The effect of monomeric and oligomeric FLAVAnols in patients with type 2 diabetes and microalbuminuria (FLAVA-trial): A double-blind randomized controlled trial.

BACKGROUND & AIMS: Microalbuminuria is an early sign of vascular complications of type 2 diabetes and predicts cardiovascular disease and mortality. Monomeric and oligomeric flavanols (MOFs) are linked to improved vascular health. The aim of this study was to assess the effect of 3 months MOFs on albuminuria and endothelial function markers in patients with type 2 diabetes and microalbuminuria. METHODS: We conducted a double-blind, placebo-controlled trial among patients with type 2 diabetes and microalbuminuria. Patients with type 2 diabetes received either 200 mg MOFs or placebo daily on top of their habitual diet and medication. The primary endpoint was the between-group difference of the change in 24-h Albumin Excretion Rate (AER) over three months. Secondary endpoints were the between-group differences of the change in plasma levels of different markers of endothelial dysfunction. Mixed-modelling was applied for the longitudinal analyses. RESULTS: Participants (n = 97) were 63.0 ± 9.5 years old; diabetes-duration was 15.7 ± 8.5 years. Median baseline AER was 60 (IQR 20-120) mg/24 h. There was no within-group difference in median change of AER from baseline to 3 months in the intervention (0 (-35-21) mg/24 h, p = 0.41) or the control group (0 (-20-10) mg/24 h, p = 0.91). There was no between-group difference in the course of AER over three months (log-transformed data: ß = -0.02 (95%CI -0.23-0.20), p = 0.88), nor in the plasma levels of the endothelial dysfunction markers. CONCLUSION: Daily 200 mg MOFs for three months on top of habitual diet and usual care did not reduce AER and plasma markers of endothelial dysfunction compared to placebo, in patients with long-term type 2 diabetes and microalbuminuria. CLINICAL TRIALS REGISTRATION: NTR4669, www.trialregister.nl.

Postoperative parathyroid hormone levels as a predictor for persistent hypoparathyroidism.

OBJECTIVE: Hypoparathyroidism is a common complication after thyroidectomy. It is not yet possible to predict in which patients hypoparathyroidism will persist. We aim to determine whether a decrease in PTH levels, measured at the first postoperative day, can identify patients with a high risk for persistent hypoparathyroidism one year after thyroidectomy. DESIGN: Prospective multi-center cohort study. METHODS: Patients undergoing total or completion thyroidectomy were included. We measured PTH levels preoperatively and on the first postoperative day. Primary outcome is the proportion of patients with persistent hypoparathyroidism, defined as the need for calcium supplementation one year after surgery. RESULTS: We included 110 patients of which 81 were used for analysis of the primary outcome. At discharge 72.8% of patients were treated with calcium supplementation. Persistent hypoparathyroidism was present in 14 patients (17.3%) at one-year follow-up, all of them had a decrease in PTH >70% at the first postoperative day. These 14 were 43.8% of the 32 patients who had such a decrease. In the group of 49 patients (59.8%) without a PTH >70% decrease, none had persistent hypoparathyroidism one year after surgery (P-value <0.001). A decrease of >70% in PTH levels had a sensitivity of 100.0% (95% CI: 85.8-100.0%), a specificity of 73.1% (95% CI: 62.5-83.7%) and an area under the curve of 0.87 (95% CI: 0.79-0.94) to predict the risk for persistent hypoparathyroidism. CONCLUSION: In our study a decrease in PTH levels of >70% after total or completion thyroidectomy is a reliable predictor for persistent hypoparathyroidism, and this should be confirmed in larger cohorts.

Cost-effectiveness of the treatments for critical limb ischemia in the elderly population.

