Assessing the Impact of EQ-5D Country-specific Value Sets on Cost-utility Outcomes.

PURPOSE: To assess the impact of EQ-5D country-specific value sets on cost-utility outcomes. METHODS: Data from 2 randomized controlled trials on low back pain (LBP) and depression were used. 3L value sets were identified from the EuroQol Web site. A nonparametric crosswalk was employed for each tariff to obtain the likely 5L values. Differences in quality-adjusted life years (QALYs) between countries were tested using paired t tests, with United Kingdom as reference. Cost-utility outcomes were estimated for both studies and both EQ-5D versions, including differences in QALYs and cost-effectiveness acceptability curves. RESULTS: For the 3L, QALYs ranged between 0.650 (Taiwan) and 0.892 (United States) in the LBP study and between 0.619 (Taiwan) and 0.879 (United States) in the depression study. In both studies, most country-specific QALY estimates differed statistically significantly from that of the United Kingdom. Incremental cost-effectiveness ratios ranged between &OV0556;2044/QALY (Taiwan) and &OV0556;5897/QALY (Zimbabwe) in the LBP study and between &OV0556;38,287/QALY (Singapore) and &OV0556;96,550/QALY (Japan) in the depression study. At the NICE threshold of &OV0556;23,300/QALY (≈£20,000/QALY), the intervention's probability of being cost-effective versus control ranged between 0.751 (Zimbabwe) and 0.952 (Taiwan) and between 0.230 (Canada) and 0.396 (Singapore) in the LBP study and depression study, respectively. Similar results were found for the 5L, with extensive differences in ICERs and moderate differences in the probability of cost-effectiveness. CONCLUSIONS: This study indicates that the use of different EQ-5D country-specific value sets impacts on cost-utility outcomes. Therefore, to account for the fact that health state preferences are affected by sociocultural differences, relevant country-specific value sets should be used.

A brief cognitive behavioural intervention is cost-effective for primary care patients with medically unexplained physical symptoms compared to usual care.

OBJECTIVE: To assess the cost-effectiveness of a brief cognitive behavioural intervention for patients with medically unexplained physical symptoms (MUPS) provided by a mental health nurse practitioner (MHNP) in primary care in comparison with usual care. METHODS: We performed an economic evaluation from a societal perspective alongside a cluster randomised controlled trial with 12 months follow-up. The primary outcome was quality-adjusted life-years (QALYs). Secondary outcomes were the RAND-36 physical component summary score (PCS), somatic symptom severity (Patient Health Questionnaire (PHQ-15), and anxiety and depression symptoms (Hospital Anxiety and Depression Scale (HADS)). Missing data were imputed using multiple imputation. We used non-parametric bootstrapping to estimate statistical uncertainty. The bootstrapped cost-effect pairs were used to estimate cost-effectiveness planes and cost-effectiveness acceptability curves. RESULTS: Mean total costs in the intervention group were significantly lower than in the usual care group (mean difference - 2300€, 95% CI -3257 to -134). The mean difference in QALYs was 0.01 (95% CI -0.01 to 0.04), in PCS 2.46 (95% CI 1.44 to 3.47), in PHQ-15 -0.26 (95% CI -0.81 to 0.28), and in HADS -0.07 (-0.81 to 0.67). At a willingness to pay of 0 € per additional unit of effect, the probability of the intervention being cost-effective was 0.93 for QALYs and 0.92 for PCS, PHQ-15 and HADS scores. CONCLUSION: Our intervention is cost-effective compared to usual care for patients with MUPS. Implementation of the intervention has the potential to result in a significant decline in costs. However, large scale implementation would require increased deployment of MHNPs.

Pain as a risk factor for suicidal ideation. A population-based longitudinal cohort study.

OBJECTIVE: To examine the longitudinal association between pain and suicidal ideation in the general adult population. METHOD: Data were used from two waves (baseline and three-year follow-up) of the Netherlands Mental Health Survey and Incidence Study-2. Persons without prior 12-month suicidal ideation at baseline were included in this study (N = 5242). Pain severity and interference due to pain in the past month were measured using the 36-item Short Form Health Survey. Suicidal ideation and DSM-IV mental disorders were assessed using the Composite International Diagnostic Interview. Logistic regression analyses were performed. RESULTS: Moderate to very severe pain (OR 3.39, p < .001) and moderate to very severe interference due to pain (OR 2.35, p .01) were associated with a higher risk for incident suicidal ideation at follow-up after adjustment for baseline sociodemographic variables and mental disorders. No interaction effects were found between pain severity or interference due to pain and mental disorders. CONCLUSION: Moderate to severe pain and interference due to pain are risk factors for suicidal ideation independently of concomitant mental disorders. We suggest taking assessment and management of suicidal ideation in patients with pain into account both in clinical treatment as well as in suicide prevention action plans.

