Optimal cut-off score for diagnosing depression with the Patient Health Questionnaire (PHQ-9): a meta-analysis

Background:

The brief Patient Health Questionnaire (PHQ-9) is commonly used to screen for depression with 10 often recommended as the cut-off score. We summarized the psychometric properties of the PHQ-9 across a range of studies and cut-off scores to select the optimal cut-off for detecting depression.

Methods:

We searched Embase, MEDLINE and PsycINFO from 1999 to August 2010 for studies that reported the diagnostic accuracy of PHQ-9 to diagnose major depressive disorders. We calculated summary sensitivity, specificity, likelihood ratios and diagnostic odds ratios for detecting major depressive disorder at different cut-off scores and in different settings. We used random-effects bivariate meta-analysis at cutoff points between 7 and 15 to produce summary receiver operating characteristic curves.

Results:

We identified 18 validation studies (n = 7180) conducted in various clinical settings. Eleven studies provided details about the diagnostic properties of the questionnaire at more than one cut-off score (including 10), four studies reported a cut-off score of 10, and three studies reported cut-off scores other than 10. The pooled specificity results ranged from 0.73 (95% confidence interval [CI] 0.63–0.82) for a cut-off score of 7 to 0.96 (95% CI 0.94–0.97) for a cut-off score of 15. There was major variability in sensitivity for cut-off scores between 7 and 15. There were no substantial differences in the pooled sensitivity and specificity for a range of cut-off scores (8–11).

Interpretation:

The PHQ-9 was found to have acceptable diagnostic properties for detecting major depressive disorder for cut-off scores between 8 and 11. Authors of future validation studies should consistently report the outcomes for different cut-off scores.Depressive disorders are still under-recognized in medical settings despite major associated disability and costs. The use of short screening questionnaires may improve the recognition of depression in different medical settings.¹ The depression module of the Patient Health Questionnaire (PHQ-9) has become increasingly popular in research and practice over the past decade.² In its initial validation study, a score of 10 or higher had a sensitivity of 88% and a specificity of 88% for detecting major depressive disorders. Thus, a score of 10 has been recommended as the cut-off score for diagnosing this condition.³In a recent review of the PHQ-9, Kroenke and colleagues argued against inflexible adherence to a single cut-off score.² A recent analysis of the management of depression in general practice in the United Kingdom showed that the accuracy of predicting major depressive disorder could be improved by using 12 as the cut-off score.⁴Given the widespread use of PHQ-9 in screening for depression and that certain cut-off scores are being recommended as part of national strategies to screen for depression (based on initial validation studies, which might not be generalizable),^4,5 we attempted to determine whether the cut-off of 10 is optimum for screening for depression. This question could not be answered by two previous systematic reviews^6,7 because of the small number of primary studies available at the time. We also aimed to provide greater clarity about the proper use of PHQ-9 given the many settings in which it is used.     

The hydrolysis of phosphatidylinositol monolayers at an air/water interface by the calcium-ion-dependent phosphatidylinositol phosphodiesterase of pig brain.

1. The activity of Ca2+-dependent phosphatidylinositol phosphodiesterase (EC 3.1.4.10) of pig brain against [32P]phosphatidylinositol monolayers at an air/water interface has been measured. As the monolayer pressure was increased a sharp cut-off of enzymic hydrolysis occurred at 33 X 10(-3) N/m. 2. The addition of either phosphatidic acid, phosphatidylglycerol or oleyl alcohol increased the film pressure at which cut off occurred, as well as increasing the rate of hydrolysis at lower pressures. 3. The rate of hydrolysis, but not the cut-off pressure, was markedly increased by oleic acid and slightly increased by phosphatidylethanolamine. 4. Phosphatidylcholine, palmitoylcholine and octadecylamine decreased the cut-off pressure, as well as the enzymic activity below this pressure. 5. Stearic acid and stearyl alcohol had no effect on either the cut-off pressure or the activity. 6. All activators decreased the length of the lag phase before enzyme activity began, and phosphatidylcholine increased it. 7. These results are compared with the stimulatory and inhibitory effects of various amphiphiles observed previously with phosphatidylinositol dispersions [Irvine, Hemington & Dawson (1979) Eur. J. Biochem. 99, 525-530], and their possible relevance to the control of the phosphatidylinositol phosphodiesterase in vivo are discussed.     

