Clinical utility of serum soluble transferrin receptor levels and comparison with bone marrow iron stores as an index for iron-deficient erythropoiesis in a heterogeneous group of patients

AIM: To evaluate the correlation between raised soluble transferrin receptor (sTfR) and stainable marrow iron, and to define the utility of sTfR in discriminating between the presence or absence of iron-deficient erythropoiesis in patients with anaemia of chronic disease. METHODS: Seventy-six consecutive adult patients without accelerated erythropoiesis who had undergone bone marrow (BM) aspiration/trephine for various clinical reasons during 2003-2006 were studied. All patients had serum iron studies (iron, transferrin and ferritin) and sTfR performed within 1 week of BM aspiration/trephine. These 76 patients were assigned to three groups based on the iron status of the BM and sTfR level: patients with normal sTfR and normal BM iron stores (n = 49), patients with an elevated sTfR and normal BM iron stores (n = 13) and patients reduced or absent BM iron stores (n = 14). Means (95% confidence interval) for mean corpuscular volume (MCV), mean corpuscular haemoglobin concentration (MCHC), red blood cell haemoglobin (RBC Hb) content and median (5th and 95th percentiles) for haemoglobin were then calculated. RESULTS: All patients with absent BM iron stores had an elevated sTfR level. Patients with normal BM iron stores and elevated sTfR levels had significantly lower Hb, MCV, MCHC and RBC Hb content than patients with normal BM iron stores and normal sTfR levels. CONCLUSION: sTfR is the most sensitive serum biochemical marker for the identification of iron-deficient erythropoiesis. Normal BM iron stores can coexist with elevated sTfR and decreased MCV and MCHC. sTfR levels correlate better than BM iron stores with decreased MCV and MCHC. Therefore, sTfR is a useful marker of iron-deficient erythropoiesis, due to both absent iron stores, and restricted iron supply due to anaemia of chronic disease. As a single investigation, however, sTfR does not discriminate between these two causes of iron-deficient erythropoiesis.     

Maternal disease stage and child undernutrition in relation to mortality among children born to HIV-infected women in Tanzania

OBJECTIVE: To examine whether maternal HIV disease stage during pregnancy and child malnutrition are associated with child mortality. DESIGN: Prospective cohort study in Tanzania. METHODS: Indicators of disease stage were assessed for 939 HIV-infected women during pregnancy and at delivery, and children's anthropometric status was obtained at scheduled monthly clinic visits after delivery. Children were followed up for survival status until 24 months after birth. RESULTS: Advanced maternal HIV disease during pregnancy (CD4 count <350 vs. >or=350 cells/mm) was associated with increased risk of child mortality through 24 months of age (hazard ratio [HR] = 1.74, 95% confidence interval [CI]: 1.32 to 2.30). CD4 count <350 cells/mm was also associated with an increased risk of death among children who remained HIV-negative during follow-up (HR = 2.00, 95% CI: 1.36 to 2.94). Low maternal hemoglobin concentration and child undernutrition were related to an increased risk of mortality in this cohort of children. CONCLUSIONS: Low maternal CD4 cell count during pregnancy is related to increased risk of mortality in children born to HIV-infected women. Care and treatment for HIV disease, including highly active antiretroviral therapy to pregnant women, could improve child survival. Prevention and treatment of undernutrition in children remain critical interventions in settings with high HIV prevalence.     