Chest pain, depression and anxiety in coronary heart disease: Consequence or cause? A prospective clinical study in primary care.

OBJECTIVE: To examine if chest pain increases the risk of depression and anxiety, or, on the other hand, depression and anxiety increase the risk of chest pain onset in patients with coronary heart disease (CHD). DESIGN: Prospective clinical study. SETTING: 16 general practices in the Greater London Primary Care Research Network. PARTICIPANTS: 803 participants with a confirmed diagnosis of CHD at baseline on the Quality and Outcomes Framework (QOF) CHD registers. MAIN OUTCOME MEASURES: Rose Angina Questionnaire, HADS depression and anxiety subscales and PHQ-9 were assessed at seven time points, each 6 months apart. Multi-Level Analysis (MLA) and Structural Equation Modelling (SEM) were applied. RESULTS: Chest pain predicts both more severe anxiety and depression symptoms at all time points until 30 months after baseline. However, although anxiety predicted chest pain in the short term with a strong association, this association did not last after 18 months. Depression had only a small, negative association with chest pain. CONCLUSIONS: In persons with CHD, chest pain increases the risk of both anxiety and depression to a great extent. However, anxiety and depression have only limited effects on the risk for chest pain. This evidence suggests that anxiety and depression tend to be consequences rather than causes of cardiac chest pain. Intervention studies that support persons with CHD by providing this information should be devised and evaluated, thus deconstructing potentially catastrophic cognitions and strengthening emotional coping.

Effectiveness of a cognitive behavioural intervention for patients with undifferentiated somatoform disorder: Results from the CIPRUS cluster randomized controlled trial in primary care.

OBJECTIVE: To examine the effectiveness of a cognitive behavioural intervention delivered by mental health nurse practitioners (MHNPs) to patients with undifferentiated somatoform disorder (USD), compared to usual care. METHODS: We conducted a cluster randomized trial among primary care patients with USD comparing the intervention to usual care. The intervention consisted of six sessions with the MHNP. Primary outcome was physical functioning (RAND-36 physical component summary score). Secondary outcomes were the RAND-36 mental component summary score and the eight subscales; anxiety and depression (Hospital Anxiety and Depression Scale) and somatic symptom severity (Patient Health Questionnaire-15). Outcomes were assessed at baseline, 2, 4 and 12 months. We analysed data using linear mixed models by intention-to-treat, and investigated effect modifiers. RESULTS: Compared to usual care (n = 87), the intervention group (n = 111) showed an improvement in physical functioning (mean difference 2.24 [95% CI 0.51; 3.97]; p = .011), a decrease in limitations due to physical problems (mean difference 10.82 [95% CI 2.14; 19.49]; p. = 0.015) and in pain (mean difference 5.08 [95% CI 0.58; 9.57]; p = .027), over 12 months. However effect sizes were small and less clinically relevant than expected. We found no differences for anxiety, depression and somatic symptom severity. Effects were larger and clinically relevant for patients with more recent symptoms and fewer physical diseases. CONCLUSION: The cognitive behavioural intervention was effective in improving pain and physical functioning components of patients' health. It was particularly suitable for patients with symptoms that had been present for a limited number of years and with few comorbid physical diseases. TRIAL REGISTRATION: The trial is registered in the Dutch Trial Registry, www.trialregister.nl, under NTR4686.

Vitamin D supplementation for the prevention of depression and poor physical function in older persons: the D-Vitaal study, a randomized clinical trial.