Emergence of power laws from partitional dynamics

This work explores the possibility of producing some specific power laws (with exponential cut-off) out from a partitional dynamics. The data obtained from the partitions of integers in the interval 1-60 have been used to find the coefficients of a power law and its exponential cut-off, and also of a single hyperbolic form after renormalization. There is also the speculation that this type of power law, so easily derived from arithmetic minimalist operations, may underlie the communication exchanges of living cells and the structural games of self-constructing agents endowed with relative structural freedom.     

Assessment of variation in bacterial composition among microhabitats in a mangrove environment using DGGE fingerprints and barcoded pyrosequencing

Here, we use DGGE fingerprinting and barcoded pyrosequencing data, at six cut-off levels (85-100%), of all bacteria, Alphaproteobacteria and Betaproteobacteria to assess composition in the rhizosphere of nursery plants and nursery-raised transplants, native plants and bulk sediment in a mangrove habitat. When comparing compositional data based on DGGE fingerprinting and barcoded pyrosequencing at different cut-off levels, all revealed highly significant differences in composition among microhabitats. Procrustes superimposition revealed that ordination results using cut-off levels from 85-100% and DGGE fingerprint data were highly congruent with the standard 97% cut-off level. The various approaches revealed a primary gradient in composition from nursery to mangrove samples. The affinity between the nursery and transplants was greatest when using Betaproteobacteria followed by Alphaproteobacteria data. There was a distinct secondary gradient in composition from transplants to bulk sediment with native plants intermediate, which was most prevalent using all bacteria at intermediate cut-off levels (92-97%). Our results show that PCR-DGGE provides a robust and cost effective exploratory approach and is effective in distinguishing among a priori defined groups.     

Screening for hemochromatosis in routine medical care: an evaluation of mean corpuscular volume and mean corpuscular hemoglobin

Our aim was to evaluate the potential utility of mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) to detect hemochromatosis. We computed the accuracy of MCV and MCH cut-off points > or = upper reference limits using data from 94 probands and 132 white controls. Our reference ranges are MCV 80.0-97.0 fL and MCH 26.0-32.0 pg. Sensitivity of MCV was 8.6-48.3% for men and 2.8-44.4% for women (cut-off points > or = 105.0 - > or = 97.0 fL, respectively). Sensitivity of MCH was 33.9-70.7% for men and 19.6-50.0% for women (cut-off points > or = 34.0 - > or = 32.0 pg, respectively). Using MCV and a hemochromatosis frequency typical of many western Caucasian populations (0.005), positive predictive values (PV+) were 2.1-100.0% in men and 4.2-100.0% in women. Using MCH, PV+ were 1.7-8.2% in men and 1.8-6.8% in women. We also calculated PV+ using the hemochromatosis frequency 0.015, which could occur in persons receiving medical care. Using MCV cut-off points > or = 101.0 fL, PV+ were 8.9-100.0% in men and 100.0% in women with maximum sensitivities of 24.1% and 25.0%, respectively. Using MCH testing, PV+ was 21.5% in men (cut-off point > or = 34.0 pg) and 18.2% in women (cut-off point > or = 33.0 pg) with sensitivities of 33.9% and 37.0%, respectively. Using MCV or MCH, sensitivity and PV+ for the HFE genotype C282Y/C282Y were generally greater than for "nonclassical" HFE genotypes. All negative predictive values in our study were > or = 98.5%. We conclude that supranormal values of MCV or MCH could be used to detect hemochromatosis in white persons of western European descent who are receiving routine medical care. Comparisons of MCV, MCH, and transferrin saturation testing and other implications of MCV and MCH testing for hemochromatosis in medical care are discussed.     

