An empirical comparison of statistical methods for multiple cut-off diagnostic test accuracy meta-analysis of the Edinburgh postnatal depression scale (EPDS) depression screening tool using published results vs individual participant data.

BACKGROUND: Selective reporting of results from only well-performing cut-offs leads to biased estimates of accuracy in primary studies of questionnaire-based screening tools and in meta-analyses that synthesize results. Individual participant data meta-analysis (IPDMA) of sensitivity and specificity at each cut-off via bivariate random-effects models (BREMs) can overcome this problem. However, IPDMA is laborious and depends on the ability to successfully obtain primary datasets, and BREMs ignore the correlation between cut-offs within primary studies. METHODS: We compared the performance of three recent multiple cut-off models developed by Steinhauser et al., Jones et al., and Hoyer and Kuss, that account for missing cut-offs when meta-analyzing diagnostic accuracy studies with multiple cut-offs, to BREMs fitted at each cut-off. We used data from 22 studies of the accuracy of the Edinburgh Postnatal Depression Scale (EPDS; 4475 participants, 758 major depression cases). We fitted each of the three multiple cut-off models and BREMs to a dataset with results from only published cut-offs from each study (published data) and an IPD dataset with results for all cut-offs (full IPD data). We estimated pooled sensitivity and specificity with 95% confidence intervals (CIs) for each cut-off and the area under the curve. RESULTS: Compared to the BREMs fitted to the full IPD data, the Steinhauser et al., Jones et al., and Hoyer and Kuss models fitted to the published data produced similar receiver operating characteristic curves; though, the Hoyer and Kuss model had lower area under the curve, mainly due to estimating slightly lower sensitivity at lower cut-offs. When fitting the three multiple cut-off models to the full IPD data, a similar pattern of results was observed. Importantly, all models had similar 95% CIs for sensitivity and specificity, and the CI width increased with cut-off levels for sensitivity and decreased with an increasing cut-off for specificity, even the BREMs which treat each cut-off separately. CONCLUSIONS: Multiple cut-off models appear to be the favorable methods when only published data are available. While collecting IPD is expensive and time consuming, IPD can facilitate subgroup analyses that cannot be conducted with published data only.

Patient perceptions of body mass index restrictions limiting fertility care for women with high body mass index.

RESEARCH QUESTION: What is the patient experience of women with high body mass index (BMI) with BMI restrictions that limit fertility care? DESIGN: Qualitative study using in-depth, semi-structured interview methodology. Interview transcripts were analysed for iterative themes in accordance with principles of grounded theory. RESULTS: Forty women with a BMI of 35 kg/m2 or higher with scheduled or completed appointment at the Reproductive Endocrinology and Infertility (REI) clinic completed an interview. Most participants experienced BMI restrictions as unjust. Many perceived that BMI restrictions on fertility care may be medically justified and were in support of weight loss discussions to improve chances of pregnancy; however, several argued that they should have autonomy to commence treatment following an individualized risk assessment. Participants offered recommendations to improve discussion of BMI restrictions and weight loss, including framing the conversation as supportive of their reproductive goals and offering proactive referral to weight loss support to prevent the perception that BMI is a categorical exclusion to future fertility care. CONCLUSIONS: Participant experiences highlight a need for enhanced strategies for communicating BMI restrictions and weight loss recommendations in ways that are perceived to be supportive of patients' fertility goals without further contributing to weight bias and stigma experienced in medical settings. Opportunities for training to mitigate experiences of weight stigma may be beneficial for clinical and non-clinical staff. Evaluation of BMI policies should be undertaken within the context of clinic policies that permit or prohibit fertility care for other high-risk groups.

Creatine kinase-MM concentration in dried blood spots from newborns and implications for newborn screening for Duchenne muscular dystrophy.