Injection drug use is an independent risk factor for iron deficiency and iron deficiency anemia among HIV-seropositive and HIV-seronegative women

The risk factors for iron deficiency and iron deficiency anemia among female injection drug users are not well characterized. We measured hemoglobin and plasma ferritin and obtained demographic information and injection drug use history in the last 6 months in a cross-sectional study of 200 female injection drug users (134 HIV-positive and 66 HIV-negative). The women were participants in a natural history study, the AIDS Linked to Intravenous Experiences study in Baltimore, Maryland. In multivariate analyses adjusting for age, hepatitis C virus status, and HIV status, injection drug use within the last 6 months was associated with iron deficiency (odds ratio [OR] = 2.61, 95% confidence interval [CI]: 1.33 to 5.09) and iron deficiency anemia (OR = 6.65, 95% CI: 2.33 to 18.9). Among 134 HIV-positive women, injection drug use in the last 6 months was associated with iron deficiency (OR = 2.43, 95% CI: 1.08 to 5.48) and iron deficiency anemia (OR = 6.05, 95% CI: 1.82 to 20.1) in multivariate analyses adjusting for hepatitis C virus status and CD4 lymphocyte count. Injection drug use seems to be associated with iron deficiency and iron deficiency anemia. Further longitudinal studies are needed to gain insight into the nature of this association.     

Difference albumin-transferrin interest in the iron deficiency detection in a cohort of 1288 schoolchildren in the district of Tunis

Iron deficiency (ID) is the most common nutritional deficiency worldwide especially among young children, women in pregnancy and breastfeeding. This study was undertaken to assess the prevalence of ID in 1288 pupil ranging in age from 11 to 14 years. Haemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular Hb (MCH), serum iron (Fe) serum transferrin (Trf), serum ferritin (Ft) and an inflammtory proteic profil (IPP) were measured. The IPP combines the analysis of protein variations: protein results are converted in percent of normal values referenced for the technique used. It has been suggested that on the protein profile, an increase in serum transferrin level compared to a normal serum albumin level (DAT: difference albumin-transferrin), appears early in the course of ID. Iron deficiency was defined by a low serum ferritin (< 15 ng/mL) and/or a pathologic DAT (> 28%). Approximately, 33.8% of children had Ft < 15 ng/mL and 12,8% had DAT > 28% while ferritin values were in the normal range. Diagnosis performance (sensitivity, specificity and diagnosis efficacy) of ferritin and DAT were compared to the performance of high serum transferrin receptor (sTfR) values in 2 populations presenting or not a biological inflammation. Only the diagnosis efficacy of DAT was constant in both situations. In conclusion, the serum ferritin concentration is the first indicator of body storage iron identifying ID, however normal or elevated values of ferritin may be difficult to interpret particulary in the presence of inflammation. sTfR and DAT values are thus reliable indicators of ID in such circumstances.     

Associations between serum transferrin receptor concentrations and erythropoietic activities according to body iron status

This study investigated the associations between serum transferrin receptor (sTfR) concentrations and erythropoietic activities during 3 stages of iron deficiency in humans. Serum iron markers, fluorescent intensity of reticulocytes, and sTfR concentrations were measured in 227 prepubescent children, age 9 to 12 yr. Reticulocyte subpopulations were analyzed by flow cytometry and sTfR concentrations were measured by enzyme immunoassay. Mean values of middle-fluorescence reticulocytes (MFR), reticulocyte maturity index (RMI), and sTfR concentrations were significantly higher in iron-deficiency anemia subjects than in healthy controls. Reticulocyte subpopulations increased gradually, as body iron status diminished; the mean values of MFR and RMI in subjects with serum ferritin concentrations < 4.0 microg/L were 3-fold higher than those in healthy controls (p < 0.01). Correlation coefficients of MFR and RMI vs log ferritin values (r = 0.43 and r = 0.42) were higher than those of MFR and RMI vs sTfR concentrations (r = 0.24 and r = 0.27) in iron-deficiency anemia subjects. In summary, iron deficiency leads to increased production of immature reticulocytes. Erythropoietic activity is more closely associated with log ferritin values than with sTfR concentrations in iron-deficiency anemia.     

