form 12 Health Survey, Version 1(SF-12v1), as a screening measure of depressive disorders., Methods: Data come from the European Study of the Epidemiology of Mental Disorders (ESEMeD), a cross-sectional survey carried out on representative samples of 21,425 individuals from the noninstitutionalized adult general population of six European countries (response rate = 61.2%). The SF-12 was administered and scored according to three algorithms: the "original" method (mental component summary of SF-12 [MCS-12]), the RAND-12 (RAND-12 Mental Health Composite [RAND-12 MHC]), and the Bidemensional Response Process Model 12 mental health score (BRP-12 MHS), based on a two-factor Item Response Theory graded response model. Thirty-day and 12-month depressive disorders (major depressive episode or dysthymia) were assessed with the Composite International Diagnostic Interview, Version 3.0, by using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria. Receiver operating characteristic curves analysis was carried out, and optimal cutoff points maximizing balance between sensitivity (SN) and specificity (SP) were chosen for the three methods., Results: Prevalence of 30-day and 12-month depressive disorders in the overall sample was 1.5% and 4.4%, respectively. The area under the curve for 30-day depressive disorders was 0.92, and it decreased to 0.85 for 12-month disorders, regardless of the scoring method. Optimal cutoff for 30-day depressive disorders was 45.6 (SN = 0.86; SP = 0.88) for the MCS-12, 44.5 for the RAND-12 MHC (SN = 0.87, SP = 0.86), and 40.2 for the BRP-12 MHS (SN = 0.87, SP = 0.87). The selected 12-month cutoffs for MCS-12 and RAND-12 MHC were between 4.2 and 5.8 points below the general population means of each country, with SN range 0.67 to 0.78 and SP range 0.77 to 0.87., Conclusions: The SF-12 yielded acceptable results for detecting both active and recent depressive disorders in general population samples, suggesting that the questionnaire could be used as a useful screening tool for monitoring the prevalence of affective disorders and for targeting treatment and prevention., (Copyright © 2013 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Background: Little population-based data exist outside the United States on the epidemiology of binge eating disorder (BED). Cross-national BED data are presented here and compared with bulimia nervosa (BN) data in the World Health Organization (WHO) World Mental Health Surveys., Methods: Community surveys with 24,124 respondents (ages 18+) across 14 mostly upper-middle and high-income countries assessed lifetime and 12-month DSM-IV mental disorders with the WHO Composite International Diagnostic Interview. Physical disorders were assessed with a chronic conditions checklist., Results: Country-specific lifetime prevalence estimates are consistently (median; interquartile range) higher for BED (1.4%; .8-1.9%) than BN (.8%; .4-1.0%). Median age of onset is in the late teens to early 20s for both disorders but slightly younger for BN. Persistence is slightly higher for BN (6.5 years; 2.2-15.4) than BED (4.3 years; 1.0-11.7). Lifetime risk of both disorders is elevated for women and recent cohorts. Retrospective reports suggest that comorbid DSM-IV disorders predict subsequent onset of BN somewhat more strongly than BED and that BN predicts subsequent comorbid disorders somewhat more strongly than does BED. Significant comorbidities with physical conditions are due almost entirely to BN and to a somewhat lesser degree BED predicting subsequent onset of these conditions. Role impairments are similar for BN and BED. Fewer than half of lifetime BN or BED cases receive treatment., Conclusions: Binge eating disorder represents a public health problem at least equal to BN. Low treatment rates highlight the clinical importance of questioning patients about eating problems even when not included among presenting complaints., (Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Better information on the human capital costs of early-onset mental disorders could increase sensitivity of policy makers to the value of expanding initiatives for early detection and treatment. Data are presented on one important aspect of these costs: the associations of early-onset mental disorders with adult household income., Methods: Data come from the World Health Organization (WHO) World Mental Health Surveys in 11 high-income, five upper-middle income, and six low/lower-middle income countries. Information about 15 lifetime DSM-IV mental disorders as of age of completing education, retrospectively assessed with the WHO Composite International Diagnostic Interview, was used to predict current household income among respondents aged 18 to 64 (n = 37,741) controlling for level of education. Gross associations were decomposed to evaluate mediating effects through major components of household income., Results: Early-onset mental disorders are associated with significantly reduced household income in high and upper-middle income countries but not low/lower-middle income countries, with associations consistently stronger among women than men. Total associations are largely due to low personal earnings (increased unemployment, decreased earnings among the employed) and spouse earnings (decreased probabilities of marriage and, if married, spouse employment and low earnings of employed spouses). Individual-level effect sizes are equivalent to 16% to 33% of median within-country household income, and population-level effect sizes are in the range 1.0% to 1.4% of gross household income., Conclusions: Early mental disorders are associated with substantial decrements in income net of education at both individual and societal levels. Policy makers should take these associations into consideration in making health care research and treatment resource allocation decisions., (Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Much is unclear about the association between attention-deficit/hyperactivity disorder (ADHD) and alcohol use (disorder). Research on this subject is hindered by the role of conduct disorder (CD). We investigate whether (1) childhood ADHD is associated with higher