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1.  Hemoglobin estimation by the HemoCue® portable hemoglobin photometer in a resource poor setting 
In resource poor settings where automated hematology analyzers are not available, the Cyanmethemoglobin method is often used. This method though cheaper, takes more time. In blood donations, the semi-quantitative gravimetric copper sulfate method which is very easy and inexpensive may be used but does not provide an acceptable degree of accuracy. The HemoCue® hemoglobin photometer has been used for these purposes. This study was conducted to generate data to support or refute its use as a point-of-care device for hemoglobin estimation in mobile blood donations and critical care areas in health facilities.
EDTA blood was collected from study participants drawn from five groups: pre-school children, school children, pregnant women, non-pregnant women and men. Blood collected was immediately processed to estimate the hemoglobin concentration using three different methods (HemoCue®, Sysmex KX21N and Cyanmethemoglobin). Agreement between the test methods was assessed by the method of Bland and Altman. The Intraclass correlation coefficient (ICC) was used to determine the within subject variability of measured hemoglobin.
Of 398 subjects, 42% were males with the overall mean age being 19.4 years. The overall mean hemoglobin as estimated by each method was 10.4 g/dl for HemoCue, 10.3 g/dl for Sysmex KX21N and 10.3 g/dl for Cyanmethemoglobin. Pairwise analysis revealed that the hemoglobin determined by the HemoCue method was higher than that measured by the KX21N and Cyanmethemoglobin. Comparing the hemoglobin determined by the HemoCue to Cyanmethemoglobin, the concordance correlation coefficient was 0.995 (95% CI: 0.994-0.996, p < 0.001). The Bland and Altman's limit of agreement was -0.389 - 0.644 g/dl with the mean difference being 0.127 (95% CI: 0.102-0.153) and a non-significant difference in variability between the two measurements (p = 0.843). After adjusting to assess the effect of other possible confounders such as sex, age and category of person, there was no significant difference in the hemoglobin determined by the HemoCue compared to Cyanmethemoglobin (coef = -0.127, 95% CI: -0.379 - 0.634).
Hemoglobin determined by the HemoCue method is comparable to that determined by the other methods. The HemoCue photometer is therefore recommended for use as on-the-spot device for determining hemoglobin in resource poor setting.
PMCID: PMC3095531  PMID: 21510885
2.  Evaluation of Hemoglobin Concentration in Pregnancy and Correlation with Different Altitude: A Study from Balochistan Plateau of Pakistan 
Anemia refers to a condition having low hemoglobin concentration. Anemia is considered a major risk factor for unfavorable pregnancy outcomes. This is the first study describing the pattern of hemoglobin concentration during pregnancy and its relationship to areas of high and low altitudes in Balochistan (the largest of Pakistan’s four provinces). The main objective of this study was to observe hemoglobin levels and prevalence of anemia among pregnant women living in the high or low altitude areas of Balochistan.
A randomized survey was conducted and blood samples were collected from 132 healthy full term pregnant women subjects and 110 unmarried females. The subjects of the current study were selected from two different areas of Balochistan (Quetta and Uthal). Hemoglobin levels of the subjects were analyzed on Microlab 300 by Merck kit. Dietary status of the subjects was assessed based on simplified associated food frequency questionnaire. The factors effecting hemoglobin in full term pregnancy at different altitudes were multi gravidity/parity (increased number of pregnancies/children), age, socio-economic and educational status.
Anemia was highly prevalent in low-altitude region (68.33%). We found statistically significant difference in mean hemoglobin level at high-altitude region (11.81 ± 1.02) and low-altitude region (10.20 ± 1.28) in pregnant females of Balochistan plateau (P < 0.001). Higher maternal age (> 35 years) has shown significantly higher anemic frequency at both high (57.89%; p < 0.002) and low (41.46%; p = 0.067) altitudes. A balanced-diet that is rich in meat products has also shown significant correlation with reduced incidences of anemia among pregnant women at both altitudes.
Hemoglobin concentration increases in the body with elevated altitudes and, thus, anemia was less frequent at high-altitude region. Factors affecting hemoglobin concentration in full term pregnancy at different altitudes included old maternal age, low body-mass index, education and diet.
PMCID: PMC4347023  PMID: 25741391
Anemia; altitude; diet; hemoglobin; pregnancy.
3.  Hemoglobin levels and anemia evaluation during pregnancy in the highlands of Tibet: a hospital-based study 
BMC Public Health  2009;9:336.
Anemia is regarded as a major risk factor for unfavorable pregnancy outcomes, but there have been no previous studies describing the pattern of hemoglobin concentration during pregnancy in Tibet and the relationship between altitude and Hb concentration in the pregnant women living in Tibet still has not been clearly established. The main objectives of this study were to study the hemoglobin levels and prevalence of anemia among pregnant women living in the highlands of Tibet and to evaluate potential associations of hemoglobin and anemia with women's characteristics.
The hospital-based study was conducted in 380 pregnant women. Their blood samples were tested and related sociodemographic information was collected. Multiple linear regression model and multiple logistic regression model were used to assess the association of pregnant women's characteristics with hemoglobin level and the occurrence of anemia. Centers for Disease Control (CDC), Dirren et al. and Dallman et al. methods were used to adjust the hemoglobin measurements based on altitude for estimating the prevalence of anemia.
The mean hemoglobin concentration was 127.6 g/L (range: 55.0-190.0 g/L). Prevalence rate of anemia in this study was 70.0%, 77.9% and 41.3%, respectively for three altitude-correction methods for hemoglobin (CDC method, Dirren et al. method, and Dallman et al. method). Gestational age, ethnicity, residence and income were significantly associated with the hemoglobin concentration and prevalence of anemia in the study population. Specially, the hemoglobin concentration of pregnant women decreased with increase in gestational age.
The hemoglobin level was low and prevalence rate of anemia was high among pregnant women in Lhasa, Tibet. Gestational age, ethnicity, residence and income were found to be significantly associated with the hemoglobin level and the occurrence of anemia in the study population.
PMCID: PMC2753353  PMID: 19754927
4.  Environmental risk factors for iron deficiency anemia in children 12–24 months old in the area of Thessalia in Greece  
Hippokratia  2008;12(4):240-250.
Background and aim: Iron deficiency anemia (IDA) is a common problem all over the world, which attacks mainly pregnant women, infants and children. The aim of the study was to estimate the prevalence of IDA in children 12–24 months old in a specific area of Thessalia, located in the central part of Greece, and to identify the environmental risk factors associated with it.
Patients and Methods: In the first part of this cross–sectional and case–control study, the hemoglobin (Hb) levels of 938 children were estimated by a mobile photometer analyzer. In the second part of the study, children with Hb < 11 gr/dl were compared with matched random selected controls in hematological, anthropometric and environmental parameters. The estimated laboratory values were Hb, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, zinc protoporphyrin, serum iron, serum ferritin, transferring saturation, total iron binding capacity and Hb electrophoresis. Finally 75 children (34 boys, 41 girls, mean age 17.51±3.5 months), who were found with IDA, constituted the case group while 75 healthy children constituted the control group.
Results: The prevalence of IDA in the region was 7.99%. At the same time, a number of children with stigma of bthalassaemia (2.13%) was discovered, something that had escaped identification. There were no differences due to the method of determination (mobile or laboratory) in the values of Hb between the two groups. Significant differences were recorded (p<0.001) in all hematological and anthropometric parameters except for head circumference. Regarding environmental factors, significant differences were found in the following parameters: ratio rooms/number of family members (p=0.01), number of family members (p=0.01), number of children in the family (p<0.001), birth rate (p<0.001), education and profession of the parents (p<0.001), source of drinking water and sewage system (p<0.001), duration of breast feeding (p<0.001), milk consumption by the child during the period of the reported research (p<0.001), child's health status according to the mother (p<0.001), and frequency of seeking pediatric care (p=0.02).
Conclusions: Although the prevalence of IDA in this area of Greece is similar to the one observed in the rest of the developed world, it still consists a public health problem. The mobile method for Hb estimation should be introduced in Greece since its reliability to detect IDA has been, once more, confirmed. The application of simple questionnaires for the detection of the environmental IDA risk factors could help in the prognosis and prevention of anemia. Further improvement of the IDA status in Greece could be achieved through the dissemination of information about iron rich foods, the amelioration of environmental conditions and the application of reliable, easy to use and cheap methods for Hb estimation.