Receiver operating characteristic curve analysis of BMI in assessing obesity among adult Bengalee males in India

The present study attempted to understand the appropriateness of different body mass index (BMI) cut-off points in assessing obesity. Four hundred thirty adult Bengalee males with mean age 36.48 +/- 12.23 years (mean +/- SD) from West Bengal, India were studied. Height, weight and percent body fat were measured and BMI was derived following standard equation. Receiver operating characteristic (ROC) curve analysis demonstrated low sensitivity and high specificity of international (> or = 30 kg/m2) and proposed (> or = 25 kg/m2) BMI cut-off points in identifying individuals with obesity. Furthermore, these international and proposed BMI cut-off points also found to be in substantial misclassification to assess obesity as much as 32.09% and 17.44% respectively. However, based on ROC curve analysis, a BMI cut-off point of > or = 24 kg/m2 revealed optimal sensitivity (83.66%) and specificity (90.61%) and as well as less misclassification (11.86%) in assessing obesity among the adult Bengalee males. The present study accentuated that the international and proposed BMI cut-off points so far might not be appropriate in assessing obesity and on the other hand, lower BMI cut-off point (> or = 24 kg/m2) has relatively high sensitivity and specificity in assessing obesity as well. Therefore, the present study envisages the requirement of further lowering down of BMI cut-off point in assessing excess body fat in adult Bengalee males.     

The filtered Fourier difference spectrum predicts psychophysical letter discrimination in the peripheral retina

We wished to devise a measure of dissimilarity (D) which could predict psychophysical discrimination performance for Snellen letter pairs in peripheral vision. Threshold size for discriminating 33 pairs of Snellen letters was measured at 30 degrees eccentricity in the nasal retina for two subjects. D was computed for each pair by performing an overlap subtraction in the spatial domain, followed by a Fast Fourier Transform on this difference image, and dividing the total power in the resultant 'difference spectrum' by the sum of the powers of the individual letter spectra. A plot of D vs. psychophysical threshold letter size gave a mean correlation of R = -0.81. When D was calculated for letters that were low-pass filtered at different cut-off frequencies, the correlation with psychophysical performance was greatest when cut-off was between 1.25-1.9 cycles/letter (R = -0.85). Conversely, when the difference spectrum was high-pass filtered at different cut-off frequencies, the correlation decreased continuously as the cut-off increased. These results imply that the band of frequencies between zero and 1.25 cycles/letter are most important for letter discrimination in peripheral vision.     

CEA和CYFRA21-1在原发性肺癌诊断中的应用价值分析

目的:评价血清癌胚抗原(carcinoembryonic antigen,CEA)和细胞角蛋白19的片段(CYFRA21-1)水平对原发性肺癌的诊断价值。方法:回顾性分析2012年5月~2013年5月我科收治的329例肺癌患者和192例肺部良性病变患者的临床资料。结果:肺癌患者血清CEA或CYFRA21-1水平随着肺癌的分期呈现逐渐上升的趋势(P0.001,P0.01)。以血清CEA≥3.4μg/L作为诊断条件诊断肺癌的灵敏度、特异度和阳性预计值预计值分别为67%、62%和75.2%;以血清CYFRA-21≥5.0 ug/L作为诊断条件诊断原发性肺癌的灵敏度、特异度和阳性预计值预计值分别为48%、87%和86.3%;以血清CEA≥3.4 ug/L和CYFRA-21≥5.0 ug/L共同作为诊断条件推断原发性肺癌的灵敏度、特异度和阳性预计值预计值分别为48%、87%和86.3%;良性肺部疾病患者中血清CEA和CYFRA-21水平同时升高者只有2%。结论:血清CEA≥3.4 ug/L和CYFRA-21≥5.0 ug/L同时升高对肺癌有具有重要的诊断价值,可有效的鉴别原发性肺癌与其它良性病变。     

Differences in serum GH cut-off values for pharmacological tests of GH secretion depend on the serum GH method. Clinical validation from the growth velocity score during the first year of treatment