INTRODUCTION/AIMS: Creatine kinase-MM (CK-MM) is a marker of skeletal muscle damage. Detection of elevated levels of CK-MM in newborns can enable an early suspicion of the diagnosis of Duchenne muscular dystrophy (DMD) before symptom onset. Our aim was to investigate CK-MM levels in DMD-affected and unaffected newborns using an immunoassay that measures CK-MM concentration in dried blood spots collected for routine newborn screening. METHODS: To validate the assay in our laboratory, CK-MM measurements and newborn demographic information were collected for 8584 de-identified specimens and 15 confirmed DMD patients. After analyzing validation data, CK-MM normal ranges were determined based on age of newborn at specimen collection. Subsequently, the assay was used to measure CK-MM concentration in 26 135 newborns as part of a consented pilot study to screen for DMD in New York State. Mean and median levels of CK-MM based on age of collection, in addition to the 2.5th, 50th, 97.5th, and 99.5th percentiles, were recalculated using the validation and screening data sets. RESULTS: Median CK-MM within 1 hour of birth was 109 ng/mL, rose to a high of 499 ng/mL at 25 hours of age, and then declined to 200 ng/mL at 2 days of life. The median continued to decline more slowly and then stabilized at approximately 40 ng/mL at 1 week of life. DISCUSSION: Because of the marked variability and elevated CK-MM levels observed within the first days of life, it is important to set multiple CK-MM age-related cut-offs when screening for DMD in newborns.

Thyroglobulin and thyroglobulin antibodies: assay-dependent management consequences in patients with differentiated thyroid carcinoma.

OBJECTIVES: International guidelines recommend fixed cut-off values for thyroglobulin (Tg). These cut-offs do not take potential assay differences into account. This study aimed to evaluate if different assays for Tg and Tg antibodies (TgAb) affect management guidance for differentiated thyroid cancer (DTC) patients. METHODS: In 793 samples derived from 413 patients with DTC, Tg and TgAb were simultaneously measured with two immunometric assays: Immulite 2000XPi and Kryptor compact plus. In addition, a qualitative measurement for TgAb interference (recovery test) was performed on the Kryptor compact plus platform. The extent to which different assays lead to different classifications of response to therapy was evaluated when applying the current cut-offs for Tg. RESULTS: Mean Tg concentrations were 37.4% lower with Kryptor as compared with Immulite. Applying guideline based cut-off values for Tg, 33 (4.7%) samples had a Tg-on concentration ≥1.0 µg/L with Immulite and <1.0 µg/L with Kryptor. Of the samples tested as TgAb+ with at least one assay (n=125), 68 (54.4%) samples showed discrepancy in TgAb status. Differences between Immulite and Kryptor measurements resulted in a change in the response to therapy classification in 94 (12.0%) measurements derived from 67 (16.2%) individual patients. CONCLUSIONS: A substantial portion of DTC patients were classified differently dependent on which Tg and TgAb assays are used, when applying the cut-off values as defined in clinical guidelines. Such differences can significantly affect clinical management. In the context of large between-method variation, the recommended Tg cut-offs in guidelines should be used with wisdom rather than as fixed cut-offs.

Tumour markers with clinically controlled cut-offs for suspected cancer.

BACKGROUND: Due to insufficient scientific evidence, panels of tumour markers (TMs) are currently not recommended for use in suspected cancer. However, recent well-designed studies have revealed a potential clinical value in lung cancer. We analysed the diagnostic accuracy of a panel of 11 circulating TMs with clinically controlled thresholds in the differentiation of cancer from nonmalignant diseases. METHODS: We prospectively recruited 4776 consecutive patients presenting with focal or nonspecific symptoms suggestive of cancer who underwent testing for 11 serum TMs before diagnosis was known. The study abided by 2015 STARD guidelines. Tumour markers included, among others, carbohydrate antigen 19-9, carcinoembryonic antigen, alpha-fetoprotein, squamous cell carcinoma-associated antigen, prostate-specific antigen (males), neuron-specific enolase, progastrin-releasing peptide and carbohydrate antigen 125. Thresholds were adjusted for the presence of kidney failure, liver disease, effusions and dermatological disorders. Results showing ≥1 TMs with concentrations above threshold were considered positive. RESULTS: Benign diseases were diagnosed in 3281 (68.7%) patients and cancer in 1495 (31.3%), with epithelial cancers in 1214 (77% at stage IV). When applying criteria for controlled thresholds, overall specificity was 98%. Overall sensitivity of the panel in epithelial cancers was 72.2%, positive predictive value 93% and negative predictive value 90.5%. The area under the receiver operating characteristic curve was 0.920 (95% confidence interval, 0.902-0.924). CONCLUSIONS: By using clinically controlled cut-offs, the combined panel demonstrated an excellent ability to discriminate epithelial cancers from nonmalignant diseases. However, its use in clinical practice would need formal validation through a multicentre controlled trial assessing a panel-guided strategy vs. standard diagnosis.