PMCID: PMC2580047  PMID: 19158969
children; iron deficiency anemia; environment; questionnaire; Greece
5.  Prevalence and severity of anemia among school children in Jimma Town, Southwest Ethiopia 
BMC Hematology  2014;14:3.
Anemia is a major health problem worldwide. Because of health and socioeconomic problems, the prevalence of anemia is higher in developing countries. Children and pregnant women are the most vulnerable groups to anemia. The aim of the present study was to determine the magnitude of anemia among school children.
A cross-sectional household survey was conducted in January 2011 on 423 children, aged 6–14 years, selected through systematic random sampling method. Sociodemographic and anthropometric data were collected using a pre-tested questionnaire. Capillary blood was taken from the fingertip of each child and hemoglobin was measured using HaemoCue digital photometer. All the necessary safety measures were taken during blood collection. Anthropometric indicators were measured using WHO’s guideline. Data analysis was made using SPSS Version 16.0 for Windows. The association between predictors and outcome variables were measured by a stepwise logistic regression model. Ethical permission was obtained; consent of the parents/guardian was taken and confidentiality was maintained.
A total of 404 children were studied. The mean age was 10.21(SD ± 1.89) years. The proportion of females was 217(53.7%). The mean hemoglobin level for both sexes was 11.59(SD ± 1.97 g/dl). The current prevalence of anemia was 152(37.6%), out of which, 73(18.1%) had mild while 79(19.6%) of them had moderate anemia. The prevalence of anemia among the age group of 6–11 years was 118(40.5%) while the prevalence among the group of 12–14 years old children was 34(30.1%). Among the selected variables in the logistic regression analysis, low family income [OR = 4.925, 95% CI(1.063,22.820)], mothers’ education [OR = 4.621, 95% CI(1.383,15.439)], intake of plant food [OR = 3.847, 95% CI(2.068, 7.157)] and intake of animal food [OR = 2.37, 95% CI(1.040,5.402)] were significantly and independently associated with anemia.
Anemia is a moderate public health problem in the study area. Family income, educational status of parents and inadequate plant and animal food intake are the predictors of anemia. Improving the economic status of the family, women education and health education about balanced animal and plant food consumption are recommended strategies to reduce the burden of anemia.
PMCID: PMC3896819  PMID: 24433408
Hemoglobin; Anemia; School children; Prevalence
6.  Major Burden of Severe Anemia from Non-Falciparum Malaria Species in Southern Papua: A Hospital-Based Surveillance Study 
PLoS Medicine  2013;10(12):e1001575.
Ric Price and colleagues use hospital-based surveillance data to estimate the risk of severe anemia and mortality associated with endemic Plasmodium species in southern Papua, Indonesia.
Please see later in the article for the Editors' Summary
The burden of anemia attributable to non-falciparum malarias in regions with Plasmodium co-endemicity is poorly documented. We compared the hematological profile of patients with and without malaria in southern Papua, Indonesia.
Methods and Findings
Clinical and laboratory data were linked for all patients presenting to a referral hospital between April 2004 and December 2012. Data were available on patient demographics, malaria diagnosis, hemoglobin concentration, and clinical outcome, but other potential causes of anemia could not be identified reliably. Of 922,120 patient episodes (837,989 as outpatients and 84,131 as inpatients), a total of 219,845 (23.8%) were associated with a hemoglobin measurement, of whom 67,696 (30.8%) had malaria. Patients with P. malariae infection had the lowest hemoglobin concentration (n = 1,608, mean = 8.93 [95% CI 8.81–9.06]), followed by those with mixed species infections (n = 8,645, mean = 9.22 [95% CI 9.16–9.28]), P. falciparum (n = 37,554, mean = 9.47 [95% CI 9.44–9.50]), and P. vivax (n = 19,858, mean = 9.53 [95% CI 9.49–9.57]); p-value for all comparisons <0.001. Severe anemia (hemoglobin <5 g/dl) was present in 8,151 (3.7%) patients. Compared to patients without malaria, those with mixed Plasmodium infection were at greatest risk of severe anemia (adjusted odds ratio [AOR] 3.25 [95% CI 2.99–3.54]); AORs for severe anaemia associated with P. falciparum, P. vivax, and P. malariae were 2.11 (95% CI 2.00–2.23), 1.87 (95% CI 1.74–2.01), and 2.18 (95% CI 1.76–2.67), respectively, p<0.001. Overall, 12.2% (95% CI 11.2%–13.3%) of severe anemia was attributable to non-falciparum infections compared with 15.1% (95% CI 13.9%–16.3%) for P. falciparum monoinfections. Patients with severe anemia had an increased risk of death (AOR = 5.80 [95% CI 5.17–6.50]; p<0.001). Not all patients had a hemoglobin measurement, thus limitations of the study include the potential for selection bias, and possible residual confounding in multivariable analyses.
In Papua P. vivax is the dominant cause of severe anemia in early infancy, mixed P. vivax/P. falciparum infections are associated with a greater hematological impairment than either species alone, and in adulthood P. malariae, although rare, is associated with the lowest hemoglobin concentration. These findings highlight the public health importance of integrated genus-wide malaria control strategies in areas of Plasmodium co-endemicity.
Please see later in the article for the Editors' Summary
Editors' Summary
Malaria—a mosquito-borne parasitic disease—is a global public health problem. Five parasites cause malaria—Plasmodium falciparum, P. vivax, P. ovale, P. malariae, and P. knowlesi. Of these, P. vivax is the commonest and most widely distributed, whereas P. falciparum causes the most deaths—about a million every year. All these parasites enter their human host when an infected mosquito takes a blood meal. The parasites migrate to the liver where they replicate and mature into a parasitic form known as merozoites. After 8–9 days, the merozoites are released from the liver cells and invade red blood cells where they replicate rapidly before bursting out and infecting more red blood cells. Malaria's recurring flu-like symptoms are caused by this cyclical increase in parasites in the blood. Malaria needs to be treated promptly with antimalarial drugs to prevent the development of potentially fatal complications. Infections with P. falciparum in particular can cause anemia (a reduction in red blood cell numbers) and can damage the brain and other vital organs by blocking the capillaries that supply these organs with blood.
Why Was This Study Done?
It is unclear what proportion of anemia is attributable to non-falciparum malarias in regions of the world where several species of malaria parasite are always present (Plasmodium co-endemicity). Public health officials in such regions need to know whether non-falciparum malarias are a major cause of anemia when designing malaria control strategies. If P. vivax, for example, is a major cause of anemia in an area where P. vivax and P. falciparum co-exist, then any malaria control strategies that are implemented need to take into account the biological differences between the parasites. In this hospital-based cohort study, the researchers investigate the burden of severe anemia from the endemic Plasmodium species in southern Papua, Indonesia.
What Did the Researchers Do and Find?
The researchers used hospital record numbers to link clinical and laboratory data for patients presenting to a referral hospital in southern Papua over an 8-year period. The hemoglobin level (an indicator of anemia) was measured in about a quarter of hospital presentations (some patients attended the hospital several times). A third of the presentations who had their hemoglobin level determined (67,696 presentations) had clinical malaria. Patients with P. malariae infection had the lowest average hemoglobin concentration. Patients with mixed species, P. falciparum, and P. vivax infections had slightly higher average hemoglobin levels but all these levels were below the normal range for people living in Papua. Among the patients who had their hemoglobin status assessed, 3.7% had severe anemia. After allowing for other factors that alter the risk of anemia (“confounding” factors such as age), patients with mixed Plasmodium infection were more than three times as likely to have severe anemia as patients without malaria. Patients with P. falciparum, P. vivax, or P. malariae infections were about twice as likely to have severe anemia as patients without malaria. About 12.2% of severe anemia was attributable to non-falciparum infections, 15.1% was attributable to P. falciparum monoinfections, and P. vivax was the dominant cause of severe anemia in infancy. Finally, compared to patients without anemia, patients with severe anemia had nearly a 6-fold higher risk of death.