BACKGROUND: Depressive symptoms and impaired physical functioning are prevalent among older adults. Supplementation with vitamin D might improve both conditions, particularly in persons with low vitamin D status. OBJECTIVE: The D-Vitaal study primarily aimed to investigate the effect of vitamin D supplementation on depressive symptoms, functional limitations, and physical performance in a high-risk older population with low vitamin D status. Secondary aims included examining the effect of vitamin D supplementation on anxiety symptoms, cognitive functioning, mobility, handgrip strength, and health-related quality of life. METHODS: This study was a randomized placebo-controlled trial with 155 participants aged 60-80 y who had clinically relevant depressive symptoms, ≥1 functional limitations, and serum 25-hydroxyvitamin D [25(OH)D] concentrations of 15-50/70 nmol/L (depending on season). Participants received 1200 IU/d vitamin D3 (n = 77) or placebo tablets (n = 78) for 12 mo. Serum 25(OH)D was measured at baseline and 6 mo; outcomes were assessed at baseline, 6 mo, and 12 mo. Linear mixed-models analyses were conducted to assess the effect of the intervention. RESULTS: The supplementation increased serum 25(OH)D concentrations in the intervention group to a mean ± SD of 85 ± 16 nmol/L compared with 43 ± 18 nmol/L in the placebo group after 6 mo (P < 0.001). No relevant differences between the treatment groups were observed regarding depressive symptoms, functional limitations, physical performance, or any of the secondary outcomes. CONCLUSIONS: Supplementation with 1200 IU/d vitamin D for 12 mo had no effect on depressive symptoms and physical functioning in older persons with relatively low vitamin D status, clinically relevant depressive symptoms, and poor physical functioning. This trial is registered with the Netherlands Trial Register (www.trialregister.nl) under NTR3845.

Diagnostic accuracy of depression questionnaires in adult patients with diabetes: A systematic review and meta-analysis.

BACKGROUND: Comorbid depression is common among patients with diabetes and has severe health consequences, but often remains unrecognized. Several questionnaires are used to screen for depression. A systematic review and meta-analysis regarding the diagnostic accuracy of depression questionnaires in adults with diabetes is unavailable. Our aim was to conduct a systematic review and meta-analysis to evaluate the diagnostic accuracy of depression questionnaires in adults with type 1 or type 2 diabetes. METHODS: PubMed, Embase and PsycINFO were searched from inception to 28 February 2018. Studies were included when the diagnostic accuracy of depression questionnaires was assessed in a diabetes population and the reference standard was a clinical interview. Data extraction was performed by one reviewer and checked by another. Two reviewers independently conducted the quality assessment (QUADAS-2). Diagnostic accuracy was pooled in bivariate random effects models. The main outcome was diagnostic accuracy, expressed as sensitivity and specificity, of depression questionnaires in an adult diabetes population. This study is reported according to PRISMA-DTA and is registered with PROSPERO (CRD42018092950). RESULTS: A total 6,097 peer-reviewed articles were screened. Twenty-one studies (N = 5,703 patients) met the inclusion criteria for the systematic review. Twelve different depression questionnaires were identified, of which the CES-D (n = 6 studies) and PHQ-9 (n = 7 studies) were the most frequently evaluated. Risk of bias was unclear for multiple domains in the majority of studies. In the meta-analyses, five (N = 1,228) studies of the CES-D (≥16), five (N = 1,642) of the PHQ-9 (≥10) and four (N = 822) of the algorithm of the PHQ-9 were included in the pooled analysis. The CES-D (≥16) had a pooled sensitivity of 85.0% (95%CI, 71.3-92.8%) and a specificity of 71.6% (95%CI, 62.5-79.2%); the PHQ-9 (≥10) had a sensitivity of 81.5% (95%CI, 57.1-93.5%) and a specificity of 79.7% (95%CI, 62.1-90.4%). The algorithm for the PHQ-9 had a sensitivity of 60.9% (95%CI, 52.3-90.8%) and a specificity of 64.0% (95%CI, 53.0-93.9%). CONCLUSIONS: This review indicates that the CES-D had the highest sensitivity, whereas the PHQ-9 had the highest specificity, although confidence intervals were wide and overlapping. The algorithm for the PHQ-9 had the lowest sensitivity and specificity. Given the variance in results and suboptimal reporting of studies, further high quality studies are needed to confirm the diagnostic accuracy of these depression questionnaires in patients with diabetes.

Patients' and practice nurses' perceptions of depression in patients with type 2 diabetes and/or coronary heart disease screened for subthreshold depression.