CT pulmonary angiography appropriateness in a single emergency department: does the use of revised Geneva score matter?

PURPOSE: To assess the percentage of computed tomography pulmonary angiography (CTPA) procedures that could have been avoided by methodical application of the Revised Geneva Score (RGS) coupled with age-adjusted D-dimer cut-offs rather than only clinical judgment in Emergency Department patients with suspected pulmonary embolism (PE). MATERIAL AND METHODS: Between November 2019 and May 2020, 437 patients with suspected PE based on symptoms and D-dimer test were included in this study. All patients underwent to CTPA. For each patient, we retrospectively calculated the age-adjusted D-dimer cut-offs and the RGS in the original version. Finally, CT images were retrospectively reviewed, and the presence of PE was recorded. RESULTS: In total, 43 (9.84%) CTPA could have been avoided by use of RGS coupled with age-adjusted D-dimer cut-offs. Prevalence of PE was 14.87%. From the analysis of 43 inappropriate CTPA, 24 (55.81%) of patients did not show any thoracic signs, two (4.65%) of patients had PE, and the remaining patients had alternative thoracic findings. CONCLUSION: The study showed good prevalence of PE diagnoses in our department using only physician assessment, although 9.84% CTPA could have been avoided by methodical application of RGS coupled with age-adjusted D-dimer cut-offs.

The utility of anthopometric indicators to identify cardiovascular risk factors in Vietnamese children.

BMI, waist circumference (WC) and waist-to-height ratio (WHtR) can be used for discriminating children and adolescents at risk of CVD. However, consensus on how to use these anthropometric indicators is lacking for children and adolescents in Asia. Discrete criteria are promoted internationally, but continuous variables could be used. Data from a survey of 10 949 Vietnamese school-aged children (6-18 years) were used to evaluate the performance of anthropometric indicators to identify elevated blood pressure (BP), dyslipidaemia or at least three cardiovascular risk factors (CVRF). Weight, height, WC and BP were measured using standardised protocols; 1009 participants who had blood lipids were analysed. AUC was used to assess the performance, and the Youden index to identify optimal cut-offs. The prevalence of elevated BP, dyslipidaemia and CVRF was 26·5, 49·3 and 12·2 %, respectively. BMI, WC and WHtR had low capacity to identify elevated BP and dyslipidaemia (AUC range 0·61-0·66) but moderate capacity to identify CVRF (0·72-0·74). Optimal BMIZ cut-offs to identify elevated BP, dyslipidaemia and CVRF were 0·40, 1·01 and 1·1 sd; for WC z-score, they were 0·06, 0·49 and 0·62 sd; for WHtR, optimal cut-offs were close to 0·5. A BMIZ cut-off of 1·0 sd and a WHtR cut-off of 0·5 would, therefore, be useful criteria to identify Vietnamese children who are likely to have CVRF. However, further validation of these criteria in other studies of Asian children and adolescents is needed.

Comparison of standard versus population-specific handgrip strength cut-off points in the detection of probable sarcopenia after launch of EWGSOP2.

