An observational study to determine the optimal physical evaluation site for detecting anemia

An observational study to determine the optimal physical evaluation site for detecting anemia | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article An observational study to determine the optimal physical evaluation site for detecting anemia Ken Horibata, Seigo Kondo, Shuji Hashimoto, Yousuke Takemura This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3865714/v2 This work is licensed under a CC BY 4.0 License Status: Posted Version 2 posted You are reading this latest preprint version Show more versions Abstract Background: Clinical pallor has traditionally served as a screening tool for anemia; however, its assessment is inherently subjective and lacks objectivity. Therefore, this study aimed to investigate the correlation between skin and mucosal color, as measured by a spectrophotometer, and venous hemoglobin (Hb) values, to identify the optimal anatomical assessment site for detecting anemia. Methods: A cross-sectional design. Ninety-two adult Japanese outpatients from an urban small hospital in Japan participated in the study. Using a spectrophotometer, the color of the lower lip and palpebral conjunctiva was measured indirectly, while the color of the nails and palms was measured directly. Skin and mucosal color were quantified using the L*a*b* color scale. The color difference (ΔE*) was employed to evaluate the discriminability of anemia identification across different assessment sites. Additionally, venous Hb values were recorded, with anemia defined as Hb <12.0 g/dL. Results: The a* values of the lip, palpebral conjunctiva, palm, and inside of the upper arm exhibited a positive correlation with Hb values and were significantly lower in the anemic group. While the ΔE* levels for the palpebral conjunctiva and lip were readily discernible by the human eye when comparing the normal and anemic groups, recognition at this level proved challenging for other sites. Conclusion: The palpebral conjunctiva and lip demonstrate potential suitability for visual diagnosis of anemia. In the nail, palm, and inside of the upper arm, anemia detection may require highly trained observation. Consequently, reliance on these sites for anemia diagnosis may lead to potential oversight. Health sciences/Diseases/Haematological diseases Health sciences/Health care/Diagnosis/Physical examination Figures Figure 1 Introduction Anemia is a widespread health concern globally, particularly affecting infants, children, young adult women, pregnant women, and the elderly. 1,2,3,4 While iron deficiency remains the primary cause of anemia, other factors such as parasitic infections and sickle cell disease contribute to its prevalence. 1 In Japan, anemia induced by parasitic infections is uncommon, with menstrual bleeding and gastrointestinal bleeding being more frequent causes. 5 Given the elevated incidence of gastric cancer in Japan, screening for anemia becomes crucial due to the potential risk of gastrointestinal bleeding and other serious blood disorders. 6 As anemia has been associated with life-threatening health issues, prompt and accurate screening is imperative for individuals suspected of having the condition. 1,3 The diagnosis of anemia involves assessing three key components: a patient's epidemiological information, medical history, and physical findings. 7-11 When clinical evaluation suggests anemia, a venous hemoglobin (Hb) test is often conducted to confirm the diagnosis. However, in certain instances, immediate performance of the venous Hb test may not be feasible, especially in resource-limited facilities or developing countries. 4,12-22 Traditionally, physicians have relied on the observation of the skin, nail bed, palpebral conjunctiva, and lip for signs of pallor to detect anemia. 8,10 Although pallor's extent is used to determine the presence or absence of anemia, a clear definition of pallor is lacking. Studies assessing the accuracy of anemia diagnosis through physical examinations in children and pregnant women residing in tropical areas revealed that pallor of the palpebral conjunctiva, nail bed, and palm could be indicative of moderate to severe anemia. 14,16,18,19,21,22 However, considerable variations in detection sensitivity and specificity were noted across studies, and meta-analysis demonstrated an overall low diagnostic performance. 12 In fact, research has indicated that the physical signs of anemia may not consistently align with venous Hb values, which serve as the most accurate indicators of anemia. 10,12,23,24 Several diagnostic studies have assessed whether the clinical evaluation of pallor can serve as a screening test for anemia. 7,8,10-12,14,18,19,21-24 We hypothesized that the color of the skin and mucosal sites traditionally employed for anemia assessment accurately reflects venous Hb values. However, clinical evaluations of pallor are inherently subjective, lacking an objective means to quantify color intensity. The most objective method for color recognition involves colorimetric measurements, providing numerical representations of colors. Therefore, the present study aimed to determine the accuracy and reliability of clinical pallor in detecting anemia by precisely comparing skin and mucosal color using a spectrophotometer with venous Hb values. The study also assessed the discriminability of clinical assessments across different sites to identify which site exhibits the highest discriminability for detecting anemia. Methods 2.1 Study participants The present study enrolled consecutive Japanese adult outpatients over 20 years old who visited Kameyama Municipal Medical Center between December 1, 2014, and February 28, 2015. Kameyama Municipal Medical Center is a small urban hospital, which is composed of 60 beds, in Kameyama City within the Mie Prefecture. The age and sex of all participants were recorded. 2.2 Laboratory measurements Venous red blood cell counts (RBCs), Hb values, and hematocrit (Ht) ratios were measured in all participants. 2.3 Color measurements Skin and mucosal color were measured using the International Commission on Illumination L*a*b* (CIELAB) color scale. The CIE is an international organization providing basic standards and procedures in all areas of light and lighting. 25 There are various ways to describe colors quantitatively. Among them, the L*a*b* system, determined by the CIE, is the standard and one of the commonly used systems in measuring color. In the CIELAB color space, values L*, a*, and b* form a three-dimensional coordinate plotting system. L* represents the lightness of the color (L*=0 indicates black and L*=100 indicates diffuse white); a* represents the position between the red and green axis (negative a* values indicate green, while positive a* values indicate red); and b* represents the position between the yellow and blue axis (negative b* values indicate blue, and positive b* values indicate yellow) (Figure 1). A handheld, portable spectrophotometer (CM-700d®, Konica Minolta, Tokyo, Japan) was used to measure color at the following sites: the lower lip, lower palpebral conjunctiva, palm, nail bed, and inside of the upper arm. Usually, skin color other than the palm is not used for evaluating anemia, but it was decided to investigate its usefulness for anemia evaluation. Therefore, the color of the inner upper arm, which is less affected by sunburn and easy to measure, was measured. The color of the palm, nail bed, and inside of the upper arm was directly measured using the spectrophotometer. 2.4 Measurement of mucosal color Since the measurement part at the tip of the spectrophotometer was not a disposable type, it was impossible to make direct contact with saliva and tear fluid in consideration of the risk of infection. Additionally, since a strong light is emitted at the time of measurement, even if direct contact is possible, the risk of retinal damage due to light must be avoided. Therefore, the only way to measure the color of mucosa using the tools we possess, we had no choice but to measure it indirectly. Although this method cannot measure the true color of mucosa, we devised a process that would minimize errors as much as possible (Figure 2). A standard color chart (CASMATCH®, BEAR Medic Corporation, Ibaraki, Japan) was affixed near the lip or eye and was photographed with a digital camera (PowerShot SX700 HS®, Canon Inc., Tokyo, Japan). Electronic image data (jpg format) was imported into a computer, and color correction was performed using the color chart in combination with image editing software (Photoshop CS6 Extended®, Adobe Systems Inc., California, United States). The photographs were printed using an inkjet printer (Pixus MG7530®, Canon Inc., Tokyo, Japan). The colors of the central portion of the lower lip and the lower palpebral conjunctiva mucosa, as displayed in the printed photograph, were measured using the spectrophotometer. Illuminance of the room was measured with every patient snapshot. 2.5 Color difference We used the color difference to assess the discriminability by site of anemia identification. Although the measurement of the color of the conjunctiva and lips is indirect, it may be inaccurate. However, by utilizing color differences, we could still achieve the objectives of this study. The color difference (ΔE*) was calculated using the following formula: Color difference indicates how easily two colors can be distinguished by the human eye. The color difference is judged using the following criterion: < 3.0, which is difficult to recognize by human eyes; 3.0–6.0 which is recognizable, with the possibility of overlooking; and ≥ 6.0, which is clearly recognizable. 26 Using color difference allows us to determine which areas are more easily identifiable for detecting anemia. 2.6 Definition of anemia Anemia is defined by the World Health Organization as a Hb value below 13.0 g/dL for men and below 12.0 g/dL for non-pregnant women. 