BACKGROUND: Comorbid depression is common in patients with type 2 diabetes (DM2) and/or coronary heart disease (CHD) and is associated with poor quality of life and adverse health outcomes. However, little is known about patients' and practice nurses' (PNs) perceptions of depression. Tailoring care to these perceptions may affect depression detection and patient engagement with treatment and prevention programs. This study aimed to explore patients' and PNs' perceptions of depression in patients with DM2/CHD screened for subthreshold depression. METHODS: A qualitative study was conducted as part of a Dutch stepped-care prevention project. Using a purposive sampling strategy, data were collected through semi-structured interviews with 15 patients and 9 PNs. After consent, all interviews were recorded, transcribed verbatim and analyzed independently by two researchers with Atlas.ti.5.7.1 software. The patient and PN datasets were inspected for commonalities using a constant comparative method, from which a final thematic framework was generated. RESULTS: Main themes were: illness perception, need for care and causes of depression. Patients generally considered themselves at least mildly depressed, but perceived severity levels were not always congruent with Patient Health Questionnaire 9 scores at inclusion. Initially recognizing or naming their mental state as a (subthreshold) depression was difficult for some. Having trouble sleeping was frequently experienced as the most burdensome symptom. Most experienced a need for care; psycho-educational advice and talking therapy were preferred. Perceived symptom severity corresponded with perceived need for care, but did not necessarily match help-seeking behaviour. Main named barriers to help-seeking were experienced stigma and lack of awareness of depression and mental health care possibilities. PNs frequently perceived patients as not depressed and with minimal need for specific care except for attention. Participants pointed to a mix of causes of depression, most related to negative life events and circumstances and perceived indirect links with DM2/CHD. CONCLUSION: Data of the interviewed patients and PNs suggest that they have different perceptions about (subthreshold) depressive illness and the need for care, although views on its causes seem to overlap more.

A supported self-help for recurrent depression in primary care; An economic evaluation alongside a multi-center randomised controlled trial.

BACKGROUND: Major depression is a prevalent mental disorder with a high risk of relapse or recurrence. Only few studies have focused on the cost-effectiveness of interventions aimed at the prevention of relapse or recurrence of depression in primary care. AIM: To evaluate the cost-effectiveness of a supported Self-help Preventive Cognitive Therapy (S-PCT) added to treatment-as-usual (TAU) compared with TAU alone for patients with a history of depression, currently in remission. METHODS: An economic evaluation alongside a multi-center randomised controlled trial was performed (n = 248) over a 12-month follow-up. Outcomes included relapse or recurrence of depression and quality-adjusted-life-years (QALYs) based on the EuroQol-5D. Analyses were performed from both a societal and healthcare perspective. Missing data were imputed using multiple imputations. Uncertainty was estimated using bootstrapping and presented using the cost-effectiveness plane and the Cost-Effectiveness Acceptability Curve (CEAC). Cost estimates were adjusted for baseline costs. RESULTS: S-PCT statistically significantly decreased relapse or recurrence by 15% (95%CI 3;28) compared to TAU. Mean total societal costs were €2,114 higher (95%CI -112;4261). From a societal perspective, the ICER for relapse or recurrence was 13,515. At a Willingness To Pay (WTP) of 22,000 €/recurrence prevented, the probability that S-PCT is cost-effective, in comparison with TAU, is 80%. The ICER for QALYs was 63,051. The CEA curve indicated that at a WTP of 30,000 €/QALY gained, the probability that S-PCT is cost-effective compared to TAU is 21%. CONCLUSIONS: Though ultimately depending on the WTP of decision makers, we expect that for both relapse or recurrence and QALYs, S-PCT cannot be considered cost-effective compared to TAU.

Predictors of Persistent Medically Unexplained Physical Symptoms: Findings From a General Population Study.

Objective: To explore the persistency of Medically Unexplained Symptoms (MUS) and its prognostic factors in the general adult population. Knowledge of prognostic factors of MUS may indicate possible avenues for intervention development. Methods: Data were derived from the Netherlands Mental Health Survey and Incidence Study-2 (NEMESIS-2), a nationally representative face-to-face cohort study among the Dutch general population aged 18-64 years. We selected subjects with MUS at baseline and who participated at follow-up (N = 324) and reassessed those subjects for having MUS at 3 year follow-up. Logistic regression analyses were used to determine risk factors for persistency of MUS. Results: 36.4% of the subjects had persistent MUS at follow-up. In logistic regression analyses adjusted for sex and age, persistency of MUS was predicted by the number of comorbid chronic medical disorder(s), lower education, female sex, not having a paid job, parental psychopathology as well as lower functioning. In the logistic regression analysis in which all significant variables adjusted for sex and age were entered simultaneously, three variables predicted persistent MUS: parental psychopathology, the number of comorbid chronic medical disorder(s) and physical functioning, with odds ratios of 2.01 (1.20-3.38), 1.19 (1.01-1.40), and 0.99 (0.97-1.00), respectively. Conclusion: In the adult general population, MUS were persistent in over one third of the subjects with MUS at baseline. Persistency was significantly predicted by parental psychopathology, number of comorbid chronic medical disorders, and physical functioning. These findings warrant further research into early intervention and treatment options for persons with an increased risk of persistent MUS.