What Do These Findings Mean?
These findings provide a comparative assessment of the pattern of anemia associated with non-falciparum malarias in Papua and an estimate of the public health importance of these malarias. Although the accuracy of these findings may be affected by residual confounding (for example, the researchers did not consider nutritional status when calculating how much malaria infection increases the risk of anemia) and other limitations of the study design, non-falciparum malarias clearly make a major contribution to the burden of anemia in southern Papua. In particular, these findings reveal the large contribution that P. vivax makes to severe anemia in infancy, show that the hematological (blood-related) impact of P. malariae is most apparent in adulthood, and suggest, in contrast to some previous reports, that mixed P. vivax/P. falciparum infection is associated with a higher risk of severe anemia than monoinfection with either species. These findings, which need to be confirmed in other settings, highlight the public health importance of implementing integrated malaria control strategies that aim to control all Plasmodium species rather than a single species in regions of Plasmodium co-endemicity.
Additional Information
Please access these websites via the online version of this summary at
This study is further discussed in a PLOS Medicine Perspective by Gosling and Hsiang
Information is available from the World Health Organization on malaria (in several languages); the 2012 World Malaria Report provides details of the current global malaria situation
The US Centers for Disease Control and Prevention provide information on malaria (in English and Spanish), including information on different Plasmodium species and a selection of personal stories about malaria
The Malaria Vaccine Initiative has fact sheets on Plasmodium falciparum malaria and on Plasmodium vivax malaria
MedlinePlus provides links to additional information on malaria and on anemia (in English and Spanish)
Information is available from the WorldWide Antimalarial Resistance Network on antimalarial drug resistance for P. falciparum and P. vivax
PMCID: PMC3866090  PMID: 24358031
7.  Iron deficiency anemia is not a rare problem among women of reproductive ages in Ethiopia: a community based cross sectional study 
In Ethiopia, the existence of iron deficiency anemia is controversial despite the fact that Ethiopia is one of the least developed in Africa with a high burden of nutrient deficiencies.
The first large nutrition study of a representative sample of women in Ethiopia was conducted from June to July 2005 and a systematically selected sub-sample of 970 of these subjects, 15 to 49 years old, were used in this analysis of nutritional anemia. Hemoglobin was measured from capillary blood using a portable HemoCue photometer. For serum ferritin, venous blood from antecubital veins was measured by an automated Elecsys 1020 using commercial kits. Diets were assessed via simplified food frequency questionnaire. The association of anemia to demographic and health variables was tested by chi-square and a stepwise backward logistic regression model was applied to test the significant associations observed in chi square tests.
Mean hemoglobin ± SD was 11.5 ± 2.1 g/dL with a 29.4% prevalence of anemia. Mean serum ferritin was 58 ± 41.1 ug/L with a 32.1% prevalence of iron deficiency. The overall prevalence rate of iron deficiency anemia was 18.0%. Prevalence of anemia, iron deficiency, and iron deficiency anemia was highest among those 31-49 years old (p < 0.05). Intake of vegetables less than once a day and meat less than once a week was common and was associated with increased anemia (p = 0.001). Although the prevalence of anemia was slightly higher among women with parasitic infestation the difference was not significant (p = 0.9). Nonetheless, anemia was significantly higher in women with history of illness and the association was retained even when the variable was adjusted for its confounding effect in the logistic regression models (AOR = 0.3; 95%CI = 0.17 to 0.5) signifying that the most probable causes of anemia is nutrition related and to some extent chronic illnesses.
Moderate nutritional anemia in the form of iron deficiency anemia is a problem in Ethiopia and therefore, the need for improved supplementation to vulnerable groups is warranted to achieve the United Nation's Millennium Development Goals. Chronic illnesses are another important cause of anemia.
PMCID: PMC2749016  PMID: 19735547
8.  Magnitude of Anemia and Associated Risk Factors among Pregnant Women Attending Antenatal Care in Shalla Woreda, West Arsi Zone, Oromia Region, Ethiopia 
Anemia during pregnancy is a common problem in developing countries and affects both the mother's and her child's health. The main objective of this study was to determine the prevalence of and the factors associated with anemia among pregnant women.
Facility based cross-sectional study design was conducted from June to August, 2011 on 374 pregnant women. Mothers who came for ANC during the study period and who met the inclusion criteria were interviewed and a capillary blood sample was taken. Hemoglobin level was determined by using HemoCue photometer, and interviewer administered questionnaire was used to collect data. Data were cleaned, coded and fed into SPSS version 16.0 for analysis.
The mean hemoglobin concentration was 12.05±1.5 g/dl and prevalence of anemia was 36.6%. Family sizes (COR=2.67, CI (1.65, 4.32), third trimester (COR=1.45, CI (1.11, 2.23), meat consumption <1x/wk (COR=3.47, CI (1.58, 7.64) and pica (COR=2.33, CI (1.52, 3.58) were significantly associated with anemia. Having five or more children (AOR=5.2, CI [1.29, 21.09]), intake of vegetables and fruits less than once per day (AOR= 6.7, CI [2.49, 17.89]), intake of tea always after meal (AOR = 12.83.CI [45-28.9]), and recurrence of illness during pregnancy (AOR=7.3, CI [2.12–25.39]) were factors associated with anemia.
This study showed that anemia is a moderate public health problem. Less frequent meat and vegetable consumption, parity ≥5 are risk factors for anemia. Therefore, reducing parity, taking balanced diet and use of mosquito nets during pregnancy are recommended.
PMCID: PMC3742894  PMID: 23950633
Hemoglobin; Anemia; Pregnancy; ANC
9.  Maternal and Perinatal Outcomes in Second Hemoglobin Measurement in Nonanemic Women at First Booking: Effect of Altitude of Residence in Peru 
ISRN Obstetrics and Gynecology  2012;2012:368571.
Objective. To determine changes in hemoglobin concentration at second measurements after a normal hemoglobin concentration was detected at first booking during pregnancy at low and at high altitudes. Methods. This is a secondary analysis of a large database obtained from the Perinatal Information System in Peru which includes 379,816 pregnant women and their babies from 43 maternity units in Peru. Results. Most women remained with normal hemoglobin values at second measurement (75.1%). However, 21.4% of women became anemic at the second measurement. In all, 2.8% resulted with moderate/severe anemia and 3.5% with erythrocytosis (Hb>14.5 g/dL). In all cases Hb was higher as altitude increased. Risk for moderate/severe anemia increased associated with higher gestational age at second measurement of hemoglobin, BMI <19.9 kg/m2, living without partner, <5 antenatal care visits, first parity, multiparity, and preeclampsia. Lower risk for moderate/severe anemia was observed with normal high Hb level at first booking living at moderate and high altitude, and high BMI. Conclusion. Prevalence of anemia increases as pregnancy progress, and that a normal value at first booking may not be considered sufficient as Hb values should be observed throughout pregnancy. BMI was a risk for anemia in a second measurement.
PMCID: PMC3345214  PMID: 22577573
10.  Evaluation of a Portable Photometer for Estimating Diesel Particulate Matter Concentrations in an Underground Limestone Mine 
Annals of Occupational Hygiene  2010;54(5):566-574.
A low cost, battery-operated, portable, real-time aerosol analyzer is not available for monitoring diesel particulate matter (DPM) concentrations in underground mines. This study summarizes a field evaluation conducted at an underground limestone mine to evaluate the potential of the TSI AM 510 portable photometer (equipped with a Dorr-Oliver cyclone and 1.0-μm impactor) to qualitatively track time-weighted average mass and elemental, organic, and total carbon (TC) measurements associated with diesel emissions. The calibration factor corrected correlation coefficient (R2) between the underground TC and photometer measurements was 0.93. The main issues holding back the use of a photometer for real-time estimation of DPM in an underground mine are the removal of non-DPM-associated particulate matter from the aerosol stream using devices, such as a cyclone and/or impactor and calibration of the photometer to mine-specific aerosol.
PMCID: PMC2913759  PMID: 20410071
diesel exhaust; diesel particulate matter; direct-reading instruments; photometer; real-time measurement
11.  The Effect of Intermittent Antenatal Iron Supplementation on Maternal and Infant Outcomes in Rural Viet Nam: A Cluster Randomised Trial 
PLoS Medicine  2013;10(6):e1001470.