Mortality in patients with successful initial response to highly active antiretroviral therapy is still higher than in non-HIV-infected individuals

Mortality in HIV-infected patients has decreased dramatically since the introduction of highly active antiretroviral therapy (HAART). We analyzed progression to death in a population of 3678 antiretroviral treatment-naive patients from the ATHENA national observational cohort from 24 weeks after the start of HAART. Mortality was compared with that in the general population in the Netherlands matched by age and gender. Only log-transformed CD4 cell count (hazard ratio [HR] = 0.50, 95% confidence interval [CI]: 0.40 to 0.61 per unit increase) and plasma viral load (HR = 0.30, 95% CI: 0.15 to 0.60, HIV RNA level <100,000 vs. > or = 100,000 copies/mL) measured at 24 weeks and infection via intravenous drug use (IDU) (HR = 0.16, 95% CI: 0.10 to 0.26, non-IDU vs. IDU) were significantly associated with progression to death. For non-IDU patients with 600 x 10 CD4 cells/L and an HIV RNA level <100,000 copies/mL at 24 weeks, mortality was predicted to be 5.3 (95% CI: 3.5 to 8.4) and 10.4 (95% CI: 6.4 to 17.4) times higher than in the general population for 25-year-old men and women, respectively, and 1.15 (95% CI: 1.08 to 1.25) and 1.29 (95% CI: 1.16 to 1.50) times higher for 65-year-old men and women, respectively. Hence, mortality in HIV-infected patients with a good initial response to HAART is still higher than in the general population.     

Sensitivity, specificity, and predictive value of serum soluble transferrin receptor at different stages of iron deficiency

This study investigated the efficiency of serum soluble transferrin receptor (sTfR) for assessing body iron status at different stages of iron deficiency. Among 72 patients with advanced iron-deficiency anemia (IDA), the sensitivity and specificity of sTfR (at a diagnostic cutoff of 3.24 mg/L) were 70.8% and 90.6%, respectively, with a positive predictive value of 85.0%. Sensitivities of sTfR in patients at the earliest stage of iron deficiency (n=41) and the intermediate stage of iron-deficient erythropoiesis (n=15) were 21.9% and 26.7%, respectively, at the same cutoff value of sTfR. Serum ferritin concentrations averaged 6.7+/-1.9 microg/L in IDA patients with sTfR <3.24 mg/L, which were significantly above the values in IDA patients with sTfR >or=3.24 mg/L (4.8+/-1.2 microg/L, p<0.05). In healthy controls, blood reticulocyte counts were significantly higher in subjects with sTfR >or=3.24 mg/L than in those with sTfR <3.24 mg/L (0.045+/- 0.013 (10(12)/L) vs 0.034+/- 0.011 (10(12)/L), p<0.05]. In conclusion, sTfR level is not a sensitive indicator for the early or intermediate stages of iron deficiency, although sTfR assay can be a useful aid in the diagnosis of advanced IDA. Serum sTfR concentration has significant relationships with blood reticulocyte counts in healthy subjects and with serum ferritin levels in IDA patients.     

Variation of soluble transferrin receptor and ferritin concentrations in human serum during recovery from exercise

Serum soluble transferrin receptor (sTfR) has been proposed as a more stable index of iron status than serum ferritin in athletes. However, the variation in sTfR concentration during recovery from acute exercise is unknown. The aim of the present study was to examine the effect of prolonged moderate exercise on ferritin and sTfR concentrations, as well as on several hematologic variables up to 24 h post-exercise. Fifteen young, untrained men exercised on a cycle ergometer for 45 min at a heart rate of 150–155 beats min⁻¹ and provided blood samples before as well as immediately, 6 h, and 24 h after exercise. Ferritin and sTfR values did not change significantly with time. sTfR levels exhibited lower variation during the observation period, the median intra-individual coefficient of variation being 5.2%, as opposed to 10.9% for ferritin. In conclusion, serum ferritin concentration is not affected by prolonged moderate exercise and can be used as a reliable index of iron status, at least for athletes not involved in extreme physical activities. Serum sTfR concentration seems to be more stable and could replace ferritin as the preferred index of iron stores if problems associated with the novelty of the assay were overcome. Electronic Publication     