Two-year effectiveness of a stepped-care depression prevention intervention and predictors of incident depression in primary care patients with diabetes type 2 and/or coronary heart disease and subthreshold depression: data from the Step-Dep cluster randomised controlled trial.

INTRODUCTION: Major depressive disorders (MDD), diabetes mellitus type 2 (DM2) and coronary heart disease (CHD) are leading contributors to the global burden of disease and often co-occur. OBJECTIVES: To evaluate the 2-year effectiveness of a stepped-care intervention to prevent MDD compared with usual care and to develop a prediction model for incident depression in patients with DM2 and/or CHD with subthreshold depression. METHODS: Data of 236 Dutch primary care patients with DM2/CHD with subthreshold depression (Patient Health Questionnaire 9 (PHQ-9) score ≥6, no current MDD according to the Mini International Neuropsychiatric Interview (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria)) who participated in the Step-Dep trial were used. A PHQ-9 score of ≥10 at minimally one measurement during follow-up (at 3, 6, 9, 12 and 24 months) was used to determine the cumulative incidence of MDD. Potential demographic and psychological predictors were measured at baseline via web-based self-reported questionnaires and evaluated using a multivariable logistic regression model. Model performance was assessed with the Hosmer-Lemeshow test, Nagelkerke's R2 explained variance and area under the receiver operating characteristic curve (AUC). Bootstrapping techniques were used to internally validate our model. RESULTS: 192 patients (81%) were available at 2-year follow-up. The cumulative incidence of MDD was 97/192 (51%). There was no statistically significant overall treatment effect over 24 months of the intervention (OR 1.37; 95% CI 0.52 to 3.55). Baseline levels of anxiety, depression, the presence of >3 chronic diseases and stressful life events predicted the incidence of MDD (AUC 0.80, IQR 0.79-0.80; Nagelkerke's R2 0.34, IQR 0.33-0.36). CONCLUSION: A model with 4 factors predicted depression incidence during 2-year follow-up in patients with DM2/CHD accurately, based on the AUC. The Step-Dep intervention did not influence the incidence of MDD. Future depression prevention programmes should target patients with these 4 predictors present, and aim to reduce both anxiety and depressive symptoms. TRIAL REGISTRATION NUMBER: NTR3715.

Management of patients with persistent medically unexplained symptoms: a descriptive study.

BACKGROUND: In 2013 the Dutch guideline for management of medically unexplained symptoms (MUS) was published. The aim of this study is to assess medical care for patients with persistent MUS as recorded in their electronic medical records, to investigate if this is in line with the national guideline for persistent MUS and whether there are changes in care over time. METHODS: We conducted an observational study of adult primary care patients with MUS. Routinely recorded health care data were extracted from electronic medical records of patients participating in an ongoing randomised controlled trial in 30 general practices in the Netherlands. Data on general practitioners' (GPs') management strategies during MUS consultations were collected in a 5-year period for each patient prior. Management strategies were categorised according to the options offered in the Dutch guideline. Changes in management over time were analysed. RESULTS: Data were collected from 1035 MUS consultations (77 patients). Beside history-taking, the most frequently used diagnostic strategies were physical examination (24.5%) and additional investigations by the GP (11.1%). Frequently used therapeutic strategies were prescribing medication (24.6%) and providing explanations (11.2%). As MUS symptoms persisted, GPs adjusted medication, discussed progress and scheduled follow-up appointments more frequently. The least frequently used strategies were exploration of all complaint dimensions (i.e. somatic, cognitive, emotional, behavioural and social) (3.5%) and referral to a psychologist (0.5%) or psychiatrist (0.1%). CONCLUSIONS: Management of Dutch GPs is partly in line with the Dutch guideline. Medication was possibly prescribed more frequently than recommended, whereas exploration of all complaint dimensions, shared problem definition and referral to mental health care were used less.

Vitamin D Status and Depressive Symptoms in Older Adults: A Role for Physical Functioning?