Beverley-Anne Biggs and colleagues conduct a community-based cluster randomized trial in rural Viet Nam to compare the effect of antenatal iron-folic acid supplementation taken daily or twice weekly on maternal and infant outcomes.
Please see later in the article for the Editors' Summary
Anemia affects over 500 million women, and in pregnancy is associated with impaired maternal and infant outcomes. Intermittent antenatal iron supplementation is an attractive alternative to daily dosing; however, the impact of this strategy on infant outcomes remains unclear. We compared the effect of intermittent antenatal iron supplementation with daily iron supplementation on maternal and infant outcomes in rural Viet Nam.
Methods and Findings
This cluster randomised trial was conducted in Ha Nam province, Viet Nam. 1,258 pregnant women (<16 wk gestation) in 104 communes were assigned to daily iron–folic acid (IFA), twice weekly IFA, or twice weekly multiple micronutrient (MMN) supplementation. Primary outcome was birth weight. Mean birth weight was 3,148 g (standard deviation 416). There was no difference in the birth weights of infants of women receiving twice weekly IFA compared to daily IFA (mean difference [MD] 28 g; 95% CI −22 to 78), or twice weekly MMN compared to daily IFA (MD −36.8 g; 95% CI −82 to 8.2). At 32 wk gestation, maternal ferritin was lower in women receiving twice weekly IFA compared to daily IFA (geometric mean ratio 0.73; 95% CI 0.67 to 0.80), and in women receiving twice weekly MMN compared to daily IFA (geometric mean ratio 0.62; 95% CI 0.57 to 0.68), but there was no difference in hemoglobin levels. Infants of mothers who received twice weekly IFA had higher cognitive scores at 6 mo of age compared to those who received daily IFA (MD 1.89; 95% CI 0.23 to 3.56).
Twice weekly antenatal IFA or MMN did not produce a clinically important difference in birth weight, when compared to daily IFA supplementation. The significant improvement in infant cognitive outcomes at 6 mo of age following twice weekly antenatal IFA requires further exploration, and provides additional support for the use of intermittent, rather than daily, antenatal IFA in populations with low rates of iron deficiency.
Trial registration
Australia New Zealand Clinical Trials Registry 12610000944033
Please see later in the article for the Editors' Summary
Editors' Summary
Anemia is a common condition in which the blood does not supply the body with enough oxygen because of a low number of red blood cells or low levels of hemoglobin—the iron-containing pigment that enables red blood cells to carry oxygen. Iron deficiency is the most common cause of anemia worldwide and, according to the World Health Organization, affects over 2 billion people: half of all pregnant women and 40% of preschool children in low- and middle-income countries are thought to be anemic. Anemia contributes to 20% of all maternal deaths and is also linked to increased maternal morbidity, higher rates of preterm birth and low birth weight, and reduced infant survival, with potential long-term consequences for child growth and development. Identifying and treating iron deficiency anemia is therefore a global health priority.
Why Was This Study Done?
Daily iron–folic acid supplementation given from early in pregnancy is the standard recommended approach to prevent and treat anemia in pregnant women, but recently the World Health Organization recommended intermittent use because of poor compliance with daily regimes (because of side effects) and poor bowel absorption. However, the evidence from many of the studies used to support this recommendation was of poor quality, and so it remains unclear whether intermittent supplementation is as, or more, effective than daily supplementation, especially in lower income settings where antenatal testing for anemia is not readily available. So in this study, the researchers conducted a community-based cluster randomized trial (where groups of people are randomized, rather than individuals) in rural Viet Nam to compare the effect of antenatal iron–folic acid supplementation taken twice weekly (either alone, or in combination with other micronutrients) with daily iron–folic acid supplementation, on maternal and infant outcomes during the first six months of life.
What Did the Researchers Do and Find?
The researchers randomized 104 communes in Ha Nam Province, Viet Nam, and enrolled 1,258 women who were less than 16 weeks pregnant into the study between September and November 2010. Although the researchers intended to register the trial before the study started, registration was delayed by a month because the supplements arrived earlier than the researchers anticipated, and they thought it best to start recruiting at that time to avoid the Vietnamese New Year, when women might be travelling. Each woman was interviewed and had blood taken for hemoglobin and iron indices (ferritin) before receiving daily iron–folic acid supplementation (426 women), twice weekly iron–folic acid supplementation (425 women), or twice weekly iron–folic acid supplementation plus micronutrients (407 women). The women had follow-up assessments at 32 weeks gestation, delivery, and at six months postpartum: their infants were assessed at birth and at six months old.
The researchers found that at enrollment, the women's average hemoglobin concentration was 123 g/l, and 12.6% of the women were anemic. At 32 weeks gestation, 10.8% of the women were anemic, but there was no difference in hemoglobin levels between the three supplement groups. The average ferritin level was 75.6 µg/l at enrollment, with 2.2% of women iron deficient. Ferritin levels decreased from enrollment to 32 weeks gestation in all supplement groups but were lower in women who took twice weekly supplements. The researchers also found that birth weight (the primary outcome) was similar in all supplement groups, and there were also no differences in gestational age or in the risk of prematurity, stillbirth, or early neonatal death. At six months, there were also no differences in the levels of infant hemoglobin, prevalence of anemia, or growth rates. However, infants born to mothers in the twice weekly iron–folic acid group had improved cognitive development compared to infants born to mothers in the daily supplement group. Finally, the researchers found that adherence rates were significantly higher in the twice weekly iron–folic acid supplement group compared to the once daily regime.
What Do These Findings Mean?
These findings suggest that in an area of Southeast Asia with low anemia prevalence, once daily antenatal supplementation with iron–folic acid did not provide any benefits in birth weight or improved infant growth over twice weekly supplementation. Furthermore, twice weekly supplementation with iron–folic acid was associated with improved maternal adherence rates and also improved cognitive development in infants aged six months—a finding that requires further study and provides added support for the use of intermittent iron–folic acid supplementation over daily supplementation.
Additional Information
Please access these websites via the online version of this summary at
The World Health Organization website has comprehensive information on anemia, including a report of global estimates and the guideline Intermittent Iron and Folic Acid Supplementation in Non-Anaemic Pregnant Women
Wikipedia provides information on iron supplementation (note: Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
PMCID: PMC3708703  PMID: 23853552
12.  Non-Invasive Measurement of Hemoglobin: Assessment of Two Different Point-of-Care Technologies 
PLoS ONE  2012;7(1):e30065.
Measurement of blood hemoglobin (Hb) concentration is a routine procedure. Using a non-invasive point-of-care device reduces pain and discomfort for the patient and allows time saving in patient care. The aims of the present study were to assess the concordance of Hb levels obtained non-invasively with the Pronto-7 monitor (version 2.1.9, Masimo Corporation, Irvine, USA) or with the NBM-200MP monitor (Orsense, Nes Ziona, Israel) and the values obtained from the usual colorimetric method using blood samples and to determine the source of discordance.
Methods and Findings
We conducted two consecutive prospective open trials enrolling patients presenting in the emergency department of a university hospital. The first was designed to assess Pronto-7™ and the second NBM-200MP™. In each study, the main outcome measure was the agreement between both methods. Independent factors associated with the bias were determined using multiple linear regression. Three hundred patients were prospectively enrolled in each study. For Pronto-7™, the absolute mean difference was 0.56 g.L−1 (95% confidence interval [CI] 0.41 to 0.69) with an upper agreement limit at 2.94 g.L−1 (95% CI [2.70;3.19]), a lower agreement limit at -1.84 g.L−1 (95% CI [-2.08;-1.58]) and an intra-class correlation coefficient at 0.80 (95% CI [0.74;0.84]). The corresponding values for the NBM-200MP™ were 0.21 [0.02;0.39], 3.42 [3.10;3.74], -3.01 [-3.32;-2.69] and 0.69 [0.62;0.75]. Multivariate analysis showed that age and laboratory values of hemoglobin were independently associated with the bias when using Pronto-7™, while perfusion index and laboratory value of hemoglobin were independently associated with the bias when using NBM-200MP™.