27 In the present study, anemia was defined as a Hb value below 12.0 g/dL in both men and women. 2.7 Sample size In the absence of previous studies on the same theme, the a* value of the palpebra of the first 10 participants was used to calculate the sample size. The average a* value of the palpebra was 33.2, with a standard deviation of 6.1. It is expected that there will be a 10% difference between the two groups. Consequently, it was calculated that 53 participants are needed in each of the two groups. 2.8 Statistical analysis Continuous variables were presented as the mean and standard deviation, and categorical variables were presented as the actual number and percentage. Categorical data were compared using the chi-squared test. The mean between the two groups (normal and anemic participants, men and women) were compared using the unpaired Student’s t-test. Associations between the two continuous variables were determined using Pearson’s correlation coefficient. A P-value < 0.05 was considered statistically significant. All statistical analyses were performed using EZR on R-commander (version 1.28 for Windows, Saitama Medical Center, Jichi Medical University, Saitama, Japan), which is a graphical user interface for R (The R Foundation for Statistical Computing, Vienna, Austria). 28 Results A total of 108 participants were enrolled. However, after excluding samples with measurement errors or missing variables, data from 92 participants were finally analyzed. The mean age was 68.5 ± 15.5 years, there were 47 men (51.1%), and the RBC values were 420.4 ± 68.2 × 104/μL, Hb 12.8 ± 2.1 g/dL, and Ht 38.5 ± 6.2%, respectively. Correlation coefficient between the venous Hb value and measured color is shown in Table 1. Characteristics and measured color according to the presence of anemia are shown in Table 2. Color differences of each site according to the range of Hb value are shown in Table 3. In the lower palpebral conjunctiva, all color differences were 6.0 or more in the normal group and the anemic group. In the lower lip, the color difference between the group of 10.0–11.9 and the group of 12.0–13.9 was 3.4, but all other color differences were 6.0 or more. In the nail, palm, and inside of the upper arm, all the color differences were less than 6.0, and it turned out that there was no color difference at the level that can recognize the color difference obviously with human eyes. The color differences between the group with Hb < 10.0 and ≥ 14.0 in the nail, between the group with Hb < 10.0 and ≥ 12.0 in the nail bed, between the group with Hb 10.0–11.9 and ≥ 14.0 in the palm, and between the group with Hb < 10.0 and ≥ 14.0 in inside of the upper arm were 3.9, 3.0 or more, 3.0, and 3.4, respectively. These may be recognized by trained human eyes. Discussion The purpose of this study was to objectively evaluate the relationship between venous Hb levels and skin/mucosal color to determine which sites are suitable for identifying anemia. Consequently, the color of the lower lip, lower palpebral conjunctiva, palm, nail bed, and inside of the upper arm demonstrated an association with Hb values. However, the results suggest that not all sites are equally crucial for evaluating anemia. We examined the association between venous Hb values and individual color elements, categorizing them into L*, a*, and b*. However, the relevance was small except for the a* value. In the lower lip, lower palpebral conjunctiva, palm, and inside of the upper arm, the a* value, an indicator of redness, exhibited a positive association with venous Hb values. However, when comparing the normal group and the anemic group, only the lower lip and lower palpebral conjunctiva showed a significant difference in the a* value. Two potential reasons are considered: (1) The a* value of the palm and inside of the upper arm may have a weak association with venous Hb values, possibly resulting in difficulty expressing the colors of these sites as red intensity even in the presence of anemia, and (2) the small number of participants with anemia might lead to inaccurate color representation at lower Hb values. In the nail and palm, the b* value, an indicator of yellowness, displayed a negative association with venous Hb values. However, when comparing the normal group and the anemic group, only the palm showed a significant difference in the b* value. At these sites, a lower venous Hb value reduced the red color, emphasizing the yellowness of the skin's original color. Regarding the L* value, an indicator of lightness, no significant difference was observed at any site between the normal and anemic groups, although in the palm and inside of the upper arm, the L* value showed a negative association with venous Hb values. It is suggested that Hb, being red in color, is slightly associated with the L* value. For easier comprehension, the color of each part was converted into color difference (ΔE*), a composite value of L*a*b*, and analyzed within each Hb value range. If the color difference between the group with Hb <11.9 and the group with 12.0 or more is 6.0 or more, it reaches a level where the difference in color is clearly noticeable to the human eye. Therefore, in the physical examination of anemia, it was determined that the palpebral conjunctiva and the lower lip are the most suitable sites. Additionally, for anemia diagnosis, pallor in the nail, palm and inside of the upper arm may be discerned by trained human eyes. According to the findings of this study, the lower palpebral conjunctiva and the lower lip, traditionally used in physical examinations, are also suitable for colorimetric evaluation in diagnosing anemia. In the nail, palm, and inside of the upper arm, anemia may be detected by trained human eyes if the venous Hb value is less than 10.0. Therefore, when utilizing these sites for anemia diagnosis, oversight is possible. 4.1 Strengths and limitations of this study The present study also had several strengths. First, this is the first study that investigated the association between the color of the lower lip, lower palpebral conjunctiva, palm, nail bed, and inside of the upper arm measured using spectrophotometer and venous Hb values among adult Japanese. Second, we provided valuable information to primary care physicians by identifying the most appropriate site for assessing anemia based on principles of color science. However, the present study had several limitations. Firstly, the biggest drawback of this study is that we could not directly measure the color of the conjunctiva and lip. We believe that it is appropriate to use color differences to indicate the ease of identifying anemia by location. Since it is possible to use indirect color measurement as a substitute for determining the ease of discrimination based on color difference, we believe that the purpose of this research can be achieved. However, the results of the correlation between color and Hb value may not be correct. Second, the study included a small sample size of patients with moderate to severe anemia (Hb < 10.0 g/dL). Thus, the usefulness of the nail bed, palm, and upper arm pallor in detecting anemia cannot be entirely discounted. Third, most of the participants were elderly, and their age distribution was biased. Fourth, since all participants were Japanese, there is bias in ethnicity. The interpretation of the results for skin color can only be applied to the Japanese. Fifth, this study assessed pallor using a spectrophotometer, which raises the question of whether the human eye can detect the same subtle differences in pallor color. Consequently, further research is necessary to determine whether human observers can reliably identify the presence or absence of anemia through training. Conclusions The palpebral conjunctiva and lip demonstrate potential suitability for visual diagnosis of anemia. In the nail, palm, and inside of the upper arm, anemia detection may require highly trained observation. Consequently, reliance on these sites for anemia diagnosis may lead to potential oversight. Declarations ACKNOWLEDGMENTS We appreciate the patient who accepted to participate this study and the support of the nursing staff of the Division of the Clinical Laboratory of Kameyama Municipal Medical Center. This study was funded by New Paradigms – Establishing Centers for Fostering Medical Researchers of the Future by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) in Japan. CONFLICT OF INTEREST STATEMENT The authors declare no conflict of interest. ETHICS STATEMENT The study was approved by the Ethics Committee of Mie University Graduate School of Medicine (No.1421). PATIENT CONSENT STATEMENT All participants signed an informed consent prior to their participation. References 1. Kassebaum NJ, Jasrasaria R, Naghavi M, Wulf SK, Johns N, Lozano R, et al. A systematic analysis of global anemia burden from 1990 to 2010. Blood. 2014;123: 615-24. 2. Li M, Hu Y, Mao D, Wnag R, Chen J, Li W, et al. Prevalence of Anemia among Chinese Rural Residents. Nutrients. 2017;9:192. 3. Brabin BJ, Premji Z, Verhoeff F. An analysis of anemia and child mortality. J Nutr . 2001;131:636S-45S. 4. Critchley J, Bates I. Haemoglobin colour scale for anaemia diagnosis where there is no laboratory: a systematic review. Int J Epidemiol. 2005;34:1425-34. 5. Shimomura T, Wakabayashi I. [Regional differences in prevalence of anemia found by periodic health checkups at workplaces in Japan]. Sangyo eiseigaku zasshi. 2010;52:21-27. [In Japanese]. 6. Hori M, Matsuda T, Shibata A, Katanoda K, Sobue T, Nishimoto H. Cancer incidence and incidence rates in Japan in 2009: a study of 32 population-based cancer registries for the Monitoring of Cancer Incidence in Japan (MCIJ) project. Jpn J Clin Oncol. 2015;45,:884-91. 7. Hung OL, Kwon NS, Cole AE, Dacpano GR, Wu T, Chiang WK, et al. Evaluation of the physician's ability to recognize the presence or absence of anemia, fever, and jaundice. Acad Emerg Med. 2000;7:146-56. 