OBJECTIVES: Depressive symptoms and low vitamin D status are common in older persons and may be associated, but findings are inconsistent. This study investigated whether 25-hydroxyvitamin D (25(OH)D) concentrations are associated with depressive symptoms in older adults, both cross-sectionally and longitudinally. We also examined whether physical functioning could explain this relationship, to gain a better understanding of the underlying mechanisms. METHODS: Data from two independent prospective cohorts of the Longitudinal Aging Study Amsterdam were used: an older cohort (≥65 years, n = 1282, assessed from 1995-2002) and a younger-old cohort (55-65 years, n = 737, assessed from 2002-2009). MEASUREMENTS: Depressive symptoms were measured at baseline and after 3 and 6 years with the Center of Epidemiological Studies Depression Scale. Cross-sectional and longitudinal linear regression techniques were used to examine the relationship between 25(OH)D and depressive symptoms. The mediating role of physical functioning was examined in the longitudinal models. RESULTS: Cross-sectionally, associations were not significant after adjustment for confounders. Longitudinally, women in the older cohort with baseline 25(OH)D concentrations up to 75 nmol/L experienced 175 to 24% more depressive symptoms in the following 6 years, compared with women with 25(OH)D concentrations >75 nmol/L. Reduced physical performance partially mediated this relationship. In men and in the younger-old cohort, no significant associations were observed. CONCLUSIONS: Older women showed an inverse relationship between 25(OH)D and depressive symptoms over time, which may partially be explained by declining physical functioning. Replication of these findings by future studies is needed.

Comparative Effect of Collaborative Care, Pain Medication, and Duloxetine in the Treatment of Major Depressive Disorder and Comorbid (Sub)Chronic Pain: Results of an Exploratory Randomized, Placebo-Controlled, Multicenter Trial (CC:PAINDIP).

OBJECTIVE: Evidence exists for the efficacy of collaborative care (CC) for major depressive disorder (MDD), for the efficacy of the consequent use of pain medication against pain, and for the efficacy of duloxetine against both MDD and neuropathic pain. Their relative effectiveness in comorbid MDD and pain has never been established so far. This study explores the effectiveness of CC with pain medication and duloxetine, and CC with pain medication and placebo, compared with duloxetine alone, on depressive and pain symptoms. This study was prematurely terminated because of massive reorganizations and reimbursement changes in mental health care in the Netherlands during the study period and is therefore of exploratory nature. METHODS: Three-armed, randomized, multicenter, placebo-controlled trial at three specialized mental health outpatient clinics with patients who screened positive for MDD. Interventions lasted 12 weeks. Pain medication was administered according to an algorithm that avoids opiate prescription as much as possible, where paracetamol, COX inhibitors, and pregabalin are offered as steps before opiates are considered. Patients who did not show up for three or more sessions were registered as non-compliant. Explorative, intention-to-treat and per protocol, multilevel regression analyses were performed. The trial is listed in the trial registration (http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1089; NTR number: NTR1089). RESULTS: Sixty patients completed the study. Patients in all treatment groups reported significantly less depressive and pain symptoms after 12 weeks. CC with placebo condition showed the fastest decrease in depressive symptoms compared with the duloxetine alone group (b = -0.78; p = 0.01). Non-compliant patients (n = 31) did not improve over the 12-week period, in contrast to compliant patients (n = 29). Pain outcomes did not differ between the three groups. CONCLUSION: In MDD and pain, patient's compliance and placebo effects are more important in attaining effect than choice of one of the treatments. Active pain management with COX inhibitors and pregabalin as alternatives to tramadol or other opiates might provide an attractive alternative to the current WHO pain ladder as it avoids opiate prescription as much as possible. The generalizability is limited due to the small sample size. Larger studies are needed.

Measurement properties of depression questionnaires in patients with diabetes: a systematic review.

PURPOSE: To conduct a systematic review on measurement properties of questionnaires measuring depressive symptoms in adult patients with type 1 or type 2 diabetes. METHODS: A systematic review of the literature in MEDLINE, EMbase and PsycINFO was performed. Full text, original articles, published in any language up to October 2016 were included. Eligibility for inclusion was independently assessed by three reviewers who worked in pairs. Methodological quality of the studies was evaluated by two independent reviewers using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist. Quality of the questionnaires was rated per measurement property, based on the number and quality of the included studies and the reported results. RESULTS: Of 6286 unique hits, 21 studies met our criteria evaluating nine different questionnaires in multiple settings and languages. The methodological quality of the included studies was variable for the different measurement properties: 9/15 studies scored 'good' or 'excellent' on internal consistency, 2/5 on reliability, 0/1 on content validity, 10/10 on structural validity, 8/11 on hypothesis testing, 1/5 on cross-cultural validity, and 4/9 on criterion validity. For the CES-D, there was strong evidence for good internal consistency, structural validity, and construct validity; moderate evidence for good criterion validity; and limited evidence for good cross-cultural validity. The PHQ-9 and WHO-5 also performed well on several measurement properties. However, the evidence for structural validity of the PHQ-9 was inconclusive. The WHO-5 was less extensively researched and originally not developed to measure depression. CONCLUSION: Currently, the CES-D is best supported for measuring depressive symptoms in diabetes patients.