Despite a relatively limited bias in both cases, the large limits of agreement found in both cases render the clinical usefulness of such devices debatable. For both devices, the bias is independently and inversely associated with the true value of hemoglobin.
Trial Registration NCT01321580 NCT01321593
PMCID: PMC3253126  PMID: 22238693
13.  Maternal Hemoglobin Concentration and Pregnancy Outcome: A Study of the Effects of Elevation in El Alto, Bolivia 
Iron-deficiency anemia is often under-diagnosed in developing countries, specifically in pregnant populations in regions of high altitude. Hemoglobin levels are not consistently adjusted for elevation, and therefore many anemic patients are left undiagnosed. The purpose of this study was to incorporate current parameters for diagnosing anemia in pregnancy at high altitudes, and to evaluate the effects of appropriately adjusted hemoglobin concentrations on pregnancy outcome. A few studies have examined the effect of elevation on hemoglobin status, and other studies have considered the effects of anemia of pregnancy; however, there is a lack of data demonstrating that altitude-adjusted hemoglobin levels accurately predict pregnancy outcome. Using the Student t-Test, multiple linear regression, and ANOVA statistical analyses, various factors of pregnancy outcome were compared between anemic and non-anemic groups, as defined by hemoglobin cut-off levels adjusted for trimester of pregnancy and altitude. When appropriate adjustments were used, maternal anemia was associated with lower infant Apgar scores at both one minute and five minutes after birth, as well as complication of labor, lower gestational age at birth, and higher parity. This study demonstrates the importance of altitude and trimester specific adjustments to maternal hemoglobin levels in order to accurately diagnose anemia in pregnancy. In addition, a clear correlation is seen between maternal hemoglobin level and pregnancy outcome.
PMCID: PMC3296152  PMID: 22399871
Iron-Deficiency Anemia; Pregnancy; Bolivia; Elevation; Altitude; Hemoglobin
14.  Anemia and associated factors among school-age children in Filtu Town, Somali region, Southeast Ethiopia 
BMC Hematology  2014;14:13.
Anemia is one of the major public health problems affecting more than half of school-age children in developing countries. Anemia among children has been conclusively seen to delay psychomotor development, poor cognitive performance, impaired immunity and decrease working capacity. The purpose of this study is to determine the prevalence and associated factors of anemia among school-age children in Filtu Town, Somali region, Southeast Ethiopia.
A community based cross-sectional study was conducted from July to August, 2013 in Filtu Town. A total of 355 school-age children between 5–15 years old were included in the study. Socio-demographic data were obtained from each participant using structured questionnaire. Hemoglobin concentration was determined by HemoCue 201+ photometer (HemoCue, Angelholm, Sweden) analyzer. Hemoglobin values below 11.5 g/dl and 12 g/dl were considered as anemic for age ranges of 5–11 and 12–15 years, respectively. Anthropometric data were taken from each study participant. Peripheral blood film and stool examination were done for hemoparasite and intestinal parasite screening, respectively. Data were analyzed using SPSS version 16.0.
Over all, prevalence of anemia was found to be 23.66%. The vast majority (73.81%) of the anemic children had mild anemia. Moderate and severe anemia accounted for 25% and 1.19% of the anemic children, respectively. Being from a family with low income (AOR = 9.44, 95% CI: 2.88, 30.99), stunted (AOR = 5.50, 95% CI: 2.83, 10.72), underweight (AOR = 2.07, 95% CI: 1.06, 4.05) and having intestinal parasite infection (AOR = 2.99, 95% CI: 1.05, 8.46) were identified as associated factors for anemia.
Anemia is a moderate public health problem in school-age children for the study area. Interventions targeting nutritional deficiencies and parasitic infections are recommended.
PMCID: PMC4147173  PMID: 25170422
Anemia; Associated factors; School-age children; Somali region
15.  Comparison of HemoCue® hemoglobin-meter and automated hematology analyzer in measurement of hemoglobin levels in pregnant women at Khartoum hospital, Sudan 
Diagnostic Pathology  2012;7:30.
Assessment of hemoglobin is one of the most reliable indicators for anemia, and is widely used to screen for anemia among pregnant women. The HemoCue® has been widely used for as a point-of-care device for hemoglobin estimation in health facilities. Previous studies showed contradictory results regarding the accuracy of HemoCue®.
This was a hospital-based cross sectional study carried- out among pregnant women at Khartoum hospital in Sudan to find out whether the measurement of hemoglobin concentration by HemoCue® using venous or capillary samples was comparable to that of the automated hematology analyzer as standard. Bland and Altman method was used to compare the measurements with an acceptable difference of ± 1.0 g/dl.
Among the 108 subjects in this study the mean (SD) level of hemoglobin level using HemoCue® venous sample, HemoCue® capillary sample and automated hematology analyzer were 12.70 (1.77), 12.87 (2.04) and 11.53 (1.63) g/dl, respectively. Although the correlations between the measurements were all significant there was no agreement between HemoCue® and automated hematology analyzer. The bias + SD (limits of agreement) for HemoCue® venous versus hematology analyzer was 1.17 ± 1.57 (-1.97, 4.31) g/dl, HemoCue® capillary versus hematology analyzer was 1.34 ± 1.85 (-2.36, 5.04) g/dl, and HemoCue® venous versus HemoCue® capillary samples was 017 ± 1.90 and (3.97-3.63) g/dl.
Hemoglobin concentration assessment by HemoCue® using either venous or capillary blood samples has shown unacceptable agreement with automated hematology analyzer.
Virtual slides
The virtual slide(s) for this article can be found here:
PMCID: PMC3342090  PMID: 22436620
16.  Validity of Medical Chart Weights and Heights for Obese Pregnant Women 
eGEMs  2014;2(1):1051.
To determine the validity of adult body weights and heights recorded in electronic medical records (EMRs) in the course of routine medical care.
EMRs allow the potential use of data collected in the course of routine medical care for a variety of research applications in many fields including epidemiology and comparative effectiveness studies. However, researchers familiar with carefully controlled measurement protocols typically used in clinical trials may question the validity of data collected in the course of routine clinical care.
Weights and heights collected during a research project that focused on weight gain during pregnancy were compared to weight and height measurements coincidently recorded in the research participant’s medical records. For weight measures (N=102), data recorded within ±14 days were compared, and for height measures (N=114), data recorded within ±5 years were compared. We assessed agreement between medical and research measurements using the concordance and intraclass correlation coefficients, and Bland and Altman’s limits of agreement.
The mean research and medical record weight measurements were 99.3 kg and 99.2 kg, respectively. The concordance and intraclass correlation coefficients for weight had similar estimates of .999 and 95 percent confidence intervals [.998, .999]. The 95 percent limits of agreement were −1.5 kg and +1.7 kg. The mean research and medical height measurements were 1.646 m and 1.654 m, respectively, and the concordance and intraclass correlation coefficients for height were .941 and .942, respectively. The 95 percent limits of agreement were −.031 m and +.047 m.
For pregnant women, body weights documented in the medical record are exchangeable with body weights recorded in a research setting. Height measurements recorded in the medical records were not in as close agreement as weights, but concordance between medical record and research height measurements are high enough to allow them to be used epidemiological and comparative effectiveness research.
PMCID: PMC4371469  PMID: 25848585
Weight; height; validity; pregnancy; medical record
17.  Gastrointestinal Helminth Infection in Pregnancy: Disease Incidence and Hematological Alterations 
Iranian Journal of Public Health  2013;42(5):497-503.
The incidence and hematological effects of helminth infection during pregnancy were investigated among pregnant women in Isiala, Mbano, Southeast Nigeria.
Totally 282 pregnant women were enlisted for the study between October 2011 and September 2012. Stool samples were examined for intestinal helminths using formalin-ether sedimentation technique. Hemoglobin (Hb) and Packed Cell Volume (PCV) levels were evaluated in venous blood samples using Sahli’s and microhaematocrit methods respectively.