8. Kalantri A, Karambelkar M, Joshi R, Kalantri S, Jajoo U. Accuracy and reliability of pallor for detecting anaemia: a hospital-based diagnostic accuracy study. PloS One. 2010;5: e8545. 9. Manesh RS, Kohlwes RJ. Palmar Crease Pallor. J Gen Intern Med. 2015;30:1034. 10. Nardone DA, Roth KM, Mazur DJ, McAfee JH. Usefulness of physical examination in detecting the presence or absence of anemia. Arch Intern Med. 1990;150:201-4. 11. Strobach RS, Anderson SK, Doll DC, Ringenberg QS. The value of the physical examination in the diagnosis of anemia. Correlation of the physical findings and the hemoglobin concentration. Arch Intern Med. 1988;148:831-2. 12. Chalco JP, Huicho L, Alamo C, Carreazo NY, Bada CA. Accuracy of clinical pallor in the diagnosis of anaemia in children: a meta-analysis. BMC Pediatr. 2005;5:46. 13. Ingram CF, Lewis SM. Clinical use of WHO haemoglobin colour scale: validation and critique. J Clin Pathol. 2000;53:933-7. 14. Kalter HD, Burnham G, Kolstad PR, Hossain M, Schillinger JA, Khan NZ, et al. Evaluation of clinical signs to diagnose anaemia in Uganda and Bangladesh, in areas with and without malaria. Bull World Health Organ. 1997;75:103-11. 15. Lewis SM, Stott GJ, Wynn KJ. An inexpensive and reliable new haemoglobin colour scale for assessing anaemia. J clin pathol. 1998;51:21-4. 16. Luby SP, Kazembe PN, Redd SC, Ziba C, Nwanyanwu OC, Hightower AW, et al. Using clinical signs to diagnose anaemia in African children. Bull World Health Organ. 1995;73,:477-82. 17. Marn H, Critchley JA. Accuracy of the WHO Haemoglobin Colour Scale for the diagnosis of anaemia in primary health care settings in low-income countries: a systematic review and meta-analysis. Lancet Glob Health. 2016;4:e251-65. 18. Mogensen CB, Soerensen J, Bjorkman A, Montgomery SM. Algorithm for the diagnosis of anaemia without laboratory facilities among small children in a malaria endemic area of rural Tanzania. Acta Trop. 2006;99:119-25. 19. Mogensen CB, Sorensen JE, Bjorkman A. Pallor as a sign of anaemia in small Tanzanian children at different health care levels. Acta Trop. 2006;99:113-8. 20. Van den Broek NR, Ntonya C, Mhango E, White SA. Diagnosing anaemia in pregnancy in rural clinics: assessing the potential of the Haemoglobin Colour Scale. Bull World Health Organ. 1999;77:15-21. 21. Weber MW, Kellingray SD, Palmer A, Jaffar S, Mulholland EK, Greenwood BM. Pallor as a clinical sign of severe anaemia in children: an investigation in the Gambia. Bull World Health Organ. 1997;75:113-8. 22. Zucker JR, Perkins BA, Jafari H, Otieno J, Obonyo C, Campbell CC. Clinical signs for the recognition of children with moderate or severe anaemia in western Kenya. Bull World Health Organ. 1997;75:97-102. 23. Butt Z, Ashfaq U, Sherazi SF, Jan NU, Shahbaz U. Diagnostic accuracy of "pallor" for detecting mild and severe anaemia in hospitalized patients. J Pak Med Assoc. 2010;60:762-5. 24. Sheth TN, Choudhry NK, Bowes M, Detsky AS. The relation of conjunctival pallor to the presence of anemia. J Gen Intern Med. 1997;12:102-6. 25. Illumination ICo. About the CIE. [Cited 11 June 2024]. Available from: https://cie.co.at/about-cie (2024) 26. Hsin-Chia C, Sheng-Jyh W. The use of visible color difference in the quantitative evaluation of color image segmentation. 2004 IEEE International Conference on Acoustics, Speech, and Signal Processing. 2004;3:iii-593-6. 27. WHO Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity. [Cited 11 June 2024]. Available from: https://www.who.int/publications/i/item/WHO-NMH-NHD-MNM-11.1 (2011) 28. Kanda Y. Investigation of the freely available easy-to-use software 'EZR' for medical statistics. Bone Marrow Transplant. 2013;48:452-8. Tables Table 1. Correlation coefficient between the venous hemoglobin (Hb) value and measured color. L* a* b* Palpebral - 0.18 0.50 † - 0.01 Lip ­ 0.09 0.42 † 0.02 Nail ­ 0.05 0.12 ­ 0.26 † Palm ­ 0.25 † 0.30 † - 0.28 † Upper arm ­ 0.25 † 0.27 † ­ 0.04 Correlations were determined using Pearson’s correlation coefficient. † Correlation coefficient with p value less than 0.05 Table 2. Characteristics and measured color according to the presence of anemia. Characteristics Total (n=92) Anemia † (n=25) Normal (n=67) P value Age, mean ± SD, years 68.5 ± 15.5 73.2 ± 15.5 66.7 ± 15.3 0.08 Men, number (%) 47 (51.1) 8 (32.0) 39 (58.2) 0.05 ‡ Illuminance of the room, mean ± SD, lux 658.2 ± 269.5 707.5 ± 112.6 0.21 Hemoglobin, g/dL ± SD 12.8 ± 2.1 10.1 ± 1.8 13.8 ± 1.2 N/A Measured color, no unit, mean ± SD Palpebral L* 52.9 ± 8.1 50.0 ± 7.4 0.11 a* 29.4 ± 8.7 36.7 ± 5.7 <0.001 b* 19.4±9.1 21.5 ± 7.5 0.26 Lip L* 59.1 ± 12.6 57.8 ± 8.8 0.58 a* 29.8 ± 6.8 34.6 ± 6.2 <0.01 b* 12.7 ± 8.9 13.1 ± 7.0 0.81 Nail L* 55.4 ± 9.3 54.3 ± 8.2 0.57 a* 4.6 ± 1.5 4.9 ± 2.1 0.52 b* 11.1 ± 2.4 10.1 ± 2.1 0.08 Palm L* 62.9 ± 2.9 61.2 ± 4.0 0.05 a* 7.2 ± 2.2 8.0 ± 2.1 0.11 b* 16.7 ± 2.8 15.3 ± 2.3 0.02 Upper arm L* 65.4 ± 3.9 65.0 ± 3.0 0.54 a* 5.0 ± 1.2 5.4 ± 1.4 0.20 b* 15.8 ± 2.5 15.4 ± 2.2 0.47 † Anemia was defined as < 12 g/dL in both men and women ‡ A p -value was determined using chi-squared test. Other all p values were determined using unpaired Student’s t-test SD, standard deviation; N/A, not applicable Table 3. Color differences of each site according to the range of Hb value. Range of Hb value <10.0 (N=8) 10.0–11.9 (N=17) 12.0–13.9 (N=39) ≥ 14.0 (N=28) Palpebral conjunctiva < 10.0 N/A — — — 10.0–11.9 5.7 N/A — — 12.0–13.9 10.5 ∗ 7.8 ∗ N/A — ≥ 14.0 10.7 ∗ 7.1 ∗ 2.6 N/A Lip < 10.0 N/A — — — 10.0–11.9 11.8 N/A — — 12.0–13.9 10.8 ∗ 3.4 † N/A — ≥ 14.0 12.1 ∗ 6.2 ∗ 3.0 N/A Nail < 10.0 N/A — — — 10.0–11.9 2.1 N/A — — 12.0–13.9 2.0 0.4 N/A — ≥ 14.0 3.9 † 2.0 2.0 N/A Palm < 10.0 N/A — — — 10.0–11.9 2.5 N/A — — 12.0–13.9 3.0 † 1.7 N/A — ≥ 14.0 4.3 † 3.0 † 1.6 N/A Upper arm < 10.0 N/A — — — 10.0–11.9 3.0 N/A — — 12.0–13.9 1.9 1.1 N/A — ≥ 14.0 3.4 † 1.1 1.5 N/A N/A, Not applicable ∗ The numerical value is a color difference of 6.0 or more between the normal group and the anemic group † The numerical value is a color difference of 3.0–6.0 between the normal group and the anemic group. The color differences were calculated using the average of the measurements of each Hb category. The color difference is judged by using the following criterion: 3.0 > is difficult to recognize by human eyes, 3.0–6.0 is recognizable, but there is a possibility of overlooking, and 6.0 ≥ is clearly recognizable. Additional Declarations The authors declare no competing interests. Cite Share Download PDF Status: Posted Version 2 posted You are reading this latest preprint version Show more versions Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3865714","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":267662738,"identity":"9508a76b-1ddd-433f-96db-9cd12a0d431f","order_by":0,"name":"Ken Horibata","email":"data:image/png;base64,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","orcid":"","institution":"Mie University","correspondingAuthor":true,"prefix":"","firstName":"Ken","middleName":"","lastName":"Horibata","suffix":""},{"id":267662739,"identity":"6b63eafa-ad04-40aa-87ea-7403e10be2e4","order_by":1,"name":"Seigo Kondo","email":"","orcid":"","institution":"Mie University","correspondingAuthor":false,"prefix":"","firstName":"Seigo","middleName":"","lastName":"Kondo","suffix":""},{"id":267662740,"identity":"a5dd32f3-656c-41d0-bfbf-adc76ac84034","order_by":2,"name":"Shuji Hashimoto","email":"","orcid":"","institution":"Mie University","correspondingAuthor":false,"prefix":"","firstName":"Shuji","middleName":"","lastName":"Hashimoto","suffix":""},{"id":267662741,"identity":"b8747b63-cca7-46e1-b4e9-48f7fa2cc8d8","order_by":3,"name":"Yousuke Takemura","email":"","orcid":"","institution":"Tokyo Women's Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yousuke","middleName":"","lastName":"Takemura","suffix":""}],"badges":[],"createdAt":"2024-01-15 07:34:05","currentVersionCode":2,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-3865714/v2","doiUrl":"https://doi.org/10.21203/rs.3.rs-3865714/v2","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":59519936,"identity":"b8ff30f0-b4fd-465b-a4d3-7e6676f4bf2b","added_by":"auto","created_at":"2024-07-02 19:00:38","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":118599,"visible":true,"origin":"","legend":"\u003cp\u003eThree-dimensional sphere of International Commission on Illumination L*a*b* (CIELAB) color space.\u003c/p\u003e\n\u003cp\u003eThe L * a * b * color space is the commonly used color system to represent object colors. It is expressed by a three-dimensional model, the three coordinates represent the lightness of the color (L*=0 indicates black and L*=100 indicates diffuse white), its position between the red and green axis (negative a* values indicate green, while positive a* values indicate red), and its position between the yellow and blue axis (negative b* values indicate blue, and positive b* values indicate yellow). Difference of two colors in space can be shown as a color difference, by measuring the Euclidean distance between two points.\u003c/p\u003e","description":"","filename":"Onlinefigure110.png","url":"https://assets-eu.researchsquare.com/files/rs-3865714/v2/1acc37cbb9b75e8573ae8eb5.png"},{"id":59520433,"identity":"020a6c38-b30e-4a0e-8e26-a417582e883f","added_by":"auto","created_at":"2024-07-02 19:08:39","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":654425,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3865714/v2/c6b0e2c0-58f6-4d6c-9c45-73c5d74f23c7.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"An observational study to determine the optimal physical evaluation site for detecting anemia","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAnemia is a widespread health concern globally,\u003csup\u003e\u0026nbsp;\u003c/sup\u003eparticularly affecting infants, children, young adult women, pregnant women, and the elderly.\u003csup\u003e1,2,3,4\u003c/sup\u003e While iron deficiency remains the primary cause of anemia, other factors such as parasitic infections and sickle cell disease contribute to its prevalence.