OBJECTIVE: We aimed to compare European Working Group on Sarcopenia in Older People (EWGSOP2)-suggested and population-specific handgrip strength (HGS) thresholds to detect probable sarcopenia and their associations with physical-performance measures and frailty. METHODS: A retrospective cross-sectional observational-study included geriatrics outpatients applied to a university-hospital. HGS, timed up and go test (TUG), and usual gait speed (UGS) were assessed. Frailty was screened by FRAIL-scale. RESULTS: A total of 1825 older adults were included (mean age, 74.5 + 7.0 years; 68.8% female). Prevalence of low-HGS were 12.2% by the EWGSOP2-recommended (27/16 kg) cut-offs and 37.5% by population-specific cut-offs (35/20 kg) (p<.001). When low-HGS was defined by EWGSOP2 suggested cut-offs, low-HGS was associated with impaired UGS, (odds ratio [OR] = 3.8, 95% confidence interval [CI]: 2.0-6.9, p<.001); impaired TUG, (OR = 4.6, 95% CI: 2.4-8.8, p<.001); and frailty (OR = 20.9, 95% CI: 8.3-53.0, p<.001). Similarly, low HGS determined by population-specific cut-off points was associated with impaired UGS (OR = 3.1, 95% CI: 2.1-6.9, p<.001); impaired TUG (OR = 6.0, 95% CI: 3.0-11.8, p<.001); and frailty (OR = 7.3, 95% CI: 4.1-13.0, p<.001). CONCLUSIONS: Application of EWGSOP2-recommended standard HGS-cut-offs showed successful application in-practice. However, use of standard HGS cut-offs may result in underdiagnosis of probable sarcopenia. Therefore, we suggest that, whenever available, use of population-specific cut-offs for HGS may be better for correctly identifying older adults at risk.

Prevalence of underweight in children and adolescents (aged 3-18 years) from Kraków (Poland) in 1983 and 2010.

OBJECTIVE: To estimate the changes in the prevalence of underweight among girls and boys living in Kraków that occurred between 1983 and 2010. DESIGN: The study was based on two cross-sectional surveys conducted in 1983 and 2010. The prevalence of underweight was estimated based on the International Obesity Task Force (IOTF) and Centers for Disease Control and Prevention (CDC) cut-off points. SETTING: The study was conducted in Kraków, Poland. PARTICIPANTS: Children aged 3-18 years (n 5245). RESULTS: Between 1983 and 2010 the prevalence of underweight decreased in both sexes. Using the IOTF criteria, the prevalence of underweight decreased from 10·5 to 10·3 % in girls and from 8·9 to 7·5 % in boys, but it was still higher in girls than in boys. According to the CDC criteria, this prevalence decreased from 5·1 to 4·4 % and from 5·9 to 4·6 %, respectively, and was slightly lower in girls. According to the IOTF criteria, underweight prevalence increased slightly during childhood in both sexes while according to the CDC criteria it decreased in boys and did not change in girls. Among juveniles and adolescents, it decreased regardless of the method used. CONCLUSIONS: The frequency of underweight in the population of children and adolescents from Kraków changed slightly in 1983 and 2010 despite economic and social changes. Depending on the cut-off points used, not only the magnitude but also the direction of changes between series could be different. In order to aid global monitoring, the prevalence of underweight as well as overweight should always be evaluated by several methods.

Need to re-look cut-off of Aspergillus-specific IgE levels in children with ABPA.

The cut-offs for total and specific IgE used for diagnosing ABPA in children have been adopted from adult literature and have not been validated in the paediatric population. To establish the ideal cut-offs of total IgE and Aspergillus-specific IgE for the diagnosis of ABPA in children. This study was a prospective observational case-control study, conducted in a tertiary care hospital in North India, enrolling 140 children with partly controlled and uncontrolled asthma. Seventy children had ABPA based on the Rosenberg-Patterson Criteria (Cases) whereas 70 children were without ABPA (Controls). All children were subjected to clinical examination and investigations such as absolute eosinophil count, total IgE, Aspergillus-specific IgE, Aspergillus skin prick test and radiological tests. ROC curve analysis was done to determine the ideal cut-offs of total and specific IgE to diagnose ABPA. The ROC curve analysis determined 1204IU/L as the cut-off value of total IgE with a sensitivity of 79.7% (95%CI 68.31% to 88.44%) and specificity of 53.1% (95%CI 40.23 to 65.7). The ROC analysis of specific IgE levels of children with ABPA determined the cut-off value of 0.49 KAU/L with a sensitivity of 94.03% (95%CI 85.41 to 98.35) and specificity of 88.89% (95%CI 75.94% to 96.29%). We propose that the cut-offs of total and specific IgE need to be relooked in the paediatric population. Cut-offs of total IgE as 1204 IU/L and for Aspergillus-specific IgE as 0.49KAU/L seem appropriate. Large multicentric studies should be conducted to determine the ideal values for diagnosing paediatric ABPA.