Forty six (16.3%) subjects were infected with at least one helminth parasite; 24 (8.5%) hookworm, 14(5.0%) and 2(0.7%) A. lumbricoides and Trichuris trichiura infections respectively. Intestinal helminthiases in pregnant women was significantly associated with age (P<0.05). The prevalence of intestinal helminthiases by parity was also significantly different (P<0.05) with primigravidae having the highest infection rate (27.5%). Hematological assessment showed that the prevalence of anemia among the women was 58.9% (mean±SD = 9.3±1.0). The differences in hemoglobin levels by age groups was statistically significant (P <0.05). The contributory effect of gastrointestinal helminths in anemia showed that infected pregnant women had lower mean hemoglobin (8.60±0.22g/dl) than the uninfected (9.72±0.07g/dl). Significant difference (t-value = 5.660, P<0.05) was observed between the Hb of the infected and uninfected pregnant women. In addition, infected pregnant women had mean PCV of 26.09±0.65% while the uninfected had 34.54±2.96%. The mean PCV of infected pregnant women was significantly different (t-value= 0.013, P<0.05) from that of the uninfected.
Anti-helminthic therapy after the first trimester should be part of the antenatal programme. Intestinal helminth infection showed significant negative correlation with Hb and PCV and contributed moderately to anemia.
PMCID: PMC3684458  PMID: 23802107
Anemia; Hematology; Hookworm; Hemoglobin; Packed cell volume
This study aims to assess the association between schistosomiasis and hookworm infection with hemoglobin levels of schoolchildren in northern Mozambique. Through a cross-sectional survey, 1,015 children from five to 12 years old in the provinces of Nampula, Cabo Delgado and Niassa were studied. Hookworm infection and urinary schistosomiasis were diagnosed, through Ritchie and filtration methods, with a prevalence of 31.3% and 59.1%, respectively. Hemoglobin levels were obtained with a portable photometer (Hemocue®). The average hemoglobin concentration was 10.8 ± 1.42 g/dL, and 62.1% of the children presented levels below 11.5 g/dL, of which 11.8% of the total number of children had hemoglobin levels below 9 g/dL. A multiple linear regression analysis demonstrated negative interactions between hemoglobin levels and ancylostomiasis, this being restricted to the province of Cabo Delgado (β = -0.55; p < 0.001) where an independent interaction between hemoglobin levels and urinary schistosomiasis was also observed (β = -0.35; p = 0.016). The logistical regression model indicated that hookworm infection represents a predictor of mild (OR = 1.87; 95% CI = 1.17-3.00) and moderate/severe anemia (OR = 2.71; 95% CI = 1.50 - 4.89). We concluded that, in the province of Cabo Delgado, hookworm and Schistosoma haematobium infections negatively influence hemoglobin levels in schoolchildren. Periodical deworming should be considered in the region. Health education and improvements in sanitary infrastructure could achieve long-term and sustainable reductions in soil-transmitted helminthiases and schistosomiasis prevalence rates.
PMCID: PMC4085861  PMID: 24879000
Hookworms; Schistosoma haematobium; Anemia; Hemoglobin; Mozambique
19.  Normal reference value of hemoglobin of middleaged women and altitude. 
AIM: In order to supply a scientific basis for uniting the normal reference value standard of hemoglobin of Chinese middlescent women. METHODS: A research is made about the relationship between the normal reference value of 25,917 examples of hemoglobin of middlescent women and altitude in 268 areas in China, the normal reference values of hemoglobin of middlescent women are determined by the hemoglobincyanide method. RESULTS: The correlation between the normal reference value of hemoglobin of middlescent women and altitude is quite significant (r = 0.827). By using the method of univariate linear regression analysis, one regression equation is inferred. CONCLUSION: If the altitude values are obtained in some areas, the normal reference value of hemoglobin of middlescent women of this area can be reckoned by using the regression equation. Furthermore, depending on the altitude, China can be divided into three districts: Qingzang District, Central District, and Eastern District.
PMCID: PMC2259123  PMID: 15989740
20.  Near-infrared frequency-domain optical spectroscopy and magnetic resonance imaging: a combined approach to studying cerebral maturation in neonatal rabbits 
Journal of biomedical optics  2005;10(1):11011.
The neonatal rabbit brain shows prolonged postnatal development both structurally and physiologically. We use noninvasive near-IR frequency-domain optical spectroscopy (NIRS) and magnetic resonance imaging (MRI) to follow early developmental changes in cerebral oxygenation and anatomy, respectively. Four groups of animals are measured: NIRS in normals, MRI in normals, and both NIRS and MRI with hypoxia-ischemia (HI) (diffusion MRI staging). NIRS and/or MRI are performed from P3 (postnatal day=P) up to P76. NIRS is performed on awake animals with a frequency-domain tissue photometer. Absolute values of oxyhemoglobin concentration ([HbO2]), deoxyhemoglobin concentration ([HbR]), total hemoglobin concentration (HbT), and hemoglobin saturation (StO2) are calculated. The brains of all animals appeared to be maturing as shown in the diffusion tensor MRI. Mean optical coefficients (reduced scattering) remained unchanged in all animals throughout. StO2 increased in all animals (40% at P9 to 65% at P43) and there are no differences between normal, HI controls, and HI brains. The measured increase in StO2 is in agreement with the reported increase in blood flow during the first 2 months of life in rabbits. HbT, which reflects blood volume, peaked at postnatal day P17, as expected since the capillary density increases up to P17 when the microvasculature matures.
PMCID: PMC2637814  PMID: 15847577
magnetic resonance imaging; diffusion; brain maturation; hemoglobin concentration; hemoglobin saturation; frequency-domain; optical spectroscopy; near infrared
21.  Prevalence of Anemia and Associated Factors among Pregnant Women in North Western Zone of Tigray, Northern Ethiopia: A Cross-Sectional Study 
Background. Anemia affects the lives of more than 2 billion people globally, accounting for over 30% of the world's population. Anemia is a global public health problem occurring at all stages of the life cycle but the burden of the problem is higher in pregnant women particularly in developing countries. The aim of this study was to determine the prevalence of anemia and associated factors among pregnant women attending antenatal clinics in north western zone of Tigray, northern Ethiopia. Methods. A facility based cross-sectional study was employed. A systematic random sampling procedure was employed to select 714 pregnant women who were attending antenatal clinics in health facilities found in the study area from April to May 2014. The data was entered and analyzed using Epi-info version 3.5.1 and SPSS version 20.0 statistical software, respectively. Logistic regression analysis was used to identify factors associated with anemia among the study participants. All tests were two-sided and p value < 0.05 was considered statistically significant. Results. The overall prevalence of anemia (hemoglobin < 11 g/dL) among the pregnant women was 36.1% (95% CI = 32.7%–39.7%) of which 58.5% were mildly, 35.7% moderately, and 5.8% severely anemic. In pregnant women, rural residence (AOR = 1.75, 95% CI = 1.01–3.04), no education/being illiterate (AOR = 1.56, 95% CI = 1.03–2.37), absence of iron supplementation during pregnancy (AOR = 2.76, 95% CI = 1.92–5.37), and meal frequency of less than two times per day (AOR = 2.28, 95% CI = 1.06–4.91) were the independent predictors for increased anemia among the pregnant women. Conclusions. Anemia was found to be moderate public health problem in the study area. Residence, educational status, iron supplementation during pregnancy, and meal frequency per day were statistically associated with anemia among the pregnant women. Awareness creation and nutrition education on the importance of taking iron supplementation and nutritional counseling on consumption of extra meal and iron-rich foods during pregnancy are recommended to prevent anemia in the pregnant women.
PMCID: PMC4475559  PMID: 26137321
22.  Polysomnography in Patients With Obstructive Sleep Apnea 
Executive Summary
The objective of this health technology policy assessment was to evaluate the clinical utility and cost-effectiveness of sleep studies in Ontario.
Clinical Need: Target Population and Condition
Sleep disorders are common and obstructive sleep apnea (OSA) is the predominant type. Obstructive sleep apnea is the repetitive complete obstruction (apnea) or partial obstruction (hypopnea) of the collapsible part of the upper airway during sleep. The syndrome is associated with excessive daytime sleepiness or chronic fatigue. Several studies have shown that OSA is associated with hypertension, stroke, and other cardiovascular disorders; many researchers believe that these cardiovascular disorders are consequences of OSA. This has generated increasing interest in recent years in sleep studies.