\u003csup\u003e1\u003c/sup\u003e In Japan, anemia induced by parasitic infections is uncommon, with menstrual bleeding and gastrointestinal bleeding being more frequent causes.\u003csup\u003e5\u003c/sup\u003e Given the elevated incidence of gastric cancer in Japan, screening for anemia becomes crucial due to the potential risk of gastrointestinal bleeding and other serious blood disorders.\u003csup\u003e\u0026nbsp;6\u0026nbsp;\u003c/sup\u003eAs anemia has been associated with life-threatening health issues, prompt and accurate screening is imperative for individuals suspected of having the condition.\u003csup\u003e\u0026nbsp;1,3\u003c/sup\u003e The diagnosis of anemia involves assessing three key components: a patient\u0026apos;s epidemiological information, medical history, and physical findings.\u003csup\u003e7-11\u0026nbsp;\u003c/sup\u003eWhen clinical evaluation suggests anemia, a venous hemoglobin (Hb) test is often conducted to confirm the diagnosis. However, in certain instances, immediate performance of the venous Hb test may not be feasible, especially in resource-limited facilities or developing countries.\u003csup\u003e\u0026nbsp;4,12-22\u0026nbsp;\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eTraditionally, physicians have relied on the observation of the skin, nail bed, palpebral conjunctiva, and lip for signs of pallor to detect anemia.\u003csup\u003e8,10\u003c/sup\u003e Although pallor\u0026apos;s extent is used to determine the presence or absence of anemia, a clear definition of pallor is lacking. Studies assessing the accuracy of anemia diagnosis through physical examinations in children and pregnant women residing in tropical areas revealed that pallor of the palpebral conjunctiva, nail bed, and palm could be indicative of moderate to severe anemia.\u003csup\u003e14,16,18,19,21,22\u003c/sup\u003e However, considerable variations in detection sensitivity and specificity were noted across studies, and meta-analysis demonstrated an overall low diagnostic performance.\u003csup\u003e12\u003c/sup\u003e In fact, research has indicated that the physical signs of anemia may not consistently align with venous Hb values, which serve as the most accurate indicators of anemia.\u003csup\u003e10,12,23,24\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eSeveral diagnostic studies have assessed whether the clinical evaluation of pallor can serve as a screening test for anemia.\u003csup\u003e\u0026nbsp;7,8,10-12,14,18,19,21-24\u003c/sup\u003e We hypothesized that the color of the skin and mucosal sites traditionally employed for anemia assessment accurately reflects venous Hb values. However, clinical evaluations of pallor are inherently subjective, lacking an objective means to quantify color intensity. The most objective method for color recognition involves colorimetric measurements, providing numerical representations of colors. Therefore, the present study aimed to determine the accuracy and reliability of clinical pallor in detecting anemia by precisely comparing skin and mucosal color using a spectrophotometer with venous Hb values. The study also assessed the discriminability of clinical assessments across different sites to identify which site exhibits the highest discriminability for detecting anemia.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003e2.1 Study participants\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe present study enrolled consecutive Japanese adult outpatients over 20 years old who visited Kameyama Municipal Medical Center between December 1, 2014, and February 28, 2015. Kameyama Municipal Medical Center is a small urban hospital, which is composed of 60 beds, in Kameyama City within the Mie Prefecture. The age and sex of all participants were recorded.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.2 Laboratory measurements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eVenous red blood cell counts (RBCs), Hb values, and hematocrit (Ht) ratios were measured in all participants.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.3 Color measurements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSkin and mucosal color were measured using the International Commission on Illumination L*a*b* (CIELAB) color scale. The CIE is an international organization providing basic standards and procedures in all areas of light and lighting.\u003csup\u003e25\u003c/sup\u003e There are various ways to describe colors quantitatively. Among them, the L*a*b* system, determined by the CIE, is the standard and one of the commonly used systems in measuring color. In the CIELAB color space, values L*, a*, and b* form a three-dimensional coordinate plotting system. L* represents the lightness of the color (L*=0 indicates black and L*=100 indicates diffuse white); a* represents the position between the red and green axis (negative a* values indicate green, while positive a* values indicate red); and b* represents the position between the yellow and blue axis (negative b* values indicate blue, and positive b* values indicate yellow) (Figure 1). A handheld, portable spectrophotometer (CM-700d\u0026reg;, Konica Minolta, Tokyo, Japan) was used to measure color at the following sites: the lower lip, lower palpebral conjunctiva, palm, nail bed, and inside of the upper arm.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eUsually, skin color other than the palm is not used for evaluating anemia, but it was decided to investigate its usefulness for anemia evaluation. Therefore, the color of the inner upper arm, which is less affected by sunburn and easy to measure, was measured. The color of the palm, nail bed, and inside of the upper arm was directly measured using the spectrophotometer.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.4 Measurement of mucosal color\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSince the measurement part at the tip of the spectrophotometer was not a disposable type, it was impossible to make direct contact with saliva and tear fluid in consideration of the risk of infection. Additionally, since a strong light is emitted at the time of measurement, even if direct contact is possible, the risk of retinal damage due to light must be avoided. Therefore, the only way to measure the color of mucosa using the tools we possess, we had no choice but to measure it indirectly. Although this method cannot measure the true color of mucosa, we devised a process that would minimize errors as much as possible (Figure 2).\u003c/p\u003e\n\u003cp\u003e A standard color chart (CASMATCH\u0026reg;, BEAR Medic Corporation, Ibaraki, Japan) was affixed near the lip or eye and was photographed with a digital camera (PowerShot SX700 HS\u0026reg;, Canon Inc., Tokyo, Japan). Electronic image data (jpg format) was imported into a computer, and color correction was performed using the color chart in combination with image editing software (Photoshop CS6 Extended\u0026reg;, Adobe Systems Inc., California, United States). The photographs were printed using an inkjet printer (Pixus MG7530\u0026reg;, Canon Inc., Tokyo, Japan). The colors of the central portion of the lower lip and the lower palpebral conjunctiva mucosa, as displayed in the printed photograph, were measured using the spectrophotometer. Illuminance of the room was measured with every patient snapshot.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.5 Color difference\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe used the color difference to assess the discriminability by site of anemia\u0026nbsp;identification. Although the measurement of the color of the conjunctiva and lips is indirect, it may be inaccurate. However, by utilizing color differences, we could still achieve the objectives of this study.\u003c/p\u003e\n\u003cp\u003eThe color difference (\u0026Delta;E*) was calculated using the following formula: \u003cimg src=\"https://myfiles.space/user_files/58850_9595ee6b312d78cf/58850_custom_files/img1719946632.png\"\u003e\u003c/p\u003e\n\u003cp\u003eColor difference indicates how easily two colors can be distinguished by the human eye.\u003c/p\u003e\n\u003cp\u003eThe color difference is judged using the following criterion: \u0026lt; 3.0,\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003ewhich is difficult to recognize by human eyes; 3.0\u0026ndash;6.0 which is recognizable, with the possibility of\u0026nbsp;overlooking; and \u0026ge; 6.0, which is clearly recognizable.\u003csup\u003e26\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eUsing color difference allows us to determine which areas are more easily identifiable for detecting anemia.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e2.6\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003eDefinition of anemia\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAnemia is defined by the World Health Organization as a Hb value below 13.0 g/dL for men and below 12.0 g/dL for non-pregnant women.\u003csup\u003e27\u003c/sup\u003e In the present study, anemia was defined as a Hb value below 12.0 g/dL in both men and women.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.7 Sample size\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn the absence of previous studies on the same theme, the a* value of the palpebra of the first 10 participants was used to calculate the sample size. The average a* value of the palpebra was 33.2, with a standard deviation of 6.1. It is expected that there will be a 10% difference between the two groups. Consequently, it was calculated that 53 participants are needed in each of the two groups.