BACKGROUND: The serum GH cut-off value for pharmacological tests of GH secretion (PhT GH) depends on the type of test and also on the method used for determining serum GH. Cut-off serum GH values as different as 5-10 ng/ml, have been reported, and have been validated biochemically. We have used the growth velocity (GV)-standard deviation score (SDS) during the first year of treatment with rhGH to validate these cut-offs on a biological basis. METHODS: Fifty pre-pubertal patients with short stature (height < or =-2 SDS and GV < or =-1.2 SDS) were studied. GH deficiency (GHD) was diagnosed in 39 patients, on the basis of clinical and auxological parameters and on the serum concentration of IGF-1, and non-GHD in the other 11 patients. Two PhT GH (arginine and clonidine) were carried out in the 50 patients. Serum GH was determined by two different methods: one detecting most of serum GH isoforms, named Total GH (HGH Bio-Tech, MAIA Clone), and another one, only detecting the 22 kDa GH, named 22K GH (GH-22K IFMA, Wallac). RESULTS: Basal data: all patients with GHD and with non-GHD had maximal serum GH response (MaxR) values below and above the cut-off, respectively, for the serum Total GH and 22K GH. The mean 22K GH/Total GH ratio was similar to previous publications. Post-rhGH treatment data: the two groups improved their height SDS during the first year of treatment, particularly patients with GHD. A receiver-operator curve was used to define the best threshold for post-treatment GV-SDS that separates GHD from non-GHD patients. This value was 1.91 GV-SDS. A negative correlation between first year treatment GV-SDS and pre-treatment serum GH MaxR was found for the two assays (p < 0.001). Then, the best cut-off GV-SDS, previously calculated with the receiver-operator curve (1.91 SDS) was used to interpolate the corresponding serum GH values, as determined by the two methods. For Total GH, the value was 10.8 ng/ml, and for 22K GH, it was 5.4 ng/ml. CONCLUSION: The cut-off values calculated by biological means to separate GHD from non-GHD were remarkably similar to those calculated biochemically (10.0 and 4.8 ng/ml, respectively) for Total and 22K GH. This is a biological validation for using different cut-off values, appropriate for each assay, to diagnose GHD.     

GH values after clonidine stimulation measured by immunofluorometric assay in normal prepubertal children and GH-deficient patients

OBJECTIVE: To establish the cut-off values of GH measured by immunofluorometric assay, a more sensitive and specific assay, in normal prepubertal children and compare their values with those of proven GH-deficient patients. METHODS: 30 normal children (20 males) and 26 patients with known causes of GH deficiency were submitted to the clonidine test and their GH values were compared. A powdered clonidine tablet (0.1 mg/m(2)) was given orally and blood samples for GH measurements were drawn at times -30, 0, 60, 90 and 120 min. RESULTS: GH peak values presented a wide variation ranging from 1.7 to 25 micro g/l (mean +/- SD = 12.87 +/- 5.8 micro g/l) in the normal group. The cut-off values for the 5th and 10th percentiles of the distribution curve were 3.3 and 5.5 micro g/l, respectively. In the GH deficiency group, maximum GH levels after clonidine stimulation ranged from <0.1 to 2.1 micro g/l (0.56 +/- 0.58 micro g/l). CONCLUSIONS: The cut-off values obtained with the immunofluorometric method are lower than the ones obtained by radioimmunoassay. We suggest a cut-off value of 3.3 micro g/l (5th percentile) that ensures 100% of sensitivity along with 93% of specificity to exclude the diagnosis of GH deficiency when using this immunofluorometric method.     

Effect of low pass filtering on joint moments from inverse dynamics: implications for injury prevention