Novel association to the proprotein convertase PCSK7 gene locus revealed by analysing soluble transferrin receptor (sTfR) levels

The level of body iron storage and the erythropoietic need for iron are indicated by the serum levels of ferritin and soluble transferrin receptor (sTfR), respectively. A meta-analysis of five genome-wide association studies on sTfR and ferritin revealed novel association to the PCSK7 and TMPRSS6 loci for sTfR and the HFE locus for both parameters. The PCSK7 association was the most significant (rs236918, P = 1.1 × 10E-27) suggesting that proprotein convertase 7, the gene product of PCSK7, may be involved in sTfR generation and/or iron homeostasis. Conditioning the sTfR analyses on transferrin saturation abolished the HFE signal and substantially diminished the TMPRSS6 signal while the PCSK7 association was unaffected, suggesting that the former may be mediated by transferrin saturation whereas the PCSK7-associated effect on sTfR generation appears to be more direct.     

Iron status and depression in premenopausal women: an MMPI study. Minnesota Multiphasic Personality Inventory.

To test the hypothesis that low iron status or other nutritional deficiencies are associated with symptoms of depression in premenopausal women, the authors related blood indices of iron status to scores on the Minnesota Multiphasic Personality Inventory (MMPI) and responses to a mood adjective checklist. Participants recruited locally provided fasting blood samples and completed the MMPI during the follicular phase of the menstrual cycle. Of 365 apparently healthy participants, 4% had hemoglobin < 120 g/L, 6% had transferrin saturation < 16%, 20% had ferritin < 12 micrograms/L, and 8% had clinically elevated scores (T > or = 70) on the Depression scale of the MMPI. The frequency of elevated MMPI Depression scores was unrelated to the frequency of low hemoglobin, transferrin saturation, or ferritin. The results do not support the hypothesis that low iron status contributes to symptoms of depression in women.     

Anemia and iron status in young fertile non-professional female athletes

We evaluated the effects of regular physical exercise on anemia and iron status in young non-professional female athletes. A total of 191 healthy white Italian women (23.5 ± 4.68 years) were analyzed; 70 were non-professional athletes performing 11.1 ± 2.63 h week⁻¹ exercise and 121 were sedentary controls. Blood markers of anemia and iron status—hemoglobin (Hb), hematocrit (Hct), red blood cells (RBC), serum ferritin, iron, transferrin (Tf), transferrin saturation (TfS), soluble transferrin receptor (sTfR), and the sTfR/log ferritin ratio (sTfR-F index)—were evaluated. Anemia threshold was Hb < 120 g l^–1. Ferritin concentrations < 12 μg l^–1 were considered as iron deficiency (ID). Frequency of anemia (15.7 versus 10.7%, P = 0.32), ID (27.1 versus 29.8%, P = 0.70), and ID anemia (8.6 versus 5.8%, P = 0.46) was not different in athletes and controls. However, athletes were threefold more likely than controls (17.1 versus 5.8%) to have serum iron < 50 μg dl^–1 [odds ratio (OR) 3.37, P = 0.012]. Low-TfS (<15%) was found in 25.7% of athletes and in 13.2% of controls, OR 2.27, P = 0.030. Elevated-sTfR (>1.76 mg l^–1) was found in 24.3% of athletes and in 12.4% of controls, OR 2.27, P = 0.034. Regular non-professional sport activity does not cause an increased rate of anemia or of iron deficiency in fertile women. However, physical exercise has an impact on iron status as it reduces serum iron and transferrin saturation, and elevates sTfR. Nearly one fifth of recreational athletes have anemia and a third have iron deficit, these conditions can decrease their physical performance.     