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.8 Statistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eContinuous variables were presented as the mean and standard deviation, and categorical variables were presented as the actual number and percentage. Categorical data were compared using the chi-squared test. The mean between the two groups (normal and anemic participants, men and women) were compared using the unpaired Student\u0026rsquo;s t-test. Associations between the two continuous variables were determined using Pearson\u0026rsquo;s correlation coefficient. A P-value \u0026lt; 0.05 was considered statistically significant. All statistical analyses were performed using EZR on R-commander (version 1.28 for Windows, Saitama Medical Center, Jichi Medical University, Saitama, Japan), which is a graphical user interface for R (The R Foundation for Statistical Computing, Vienna, Austria).\u003csup\u003e28\u003c/sup\u003e\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 108 participants were enrolled. However, after excluding samples with measurement errors or missing variables, data from 92 participants were finally analyzed. The mean age was 68.5 \u0026plusmn; 15.5 years, there were 47 men (51.1%), and the RBC values were 420.4 \u0026plusmn; 68.2 \u0026times; 104/\u0026mu;L, Hb 12.8 \u0026plusmn; 2.1 g/dL, and Ht 38.5 \u0026plusmn; 6.2%, respectively. Correlation coefficient between the venous Hb value and measured color is shown in Table 1. Characteristics and measured color according to the presence of anemia are shown in Table 2. Color differences of each site according to the range of Hb value are shown in Table 3.\u003c/p\u003e\n\u003cp\u003eIn the lower palpebral conjunctiva, all color differences were 6.0 or more in the normal group and the anemic group. In the lower lip, the color difference between the group of 10.0\u0026ndash;11.9 and the group of 12.0\u0026ndash;13.9 was 3.4, but all other color differences were 6.0 or more. In the nail, palm, and inside of the upper arm, all the color differences were less than 6.0, and it turned out that there was no color difference at the level that can recognize the color difference obviously with human eyes. The color differences between the group with Hb \u0026lt; 10.0 and \u0026ge; 14.0 in the nail, between the group with Hb \u0026lt; 10.0 and \u0026ge; 12.0 in the nail bed, between the group with Hb 10.0\u0026ndash;11.9 and \u0026ge; 14.0 in the palm, and between the group with Hb \u0026lt; 10.0 and \u0026ge; 14.0 in inside of the upper arm were 3.9, 3.0 or more, 3.0, and 3.4, respectively. These may be recognized by trained human eyes.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe purpose of this study was to objectively evaluate the relationship between venous Hb levels and skin/mucosal color to determine which sites are suitable for identifying anemia. Consequently, the color of the lower lip, lower palpebral conjunctiva, palm, nail bed, and inside of the upper arm demonstrated an association with Hb values. However, the results suggest that not all sites are equally crucial for evaluating anemia.\u003c/p\u003e\n\u003cp\u003eWe examined the association between venous Hb values and individual color elements, categorizing them into L*, a*, and b*. However, the relevance was small except for the a* value. In the lower lip, lower palpebral conjunctiva, palm, and inside of the upper arm, the a* value, an indicator of redness, exhibited a positive association with venous Hb values. However, when comparing the normal group and the anemic group, only the lower lip and lower palpebral conjunctiva showed a significant difference in the a* value. Two potential reasons are considered: (1) The a* value of the palm and inside of the upper arm may have a weak association with venous Hb values, possibly resulting in difficulty expressing the colors of these sites as red intensity even in the presence of anemia, and (2) the small number of participants with anemia might lead to inaccurate color representation at lower Hb values.\u003c/p\u003e\n\u003cp\u003eIn the nail and palm, the b* value, an indicator of yellowness, displayed a negative association with venous Hb values. However, when comparing the normal group and the anemic group, only the palm showed a significant difference in the b* value. At these sites, a lower venous Hb value reduced the red color, emphasizing the yellowness of the skin\u0026apos;s original color. Regarding the L* value, an indicator of lightness, no significant difference was observed at any site between the normal and anemic groups, although in the palm and inside of the upper arm, the L* value showed a negative association with venous Hb values. It is suggested that Hb, being red in color, is slightly associated with the L* value.\u003c/p\u003e\n\u003cp\u003eFor easier comprehension, the color of each part was converted into color difference (\u0026Delta;E*), a composite value of L*a*b*, and analyzed within each Hb value range. If the color difference between the group with Hb \u0026lt;11.9 and the group with 12.0 or more is 6.0 or more, it reaches a level where the difference in color is clearly noticeable to the human eye. Therefore, in the physical examination of anemia, it was determined that the palpebral conjunctiva and the lower lip are the most suitable sites. Additionally, for anemia diagnosis, pallor in the nail, palm and inside of the upper arm may be discerned by trained human eyes.\u003c/p\u003e\n\u003cp\u003eAccording to the findings of this study, the lower palpebral conjunctiva and the lower lip, traditionally used in physical examinations, are also suitable for colorimetric evaluation in diagnosing anemia. In the nail, palm, and inside of the upper arm, anemia may be detected by trained human eyes if the venous Hb value is less than 10.0. Therefore, when utilizing these sites for anemia diagnosis, oversight is possible.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e4.1 Strengths and limitations of this study\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe present study also had several strengths. First, this is the first study that investigated the association between the color of the lower lip, lower palpebral conjunctiva, palm, nail bed, and inside of the upper arm measured using spectrophotometer and venous Hb values among adult Japanese. Second, we provided valuable information to primary care physicians by identifying the most appropriate site for assessing anemia based on principles of color science.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHowever, the present study had several limitations. Firstly, the biggest drawback of this study is that we could not directly measure the color of the conjunctiva and lip. We believe that it is appropriate to use color differences to indicate the ease of identifying anemia by location. Since it is possible to use indirect color measurement as a substitute for determining the ease of discrimination based on color difference, we believe that the purpose of this research can be achieved. However, the results of the correlation between color and Hb value may not be correct. Second, the study included a small sample size of patients with moderate to severe anemia (Hb \u0026lt; 10.0 g/dL). Thus, the usefulness of the nail bed, palm, and upper arm pallor in detecting anemia cannot be entirely discounted. Third, most of the participants were elderly, and their age distribution was biased. Fourth, since all participants were Japanese, there is bias in ethnicity. The interpretation of the results for skin color can only be applied to the Japanese. Fifth, this study assessed pallor using a spectrophotometer, which raises the question of whether the human eye can detect the same subtle differences in pallor color. Consequently, further research is necessary to determine whether human observers can reliably identify the presence or absence of anemia through training.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThe palpebral conjunctiva and lip demonstrate potential suitability for visual diagnosis of anemia. In the nail, palm, and inside of the upper arm, anemia detection may require highly trained observation. Consequently, reliance on these sites for anemia diagnosis may lead to potential oversight.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eACKNOWLEDGMENTS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe appreciate the patient who accepted to participate this study and the support of the nursing staff of the Division of the Clinical Laboratory of Kameyama Municipal Medical Center. This study was funded by New Paradigms \u0026ndash; Establishing Centers for Fostering Medical Researchers of the Future by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) in Japan.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCONFLICT OF INTEREST STATEMENT\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eETHICS STATEMENT\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Ethics Committee of Mie University Graduate School of Medicine (No.1421).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePATIENT CONSENT STATEMENT\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll participants signed an informed consent prior to their participation.\u003c/p\u003e"},{"header":"References","content":"\u003cp\u003e1. Kassebaum NJ, Jasrasaria R, Naghavi M, Wulf SK, Johns N, Lozano R, et al. A systematic analysis of global anemia burden from 1990 to 2010. Blood. 2014;123: 615-24.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e2. Li M, Hu Y, Mao D, Wnag R, Chen J, Li W, et al. Prevalence of Anemia among Chinese Rural Residents. Nutrients. 2017;9:192.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e3. Brabin BJ, Premji Z, Verhoeff F. An analysis of anemia and child mortality. J Nutr\u003cem\u003e.\u003c/em\u003e 2001;131:636S-45S.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e4. Critchley J, Bates I. Haemoglobin colour scale for anaemia diagnosis where there is no laboratory: a systematic review.\u003cem\u003e\u0026nbsp;\u003c/em\u003eInt J Epidemiol. 2005;34:1425-34.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e5. Shimomura T, Wakabayashi I. [Regional differences in prevalence of anemia found by periodic health checkups at workplaces in Japan]. Sangyo eiseigaku zasshi. 