OBJECTIVE: The treatment of critical limb ischemia (CLI), with the intention to prevent limb loss, is often an intensive and expensive therapy. The aim of this study was to examine the cost-effectiveness of endovascular and conservative treatment of elderly CLI patients unsuitable for surgery. METHODS: In this prospective observational cohort study, data were gathered in two Dutch peripheral hospitals. CLI patients aged 70 years or older were included in the outpatient clinic. Exclusion criteria were malignant disease, lack of language skills, and cognitive impairment; 195 patients were included and 192 patients were excluded. After a multidisciplinary vascular conference, patients were divided into three treatment groups (endovascular revascularization, surgical revascularization, or conservative therapy). Subanalyses based on age were made (70-79 years and ≥80 years). The follow-up period was 2 years. Cost-effectiveness of endovascular and conservative treatment was quantified using incremental cost-effectiveness ratios (ICERs) in euros per quality-adjusted life-years (QALYs). RESULTS: At baseline, patients allocated to surgical revascularization had better health states, but the health states of endovascular revascularization and conservative therapy patients were comparable. With an ICER of €38,247.41/QALY (∼$50,869/QALY), endovascular revascularization was cost-effective compared with conservative therapy. This is favorable compared with the Dutch applicable threshold of €80,000/QALY (∼$106,400/QALY). The subanalyses also established that endovascular revascularization is a cost-effective alternative for conservative treatment both in patients aged 70 to 79 years (ICER €29,898.36/QALY; ∼$39,765/QALY) and in octogenarians (ICER €56,810.14/QALY; ∼$75,557/QALY). CONCLUSIONS: Our study has shown that endovascular revascularization is cost-effective compared with conservative treatment of CLI patients older than 70 years and also in octogenarians. Given the small absolute differences in costs and effects, physicians should also consider individual circumstances that can alter the outcome of the intervention. Cost-effectiveness remains one of the aspects to take into consideration in making a clinical decision.

Implementation of evidence-based treatments for borderline personality disorder: The impact of organizational changes on treatment outcome of mentalization-based treatment.

The quality of implementation of evidence-based treatment programs for borderline personality disorder (BPD) in routine clinical care is a neglected issue. The first aim of this mixed-method naturalistic study was to explore the impact of organizational changes on treatment effectiveness of a day-hospital programme of mentalization-based treatment. Consecutively referred BPD patients were divided into a pre-reorganization cohort (PRE-REORG) and a cohort during reorganization (REORG). Psychiatric symptoms (Brief Symptom Inventory) and personality functioning (Severity Indices of Personality Problems-118) before treatment and at 18- and 36-month follow-up were compared using multilevel modelling. Effect sizes in the PRE-REORG cohort were approximately twice as large at 18 months (PRE-REORG: range 0.81-1.22; REORG: range 0.03-0.71) and three times as large at 36 months (PRE-REORG: range 0.81-1.80; REORG: range 0.27-0.81). The quantitative results of this study suggest that even when mentalization-based treatment is successfully implemented and the structure of the programme remains intact, major organizational changes may have a considerable impact on its effectiveness. Second, we aimed to explore the impact of the reorganization on adherence at organizational, team and therapist level. The qualitative results of this study indicate that the organizational changes were negatively related to adherence to the treatment model at organizational, team and therapist level, which in turn was associated with a decrease in treatment effectiveness. The implications of these findings for the implementation of effective treatments for BPD in routine clinical practice are discussed. Copyright © 2017 John Wiley & Sons, Ltd.

Effectiveness of Day Hospital Mentalization-Based Treatment for Patients with Severe Borderline Personality Disorder: A Matched Control Study.

The present study extends the body of evidence regarding the effectiveness of day hospital Mentalization-Based Treatment (MBT) by documenting the treatment outcome of a highly inclusive group of severe borderline personality disorder (BPD) patients, benchmarked by a carefully matched group who received other specialized psychotherapeutic treatments (OPT). Structured diagnostic interviews were conducted to assess diagnostic status at baseline. Baseline, 18-month treatment outcome and 36-month treatment outcome (after the maintenance phase) on psychiatric symptoms (Brief Symptom Inventory) and personality functioning (118-item Severity Indices of Personality Problems) were available for 29 BPD patients assigned to MBT, and an initial set of 175 BPD patients assigned to OPT. Propensity scores were used to determine the best matches for the MBT patients within the larger OPT group, yielding 29 MBT and 29 OPT patients for direct comparison. Treatment outcome was analysed using multilevel modelling. Pre to post effect sizes were consistently (very) large for MBT, with a Cohen's d of -1.06 and -1.42 for 18 and 36 months, respectively, for the reduction in psychiatric symptoms, and ds ranging from 0.81 to 2.08 for improvement in domains of personality functioning. OPT also yielded improvement across domains but generally of moderate magnitude. In conclusion, the present matched control study, executed by an independent research institute outside the UK, demonstrated the effectiveness of day hospital MBT in a highly inclusive and severe group of BPD patients, beyond the benchmark provided by a mix of specialized psychotherapy programmes. Interpretation of the (large) between condition effects warrants cautionary caveats given the non-randomized design, as well as variation in treatment dosages.

