Comparative study of efficacy and safety of intravenous ferric carboxy maltose versus iron sucrose in treatment of postpartum iron deficiency anemia

Background: As postpartum iron deficiency anemia is observed in about 65% of women in India, it is the major contributing factor and indirect cause of maternal death. Postpartum anemia may lead to postpartum depression, stress, anxiety and cognitive impairment. Adequate treatment of anemia in postpartum period will have improved life quality in women in child bearing age so this study was designed with the objective to compare the safety and efficacy of intravenous FCM versus iron sucrose in treatment of postpartum iron deficiency anemia.Methods: It was a prospective observational study of postpartum women (within 10 days of delivery) with iron deficiency anemia (7-9 gm%) who delivered in LG hospital, Ahmedabad. A sample size of 215 women was estimated based on prevalence of anemia which is 65% among postpartum women in India including dropout rate of 10% which were further divided into 2 groups. Group 1: iron sucrose group, Group 2: ferric carboxy maltose group.Results: FCM has greater rise in Hb, less side effects, and easy administration of dose as compared to iron sucrose. The rise in Hb with FCM as compared to iron sucrose is (4.6 versus 3.5 respectively).Conclusions: FCM has more safety and efficacy as compared to iron sucrose in treatment of postpartum iron deficiency anemia

Streamlined design of a self-inactivating feline immunodeficiency virus vector for transducing ex vivo dendritic cells and T lymphocytes.

BACKGROUND: Safe and efficient vector systems for delivering antigens or immunomodulatory molecules to dendritic cells (DCs), T lymphocytes or both are considered effective means of eliciting adaptive immune responses and modulating their type, extent, and duration. As a possible tool toward this end, we have developed a self-inactivating vector derived from feline immunodeficiency virus (FIV) showing performance characteristics similar to human immunodeficiency virus-derived vectors but devoid of the safety concerns these vectors have raised. METHODS: The pseudotyped FIV particles were generated with a three-plasmid system consisting of: the packaging construct, providing Gag, Pol and the accessory proteins; the vector(s), basically containing FIV packaging signal (psi), Rev responsive element, R-U5 region at both ends, and the green fluorescent protein as reporter gene; and the Env plasmid, encoding the G protein of vesicular stomatitis virus (VSV-G) or the chimeric RD114 protein. Both packaging and vector constructs were derived from p34TF10, a replication competent molecular clone of FIV. The pseudotyped particles were produced by transient transfection in the Crandell feline fibroblast kidney (CrFK) or the human epithelial (293T) cell line. RESULTS: To broaden its species tropism, the final vector construct was achieved through a series of intermediate constructs bearing a longer psi, the FIV central polypurin tract sequence (cPPT), or the woodchuck hepatitis post-regulatory element (WPRE). These constructs were compared for efficiency and duration of transduction in CrFK or 293T cells and in the murine fibroblast cell line NIH-3T3. Whereas psi elongation and cPPT addition did not bring any obvious benefit, insertion of WPRE downstream GFP greatly improved vector performances. To maximize the efficiency of transduction for ex-vivo murine DCs and T-lymphocytes, this construct was tested with VSV-G or RD114 and using different transduction protocols. The results indicated that the FIV construct derived herein stably transduced both cell types, provided that appropriate vector makeup and transduction protocol were used. Further, transduced DCs underwent changes suggestive of an induced maturation. CONCLUSION: In contrast to previously described FIV vectors that were poorly efficient in delivering genetic material to DCs and T lymphocytes, the vector developed herein has potential for use in experimental immunization strategies