2010;52:21-27. [In Japanese].\u003c/p\u003e\n\u003cp\u003e6. Hori M, Matsuda T, Shibata A, Katanoda K, Sobue T, Nishimoto H. Cancer incidence and incidence rates in Japan in 2009: a study of 32 population-based cancer registries for the Monitoring of Cancer Incidence in Japan (MCIJ) project. Jpn J Clin Oncol. 2015;45,:884-91.\u003c/p\u003e\n\u003cp\u003e7. Hung OL, Kwon NS, Cole AE, Dacpano GR, Wu T, Chiang WK, et al. Evaluation of the physician\u0026apos;s ability to recognize the presence or absence of anemia, fever, and jaundice. Acad Emerg Med. 2000;7:146-56.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e8. Kalantri A, Karambelkar M, Joshi R, Kalantri S, Jajoo U. Accuracy and reliability of pallor for detecting anaemia: a hospital-based diagnostic accuracy study. PloS One. 2010;5: e8545.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e9. Manesh RS, Kohlwes RJ. Palmar Crease Pallor. J Gen Intern Med. 2015;30:1034.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e10. Nardone DA, Roth KM, Mazur DJ, McAfee JH. Usefulness of physical examination in detecting the presence or absence of anemia. Arch Intern Med. 1990;150:201-4.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e11. Strobach RS, Anderson SK, Doll DC, Ringenberg QS. The value of the physical examination in the diagnosis of anemia. Correlation of the physical findings and the hemoglobin concentration. Arch Intern Med. 1988;148:831-2.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e12. Chalco JP, Huicho L, Alamo C, Carreazo NY, Bada CA. Accuracy of clinical pallor in the diagnosis of anaemia in children: a meta-analysis. BMC Pediatr. 2005;5:46.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e13. Ingram CF, Lewis SM. Clinical use of WHO haemoglobin colour scale: validation and critique.\u003cem\u003e\u0026nbsp;\u003c/em\u003eJ Clin Pathol. 2000;53:933-7.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e14. Kalter HD, Burnham G, Kolstad PR, Hossain M, Schillinger JA, Khan NZ, et al. Evaluation of clinical signs to diagnose anaemia in Uganda and Bangladesh, in areas with and without malaria. Bull World Health Organ. 1997;75:103-11.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e15. Lewis SM, Stott GJ, Wynn KJ. An inexpensive and reliable new haemoglobin colour scale for assessing anaemia. J clin pathol. 1998;51:21-4.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e16. Luby SP, Kazembe PN, Redd SC, Ziba C, Nwanyanwu OC, Hightower AW, et al. Using clinical signs to diagnose anaemia in African children. Bull World Health Organ. 1995;73,:477-82.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e17. Marn H, Critchley JA. Accuracy of the WHO Haemoglobin Colour Scale for the diagnosis of anaemia in primary health care settings in low-income countries: a systematic review and meta-analysis. Lancet Glob Health. 2016;4:e251-65.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e18. Mogensen CB, Soerensen J, Bjorkman A, Montgomery SM. Algorithm for the diagnosis of anaemia without laboratory facilities among small children in a malaria endemic area of rural Tanzania. Acta Trop.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e2006;99:119-25.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e19. Mogensen CB, Sorensen JE, Bjorkman A. Pallor as a sign of anaemia in small Tanzanian children at different health care levels.\u0026nbsp;Acta Trop. 2006;99:113-8.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e20. Van den Broek NR, Ntonya C, Mhango E, White SA. Diagnosing anaemia in pregnancy in rural clinics: assessing the potential of the Haemoglobin Colour Scale. Bull World Health Organ. 1999;77:15-21.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e21. Weber MW, Kellingray SD, Palmer A, Jaffar S, Mulholland EK, Greenwood BM. Pallor as a clinical sign of severe anaemia in children: an investigation in the Gambia. Bull World Health Organ. 1997;75:113-8.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e22. Zucker JR, Perkins BA, Jafari H, Otieno J, Obonyo C, Campbell CC. Clinical signs for the recognition of children with moderate or severe anaemia in western Kenya. Bull World Health Organ. 1997;75:97-102.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e23. Butt Z, Ashfaq U, Sherazi SF, Jan NU, Shahbaz U. Diagnostic accuracy of \u0026quot;pallor\u0026quot; for detecting mild and severe anaemia in hospitalized patients.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eJ Pak Med Assoc. 2010;60:762-5.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e24. Sheth TN, Choudhry NK, Bowes M, Detsky AS. The relation of conjunctival pallor to the presence of anemia. J Gen Intern Med. 1997;12:102-6.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e25. Illumination ICo. About the CIE. [Cited 11 June 2024]. Available from:\u0026nbsp;\u003ca href=\"https://cie.co.at/about-cie\"\u003ehttps://cie.co.at/about-cie\u003c/a\u003e (2024)\u003c/p\u003e\n\u003cp\u003e26. Hsin-Chia C, Sheng-Jyh W. The use of visible color difference in the quantitative evaluation of color image segmentation. 2004 IEEE International Conference on Acoustics, Speech, and Signal Processing. 2004;3:iii-593-6.\u003c/p\u003e\n\u003cp\u003e27. WHO Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity. [Cited 11 June 2024]. Available from:\u0026nbsp;\u003ca href=\"https://www.who.int/publications/i/item/WHO-NMH-NHD-MNM-11.1\"\u003ehttps://www.who.int/publications/i/item/WHO-NMH-NHD-MNM-11.1\u003c/a\u003e (2011)\u003c/p\u003e\n\u003cp\u003e28. Kanda Y. Investigation of the freely available easy-to-use software \u0026apos;EZR\u0026apos; for medical statistics. Bone Marrow Transplant. 2013;48:452-8.\u0026nbsp;\u003c/p\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1. Correlation coefficient between the venous hemoglobin (Hb) value and measured color. \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eL*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ea*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eb*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003ePalpebral\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e- 0.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e0.50\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e- 0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003eLip\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026shy; 0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e0.42\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003eNail\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026shy; 0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026shy; 0.26\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003ePalm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026shy; 0.25\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e0.30\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e- 0.28\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003eUpper arm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026shy; 0.25\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e0.27\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026shy; 0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eCorrelations were determined using Pearson\u0026rsquo;s correlation coefficient.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e\u0026dagger;\u003c/sup\u003eCorrelation coefficient with\u003cem\u003e\u0026nbsp;p\u003c/em\u003e value less than 0.05\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cbr\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2. Characteristics and measured color according to the presence of anemia.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"605\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.980132450331126%\"\u003e\n \u003cp\u003e\u003cstrong\u003eCharacteristics\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.966887417218543%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.562913907284768%\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003cp\u003e(n=92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.70860927152318%\"\u003e\n \u003cp\u003eAnemia\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003e(n=25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.70860927152318%\"\u003e\n \u003cp\u003eNormal\u003c/p\u003e\n \u003cp\u003e(n=67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.072847682119205%\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.980132450331126%\"\u003e\n \u003cp\u003eAge, mean\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u0026plusmn; SD, years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.966887417218543%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.562913907284768%\"\u003e\n \u003cp\u003e68.5 \u0026plusmn; 15.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.70860927152318%\"\u003e\n \u003cp\u003e73.2 \u0026plusmn; 15.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.70860927152318%\"\u003e\n \u003cp\u003e66.7 \u0026plusmn; 15.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.072847682119205%\"\u003e\n \u003cp\u003e0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.980132450331126%\"\u003e\n \u003cp\u003eMen, number (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.966887417218543%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.562913907284768%\"\u003e\n \u003cp\u003e47 (51.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.70860927152318%\"\u003e\n \u003cp\u003e8 (32.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.70860927152318%\"\u003e\n \u003cp\u003e39 (58.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.072847682119205%\"\u003e\n \u003cp\u003e0.05\u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.980132450331126%\"\u003e\n \u003cp\u003eIlluminance of the room, mean\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u0026plusmn; SD, lux\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.966887417218543%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.562913907284768%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.70860927152318%\"\u003e\n \u003cp\u003e658.2 \u0026plusmn; 269.