Iron,haptoglobin phenotype,and HIV-1 viral load: a cross-sectional study among pregnant Zimbabwean women

BACKGROUND: Viral load is a determinant of HIV-1 progression and transmission. Iron status and the phenotype of haptoglobin, a heme-binding acute phase reactant, may be determinants of viral load. We aimed to describe the effect of iron status, haptoglobin phenotype (Hp), and other predictors on HIV-1 viral load. METHODS: Based on a cross-sectional study among 1669 antenatal care attenders (22-35 weeks) in Zimbabwe, 526 (31.5%) were found to be HIV infected. The role of season, age, gravidity, gestational age, malaria parasitemia, Hp, and elevated serum alpha(1)-antichymotrypsin (ACT) as well as serum ferritin, folate, retinol, and beta-carotene on HIV viral load among the 526 HIV-infected women was assessed using multiple linear regression analysis. RESULTS: The distribution of Hp 1-1 (32%), Hp 2-1 (48%), and Hp 2-2 (20%) was not different from that of 53 uninfected women. Mean viral load was 3.85 log(10) (95% CI: 3.77-3.93) genome equivalents (geq)/mL, ranging from 3.77 (95% CI: 3.64-3.90) geq/mL in women with Hp 1-1 to 4.05 (95% CI: 3.81-4.21) geq/mL in women with Hp 2-2. With elevated serum ACT controlled for, women with Hp 2-2 had viral loads twice (95% CI: 1.4-4.0, p =.002) that of women with Hp 1-1, whereas those with serum ferritin <6 micro g/L had viral loads less than one third (95% CI: 0.13-0.53, p =.013) that of women with serum ferritin >24 micro g/L. Viral loads were also higher in women enrolled in the early rainy season compared with the dry season, in gravidae 4+ compared with gravidae 1 through 3, and in those with moderately elevated compared with low serum alpha(1)-antichymotrypsin, but neither age, gestational age, serum folate, serum retinol, nor serum beta-carotene were predictors. CONCLUSION: Storage iron, Hp 2-2, and elevated ACT are independent positive predictors of HIV-1 viral load. The positive relationship between serum ferritin and viral load was not the result of an acute phase response or iron accumulation with advanced HIV infection. A possible detrimental role of iron in HIV infection would have serious public health implications.     

Reduced mortality associated with breast-feeding-acquired HIV infection and breast-feeding among HIV-infected children in Zambia

OBJECTIVES: In developing countries, where mother-to-child transmission of HIV through breast-feeding is common, little is known about the impact of postpartum transmission on child survival. This study assessed whether children infected postpartum have longer survival from time of infection versus those infected during gestation or delivery. DESIGN: We used a prospective cohort study to analyze data from 213 HIV-infected children enrolled in a breast-feeding intervention trial in Lusaka, Zambia (2001 to 2004). METHODS: We compared mortality 1 year after HIV infection in children stratified by age of infection: 0 to 3 days (intrauterine [IU] group), 4 to 40 days (intrapartum/early postpartum [IP/EPP] group), and >40 days (postpartum [PP] group). RESULTS: A total of 61, 71, and 81 children were infected in the IU, IP/EPP, and PP groups, respectively. Children with intrauterine or intrapartum/early postpartum transmission had higher mortality over the first 12 months after infection than children with postpartum transmission (P = 0.001 and P = 0.006, respectively); no differences were detected between children with intrauterine and intrapartum/early postpartum transmission. Nearly 20% of the IU and IP/EPP groups died by 100 days after infection, whereas nearly 10% of the PP group had died by this time. After adjusting for birth weight, maternal CD4 cell count, breast-feeding, and maternal death, children infected postpartum had one quarter the mortality rate (hazard ratio [HR] = 0.27, 95% confidence interval [CI]: 0.15 to 0.50) of those infected in utero. Stopping breast-feeding increased mortality in infected children (HR = 3.1, 95% CI: 1.8 to 5.3). CONCLUSIONS: This study demonstrates a survival benefit among children infected postpartum versus children infected during pregnancy or delivery and a benefit to increased breast-feeding duration among infected children. Testing children for HIV early may provide a means to allow for earlier intervention.     