Kidney Function, Albuminuria and Life Expectancy

Background: Lower estimated glomerular filtration rate is associated with reduced life expectancy. Whether this association is modified by the presence or absence of albuminuria, another cardinal finding of chronic kidney disease, is unknown. Objective: Our objective was to estimate the life expectancy of middle-aged men and women with varying levels of eGFR and concomitant albuminuria. Design: A retrospective cohort study. Setting: A large population-based cohort identified from the provincial laboratory registry in Alberta, Canada. Participants: Adults aged ≥30 years who had outpatient measures of serum creatinine and albuminuria between May 1, 2002 and March 31, 2008. Measurements: Predictor : Baseline levels of kidney function identified from serum creatinine and albuminuria measurements. Outcomes : all cause mortality during the follow-up. Methods: Patients were categorized based on their estimated glomerular filtration rate (eGFR) (≥60, 45–59, 30–44, and 15–29 mL/min/1 · 73 m 2 ) as well as albuminuria (normal, mild, and heavy) measured by albumin-to-creatinine ratio or urine dipstick. The abridged life table method was applied to calculate the life expectancies of men and women from age 40 to 80 years across combined eGFR and albuminuria categories. We also categorized participants by severity of kidney disease (low risk, moderately increased risk. high risk, and very high risk) using the combination of eGFR and albuminuria levels. Results: Among men aged 50 years and with eGFR ≥60 mL/min/1.73 m 2 , estimated life expectancy was 24.8 (95% CI: 24.6–25.0), 17.5 (95% CI: 17.1–17.9), and 13.5 (95% CI: 12.6–14.3) years for participants with normal, mild and heavy albuminuria respectively. Life expectancy for men with mild and heavy albuminuria was 7.3 (95% CI: 6.9–7.8) and 11.3 (95% CI: 10.5–12.2) years shorter than men with normal proteinuria, respectively. A reduction in life expectancy was associated with an increasing severity of kidney disease; 24.8 years for low risk (95% CI: 24.6–25.0), 19.1 years for moderately increased risk (95% CI: 18.7–19.5), 14.2 years for high risk (95% CI: 13.5–15.0), and 9.6 years for very high risk (95% CI: 8.4–10.8). Among women of similar age and kidney function, estimated life expectancy was 28.9 (95% CI: 28.7–29.1), 19.8 (95% CI: 19.2–20.3), and 14.8 (95% CI: 13.5–16.0) years for participants with normal, mild and heavy albuminuria respectively. Life expectancy for women with mild and heavy albuminuria was 9.1 (95% CI: 8.5–9.7) and 14.2 (95% CI: 12.9–15.4) years shorter than the women with normal proteinuria, respectively. For women also a graded reduction in life expectancy was observed across the increasing severity of kidney disease; 28.9 years for low risk (95% CI: 28.7–29.1), 22.5 years for moderately increased risk (95% CI: 22.0–22.9), 16.5 years for high risk (95% CI: 15.4–17.5), and 9.2 years for very high risk (95% CI: 7.8–10.7). Limitations: Possible misclassification of long-term kidney function categories cannot be eliminated. Possibility of confounding due to concomitant comorbidities cannot be ruled out. Conclusion: The presence and degree of albuminuria was associated with lower estimated life expectancy for both gender and was especially notable in those with eGFR ≥30 mL/min/1.73 m 2 . Life expectancy associated with a given level of eGFR differs substantially based on the presence and severity of albuminuria

Effects of timing and extent of smoking, type of cigarettes, and concomitant risk factors on the association between smoking and subclinical atherosclerosis

Background and Purpose \u2014 The purpose of this study was to evaluate the effects of timing and extent of smoking, type of cigarettes, and concomitant vascular risk factors (VRFs) on the association between smoking and carotid intima-media thickness (C-IMT) in a lipid clinic population. Methods \u2014 1804 patients (869 men, age 21 to 85 year) participated in the study. Smoking habits were recorded and C-IMTs were measured by B-mode ultrasound. The associations of C-IMT with smoking status (never, former, and current) and with the cigarettes\u2019 content of tar, nicotine, and carbon monoxide (alone or combined to define \u201clight\u201d or \u201cregular\u201d cigarettes) as well as the interactions between smoking status, gender, and VRFs were evaluated before and after adjustment for confounders. Results \u2014 C-IMT was highest in current smokers, lower in former, and lowest in never smokers. C-IMT of former and current smokers differed only after data adjustment for variables describing the extent and timing of smoking exposure. C-IMT was positively related to the number of pack-years (number of cigarettes smoked per day [cigarettes/d] multiplied by number of years smoked/20) in both former and current smokers. There were no differences in C-IMT between smokers of cigarettes with high or low nicotine, tar, or carbon monoxide content. Both diabetes and hypertension interacted positively with smoking in determining C-IMTs. Conclusions \u2014 In the present cross-sectional observational investigation, carried out in a cohort of patients attending a lipid clinic, consumption of light cigarettes does not reduce the atherogenic effect of smoking on C-IMT. The number of pack-years, cigarettes/d, and years of smoking are relevant covariates in evaluating the effects of smoking on vascular health. The presence of diabetes or hypertension strengthens the association between smoking and cardiovascular risk