The Technology Being Reviewed
There is no ‘gold standard’ for the diagnosis of OSA, which makes it difficult to calibrate any test for diagnosis. Traditionally, polysomnography (PSG) in an attended setting (sleep laboratory) has been used as a reference standard for the diagnosis of OSA. Polysomnography measures several sleep variables, one of which is the apnea-hypopnea index (AHI) or respiratory disturbance index (RDI). The AHI is defined as the sum of apneas and hypopneas per hour of sleep; apnea is defined as the absence of airflow for ≥ 10 seconds; and hypopnea is defined as reduction in respiratory effort with ≥ 4% oxygen desaturation. The RDI is defined as the sum of apneas, hypopneas, and abnormal respiratory events per hour of sleep. Often the two terms are used interchangeably. The AHI has been widely used to diagnose OSA, although with different cut-off levels, the basis for which are often unclear or arbitrarily determined. Generally, an AHI of more than five events per hour of sleep is considered abnormal and the patient is considered to have a sleep disorder. An abnormal AHI accompanied by excessive daytime sleepiness is the hallmark for OSA diagnosis. For patients diagnosed with OSA, continuous positive airway pressure (CPAP) therapy is the treatment of choice. Polysomnography may also used for titrating CPAP to individual needs.
In January 2005, the College of Physicians and Surgeons of Ontario published the second edition of Independent Health Facilities: Clinical Practice Parameters and Facility Standards: Sleep Medicine, commonly known as “The Sleep Book.” The Sleep Book states that OSA is the most common primary respiratory sleep disorder and a full overnight sleep study is considered the current standard test for individuals in whom OSA is suspected (based on clinical signs and symptoms), particularly if CPAP or surgical therapy is being considered.
Polysomnography in a sleep laboratory is time-consuming and expensive. With the evolution of technology, portable devices have emerged that measure more or less the same sleep variables in sleep laboratories as in the home. Newer CPAP devices also have auto-titration features and can record sleep variables including AHI. These devices, if equally accurate, may reduce the dependency on sleep laboratories for the diagnosis of OSA and the titration of CPAP, and thus may be more cost-effective.
Difficulties arise, however, when trying to assess and compare the diagnostic efficacy of in-home PSG versus in-lab. The AHI measured from portable devices in-home is the sum of apneas and hypopneas per hour of time in bed, rather than of sleep, and the absolute diagnostic efficacy of in-lab PSG is unknown. To compare in-home PSG with in-lab PSG, several researchers have used correlation coefficients or sensitivity and specificity, while others have used Bland-Altman plots or receiver operating characteristics (ROC) curves. All these approaches, however, have potential pitfalls. Correlation coefficients do not measure agreement; sensitivity and specificity are not helpful when the true disease status is unknown; and Bland-Altman plots measure agreement (but are helpful when the range of clinical equivalence is known). Lastly, receiver operating characteristics curves are generated using logistic regression with the true disease status as the dependent variable and test values as the independent variable. Thus, each value of the test is used as a cut-point to measure sensitivity and specificity, which are then plotted on an x-y plane. The cut-point that maximizes both sensitivity and specificity is chosen as the cut-off level to discriminate between disease and no-disease states. In the absence of a gold standard to determine the true disease status, ROC curves are of minimal value.
At the request of the Ontario Health Technology Advisory Committee (OHTAC), MAS has thus reviewed the literature on PSG published over the last two years to examine new developments.
Review Strategy
There is a large body of literature on sleep studies and several reviews have been conducted. Two large cohort studies, the Sleep Heart Health Study and the Wisconsin Sleep Cohort Study, are the main sources of evidence on sleep literature.
To examine new developments on PSG published in the past two years, MEDLINE, EMBASE, MEDLINE In-Process & Other Non-Indexed Citations, the Cochrane Database of Systematic Reviews and Cochrane CENTRAL, INAHTA, and websites of other health technology assessment agencies were searched. Any study that reported results of in-home or in-lab PSG was included. All articles that reported findings from the Sleep Heart Health Study and the Wisconsin Sleep Cohort Study were also reviewed.
Diffusion of Sleep Laboratories
To estimate the diffusion of sleep laboratories, a list of sleep laboratories licensed under the Independent Health Facility Act was obtained. The annual number of sleep studies per 100,000 individuals in Ontario from 2000 to 2004 was also estimated using administrative databases.
Summary of Findings
Literature Review
A total of 315 articles were identified that were published in the past two years; 227 were excluded after reviewing titles and abstracts. A total of 59 articles were identified that reported findings of the Sleep Heart Health Study and the Wisconsin Sleep Cohort Study.
Based on cross-sectional data from the Wisconsin Sleep Cohort Study of 602 men and women aged 30 to 60 years, it is estimated that the prevalence of sleep-disordered breathing is 9% in women and 24% in men, on the basis of more than five AHI events per hour of sleep. Among the women with sleep disorder breathing, 22.6% had daytime sleepiness and among the men, 15.5% had daytime sleepiness. Based on this, the prevalence of OSA in the middle-aged adult population is estimated to be 2% in women and 4% in men.
Snoring is present in 94% of OSA patients, but not all snorers have OSA. Women report daytime sleepiness less often compared with their male counterparts (of similar age, body mass index [BMI], and AHI). Prevalence of OSA tends to be higher in older age groups compared with younger age groups.
Diagnostic Value of Polysomnography
It is believed that PSG in the sleep laboratory is more accurate than in-home PSG. In the absence of a gold standard, however, claims of accuracy cannot be substantiated. In general, there is poor correlation between PSG variables and clinical variables. A variety of cut-off points of AHI (> 5, > 10, and > 15) are arbitrarily used to diagnose and categorize severity of OSA, though the clinical importance of these cut-off points has not been determined.
Recently, a study of the use of a therapeutic trial of CPAP to diagnose OSA was reported. The authors studied habitual snorers with daytime sleepiness in the absence of other medical or psychiatric disorders. Using PSG as the reference standard, the authors calculated the sensitivity of this test to be 80% and its specificity to be 97%. Further, they concluded that PSG could be avoided in 46% of this population.
Obstructive Sleep Apnea and Obesity
Obstructive sleep apnea is strongly associated with obesity. Obese individuals (BMI >30 kg/m2) are at higher risk for OSA compared with non-obese individuals and up to 75% of OSA patients are obese. It is hypothesized that obese individuals have large deposits of fat in the neck that cause the upper airway to collapse in the supine position during sleep. The observations reported from several studies support the hypothesis that AHIs (or RDIs) are significantly reduced with weight loss in obese individuals.
Obstructive Sleep Apnea and Cardiovascular Diseases
Associations have been shown between OSA and comorbidities such as diabetes mellitus and hypertension, which are known risk factors for myocardial infarction and stroke. Patients with more severe forms of OSA (based on AHI) report poorer quality of life and increased health care utilization compared with patients with milder forms of OSA. From animal models, it is hypothesized that sleep fragmentation results in glucose intolerance and hypertension. There is, however, no evidence from prospective studies in humans to establish a causal link between OSA and hypertension or diabetes mellitus. It is also not clear that the associations between OSA and other diseases are independent of obesity; in most of these studies, patients with higher values of AHI had higher values of BMI compared with patients with lower AHI values.
A recent meta-analysis of bariatric surgery has shown that weight loss in obese individuals (mean BMI = 46.8 kg/m2; range = 32.30–68.80) significantly improved their health profile. Diabetes was resolved in 76.8% of patients, hypertension was resolved in 61.7% of patients, hyperlipidemia improved in 70% of patients, and OSA resolved in 85.7% of patients. This suggests that obesity leads to OSA, diabetes, and hypertension, rather than OSA independently causing diabetes and hypertension.
Health Technology Assessments, Guidelines, and Recommendations
In April 2005, the Centers for Medicare and Medicaid Services (CMS) in the United States published its decision and review regarding in-home and in-lab sleep studies for the diagnosis and treatment of OSA with CPAP. In order to cover CPAP, CMS requires that a diagnosis of OSA be established using PSG in a sleep laboratory. After reviewing the literature, CMS concluded that the evidence was not adequate to determine that unattended portable sleep study was reasonable and necessary in the diagnosis of OSA.