Illness burden and physical outcomes associated with collaborative care in patients with comorbid depressive disorder in chronic medical conditions: A systematic review and meta-analysis.

OBJECTIVE: Collaborative care (CC) improves depressive symptoms in people with comorbid depressive disorder in chronic medical conditions, but its effect on physical symptoms has not yet systematically been reviewed. This study aims to do so. METHODS: Systematic review and meta-analysis was conducted using PubMed, the Cochrane Library, and the European and US Clinical Trial Registers. Eligible studies included randomized controlled trials (RCTs) of CC compared to care as usual (CAU), in primary care and general hospital setting, reporting on physical and depressive symptoms as outcomes. Overall treatment effects were estimated for illness burden, physical outcomes and depression, respectively. RESULTS: Twenty RCTs were included, with N=4774 patients. The overall effect size of CC versus CAU for illness burden was OR 1.64 (95%CI 1.47;1.83), d=0.27 (95%CI 0.21;0.33). Best physical outcomes in CC were found for hypertension with comorbiddepression. Overall, depression outcomes were better for CC than for CAU. Moderator analyses did not yield statistically significant differences. CONCLUSIONS: CC is more effective than CAU in terms of illness burden, physical outcomes and depression, in patients with comorbid depression in chronic medical conditions. More research covering multiple medical conditions is needed. PROTOCOL REGISTRATION NUMBER: The protocol for this systematic review and meta-analysis has been registered at the International Prospective Register of Systematic Reviews (PROSPERO) on February 19th 2016: http://www.crd.york.ac.uk/PROSPERO/DisplayPDF.php?ID=CRD42016035553.

Pain as a risk factor for common mental disorders. Results from the Netherlands Mental Health Survey and Incidence Study-2: a longitudinal, population-based study.

Pain might be an important risk factor for common mental disorders. Insight into the longitudinal association between pain and common mental disorders in the general adult population could help improve prevention and treatment strategies. Data were used from the first 2 waves of the Netherlands Mental Health Survey and Incidence Study-2, a psychiatric epidemiological cohort study among the Dutch general population aged 18 to 64 years at baseline (N = 5303). Persons without a mental disorder 12 months before baseline were selected as the at-risk group (n = 4974 for any mood disorder; n = 4979 for any anxiety disorder; and n = 5073 for any substance use disorder). Pain severity and interference due to pain in the past month were measured at baseline using the Short Form Health Survey. DSM-IV mental disorders were assessed at both waves using the Composite International Diagnostic Interview version 3.0. Moderate to very severe pain was associated with a higher risk of mood (odds ratio [OR] = 2.10, 95% confidence interval [CI] = 1.33-3.29) or anxiety disorders (OR = 2.12, 95% CI = 1.27-3.55). Moderate to very severe interference due to pain was also associated with a higher risk of mood (OR = 2.14, 95% CI = 1.30-3.54) or anxiety disorders (OR = 1.92, 95% CI = 1.05-3.52). Pain was not significantly associated with substance use disorders. No interaction effects were found between pain severity or interference due to pain and a previous history of mental disorders. Moderate to severe pain and interference due to pain are strong risk factors for first-incident or recurrent mood and anxiety disorders, independent of other mental disorders. Pain management programs could therefore possibly also serve as a preventative program for mental disorders.

Systematic review of measurement properties of questionnaires measuring somatization in primary care patients.