Overview of the Alberta Kidney Disease Network

<p>Abstract</p> <p>Background</p> <p>The Alberta Kidney Disease Network is a collaborative nephrology research organization based on a central repository of laboratory and administrative data from the Canadian province of Alberta.</p> <p>Description</p> <p>The laboratory data within the Alberta Kidney Disease Network can be used to define patient populations, such as individuals with chronic kidney disease (using serum creatinine measurements to estimate kidney function) or anemia (using hemoglobin measurements). The administrative data within the Alberta Kidney Disease Network can also be used to define cohorts with common medical conditions such as hypertension and diabetes. Linkage of data sources permits assessment of socio-demographic information, clinical variables including comorbidity, as well as ascertainment of relevant outcomes such as health service encounters and events, the occurrence of new specified clinical outcomes and mortality.</p> <p>Conclusion</p> <p>The unique ability to combine laboratory and administrative data for a large geographically defined population provides a rich data source not only for research purposes but for policy development and to guide the delivery of health care. This research model based on computerized laboratory data could serve as a prototype for the study of other chronic conditions.</p

Glomerular Autoimmune Multicomponents of Human Lupus Nephritis In Vivo (2): Planted Antigens.

Glomerular planted antigens (histones,DNA,andC1q) arepotential targets of autoimmunity in lupus nephritis (LN). However, the characterization of these antigens in human glomeruli in vivo remains inconsistent. We eluted glomerular autoantibodies recognizing planted antigens from laser-microdissected renal biopsy samples of 20 patientswith LN. Prevalent antibody isotypes were defined, levelswere determined, and glomerular colocalization was investigated. Renal and circulating antibodieswerematched, and serum levelswere compared in 104 patients with LN, 84 patients with SLE without LN, and 50 patients with rheumatoid arthritis (RA). Autoantibodies against podocyte antigens (antia-enolase/antiannexin AI) were also investigated. IgG2 autoantibodies against DNA, histones (H2A, H3, and H4), and C1q were detected in 50%, 55%, and 70% of biopsy samples, respectively. Anti-DNA IgG3 was the unique non-IgG2 anti-DNA deposit, and anti-C1q IgG4 was mainly detected in subepithelial membranous deposits. Anti-H3, anti-DNA, and anti-C1q IgG2 autoantibodies were also prevalent in LN serum, which also contained IgG3 against the antigen panel and anti-C1q IgG4. Serum and glomerular levels of autoantibodies were not strictly associated. High serum levels of all autoantibodies detected, including anti a-enolase and antiannexin AI, identified LN versus SLE and RA. Anti-H3 and antia-enolase IgG2 levels had the most remarkable increase in LN serum and represented a discriminating feature of LN in principal component analysis. The highest levels of these two autoantibodies were also associated with proteinuria.3.5 g/24 hours and creatinine&gt;1.2 mg/dl. Our findings suggest that timely autoantibody characterization might allow outcome prediction and targeted therapies for patients with nephritis

Vitamin D deficiency is associated with sudden cardiac death, combined cardiovascular events, and mortality in haemodialysis patients

Dialysis patients experience an excess mortality, predominantly of sudden cardiac death (SCD). Accumulating evidence suggests a role of vitamin D for myocardial and overall health. This study investigated the impact of vitamin D status on cardiovascular outcomes and fatal infections in haemodialysis patients. 25-hydroxyvitamin D [25(OH)D] was measured in 1108 diabetic haemodialysis patients who participated in the German Diabetes and Dialysis Study and were followed up for a median of 4 years. By Cox regression analyses, we determined hazard ratios (HR) for pre-specified, adjudicated endpoints according to baseline 25(OH)D levels: SCD (n = 146), myocardial infarction (MI, n = 174), stroke (n = 89), cardiovascular events (CVE, n = 414), death due to heart failure (n = 37), fatal infection (n = 111), and all-cause mortality (n = 545). Patients had a mean age of 66 +/- 8 years (54% male) and median 25(OH)D of 39 nmol/L (interquartile range: 28-55). Patients with severe vitamin D deficiency [25(OH)D of 75 nmol/L [HR: 2.99, 95% confidence interval (CI): 1.39-6.40]. Furthermore, CVE and all-cause mortality were strongly increased (HR: 1.78, 95% CI: 1.18-2.69, and HR: 1.74, 95% CI: 1.22-2.47, respectively), all persisting in multivariate models. There were borderline non-significant associations with stroke and fatal infection while MI and deaths due to heart failure were not meaningfully affected. Severe vitamin D deficiency was strongly associated with SCD, CVE, and mortality, and there were borderline associations with stroke and fatal infection. Whether vitamin D supplementation decreases adverse outcomes requires further evaluation.Clinical epidemiolog