The Patient Health Questionnaire-9 for detection of major depressive disorder in primary care: consequences of current thresholds in a crosssectional study

<p>Abstract</p> <p>Background</p> <p>There is a need for brief instruments to ascertain the diagnosis of major depressive disorder. In this study, we present the reliability, construct validity and accuracy of the PHQ-9 and PHQ-2 to detect major depressive disorder in primary care.</p> <p>Methods</p> <p>Cross-sectional analyses within a large prospective cohort study (PREDICT-NL). Data was collected in seven large general practices in the centre of the Netherlands. 1338 subjects were recruited in the general practice waiting room, irrespective of their presenting complaint. The diagnostic accuracy (the area under the ROC curve and sensitivities and specificities for various thresholds) was calculated against a diagnosis of major depressive disorder determined with the Composite International Diagnostic Interview (CIDI).</p> <p>Results</p> <p>The PHQ-9 showed a high degree of internal consistency (ICC = 0.88) and test-retest reliability (correlation = 0.94). With respect to construct validity, it showed a clear association with functional status measurements, sick days and number of consultations. The discriminative ability was good for the PHQ-9 (area under the ROC curve = 0.87, 95% CI: 0.84-0.90) and the PHQ-2 (ROC area = 0.83, 95% CI 0.80-0.87). Sensitivities at the recommended thresholds were 0.49 for the PHQ-9 at a score of 10 and 0.28 for a categorical algorithm. Adjustment of the threshold and the algorithm improved sensitivities to 0.82 and 0.84 respectively but the specificity decreased from 0.95 to 0.82 (threshold) and from 0.98 to 0.81 (algorithm). Similar results were found for the PHQ-2: the recommended threshold of 3 had a sensitivity of 0.42 and lowering the threshold resulted in an improved sensitivity of 0.81.</p> <p>Conclusion</p> <p>The PHQ-9 and the PHQ-2 are useful instruments to detect major depressive disorder in primary care, provided a high score is followed by an additional diagnostic work-up. However, often recommended thresholds for the PHQ-9 and the PHQ-2 resulted in many undetected major depressive disorders.</p

Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]

Evidence synthesis to inform model-based cost-effectiveness evaluations of diagnostic tests: a methodological systematic review of health technology assessments

Background: Evaluations of diagnostic tests are challenging because of the indirect nature of their impact on patient outcomes. Model-based health economic evaluations of tests allow different types of evidence from various sources to be incorporated and enable cost-effectiveness estimates to be made beyond the duration of available study data. To parameterize a health-economic model fully, all the ways a test impacts on patient health must be quantified, including but not limited to diagnostic test accuracy. Methods: We assessed all UK NIHR HTA reports published May 2009-July 2015. Reports were included if they evaluated a diagnostic test, included a model-based health economic evaluation and included a systematic review and meta-analysis of test accuracy. From each eligible report we extracted information on the following topics: 1) what evidence aside from test accuracy was searched for and synthesised, 2) which methods were used to synthesise test accuracy evidence and how did the results inform the economic model, 3) how/whether threshold effects were explored, 4) how the potential dependency between multiple tests in a pathway was accounted for, and 5) for evaluations of tests targeted at the primary care setting, how evidence from differing healthcare settings was incorporated. Results: The bivariate or HSROC model was implemented in 20/22 reports that met all inclusion criteria. Test accuracy data for health economic modelling was obtained from meta-analyses completely in four reports, partially in fourteen reports and not at all in four reports. Only 2/7 reports that used a quantitative test gave clear threshold recommendations. All 22 reports explored the effect of uncertainty in accuracy parameters but most of those that used multiple tests did not allow for dependence between test results. 7/22 tests were potentially suitable for primary care but the majority found limited evidence on test accuracy in primary care settings. Conclusions: The uptake of appropriate meta-analysis methods for synthesising evidence on diagnostic test accuracy in UK NIHR HTAs has improved in recent years. Future research should focus on other evidence requirements for cost-effectiveness assessment, threshold effects for quantitative tests and the impact of multiple diagnostic tests

Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]

A Mathematical Model Gives Insights into the Effects of Vitamin B-6 Deficiency on 1-Carbon and Glutathione Metabolism1–3

We experimented with a mathematical model for 1-carbon metabolism and glutathione (GSH) synthesis to investigate the effects of vitamin B-6 deficiency on the reaction velocities and metabolite concentrations in this metabolic network. The mathematical model enabled us to independently alter the activities of each of the 5 vitamin B-6–dependent enzymes and thus determine which inhibitions were responsible for the experimentally observed consequences of a vitamin B-6 deficiency. The effect of vitamin B-6 deficiency on serine and glycine concentrations in tissues and plasma was almost entirely due to its effects on the activity of glycine decarboxylase. The effect of vitamin B-6 restriction on GSH concentrations appeared to be indirect, arising from the fact that vitamin B-6 restriction increases oxidative stress, which, in turn, affects several enzymes in 1-carbon metabolism as well as the GSH transporter. Vitamin B-6 restriction causes an abnormally high and prolonged homocysteine response to a methionine load test. This effect appeared to be mediated solely by its effects on cystathionine β-synthase. Reduction of the enzymatic activity of serine hydroxymethyltransferase (SHMT) had negligible effects on most metabolite concentrations and reaction velocities. Reduction or total elimination of cytoplasmic SHMT had a surprisingly moderate effect on metabolite concentrations and reaction velocities. This corresponds to the experimental findings that a reduction in the enzymatic activity of SHMT has little effect on 1-carbon metabolism. Our simulations showed that the primary function of SHMT was to increase the rate by which the glycine-serine balance was reequilibrated after a perturbation