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.70860927152318%\"\u003e\n \u003cp\u003e707.5 \u0026plusmn; 112.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.072847682119205%\"\u003e\n \u003cp\u003e0.21\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.980132450331126%\"\u003e\n \u003cp\u003eHemoglobin, g/dL \u0026plusmn; SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.966887417218543%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.562913907284768%\"\u003e\n \u003cp\u003e12.8 \u0026plusmn; 2.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.70860927152318%\"\u003e\n \u003cp\u003e10.1 \u0026plusmn; 1.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.70860927152318%\"\u003e\n \u003cp\u003e13.8 \u0026plusmn; 1.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.072847682119205%\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.980132450331126%\"\u003e\n \u003cp\u003e\u003cstrong\u003eMeasured color, no unit,\u0026nbsp;\u003c/strong\u003emean\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u0026plusmn; SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.966887417218543%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.562913907284768%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.70860927152318%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.70860927152318%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.072847682119205%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.980132450331126%\"\u003e\n \u003cp\u003ePalpebral\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.966887417218543%\" valign=\"top\"\u003e\n \u003cp\u003eL*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.562913907284768%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.70860927152318%\"\u003e\n \u003cp\u003e52.9 \u0026plusmn; 8.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.70860927152318%\"\u003e\n \u003cp\u003e50.0 \u0026plusmn; 7.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.072847682119205%\"\u003e\n \u003cp\u003e0.11\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.980132450331126%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.966887417218543%\" valign=\"top\"\u003e\n \u003cp\u003ea*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.562913907284768%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.70860927152318%\"\u003e\n \u003cp\u003e29.4 \u0026plusmn; 8.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.70860927152318%\"\u003e\n \u003cp\u003e36.7 \u0026plusmn; 5.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.072847682119205%\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.980132450331126%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.966887417218543%\" valign=\"top\"\u003e\n \u003cp\u003eb*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.562913907284768%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.70860927152318%\"\u003e\n \u003cp\u003e19.4\u0026plusmn;9.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.70860927152318%\"\u003e\n \u003cp\u003e21.5 \u0026plusmn; 7.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.072847682119205%\"\u003e\n \u003cp\u003e0.26\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.980132450331126%\"\u003e\n \u003cp\u003eLip\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.966887417218543%\" valign=\"top\"\u003e\n \u003cp\u003eL*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.562913907284768%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.70860927152318%\"\u003e\n \u003cp\u003e59.1 \u0026plusmn; 12.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.70860927152318%\"\u003e\n \u003cp\u003e57.8 \u0026plusmn; 8.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.072847682119205%\"\u003e\n \u003cp\u003e0.58\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.980132450331126%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.966887417218543%\" valign=\"top\"\u003e\n \u003cp\u003ea*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.562913907284768%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.70860927152318%\"\u003e\n \u003cp\u003e29.8 \u0026plusmn; 6.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.70860927152318%\"\u003e\n \u003cp\u003e34.6 \u0026plusmn; 6.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.072847682119205%\"\u003e\n \u003cp\u003e\u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.980132450331126%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.966887417218543%\" valign=\"top\"\u003e\n \u003cp\u003eb*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.562913907284768%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.70860927152318%\"\u003e\n \u003cp\u003e12.7 \u0026plusmn; 8.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.70860927152318%\"\u003e\n \u003cp\u003e13.1 \u0026plusmn; 7.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.072847682119205%\"\u003e\n \u003cp\u003e0.81\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.980132450331126%\"\u003e\n \u003cp\u003eNail\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.966887417218543%\" valign=\"top\"\u003e\n \u003cp\u003eL*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.562913907284768%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.70860927152318%\"\u003e\n \u003cp\u003e55.4 \u0026plusmn; 9.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.70860927152318%\"\u003e\n \u003cp\u003e54.3 \u0026plusmn; 8.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.072847682119205%\"\u003e\n \u003cp\u003e0.57\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.980132450331126%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.966887417218543%\" valign=\"top\"\u003e\n \u003cp\u003ea*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.562913907284768%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.70860927152318%\"\u003e\n \u003cp\u003e4.6 \u0026plusmn; 1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.70860927152318%\"\u003e\n \u003cp\u003e4.9 \u0026plusmn; 2.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.072847682119205%\"\u003e\n \u003cp\u003e0.52\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.980132450331126%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.966887417218543%\" valign=\"top\"\u003e\n \u003cp\u003eb*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.562913907284768%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.70860927152318%\"\u003e\n \u003cp\u003e11.1 \u0026plusmn; 2.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.70860927152318%\"\u003e\n \u003cp\u003e10.1 \u0026plusmn; 2.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.072847682119205%\"\u003e\n \u003cp\u003e0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.980132450331126%\"\u003e\n \u003cp\u003ePalm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.966887417218543%\" valign=\"top\"\u003e\n \u003cp\u003eL*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.562913907284768%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.70860927152318%\"\u003e\n \u003cp\u003e62.9 \u0026plusmn; 2.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.70860927152318%\"\u003e\n \u003cp\u003e61.2 \u0026plusmn; 4.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.072847682119205%\"\u003e\n \u003cp\u003e0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.980132450331126%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.966887417218543%\" valign=\"top\"\u003e\n \u003cp\u003ea*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.562913907284768%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.70860927152318%\"\u003e\n \u003cp\u003e7.2 \u0026plusmn; 2.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.70860927152318%\"\u003e\n \u003cp\u003e8.0 \u0026plusmn; 2.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.072847682119205%\"\u003e\n \u003cp\u003e0.11\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.980132450331126%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.966887417218543%\" valign=\"top\"\u003e\n \u003cp\u003eb*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.562913907284768%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.70860927152318%\"\u003e\n \u003cp\u003e16.7 \u0026plusmn; 2.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.70860927152318%\"\u003e\n \u003cp\u003e15.3 \u0026plusmn; 2.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.072847682119205%\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.980132450331126%\"\u003e\n \u003cp\u003eUpper arm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.966887417218543%\" valign=\"top\"\u003e\n \u003cp\u003eL*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.562913907284768%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.70860927152318%\"\u003e\n \u003cp\u003e65.4 \u0026plusmn; 3.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.70860927152318%\"\u003e\n \u003cp\u003e65.0 \u0026plusmn; 3.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.072847682119205%\"\u003e\n \u003cp\u003e0.54\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.980132450331126%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.966887417218543%\" valign=\"top\"\u003e\n \u003cp\u003ea*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.562913907284768%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.70860927152318%\"\u003e\n \u003cp\u003e5.0 \u0026plusmn; 1.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.70860927152318%\"\u003e\n \u003cp\u003e5.4 \u0026plusmn; 1.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.072847682119205%\"\u003e\n \u003cp\u003e0.20\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.980132450331126%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.966887417218543%\" valign=\"top\"\u003e\n \u003cp\u003eb*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.562913907284768%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.70860927152318%\"\u003e\n \u003cp\u003e15.8 \u0026plusmn; 2.