Analyses of joint moments are important in the study of human motion, and are crucial for our understanding of e.g. how and why ACL injuries occur. Such analyses may be affected by artifacts due to inconsistencies in the equations of motion when force and movement data are filtered with different cut-off frequencies. The purpose of this study was to quantify the effect of these artifacts, and compare joint moments calculated with the same or different cut-off frequency for the filtering of force and movement data. 123 elite handball players performed sidestep cutting while the movement was recorded by eight 240 Hz cameras and the ground reaction forces were recorded by a 960 Hz force plate. Knee and hip joint moments were calculated through inverse dynamics, with four different combinations of cut-off frequencies for signal filtering: movement 10 Hz, force 10 Hz, (10-10); movement 15 Hz, force 15 Hz; movement 10 Hz, force 50 Hz (10-50); movement 15 Hz, force 50 Hz. The results revealed significant differences, especially between conditions with different filtering of force and movement. Mean (SD) peak knee abduction moment for the 10-10 and 10-50 condition were 1.27 (0.53) and 1.64 (0.68) Nm/kg, respectively. Ranking of players based on knee abduction moments were affected by filtering condition. Out of 20 players with peak knee abduction moment higher than mean+1S D with the 10-50 condition, only 11 were still above mean+1 SD when the 10-10 condition was applied. Hip moments were very sensitive to filtering cut-off. Mean (SD) peak hip flexion moment was 3.64 (0.75) and 5.92 (1.80) under the 10-10 and 10-50 conditions, respectively. Based on these findings, force and movement data should be processed with the same filter. Conclusions from previous inverse dynamics studies, where this was not the case, should be treated with caution.     

Selecting a screening cut-off point or diagnostic criterion for comparing prevalences of disease

Comparisons of population prevalences of disease or of inadequate nutriture, across locations or over time (as in monitoring to detect a change in prevalence) are important activities in epidemiology and public health. The data collected are often counts based on a dichotomy of a continuous indicator variable, and performance of the test procedure depends on the cut-off point used. This cut-off may be chosen to optimize performance, on the assumption that the indicator has a mixed normal distribution with unknown mixing proportion corresponding to the unknown prevalence of disease. Results of James (1978, Biometrics 34, 265-275) are applied and extended to the context of monitoring. Charts are presented to facilitate determination of the optimal cut-off, and examples are given for several indicators of nutritional status.     

Enzymatic Synthesis of Acarviosyl-maltooligosaccharides Using Disproportionating Enzyme 1

The soluble and insoluble fractions obtained after sonication and centrifugation of Bifidobacterium adolescentis M101–4 cells were examined, and both of these fractions exhibited mitogenic activity in art assay of murine splenocytes and Peyer’s patch cells in vitro. The soluble fraction was further treated by a 6-step procedure involving proteinase K-treatment, ultrafiltration with a 50-kDa cut-off molecular-sieving membrane, anion-exchange chromatography, dialysis, ultrafiltration through a 6-kDa cut-off membrane filter, and gel-filtration to yield a soluble high molecular weight fraction (SHF) which was effective for stimulating the proliferation of murine splenocytes. Almost three quarters of this fraction by weight was found to consist of carbohydrates containing glucose and galactose as major constituents, and the average molecular weight was estimated to be between 60,000 and 2,460,000, with the main peak at 1,550,000 Da, by the retention time of gel permeation chromatography. A structural analysis by ¹H- and ¹³C-nuclear magnetic resonance and methylation indicated that SHF contained polysaccharides consisting of -4Galp1-, -4Glcp1-, and -6Glcp1- as the major residues, and Galf1- and -6Galf1- as the minor residues. Immunopotentiating SHF was found to contain galactofuranosyl residues as characteristic constituents which had not been previously detected in other soluble fractions from Gram-positive bacteria.     

Variations in the short wavelength cut-off of the solar UV spectra.

Cloud and solar zenith angle (SZA) are two major factors that influence the magnitude of the biologically damaging UV (UVBD) irradiances for humans. However, the effect on the short wavelength cut-off due to SZA and due to clouds has not been investigated for biologically damaging UV for cataracts. This research aims to investigate the influence of cloud and SZA on the short wavelength cut-off of the spectral UVBD for cataracts. The spectral biologically damaging UV for cataracts on a horizontal plane was calculated by weighting the spectral UV measured with a spectroradiometer with the action spectrum for the induction of cataracts in a porcine lens. The UV spectra were obtained on an unshaded plane at a latitude of 29.5 degrees S. The cut-off wavelength (lambdac) was defined as the wavelength at which the biologically damaging spectral irradiance was 0.1% of the maximum biologically damaging irradiance for that scan. For the all sky conditions, the short wavelength cut-off ranged by 12 nm for the SZA range of 5 to 80 degrees and the maximum in the spectral UVBD ranged by 15 nm. Similarly, for the cloud free cases, the short wavelength cut-off ranged by 9 nm for the same SZA range. Although, cloud has a large influence on the magnitude of the biologically damaging UV for cataracts, the influence of cloud on the short wavelength cut-off for the biologically damaging UV for cataracts is less than the influence of the solar zenith angle.     