Ethnicity-specific cut-offs that predict co-morbidities: the way forward for optimal utility of obesity indicators.

Obesity indicators are useful clinical tools in the measurement of obesity, but it is important for clinicians to appropriately interpret their values in individuals with different ethnicities. Future research is needed to identify optimal cut-offs that can predict the occurrence of cardio-metabolic comorbidities in individuals of different ethnic descent. Assessment of more recently developed indicators like the Edmonton Obesity Staging System and visceral adipose tissue are able to appropriately identify metabolically at-risk individuals.

A semi-quantitative rapid multi-range gradient lateral flow immunoassay for procalcitonin.

A rapid semi-quantitative gradient lateral flow immunoassay (LFIA) of procalcitonin (PCT), a peptide precursor of the hormone calcitonin, was developed. The method is based on particular analyte cut-offs by immobilizing specific antibodies on the test strip with a consistent (gradient) increase in concentration from line to line. Semi-quantitative multi-range analysis is evaluated visually by counting the number of colored test lines corresponding to a certain concentration range of sepsis marker: [PCT]˂0.25; 0.25 ≤ [PCT] < 0.5; 0.5 ≤ [PCT] < 2; 2 ≤ [PCT] < 10; [PCT] ≥ 10 ng·mL-1. This multi-range gradient LFIA was implemented by using two types of label: spherical gold nanoparticles (35 nm) and hierarchical popcorn-like gold nanoparticles (100 nm). The comparison of this LFIA with an ELISA (for n = 82) yielded 87.5% and 76.6% sensitivities, and 92.3% and 92.3% specificities, respectively. Thus, multi-range gradient LFIA performs well at PCT thresholds, which is important for early diagnosis of sepsis and severe bacterial infection. In our perception, this method has a wide scope in that it may be implemented in numerous other LFIA based test systems. Graphical abstract Schematic of the gradient lateral flow immunoassay for determination of clinically relevant procalcitonin ranges. It allows to reach the correlation between the number of developed test lines and procalcitonin concentration range in serum by pre-immobilization of capture antibodies in a consistently (gradient) increasing concentration.

[Development and validation of a simplified height-specific blood pressure cutoffs table for screening hypertension in Chinese children and adolescents].

Objective: To develop and validate a simplified height-specific blood pressure cutoffs table for screening hypertension in Chinese children and adolescents. Methods: We developed a simplified height-specific blood pressure cut offs table according to Chinese Blood Pressure Reference for Children and Adolescents aged 7-18 years (WS/T 610-2018) (hereafter referred to as "complex definition"). Populations from Early Warning, Diagnosis and Treatment of Children Cardiovascular Disease Project ("Ji'nan sample") and Shandong Children Cardiovascular Cohort Study Project ("Zibo sample") were used as validation populations for evaluating the screening effect of the simplified table for elevated blood pressure and hypertension in children and adolescents. Results: We developed simplified height-specific blood pressure cutoffs table including 7 height groups and 28 cutoffs. Both Ji'nan and Zibo samples were selected by convenient sampling method, and the former included 7 233 participants aged 7 to 17 years, among whom 3 790 (52.4%) were boys. Latter population included 1 277 participants aged 7 to 11 years, among whom 681 (53.3%) were boys. The simplified table performed well for identifying elevated blood pressure in Ji'nan sample, with values of area under the receiver operating curve (AUC) (95%CI), sensitivity, specificity, and Kappa statistic as 0.96 (0.95-0.97), 93.0%, 98.5% and 0.91, respectively, which were similar with results in Zibo sample [the values were 0.92 (0.90-0.95), 87.0%, 98.0% and 0.85, respectively]. The simplified table also performed well for identifying hypertension in Ji'nan sample with values of AUC (95%CI), sensitivity, specificity, and Kappa statistic as 0.92 (0.91-0.94), 86.9%, 98.1% and 0.85, respectively, which were similar with results in Zibo sample [the values were 0.94 (0.91-0.96), 88.2%, 98.9% and 0.88, respectively]. Conclusion: Screening for elevated and high blood pressure based on simplified height-specific blood pressure cutoffs table is easy to use and it shows satisfying effect.