prevalence and earlier onset of alcohol initiation, regular alcohol use and alcohol use disorder (AUD) (2) CD mediates or modifies this association., Methods: Data were derived from the baseline assessment of the Netherlands Mental Health Survey and Incidence Study-2, a general population study. ADHD and CD were assessed among respondents aged 18-44 (n=3309). ADHD, CD, and alcohol use (disorder) were assessed using the Composite International Diagnostic Interview 3.0., Results: Lifetime prevalence was 2.9% for ADHD, 5.6% for CD, 94.3% for alcohol initiation, 85.7% for regular alcohol use and 19.0% for AUD; mean ages of onset were 6.7, 11.5, 14.8, 16.7 and 19.2 years, respectively. After correction for gender and age, ADHD was associated with a higher prevalence of all three stages of alcohol use, but not with earlier onset of these stages. The association between ADHD and prevalence of AUD was fully explained by a mediating role of CD. CD did not modify the associations between ADHD and prevalence and onset of alcohol use (disorder)., Conclusions: The mediating role of CD in the association between ADHD and AUD suggests a developmental pathway from ADHD to CD and subsequent AUD. Early interventions in children with ADHD may prevent CD and subsequent onset of AUD., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objective: Currently, little is known about psychiatric disorders in the period following on the first year after burn. We examined the prevalence of DSM-IV Axis I disorders in burn patients 1-4 years after burn, using a standardized structured clinical interview and comparing findings with a representative general population sample., Methods: Ninety patients admitted to five burn centres were assessed with the 12-month Composite International Diagnostic Interview. Results were compared to an age and gender matched nation based norm group., Results: Twelve-month prevalence for any DSM-IV study disorder was 39%. Prevalence for any after burn onset disorder was 28%. Most prevailing were major depression (10%), generalized anxiety disorder (10%), and PTSD (7%). The comorbidity-proportions for PTSD and generalized anxiety disorder where the highest. Fifty-seven percent of all burn onset disorders started within 1 year after the trauma and 21% within the next year. Burn patients had significantly higher prevalence rates for DSM-IV disorders than people from the general population sample., Conclusion: Psychiatric morbidity among burn patients, 1-4 years after burn, is considerable and higher than what may be expected in the general population. A 2-year follow-up for anxiety and depression disorder is warranted., (Copyright © 2011 Elsevier Ltd and ISBI. All rights reserved.)

Background: Controversy exists about the utility of DSM-IV posttraumatic stress disorder (PTSD) criterion A2 (A2): that exposure to a potentially traumatic experience (PTE; PTSD criterion A1) is accompanied by intense fear, helplessness, or horror., Methods: Lifetime DSM-IV PTSD was assessed with the Composite International Diagnostic Interview in community surveys of 52,826 respondents across 21 countries in the World Mental Health Surveys., Results: Of 28,490 representative PTEs reported by respondents, 37.6% met criterion A2, a proportion higher than the proportions meeting other criteria (B-F; 5.4%-9.6%). Conditional prevalence of meeting all other criteria for a diagnosis of PTSD given a PTE was significantly higher in the presence (9.7%) than absence (.1%) of A2. However, as only 1.4% of respondents who met all other criteria failed A2, the estimated prevalence of PTSD increased only slightly (from 3.64% to 3.69%) when A2 was not required for diagnosis. Posttraumatic stress disorder with or without criterion A2 did not differ in persistence or predicted consequences (subsequent suicidal ideation or secondary disorders) depending on presence-absence of A2. Furthermore, as A2 was by far the most commonly reported symptom of PTSD, initial assessment of A2 would be much less efficient than screening other criteria in quickly ruling out a large proportion of noncases., Conclusions: Removal of A2 from the DSM-IV criterion set would reduce the complexity of diagnosing PTSD, while not substantially increasing the number of people who qualify for diagnosis. Criterion A2 should consequently be reconceptualized as a risk factor for PTSD rather than as a diagnostic requirement., (Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: It is unclear whether the normative sequence of drug use initiation, beginning with tobacco and alcohol, progressing to cannabis and then other illicit drugs, is due to causal effects of specific earlier drug use promoting progression, or to influences of other variables such as drug availability and attitudes. One way to investigate this is to see whether risk of later drug use in the sequence, conditional on use of drugs earlier in the sequence, changes according to time-space variation in use prevalence. We compared patterns and order of initiation of alcohol, tobacco, cannabis, and other illicit drug use across 17 countries with a wide range of drug use prevalence., Method: Analyses used data from World Health Organization (WHO) World Mental Health (WMH) Surveys, a series of parallel community epidemiological surveys using the same instruments and field procedures carried out in 17 countries throughout the world., Results: Initiation of "gateway" substances (i.e. alcohol, tobacco and cannabis) was differentially associated with subsequent onset of other illicit drug use based on background prevalence of gateway substance use. Cross-country differences in substance use prevalence also corresponded to differences in the likelihood of individuals reporting a non-normative sequence of substance initiation., Conclusion: These results suggest the "gateway" pattern at least partially reflects unmeasured common causes rather than causal effects of specific drugs on subsequent use of others. This implies that successful efforts to prevent use of specific "gateway" drugs may not in themselves lead to major reductions in the use of later drugs., (Copyright 2009 Elsevier Ireland Ltd. All rights reserved.)