Effects of Potassium Deficiency on the Photosynthesis and Respiration of Leaves of Sugar Beet under Conditions of Low Sodium Supply

Sugar beet plants (Beta vulgaris L. cv. F58-554H1) were germinated and cultured under standardized environmental conditions. The effects of K deficiency on photosynthetic and respiratory CO₂ exchange rates of attached leaves were studied under conditions of low Na supply by withholding both Na and K from the culture medium at cut-off (28 days after planting). Potassium and Na concentrations in the leaf blade and petiole decreased rapidly during the 8 days after cut-off, then more slowly.     

Diagnostic accuracy of urinary spot protein:creatinine ratio for proteinuria in hypertensive pregnant women: systematic review

Objective To review the spot protein:creatinine ratio and albumin:creatinine ratio as diagnostic tests for significant proteinuria in hypertensive pregnant women.Design Systematic review.Data sources Medline and Embase, the Cochrane Library, reference lists, and experts.Review methods Literature search (1980-2007) for articles of the spot protein:creatinine ratio or albumin:creatinine ratio in hypertensive pregnancy, with 24 hour proteinuria as the comparator.Results 13 studies concerned the spot protein:creatinine ratio (1214 women with primarily gestational hypertension). Nine studies reported sensitivity and specificity for eight cut-off points, median 24 mg/mmol (range 17-57 mg/mmol; 0.15-0.50 mg/mg). Laboratory assays were not well described. Diagnostic test characteristics were recalculated for a cut-off point of 30 mg/mmol. No significant heterogeneity in cut-off points was found between studies over a range of proteinuria. Pooled values gave a sensitivity of 83.6% (95% confidence interval 77.5% to 89.7%), specificity of 76.3% (72.6% to 80.0%), positive likelihood ratio of 3.53 (2.83 to 4.49), and negative likelihood ratio of 0.21 (0.13 to 0.31) (nine studies, 1003 women). Two studies of the spot albumin:creatinine ratio (225 women) found optimal cut-off points of 2 mg/mmol for proteinuria of 0.3 g/day or more and 27 mg/mmol for albuminuria.Conclusion The spot protein:creatinine ratio is a reasonable “rule-out” test for detecting proteinuria of 0.3 g/day or more in hypertensive pregnancy. Information on use of the albumin:creatinine ratio in these women is insufficient.     

Optimal Optic Nerve Sheath Diameter Threshold for the Identification of Elevated Opening Pressure on Lumbar Puncture in a Chinese Population

Ultrasonography of the optic nerve sheath diameter (ONSD) is a non-invasive and rapid method that might be helpful in the identification of increased intracranial pressure (ICP). The use of an ONSD greater than 5 mm on ultrasound as an indicator of increased ICP in a Caucasian population has been studied. However, the cut-off point of this predictor in Chinese patients has not been established. Thus, we conducted this study to identify the ONSD criterion for the detection of elevated opening pressure on lumbar puncture (LP) in a Chinese population and to investigate the influencing factors. This study was a blind cross-sectional study. Patients who presented with suspected increased ICP were included. The opening pressure on LP of each participant was confirmed. We analyzed the clinical differences between the groups of patients with abnormal and normal opening pressures on LP. A receiver operating characteristic curve was constructed to determine the ONSD cut-off point for the identification of abnormal opening pressure on LP. In total, 279 patients were recruited, and 101 patients presented with elevated opening pressure on LP. ONSD was a significant independent predictor of elevated opening pressure on LP (p<0.001). However, no statistical significance was observed regarding the factors that might have affected this relationship including gender, age, body mass index, waistline, head circumference, hypertension and pathological subtype. The ONSD cut-off point for the identification of elevated opening pressure on LP was 4.1 mm; this cut-off yielded a sensitivity of 95% and a specificity of 92%. ONSD is a strong and accurate predictor of elevated opening pressure on LP. The cut-off point of this predictor in a Chinese population was remarkably lower than that found in a Caucasian population. Thus, ethnic differences should be noted when using the ONSD as an indicator of increased ICP.     