Day hospital Mentalization-based treatment versus intensive outpatient Mentalization-based treatment for patients with severe borderline personality disorder: protocol of a multicentre randomized clinical trial.

BACKGROUND: Borderline personality disorder (BPD) is associated with a high socioeconomic burden. Although a number of evidence-based treatments for BPD are currently available, they are not widely disseminated; furthermore, there is a need for more research concerning their efficacy and cost-effectiveness. Such knowledge promises to lead to more efficient use of resources, which will facilitate the effective dissemination of these costly treatments. This study focuses on the efficacy and cost-effectiveness of Mentalization-Based Treatment (MBT), a manualized treatment for patients with BPD. Studies to date have either investigated MBT in a day hospitalization setting (MBT-DH) or MBT offered in an intensive outpatient setting (MBT-IOP). No trial has compared the efficacy and cost-effectiveness of these MBT programmes. As both interventions differ considerably in terms of intensity of treatment, and thus potentially in terms of efficacy and cost-effectiveness, there is a need for comparative trials. This study therefore sets out to investigate the efficacy and cost-effectiveness of MBT-DH versus MBT-IOP in patients with BPD. A secondary aim is to investigate the association between baseline measures and outcome, which might improve treatment selection and thus optimize efficacy and cost-effectiveness. METHODS/DESIGN: A multicentre randomized controlled trial comparing MBT-DH versus MBT-IOP in severe BPD patients. Patients are screened for BPD using the Structured Clinical Interview for DSM-IV Axis II Personality Disorders, and are assessed before randomization, at the start of treatment and 6, 12, 18, 24, 30 and 36 months after the start of treatment. Patients who refuse to participate will be offered care as usual in the same treatment centre. The primary outcome measure is symptom severity as measured by the Brief Symptom Inventory. Secondary outcome measures include parasuicidal behaviour, depression, substance use, social, interpersonal, and personality functioning, attachment, mentalizing capacities, and quality of life. All analyses will be conducted based on the intention-to-treat principle. Cost-effectiveness will be calculated based on costs per quality-adjusted life-year. DISCUSSION: This multisite randomized trial will provide data to refine criteria for treatment selection for severe BPD patients and promises to optimize (cost-)effectiveness of the treatment of BPD patients. TRIAL REGISTRATION: NTR2292 . Registered 16 April 2010.

Attachment in families with Huntington's disease. A paradigm in clinical genetics.

OBJECTIVE: Based on the premise that attachment experiences lead to a working model for social relationships throughout life, this study investigates if there is a difference between adult attachment representations in individuals who were brought up by a parent with Huntington's disease (HD), compared to a non-clinical population. Specific events in the parents' disease process, especially those leading to trauma and loss will receive attention. METHODS: Using the Adult Attachment Interview, adult attachment representations were investigated in 32 unaffected adults at 50% risk for HD who were raised by an affected parent. RESULTS: We found a lower percentage of secure attachment representations, a higher percentage of preoccupied representations, and a higher percentage of unresolved/disorganized representations in our sample, compared to a non-clinical population. A relatively late start of the parent's HD career was associated with a secure adult attachment representation. Death of the HD parent before the child's 18th birthday was associated with an unresolved/disorganized adult attachment representation. CONCLUSION: Growing up in a family where one of the parents has Huntington's disease appears to affect the offspring's adult attachment representation. PRACTICE IMPLICATIONS: This study can be of relevance for genetic counselling, as well as for counselling and intervention in childrearing matters.