In May 2005, the Canadian Coordinating Office of Health Technology Assessment (CCOHTA) published a review of guidelines for referral of patients to sleep laboratories. The review included 37 guidelines and associated reviews that covered 18 applications of sleep laboratory studies. The CCOHTA reported that the level of evidence for many applications was of limited quality, that some cited studies were not relevant to the recommendations made, that many recommendations reflect consensus positions only, and that there was a need for more good quality studies of many sleep laboratory applications.
As of the time of writing, there are 97 licensed sleep laboratories in Ontario. In 2000, the number of sleep studies performed in Ontario was 376/100,000 people. There was a steady rise in sleep studies in the following years such that in 2004, 769 sleep studies per 100,000 people were performed, for a total of 96,134 sleep studies. Based on prevalence estimates of the Wisconsin Sleep Cohort Study, it was estimated that 927,105 people aged 30 to 60 years have sleep-disordered breathing. Thus, there may be a 10-fold rise in the rate of sleep tests in the next few years.
Economic Analysis
In 2004, approximately 96,000 sleep studies were conducted in Ontario at a total cost of ~$47 million (Cdn). Since obesity is associated with sleep disordered breathing, MAS compared the costs of sleep studies to the cost of bariatric surgery. The cost of bariatric surgery is $17,350 per patient. In 2004, Ontario spent $4.7 million per year for 270 patients to undergo bariatric surgery in the province, and $8.2 million for 225 patients to seek out-of-country treatment. Using a Markov model, it was concluded that shifting costs from sleep studies to bariatric surgery would benefit more patients with OSA and may also prevent health consequences related to diabetes, hypertension, and hyperlipidemia. It is estimated that the annual cost of treating comorbid conditions in morbidly obese patients often exceeds $10,000 per patient. Thus, the downstream cost savings could be substantial.
Considerations for Policy Development
Weight loss is associated with a decrease in OSA severity. Treating and preventing obesity would also substantially reduce the economic burden associated with diabetes, hypertension, hyperlipidemia, and OSA. Promotion of healthy weights may be achieved by a multisectorial approach as recommended by the Chief Medical Officer of Health for Ontario. Bariatric surgery has the potential to help morbidly obese individuals (BMI > 35 kg/m2 with an accompanying comorbid condition, or BMI > 40 kg/m2) lose weight. In January 2005, MAS completed an assessment of bariatric surgery, based on which OHTAC recommended an improvement in access to these surgeries for morbidly obese patients in Ontario.
Habitual snorers with excessive daytime sleepiness have a high pretest probability of having OSA. These patients could be offered a therapeutic trial of CPAP to diagnose OSA, rather than a PSG. A majority of these patients are also obese and may benefit from weight loss. Individualized weight loss programs should, therefore, be offered and patients who are morbidly obese should be offered bariatric surgery.
That said, and in view of the still evolving understanding of the causes, consequences and optimal treatment of OSA, further research is warranted to identify which patients should be screened for OSA.
PMCID: PMC3379160  PMID: 23074483
23.  Population-based screening for anemia using first-time blood donors 
American journal of hematology  2012;87(5):496-502.
Anemia is an important public health concern. Data from population-based surveys such as the National Health and Nutrition Examination Survey (NHANES) are the gold standard, but are obtained infrequently and include only small samples from certain minority groups.
We assessed whether readily available databases of blood donor hemoglobin values could be used as a surrogate for population hemoglobin values from NHANES.
Blood donor venous and fingerstick hemoglobin values were compared to 10,254 NHANES 2005-2008 venous hemoglobin values using demographically stratified analyses and ANOVA. Fingerstick hemoglobins or hematocrits were converted to venous hemoglobin estimates using regression analysis.
Venous hemoglobin values from 1,609 first time donors correlated extremely well with NHANES data across different age, gender and demographic groups. Cigarette smoking increased hemoglobin by 0.26 to 0.59 g/dL depending on intensity. Converted fingerstick hemoglobin from 36,793 first time donors agreed well with NHANES hemoglobin (weighted mean hemoglobin of 15.53 g/dL for donors and 15.73 g/dL for NHANES) with similar variation in mean hemoglobin by age. However, compared to NHANES, the larger donor dataset showed reduced differences in mean hemoglobin between Blacks and other races/ethnicities.
Overall, first-time donor fingerstick hemoglobins approximate U.S. population data and represent a readily available public health resource for ongoing anemia surveillance.
PMCID: PMC3525330  PMID: 22460662
Erythrocyte count; Hematologic tests; Anemia; United States; blood donors; African Continental Ancestry Group
24.  Comparability of hemoglobin A1c level measured in capillary versus venous blood sample applying two point-of-care instruments 
The present study is designed to evaluate the validity of the measurement of capillary blood hemoglobin A1c levels in comparison with venous blood hemoglobin A1c.
The data of this cross-sectional study are collected from a sample of 45 Iranian diabetic patients referred to one particular laboratory for the assessment of HbA1c level during a period from April to December 2013. Venous and simultaneous capillary blood samples were obtained from each subject for measurement of hemoglobin A1c levels. Both samples were tested using two different NGSP certified systems: CERA STAT 2000 (Ceragem Medisys Inc) and NycoCard Reader II (Axis-Shield).
The mean hemoglobin A1c in venous and capillary blood samples measured using CERA STAT 2000 assays were 6.30 ± 1.68% and 6.34 ± 1.65% respectively (p = 0.590). However, when NycoCard Reader II assay was employed, the mean hemoglobin A1c in venous and capillary blood samples were 6.73 ± 1.35% and 6.92 ± 1.50% (p = 0.007). Moreover, a strong correlation was observed between venous and capillary hemoglobin A1c levels with Pearson’s concordance correlation coefficients of 0.96 and 0.94 with the use of NycoCard Reader II and CERA STAT 2000 assays respectively. Application of CERA STAT 2000 demonstrated to be of a considerably higher value using the ROC curve analysis assay (AUC = 0.991). Also, similar analysis by using NycoCard Reader II assay demonstrated that capillary hemoglobin A1c measurement had high value for differentiation of uncontrolled from controlled blood glucose level (AUC = 0.935).
It was demonstrated that capillary hemoglobin A1c measurement had a considerably high value for differentiating between poorly-controlled and well-controlled blood glucose levels.
PMCID: PMC4234901  PMID: 25408924
25.  The Reliability of Portable Fixed Dynamometry During Hip and Knee Strength Assessments 
Journal of Athletic Training  2010;45(4):349-356.
Insufficient lower extremity strength may be a risk factor for lower extremity injuries such as noncontact anterior cruciate ligament tears. Therefore, clinicians need reliable instruments to assess strength deficiencies.
To assess the intrarater, interrater, intrasession, and intersession reliability of a portable fixed dynamometer in measuring the strength of the hip and knee musculature.
Crossover study.
Sports medicine research laboratory.
Patients or Other Participants:
Three raters (A, B, C) participated in this 2-phase study. Raters A and B tested 11 healthy college graduate students (2 men, 9 women) in phase 1. Raters A and C tested 26 healthy college undergraduate students (7 men, 19 women) in phase 2.
Main Outcome Measure(s):
The dependent variables for the study were hip adductor, hip abductor, hip flexor, hip extensor, hip internal rotator, hip external rotator, knee flexor, and knee extensor peak force.
The phase 1 intrasession intraclass correlation coefficients for sessions 1, 2, and 3 ranged from 0.88 to 0.99 (SEM  =  0.08–3.02 N), 0.85 to 0.99 (SEM  =  0.26–3.88 N), and 0.92 to 0.96 (SEM  =  0.52–2.76 N), respectively. Intraclass correlation coefficients ranged from 0.57 to 0.95 (SEM  =  1.72–13.15 N) for phase 1 intersession values, 0.70 to 0.94 (SEM  =  1.42–9.20 N) for phase 2 intrarater reliability values, and 0.69 to 0.88 (SEM  =  1.20–8.50 N) for phase 2 interrater values.
The portable fixed dynamometer showed good to high intrasession and intersession reliability values for hip and knee strength. Intrarater and interrater reliability were fair to high, except for hip internal rotation, which showed poor reliability.
PMCID: PMC2902028  PMID: 20617909
isometric activity; lower extremity

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