Risk of COVID-19 and its complications in patients with atopic dermatitis undergoing dupilumab treatment—a population-based cohort study

The risk of coronavirus disease (COVID-19) infection and its complications among patients with atopic dermatitis (AD) treated by dupilumab is yet to be determined. We aimed to assess the risk of SARS-CoV-2 infection, COVID-19-associated hospitalization, and mortality among patients with AD treated by dupilumab. A population-based cohort study was conducted to compare AD patients treated by dupilumab (n?=?238) with those treated by prolonged systemic corticosteroids (≥?3 months; n?=?1,023), phototherapy (n?=?461), and azathioprine or mycophenolate mofetil (MMF; n?=?194) regarding the incidence of COVID-19 and its complications. The incidence rate of COVID-19, COVID-19-associated hospitalization, and mortality among patients treated by dupilumab was 70.1 (95% CI, 40.5–116.4), 5.0 (95% CI, 0.3–24.7), and 0.0 per 1,000 person-year, respectively. The use of dupilumab was not associated with an increased risk of SARS-CoV-2 infection [adjusted HR for dupilumab vs. prolonged systemic corticosteroids: 1.13 (95% CI, 0.61–2.09); dupilumab vs. phototherapy: 0.80 (95% CI, 0.42–1.53); dupilumab vs. azathioprine/MMF: 1.10 (95% CI, 0.45–2.65)]. Dupilumab was associated with a comparable risk of COVID-19-associated hospitalization [adjusted HR for dupilumab vs. prolonged systemic corticosteroids: 0.35 (95% CI, 0.05–2.71); dupilumab vs. phototherapy: 0.43 (95% CI, 0.05–3.98); dupilumab vs. azathioprine/MMF: 0.25 (95% CI, 0.02–2.74)]. When applicable, the risk of mortality was not elevated in patients with AD treated by dupilumab [HR for dupilumab vs. prolonged systemic corticosteroids: 0.04 (95% CI, 0.00–225.20)]. To conclude, dupilumab does not impose an increased risk of SARS-CoV-2 infection or COVID-19 complications in patients with AD. Dupilumab should be continued and considered as a safe drug for moderate-to-severe AD during the pandemic.

     

Impact of neighborhood-level socioeconomic status on HIV disease progression in a universal health care setting

OBJECTIVES: The objectives of this study were to examine neighborhood measures of socioeconomic status and their effect on the risk of mortality among HIV-positive persons accessing and not accessing treatment, the effects of late access to treatment by CD4 cell count, and survival among those who accessed treatment. METHODS: We limited our analysis to the era of highly active antiretroviral therapy (HAART). We used individual-level patient and clinical characteristics and neighborhood-level socioeconomic data to address our objectives. The Pearson chi2 and Wilcoxon sign rank tests were used to compare mortality among HIV-positive persons accessing and not accessing treatment, logistic regression models were used to compare persons who accessed treatment with low CD4 cell counts (<50 cells/mm(3)) with those who accessed treatment earlier (CD4 count > or =50 cells/mm(3)), and Weibull survival models were used to compare mortality among those who accessed treatment. RESULTS: Forty percent of people who died from HIV/AIDS-related causes never accessed treatment. Among those who accessed treatment, 16% did so when their CD4 counts were <50 cells/mm(3). Unemployment was associated with delayed access to treatment (odds ratio = 1.41, 95% confidence interval [CI]: 1.14 to 1.74). Postsecondary education (hazard ratio [HR] = 0.80, 95% CI: 0.71 to 0.91) and percent of residents below the poverty line (HR = 1.07, 95% CI: 1.01 to 1.13) were associated with mortality. CONCLUSIONS: In a setting where treatment for HIV is free of charge, a significant number of HIV-positive persons did not access HAART. Low socioeconomic status was associated with this delay and with increased mortality among persons receiving HAART. Social and health policy initiatives, beyond free and universal health care, are required to optimize access to HAART.     