Objective: The purpose of this study was to analyze and compare different valuation methods for population health status measured by the EuroQol-5D (EQ-5D) in three European countries., Methods: A representative survey of the noninstitutionalized population aged 18 and above was conducted in three European countries (Germany, The Netherlands, and Spain). A total of 11,932 respondents were interviewed using the EQ-5D self-classifier. Health state values based on community preferences (EQ-5D index) were calculated for each country using four different value sets: national value sets based on the time trade-off (TTO) and the visual analogue scale (VAS), the UK TTO-based value set and the European VAS-based value set. Linear regression analysis was conducted to evaluate the factors associated with different EQ-5D index scores depending on the value set used. Loss of quality-adjusted life-years (QALYs) was calculated for each country using the four value sets by multiplying the age and gender-specific values with the respective population size., Results: In all countries, means of all EQ-5D index scores were higher for men than women, and decreased with age. Index scores calculated using the national value set based on TTO were higher than those calculated using the UK TTO-based value set and, also, slightly higher than those calculated using the European VAS-based value set or the national value set based on the VAS. The mean loss of QALYs estimated for Germany per inhabitant varied between 0.062 (national value set based on TTO) and 0.094 (European VAS-based value set). In The Netherlands, the mean loss of QALYs per inhabitant ranged from 0.090 (national value set based on TTO) to 0.125 (national value set based on VAS). In Spain, the mean loss of QALYs per inhabitant ranged between 0.072 (national value set based on TTO) and 0.085 (European VAS-based value set)., Conclusions: In general, the differences among countries and valuations were rather small; nevertheless, some important variations should be taken into account while applying different valuation methods to the EQ-5D descriptive system. The associations between sociodemographic variables and health state scores remained the same across countries regardless of which value sets were used. Using different valuation methods lead to different QALY losses. To overcome this problem in international surveys aimed to compare health state scores or QALYs, it is advisable to use a single valuation method, making these scores comparable.

Background: Although it is known that childhood attention-deficit/hyperactivity disorder (ADHD) often persists into adulthood, childhood predictors of this persistence have not been widely studied., Methods: Childhood history of ADHD and adult ADHD were assessed in 10 countries in the World Health Organization World Mental Health Surveys. Logistic regression analysis was used to study associations of retrospectively reported childhood risk factors with adult persistence among the 629 adult respondents with childhood ADHD. Risk factors included age; sex; childhood ADHD symptom profiles, severity, and treatment; comorbid child/adolescent DSM-IV disorders; childhood family adversities; and child/adolescent exposure to traumatic events., Results: An average of 50% of children with ADHD (range: 32.8%-84.1% across countries) continued to meet DSM-IV criteria for ADHD as adults. Persistence was strongly related to childhood ADHD symptom profile (highest persistence associated with the attentional plus impulsive-hyperactive type, odds ratio [OR]=12.4, compared with the lowest associated with the impulsive-hyperactive type), symptom severity (OR=2.0), comorbid major depressive disorder (MDD; OR=2.2), high comorbidity (>or=3 child/adolescent disorders in addition to ADHD; OR=1.7), paternal (but not maternal) anxiety mood disorder (OR=2.4), and parental antisocial personality disorder (OR=2.2). A multivariate risk profile of these variables significantly predicts persistence of ADHD into adulthood (area under the receiving operator characteristic curve=.76)., Conclusions: A substantial proportion of children with ADHD continue to meet full criteria for ADHD as adults. A multivariate risk index comprising variables that can be assessed in adolescence predicts persistence with good accuracy.