OBJECTIVE: The aim of this review is to critically appraise the evidence on measurement properties of self-report questionnaires measuring somatization in adult primary care patients and to provide recommendations about which questionnaires are most useful for this purpose. METHODS: We assessed the methodological quality of included studies using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist. To draw overall conclusions about the quality of the questionnaires, we conducted an evidence synthesis using predefined criteria for judging the measurement properties. RESULTS: We found 24 articles on 9 questionnaires. Studies on the Patient Health Questionnaire-15 (PHQ-15) and the Four-Dimensional Symptom Questionnaire (4DSQ) somatization subscale prevailed and covered the broadest range of measurement properties. These questionnaires had the best internal consistency, test-retest reliability, structural validity, and construct validity. The PHQ-15 also had good criterion validity, whereas the 4DSQ somatization subscale was validated in several languages. The Bodily Distress Syndrome (BDS) checklist had good internal consistency and structural validity. Some evidence was found for good construct validity and criterion validity of the Physical Symptom Checklist (PSC-51) and good construct validity of the Symptom Check-List (SCL-90-R) somatization subscale. However, these three questionnaires were only studied in a small number of primary care studies. CONCLUSION: Based on our findings, we recommend the use of either the PHQ-15 or 4DSQ somatization subscale for somatization in primary care. Other questionnaires, such as the BDS checklist, PSC-51 and the SCL-90-R somatization subscale show promising results but have not been studied extensively in primary care.

Effectiveness of a stepped-care intervention to prevent major depression in patients with type 2 diabetes mellitus and/or coronary heart disease and subthreshold depression: A pragmatic cluster randomized controlled trial.

PURPOSE: Given the public health significance of poorly treatable co-morbid major depressive disorders (MDD) among patients with type 2 diabetes mellitus (DM2) and coronary heart disease (CHD), we need to investigate whether strategies to prevent the development of major depression could reduce its burden of disease. We therefore evaluated the effectiveness of a stepped-care program for subthreshold depression in comparison with usual care in patients with DM2 and/or CHD. METHODS: A cluster randomized controlled trial, with 27 primary care centers serving as clusters. A total of 236 DM2 and/or CHD patients with subthreshold depression (nine item Patient Health Questionnaire (PHQ-9) score ≥ 6, no current MDD according to DSM-IV criteria) were allocated to the intervention group (N = 96) or usual care group (n = 140). The stepped-care program was delivered by trained practice nurses during one year and consisted of four sequential treatment steps: watchful waiting, guided self-help, problem solving treatment and referral to the general practitioner. The primary outcome was the 12-month cumulative incidence of MDD as measured with the Mini International Neuropsychiatric Interview (MINI). Secondary outcomes included severity of depression (measured by PHQ-9) at 3, 6, 9 and 12 months. RESULTS: Of 236 patients (mean age, 67,5 (SD 10) years; 54.7% men), 210 (89%) completed the MINI at 12 months. The cumulative incidence of MDD was 9 of 89 (10.1%) participants in the intervention group and 12 of 121 (9.9%) participants in the usual care group. We found no statistically significant overall effect of the intervention (OR = 1.21; 95% confidence interval (0.12 to 12.41)) and there were no statistically significant differences in the course or severity of depressive symptoms between the two groups. CONCLUSIONS: This study suggest that Step-Dep was not more effective in preventing MDD than usual care in a primary care population with DM2 and/or CHD and subthreshold depression.

Longitudinal associations of multiple physical symptoms with recurrence of depressive and anxiety disorders.

OBJECTIVE: To examine longitudinal associations of multiple physical symptoms with recurrence of depressive and anxiety disorders. METHODS: Follow-up data of 584 participants with remitted depressive or anxiety disorders were used from the Netherlands Study of Depressive and Anxiety disorders. Multiple physical symptoms were measured at baseline (T1) and two-year follow-up (T2) by the Four-Dimensional Symptom Questionnaire (4DSQ) somatization subscale. Recurrence of depressive and anxiety disorders was assessed at two-year (T2) and four-year (T4) follow-up with the Composite International Diagnostic Interview. Logistic Generalized Estimating Equations were used to examine associations of multiple physical symptoms with recurrence of depressive and anxiety disorders. Depressive (IDS-SR) and anxiety symptoms (BAI), and other relevant covariates were taken into account. RESULTS: Multiple physical symptoms were significantly associated with recurrence of depression (OR=1.04, 95%CI=1.00-1.08), anxiety (OR=1.07, 95%CI=1.03-1.12), and depressive or anxiety disorders (OR=1.06, 95%CI=1.02-1.10), on average over time. Odds ratios did not change substantially when the IDS-SR mood-cognition and BAI subjective scale were included as covariates. CONCLUSION: The presence of multiple physical symptoms was positively related to recurrence of depressive and anxiety disorders, independent of depressive and anxiety symptoms. Knowledge of risk factors for recurrence of depressive and anxiety disorders, such as the presence of multiple physical symptoms, could provide possibilities for better targeting interventions to prevent recurrence.