Revised and extended serum cotinine cut-offs to classify smokers and non-smokers.

PURPOSE: To revise and extend the previously published serum cotinine cut offs to classify smokers and non-smokers for US adolescents and adults. MATERIALS AND METHODS: Cross-sectional data (N = 10171) from National Health and Nutrition Examination Survey for 2011-2014 were used to compute serum cotinine cut-offs to classify smokers and non-smokers for US adults aged ≥20 years and 2007-2014 (N = 4583) data were used to compute serum cotinine cut-offs for US adolescents aged 12-19 years. RESULTS: Specificities and sensitivities for the cut-offs among adults were ≥95% and ≥75% among adolescents. For adults, serum cotinine cut-offs in ng/mL to classify smokers from non-smokers were 3.3 for the total population, 4.13 for males, 2.99 for females, 4.03 for non-Hispanic whites, 8.85 for non-Hispanic blacks, 0.377 for Mexican Americans, 1.72 for other Hispanics and 1.41 for non-Hispanic Asians. For adolescents, serum cotinine cut-offs in ng/mL to classify smokers from non-smokers were 0.765 for the total population, 1.1 for males, 0.408 for females, 1.2 for non-Hispanic whites, 1.98 for non-Hispanic blacks, 0.215 for Mexican Americans and 0.321 for other Hispanics. CONCLUSIONS: Serum cotinine cut-offs to distinguish smokers from non-smokers for US adults and adolescents were developed.

Vitamin D status in healthy black African adults at a tertiary hospital in Nairobi, Kenya: a cross sectional study.

BACKGROUND: Vitamin D has been known since the twentieth Century for its benefits in bone health. Recent observational studies have demonstrated its benefits in infectious diseases such as tuberculosis and non-communicable diseases such as diabetes mellitus, cardiovascular diseases and cancer. This has led to a dramatic increase in testing among adults. The cut-offs for vitamin D deficiency have been debated for decades and the current cut off is derived from a Caucasian population. Studies done among black African adults in Africa are few with vitamin D deficiency ranging from 5 to 91%. A few cut- offs have correlated vitamin D deficiency to physiological markers such as parathyroid hormone (PTH), calcium and phosphate with varying results. METHODS: This was a cross sectional study carried out among blood donors at Aga Khan University hospital, Nairobi (AKUHN) from March to May 2015. Vitamin D (25(OH)D) levels were assayed and correlated with PTH, calcium and phosphate. RESULTS: A total of 253 individuals were included in the final analysis. The proportion of study participants who had a 25(OH) D level of < 20 ng/ml thus classified as vitamin D deficient was 17.4% (95% C.I 12.73-22.07). The 25(OH) D level that coincided with a significant increase in PTH was 30 ng/ml. Males were less likely to be vitamin D deficient (O.R 0.48 (C.I 0.233-0.993) p 0.04). Sunshine exposure for ≥3 h per day reduced the odds of being Vitamin D deficient though this was not statistically significant after multivariate regression analysis. CONCLUSIONS: We found a much lower prevalence of Vitamin D deficiency compared to many similar studies carried out in sub-Saharan Africa possibly due to the recruitment of healthy individuals and the proximity of Nairobi to the equator which allows for considerable exposure to sunshine. Vitamin D levels below 30 ng/mL was associated with a significant rise in PTH levels, suggesting that this cut off could be appropriate for defining Vitamin D deficiency in the population served by our laboratory.

Mid-upper arm circumference in detection of weight-for-height Z-score below -3 in children aged 6-59 months.