Objective: The WHODAS-II was substantially modified for use in the World Mental Health Surveys. This article considers psychometric properties and implications of filter items used to reduce respondent burden of the modified WHODAS-II., Study Design and Setting: Seventeen surveys in 16 countries administered a modified WHODAS-II to population samples (N=38,934 adults). Modifications included introducing filter questions for four subscales and substituting questions on the number of days activity was limited for the Life Activities domain. We evaluated distributional properties, reliability, and validity of the modified WHODAS-II., Results: Most respondents (77%-99%) had zero scores on filtered subscales. Lower bound estimates of internal consistency (alpha) for the filtered subscales were typically in the 0.70s, but were higher for the Global scale. Loadings of subscale scores on a Global Disability factor were moderate to high. Correlations with the Sheehan Disability Scale were modest but consistently positive, while correlations with SF-12 Physical Component Summary were considerably higher. Cross-national variability in disability scores was observed, but was not readily explainable., Conclusions: Internal consistency and validity of the modified WHODAS-II was generally supported, but use of filter questions impaired measurement properties. Group differences in modified WHODAS-II disability scores may be compared within, but not necessarily across, countries.

Background: Mental disorders are major causes of disability worldwide, including in the low-income and middle-income countries least able to bear such burdens. We describe mental health care in 17 countries participating in the WHO world mental health (WMH) survey initiative and examine unmet needs for treatment., Methods: Face-to-face household surveys were undertaken with 84,850 community adult respondents in low-income or middle-income (Colombia, Lebanon, Mexico, Nigeria, China, South Africa, Ukraine) and high-income countries (Belgium, France, Germany, Israel, Italy, Japan, Netherlands, New Zealand, Spain, USA). Prevalence and severity of mental disorders over 12 months, and mental health service use, were assessed with the WMH composite international diagnostic interview. Logistic regression analysis was used to study sociodemographic predictors of receiving any 12-month services., Findings: The number of respondents using any 12-month mental health services (57 [2%; Nigeria] to 1477 [18%; USA]) was generally lower in developing than in developed countries, and the proportion receiving services tended to correspond to countries' percentages of gross domestic product spent on health care. Although seriousness of disorder was related to service use, only five (11%; China) to 46 (61%; Belgium) of patients with severe disorders received any care in the previous year. General medical sectors were the largest sources of mental health services. For respondents initiating treatments, 152 (70%; Germany) to 129 (95%; Italy) received any follow-up care, and one (10%; Nigeria) to 113 (42%; France) received treatments meeting minimum standards for adequacy. Patients who were male, married, less-educated, and at the extremes of age or income were treated less., Interpretation: Unmet needs for mental health treatment are pervasive and especially concerning in less-developed countries. Alleviation of these unmet needs will require expansion and optimum allocation of treatment resources.

Heat shock proteins (HSPs) of endogenous and exogenous origin are suspected contributors to the initiation and aggravation of vascular pathologies like atherosclerosis and restenosis. Toll-like receptors (TLRs) 2 and 4 are well-known receptors for exogenous pathogen-associated molecular patterns and have recently been thought to play a role in HSP60-induced cellular activation. We hypothesized that human HSP60 directly stimulates venous smooth muscle cell (VSMC) proliferation through a TLR-dependent mechanism. Localization of HSP60, TLR2 and TLR4 was studied in failed venous grafts and normal venous tissue by double immunostaining. In vitro VSMCs were incubated for 48 h with recombinant human HSP60. In other experiments, VSMCs were pre-incubated for 30 min with specific anti-TLR2 and anti-TLR4 antibodies. VSMC proliferation was determined by Ki67 immunoreactivity, and mean values were compared between experimental and control groups. In addition, human embryonic kidney (HEK) cells transfected with human TLR2 or TLR4/MD-2 were exposed to HSP60 for 48 h, and proliferation was determined by using a hemocytometer. Co-localization of HSP60 and TLRs was detected in all neointimal lesions but was virtually absent in normal veins. Human HSP60 stimulated VSMC proliferation in a concentration-dependent fashion. In addition, TLR2 and TLR4 antibodies attenuated VSMC proliferation. The role of TLR-mediated stimulation of cell proliferation by HSP60 was supported by the significant increase in proliferation of transfected HEK cells. These findings provide supporting evidence for the role of HSP60 and TLR2 and TLR4 in vascular disease. Moreover, our data surpass the infection- and autoimmunity-based hypotheses of cardiovascular disease and suggest an additional HSP60-related autocrine process.