Predictors and clinical impact of inappropriate implantable cardioverter-defibrillator shocks in Korean patients

Limited data are available on inappropriate shocks in Korean patients implanted with an implantable cardioverter-defibrillator (ICD). We investigated the impact of inappropriate shocks on clinical outcomes. This retrospective, single-center study included 148 patients treated between October 1999 and June 2011. The primary outcome was a composite event of all-cause mortality or hospitalization for any cardiac reason. The median follow-up duration was 29 months (interquartile range: 8 to 53). One or more inappropriate shocks occurred in 34 (23.0%) patients. A history of atrial fibrillation was the only independent predictor of inappropriate shock (hazard ratio [HR]: 4.16, 95% confidence interval [CI]: 1.89-9.15, P < 0.001). Atrial fibrillation was the most common cause of inappropriate shock (67.7%), followed by supraventricular tachycardia (23.5%), and abnormal sensing (8.8%). A composite event of all-cause mortality or hospitalizations for any cardiac reason during follow-up was not significantly different between patients with or without inappropriate shock (inappropriate shock vs no inappropriate shock: 35.3% vs 35.4%, adjusted HR: 1.06, 95% CI: 0.49-2.29, P = 0.877). Inappropriate shocks do not affect clinical outcomes in patients implanted with an ICD, although the incidence of inappropriate shocks is high.     

Predictors of antiretroviral treatment failure in an urban HIV clinic

BACKGROUND: Predictors of antiretroviral treatment (ART) failure are not well characterized for heterogeneous clinic populations. METHODS: A retrospective analysis was conducted of HIV-infected patients followed in an urban HIV clinic with an HIV RNA measurement < or =400 copies/mL on ART between January 1, 2003, and December 31, 2004. The primary endpoint was treatment failure, defined as virologic failure (> or =1 HIV RNA measurement >400 copies/mL), unsanctioned stopping of ART, or loss to follow-up. Prior ART adherence and other baseline patient characteristics, determined at the time of the first suppressed HIV RNA load on or after January 1, 2003, were extracted from the electronic health record (EHR). Predictors of failure were assessed using proportional hazards modeling. RESULTS: Of 829 patients in the clinic, 614 had at least 1 HIV RNA measurement < or =400 copies/mL during the study period. Of these, 167 (27.2%) experienced treatment failure. Baseline characteristics associated with treatment failure in the multivariate model were: poor adherence (hazard ratio [HR] = 3.44; 95% confidence interval [CI]: 2.34 to 5.05), absolute neutrophil count <1000/mm (HR = 2.90, 95% CI: 1.26 to 6.69), not suppressed on January 1, 2003 (HR = 2.69, 95% CI: 1.78 to 4.07) or <12 months of suppression (HR = 1.64, 95% CI: 1.10 to 2.45), CD4 count <200 cells/mm (HR = 1.90, 95% CI: 1.31 to 2.76), nucleoside-only regimen (HR = 1.75, 95% CI: 1.08 to 2.82), prior virologic failure (HR = 1.70, 95% CI: 1.22 to 2.39) and > or =1 missed visit in the prior year (HR = 1.56, 95% CI: 1.13 to 2.16). CONCLUSIONS: More than one quarter of patients in a heterogeneous clinic population had treatment failure over a 2-year period. Prior ART adherence and other EHR data readily identify patient characteristics that could trigger specific interventions to improve ART outcomes.     