OBJECTIVE: To evaluate the predictive ability of mid-upper arm circumference (MUAC) for detecting severe wasting (weight-for-height Z-score (WHZ) <-3) among children aged 6-59 months. DESIGN: Cross-sectional survey. SETTING: Rural Uttar Pradesh, India. SUBJECTS: Children (n 18 456) for whom both WHZ (n 18 463) and MUAC were available. RESULTS: The diagnostic test accuracy of MUAC for severe wasting was excellent (area under receiver-operating characteristic curve = 0·933). Across the lower range of MUAC cut-offs (110-120 mm), specificity was excellent (99·1-99·9 %) but sensitivity was poor (13·4-37·2 %); with higher cut-offs (140-150 mm), sensitivity increased substantially (94·9-98·8 %) but at the expense of specificity (37·6-71·9 %). The optimal MUAC cut-off to detect severe wasting was 135 mm. Although the prevalence of severe wasting was constant at 2·2 %, the burden of severe acute malnutrition, defined as either severe wasting or low MUAC, increased from 2·46 to 17·26 % with cut-offs of <115 and <135 mm, respectively. An MUAC cut-off <115 mm preferentially selected children aged ≤12 months (OR=11·8; 95 % CI 8·4, 16·6) or ≤24 months (OR=23·4; 95 % CI 12·7, 43·4) and girls (OR=2·2; 95 % CI 1·6, 3·2). CONCLUSIONS: Based on important considerations for screening and case detection in the community, modification of the current WHO definition of severe acute malnutrition may not be warranted, especially in the Indian context.

A time-adjusted cortisol cut-off can reduce referral rate for Synacthen stimulation test whilst maintaining diagnostic performance.

OBJECTIVE: Cortisol cut-offs can predict requirement for Synacthen stimulation tests (SST). We assessed the performance of a standard cortisol cut-off (375 nmol/L) across the morning and compared this with a time-adjusted cut-off. DESIGN: Retrospective audit PATIENTS: Community reference set (n=12 550) and SST patients (n=757). MEASUREMENTS: In the reference population, time-specific cortisol medians were calculated and used to convert cortisol to time-adjusted Multiples of the Median (MoM). In 757 SST patients, the predictive performance of a standard cortisol cut-off (375 nmol/L) and its time-adjusted MoM equivalent were compared. RESULTS: Median cortisol decreased by ~30 nmol/L per hour between 0700 and 1200h. In the reference population, proportions below the 375 nmol/L cut-off increased throughout the morning (range 35%-64%), whereas using the time-adjusted MoM cut-off proportions were consistent (range 46%-50%), with a 17% maximal difference in referral rates between the two cut-offs after 1100h. A similar pattern was noted in the SST cohort. When a cortisol MoM cut-off was used to predict SST success, the excess proportion of patients tested and misclassification rates were lower and more consistent than when the standard cut-off was used. A median cortisol of 375 nmol/L equated to 444 and 313 nmol/L before 0800 and after 1100 h, respectively. CONCLUSION: The use of a standard cortisol cut-off results in 17% more patients being referred for SST later in the morning. A time-adjusted cortisol cut-off provides consistent and lower referral rates, whilst maintaining similar or better performance than a standard single cut-off in predicting outcome of SST.

Defining functioning categories in axial Spondyloarthritis: the role of the ASAS Health Index.

The Assessment of SpondyloArthritis international Society Health Index (ASAS HI) is an inclusive questionnaire, able to describe the total impairments and restrictions due to axial spondyloarthritis (axSpA). Considering the relationship between ASAS HI and the Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP, the aim of this study is to establish the ASAS HI cut-off values for functioning categories employing the ASDAS-CRP disease activity states in axSpA patients. ASAS HI and ASDAS-CPR were obtained from 140 consecutive axSpA patients, divided in the four ASDAS-CRP disease activity categories. High and very high disease activity were considered together. The ASAS HI cut-offs were obtained from the arithmetic mean, rounded off to the closest whole number, of the 75th percentile mean value of a lower rank and the 25th percentile mean value of the adjacent higher rank. This approach was applied in the transition from inactive disease and moderate disease activity, and in the transition from moderate disease activity and high/very high disease activity. Twenty-three patients were classified as having inactive disease, 36 were classified as having moderate disease activity, and 81 were in a high/very high disease activity state. Using the approach of the 75th-25th percentile mean values of adjacent disease activity states, the ASAS HI cut-offs resulted: ≤4 to dinstinguish a normal functioning, >4 and ≤8 to distinguish a moderate impairment of functioning, and >8 to distinguish a severe impairment of functioning. ASAS HI seems a reliable tool to define functioning categories in patients with axSpA.