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.70860927152318%\"\u003e\n \u003cp\u003e15.4 \u0026plusmn; 2.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.072847682119205%\"\u003e\n \u003cp\u003e0.47\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003csup\u003e\u0026dagger;\u003c/sup\u003eAnemia was defined as \u0026lt; 12 g/dL in both men and women\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e\u0026Dagger;\u003c/sup\u003eA \u003cem\u003ep\u003c/em\u003e-value was determined using chi-squared test. Other all \u003cem\u003ep\u003c/em\u003e values were determined using unpaired Student\u0026rsquo;s t-test\u003c/p\u003e\n\u003cp\u003eSD, standard deviation; N/A, not applicable\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cbr\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3. Color differences of each site according to the range of Hb value.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"520\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.094412331406552%\"\u003e\n \u003cp\u003eRange of Hb value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e\u0026lt;10.0\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(N=8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e10.0\u0026ndash;11.9\u003c/p\u003e\n \u003cp\u003e(N=17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e12.0\u0026ndash;13.9\u003c/p\u003e\n \u003cp\u003e(N=39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e\u0026ge;\u0026nbsp;14.0\u003c/p\u003e\n \u003cp\u003e(N=28)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.094412331406552%\"\u003e\n \u003cp\u003ePalpebral conjunctiva\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.094412331406552%\"\u003e\n \u003cp\u003e\u0026lt; 10.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.094412331406552%\"\u003e\n \u003cp\u003e10.0\u0026ndash;11.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e5.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.094412331406552%\"\u003e\n \u003cp\u003e12.0\u0026ndash;13.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e10.5\u003csup\u003e\u0026lowast;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e7.8\u003csup\u003e\u0026lowast;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.094412331406552%\"\u003e\n \u003cp\u003e\u0026ge;\u0026nbsp;14.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e10.7\u003csup\u003e\u0026lowast;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e7.1\u003csup\u003e\u0026lowast;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e2.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.094412331406552%\"\u003e\n \u003cp\u003eLip\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.094412331406552%\"\u003e\n \u003cp\u003e\u0026lt; 10.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.094412331406552%\"\u003e\n \u003cp\u003e10.0\u0026ndash;11.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e11.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.094412331406552%\"\u003e\n \u003cp\u003e12.0\u0026ndash;13.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e10.8\u003csup\u003e\u0026lowast;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e3.4\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.094412331406552%\"\u003e\n \u003cp\u003e\u0026ge;\u0026nbsp;14.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e12.1\u003csup\u003e\u0026lowast;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e6.2\u003csup\u003e\u0026lowast;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e3.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.094412331406552%\"\u003e\n \u003cp\u003eNail\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.094412331406552%\"\u003e\n \u003cp\u003e\u0026lt; 10.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.094412331406552%\"\u003e\n \u003cp\u003e10.0\u0026ndash;11.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e2.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.094412331406552%\"\u003e\n \u003cp\u003e12.0\u0026ndash;13.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e2.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.094412331406552%\"\u003e\n \u003cp\u003e\u0026ge;\u0026nbsp;14.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e3.9\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e2.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e2.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.094412331406552%\"\u003e\n \u003cp\u003ePalm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.094412331406552%\"\u003e\n \u003cp\u003e\u0026lt; 10.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.094412331406552%\"\u003e\n \u003cp\u003e10.0\u0026ndash;11.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e2.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.094412331406552%\"\u003e\n \u003cp\u003e12.0\u0026ndash;13.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e3.0\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e1.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.094412331406552%\"\u003e\n \u003cp\u003e\u0026ge;\u0026nbsp;14.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e4.3\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e3.0\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e1.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.094412331406552%\"\u003e\n \u003cp\u003eUpper arm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.094412331406552%\"\u003e\n \u003cp\u003e\u0026lt; 10.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.094412331406552%\"\u003e\n \u003cp\u003e10.0\u0026ndash;11.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e3.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.094412331406552%\"\u003e\n \u003cp\u003e12.0\u0026ndash;13.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e1.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e1.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.094412331406552%\"\u003e\n \u003cp\u003e\u0026ge;\u0026nbsp;14.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e3.4\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e1.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003e1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.726396917148364%\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eN/A, Not applicable\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e\u0026lowast;\u003c/sup\u003eThe numerical value is a color difference of 6.0 or more between the normal group and the anemic group\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e\u0026dagger;\u003c/sup\u003eThe numerical value is a color difference of 3.0\u0026ndash;6.0 between the normal group and the anemic group.\u003c/p\u003e\n\u003cp\u003eThe color differences were calculated using the average of the measurements of each Hb category. The color difference is judged by using the following criterion: 3.0 \u0026gt; is difficult to recognize by human eyes, 3.0\u0026ndash;6.0 is recognizable, but there is a possibility of overlooking, and 6.0 \u0026ge; is clearly recognizable.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-3865714/v2","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3865714/v2","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground: Clinical pallor has traditionally served as a screening tool for anemia; however, its assessment is inherently subjective and lacks objectivity. Therefore, this study aimed to investigate the correlation between skin and mucosal color, as measured by a spectrophotometer, and venous hemoglobin (Hb) values, to identify the optimal anatomical assessment site for detecting anemia.\u003c/p\u003e\n\u003cp\u003eMethods: A cross-sectional design. Ninety-two adult Japanese outpatients from an urban small hospital in Japan participated in the study. Using a spectrophotometer, the color of the lower lip and palpebral conjunctiva was measured indirectly, while the color of the nails and palms was measured directly. Skin and mucosal color were quantified using the L*a*b* color scale. The color difference (ΔE*) was employed to evaluate the discriminability of anemia identification across different assessment sites. Additionally, venous Hb values were recorded, with anemia defined as Hb \u0026lt;12.0 g/dL.\u003c/p\u003e\n\u003cp\u003eResults: The a* values of the lip, palpebral conjunctiva, palm, and inside of the upper arm exhibited a positive correlation with Hb values and were significantly lower in the anemic group. While the ΔE* levels for the palpebral conjunctiva and lip were readily discernible by the human eye when comparing the normal and anemic groups, recognition at this level proved challenging for other sites.\u003c/p\u003e\n\u003cp\u003eConclusion: The palpebral conjunctiva and lip demonstrate potential suitability for visual diagnosis of anemia. In the nail, palm, and inside of the upper arm, anemia detection may require highly trained observation. Consequently, reliance on these sites for anemia diagnosis may lead to potential oversight.\u003c/p\u003e","manuscriptTitle":"An observational study to determine the optimal physical evaluation site for detecting anemia","msid":"","msnumber":"","nonDraftVersions":[{"code":2,"date":"2024-07-02 19:00:33","doi":"10.21203/rs.3.rs-3865714/v2","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}},{"code":1,"date":"2024-01-17 16:18:47","doi":"10.21203/rs.3.rs-3865714/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3c8e65c1-041d-4682-90a1-03859275f29e","owner":[],"postedDate":"July 2nd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":28203044,"name":"Health sciences/Diseases/Haematological diseases"},{"id":28203045,"name":"Health sciences/Health care/Diagnosis/Physical examination"}],"tags":[],"updatedAt":"2024-04-03T10:42:31+00:00","versionOfRecord":[],"versionCreatedAt":"2024-07-02 19:00:33","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v2","identity":"rs-3865714","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3865714","identity":"rs-3865714","version":["v2"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}