Age-related differences in asthma outcomes in the United States, 1988-2006

BackgroundRelatively little is known about the effect of age on asthma outcomes in adults, particularly at a national level.ObjectiveTo investigate age-related differences in asthma outcomes in a nationally representative, longitudinal study.MethodsWe analyzed data from the Third National Health and Nutrition Examination Survey (1988-1994) with linked mortality files through 2006. Adults with physician-diagnosed asthma were identified and were divided into 2 age groups: younger adults (17-54 years of age) and older adults (55 years or older). The outcome measures were both cross-sectional (health care use, comorbidity, and lung function) and longitudinal (all-cause mortality).ResultsThere were an estimated 9,566,000 adults with current asthma. Of these, 73% were younger adults and 27% older adults. Compared with younger adults, older adults had more hospitalizations in the past year, more comorbidities, and poorer lung function (eg, lower forced expiratory volume in 1 second) (P < .05 for all). During a median follow-up of 15 years, significant baseline predictors of higher all-cause mortality included older age (≥55 vs <55 years old: adjusted hazard ratio [HR], 6.77; 95% confidence interval [CI], 3.15-14.54), poor health status (fair and poor vs excellent health status: adjusted HR, 10.07; 95% CI, 3.75-27.01), and vitamin D deficiency (vitamin D level <30 vs ≥50 nmol/L: adjusted HR, 2.19; 95% CI, 1.05-4.58), whereas Mexican American ethnicity (adjusted HR, 0.31; 95% CI, 0.14-0.65) was associated with lower mortality. Controlling for age, asthma was not associated with increased all-cause mortality (adjusted HR, 1.28; 95% CI, 0.99-1.65).ConclusionOlder adults with asthma have a substantial burden of morbidity and increased mortality. The ethnic differences in asthma mortality and the vitamin D–mortality link merit further investigation.     

Serum transferrin receptor-ferritin index shows concomitant iron deficiency anemia and anemia of chronic disease is common in patients with rheumatoid arthritis in north India

Anemia is a frequent cause of morbidity in patients with rheumatoid arthritis (RA). We studied the prevalence of anemia of chronic disorders (ACD) and ACD with coexistent iron deficiency anemia (IDA) in patients with RA using sTfR/log ferritin ratio (sTfR - F index). Complete blood counts, percent transferrin saturation, serum ferritin, sTfR, sTfR-F index measurements were carried out in 100 anemic RA patients. Twenty-five IDA subjects without any other illness and 25 age- and sex-matched normal controls were studied. Prevalence of anemia in RA patients was 50.5%. Patients with sTfR-F index value < 1.5 were classified as pure ACD and patients with sTfR-F index value> 1.5 were classified as ACD with coexistent IDA. Using these criteria, 20% patients were found to have pure ACD and 80% patients had coexistent ACD and IDA. In the normal control group, sTfR-F index was found to be 0.16-1.8. We found that sTfR-F index can clearly distinguish IDA control cases and normal subjects with no overlap in the range of sTfR-F index.     

The assessment of serum soluble transferrin receptor in alcoholics

The consumption of large amounts of alcohol disturbs body iron metabolism and leads to increase of body iron stores and may cause various hematologic changes. Both, iron overload and iron depletion could have effect on the metabolic, transit and storage pools. These pools and its indicators were evaluated previously in abusers, but there is no information concerning the serum soluble transferrin receptor (sTfR) as a new marker of transit compartment. Therefore, the aim of this study was to assess the sTfR and compare it to the other indicators of transit pool in alcoholics. sTfR was measured immunoturbidimetrically. The markers of alcohol abuse, metabolic, transport and storage pools and the other hematologic assays were determined by routine laboratory methods. The tested group consisted of 148 alcoholics. The abusers were not affected by anemia. Every second patient had increased iron storage pool. Serum iron level only tended to increase. The mean serum sTfR did not show any significant difference and the mean transferrin–ferritin index (sTfR/log ferritin ratio) was significantly decreased compared with the controls. None of the transit pool markers presented significant differences between subgroups classified according to liver enzyme activities. We suggest that the iron excess in alcoholics did not limit the cellular iron uptake by transferrin receptor-mediated endocytosis which was confirmed by the unchanged level of serum soluble transferrin receptor. Additionally, the serum sTfR in alcohol abusers is independent of the weekly alcohol intake, age of the patients, duration of dependence, time of abstinence, time of last drinking and the liver function tests.