Detecting TSH-receptor antibodies with the recombinant TBII assay: technical and clinical evaluation.

We evaluated the technical robustness of the new commercial TBII assay using human recombinant TSH-R, and describe its use for the clinician in the routine laboratory. The human recombinant TSH-R assay (DYNOtest TRAK human) was compared to a conventional TBII assay (TSH-REZAK). Specificity was adjusted at 99.1% for both assays by ROC plot analysis including 113 healthy individuals. Sensitivity in 115 patients with active Graves' Disease (GD) was 98.2% for the DYNOtest TRAK human compared to 68.4% for the TSH-REZAK (p<0.0001). Comparison of the ROC-calculated cut off confirmed the recommended cut-off for the DYNOtest TRAK human, since 11% inhibition of tracer equals 1 IU/L, which is recommended as the grey zone. At the recommended cut-off (2 IU/L, 22% inhibition), the sensitivity is still 93.9% with 100% specificity. The ROC plot-derived cut-off of the TSH-REZAK (4.4%, 2 to 10 U/L) is below the grey zone of 10-15 U/L. At the recommended cut off of 15 U/L, the sensitivity is 43.0% with a specificity of 100%. Both assays showed a good correlation (r = 0.82, p < 0.0001); however, assay comparison revealed a constant bias in favour of the DYNOtest TRAK human. Applying the ROC plot-derived cut-off of 11 % inhibition (1 IU/L) for the DYNOtest TRAK human, we found 15 of 50 patients with autoimmune thyroiditis (AIT) and 6 of 23 patients with goitre (all < 1.5 IU/L). These patients would have been missed using the recommended 2 IU/L. The difference in sensitivity between the DYNOtest TRAK human and the TSH-REZAK was highly significant in the GD group, but not in other groups, indicating that the DYNOtest TRAK human has a higher sensitivity for GD without compromising specificity. In summary, the proposed high sensitivity of the new TBII assay using human recombinant TSH-R could be confirmed with the commercial product. This method offers a clear advantage over conventional TBII assays to confirm or exclude the diagnosis of GD. The recommended cut-off is very stringent, and until we have more information on the clinical relevance of low-level TBII between 1 and 1.5 IU/L, those patients should be monitored for the development of autoimmune thyroid disease.     

Elevated CEA and CA19-9 serum levels independently predict advanced pancreatic cancer at diagnosis

Abstract

Purpose: It is suggested that tumour markers carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) could be used to predict the stage of pancreatic cancer. However, optimal cut-off values for CEA and CA19-9 are disputable. This study aimed to assess the value of CEA and CA19-9 serum levels at diagnosis of pancreatic ductal adenocarcinoma (PDAC) as predictors for the advanced stage of PDAC in patients discussed at pancreatic multidisciplinary team (MDT) meetings.

Methods: Patients with suspected PDAC discussed at MDT meetings from 2013 to 2017 were reviewed, in order to determine optimal cut-off values of both CEA and CA19-9.

Results: In total, 375 patients were included. Optimal cut-off values for predicting advanced PDAC were 7.0?ng/ml for CEA and 305.0?U/ml for CA19-9, resulting in positive predictive values of 83.3%, 73.6%, and 91.4% for CEA, CA19-9 and combined, respectively. Both tumour markers were independent predictors of advanced PDAC, demonstrated by an odds ratio of 4.21 (95% CI:1.85–9.56; p?=?0.001) for CEA and 2.58 for CA19-9 (95% CI:1.30–5.14; p?=?0.007).

Conclusions: CEA appears to be a more robust predictor of advanced PDAC than CA19-9. Implementing CEA and CA19-9 serum levels during MDT meetings as an additional tool for establishing tumour resectability is worthwhile for tailored diagnostics.