Iron deficiency anaemia: experiences and challenges.

Iron deficiency remains the largest nutritional deficiency worldwide and the main cause of anaemia. Severe iron deficiency leads to anaemia known as iron deficiency anaemia (IDA), which affects a total of 1·24 billion people, the majority of whom are children and women from resource-poor countries. In sub-Saharan Africa, iron deficiency is frequently exacerbated by concomitant parasitic and bacterial infections and contributes to over 120 000 maternal deaths a year, while it irreparably limits the cognitive development of children and leads to poor outcomes in pregnancy.Currently available iron compounds are cheap and readily available, but constitute a non-physiological approach to providing iron that leads to significant side effects. Consequently, iron deficiency and IDA remain without an effective treatment, particularly in populations with high burden of infectious diseases. So far, despite considerable investment in the past 25 years in nutrition interventions with iron supplementation and fortification, we have been unable to significantly decrease the burden of this disease in resource-poor countries.If we are to eliminate this condition in the future, it is imperative to look beyond the strategies used until now and we should make an effort to combine community engagement and social science approaches to optimise supplementation and fortification programmes

Transcranial Doppler in a Hispanic–Mestizo population with neurological diseases: a study of sonographic window and its determinants

Between 5% and 37% of patients are not suitable for transtemporal insonation with transcranial Doppler (TCD). This unsuitability is particularly frequent in elderly females and non-Caucasians. We aim to evaluate TCD efficiency in a mixed Hispanic population in Santiago, Chile and to determine whether factors associated with the presence of optimal windows depend exclusively on patient-related elements. Seven hundred forty-nine patients were evaluated with power mode TCD. Optimal temporal windows (TWs) included detection of the middle, anterior, posterior cerebral arteries and terminal carotid. The patient's age and sex, the location of the examination, the time of day, whether the test was conducted on weekends and whether mechanical ventilation was used were recorded. Percentages of optimal windows were calculated. Examinations were deemed ideal if both TWs were optimal. TWs were obtained in 82% of cases. In univariate analyses, male sex (P < 0.001), an age below 60 years (P < 0.0001) and mechanical ventilation (P= 0.04) correlated with ideal TWs. Using logistic regression where dependent variable was a non-ideal window only male sex odds ratio (OR) 2.3 (1.51–3.45) and age below 60 OR 13.8 (7.8–24.6) were statistically significant. Our findings indicate that Hispanic populations have detection rates for TWs similar to Europeans and are affected by patient-related elements

Cluster-randomized, crossover trial of head positioning in acute stroke

The role of supine positioning after acute stroke in improving cerebral blood flow and the countervailing risk of aspiration pneumonia have led to variation in head positioning in clinical practice. We wanted to determine whether outcomes in patients with acute ischemic stroke could be improved by positioning the patient to be lying flat (i.e., fully supine with the back horizontal and the face upwards) during treatment to increase cerebral perfusion. METHODS In a pragmatic, cluster-randomized, crossover trial conducted in nine countries, we assigned 11,093 patients with acute stroke (85% of the strokes were ischemic) to receive care in either a lying-flat position or a sitting-up position with the head elevated to at least 30 degrees, according to the randomization assignment of the hospital to which they were admitted; the designated position was initiated soon after hospital admission and was maintained for 24 hours. The primary outcome was degree of disability at 90 days, as assessed with the use of the modified Rankin scale (scores range from 0 to 6, with higher scores indicating greater disability and a score of 6 indicating death). RESULTS The median interval between the onset of stroke symptoms and the initiation of the assigned position was 14 hours (interquartile range, 5 to 35). Patients in the lying-flat group were less likely than patients in the sitting-up group to maintain the position for 24 hours (87% vs. 95%, P\u3c0.001). In a proportional-odds model, there was no significant shift in the distribution of 90-day disability outcomes on the global modified Rankin scale between patients in the lying-flat group and patients in the sitting-up group (unadjusted odds ratio for a difference in the distribution of scores on the modified Rankin scale in the lying-flat group, 1.01; 95% confidence interval, 0.92 to 1.10; P = 0.84). Mortality within 90 days was 7.3% among the patients in the lying-flat group and 7.4% among the patients in the sitting-up group (P = 0.83). There were no significant betweengroup differences in the rates of serious adverse events, including pneumonia. CONCLUSIONS Disability outcomes after acute stroke did not differ significantly between patients assigned to a lying-flat position for 24 hours and patients assigned to a sitting-up position with the head elevated to at least 30 degrees for 24 hours

The effects of iron fortification on the gut microbiota in African children: a randomized controlled trial in Cote d'Ivoire.

BACKGROUND: Iron is essential for the growth and virulence of many pathogenic enterobacteria, whereas beneficial barrier bacteria, such as lactobacilli, do not require iron. Thus, increasing colonic iron could select gut microbiota for humans that are unfavorable to the host. OBJECTIVE: The objective was to determine the effect of iron fortification on gut microbiota and gut inflammation in African children. DESIGN: In a 6-mo, randomized, double-blind, controlled trial, 6-14-y-old Ivorian children (n = 139) received iron-fortified biscuits, which contained 20 mg Fe/d, 4 times/wk as electrolytic iron or nonfortifoed biscuits. We measured changes in hemoglobin concentrations, inflammation, iron status, helminths, diarrhea, fecal calprotectin concentrations, and microbiota diversity and composition (n = 60) and the prevalence of selected enteropathogens. RESULTS: At baseline, there were greater numbers of fecal enterobacteria than of lactobacilli and bifidobacteria (P < 0.02). Iron fortification was ineffective; there were no differences in iron status, anemia, or hookworm prevalence at 6 mo. The fecal microbiota was modified by iron fortification as shown by a significant increase in profile dissimilarity (P < 0.0001) in the iron group as compared with the control group. There was a significant increase in the number of enterobacteria (P < 0.005) and a decrease in lactobacilli (P < 0.0001) in the iron group after 6 mo. In the iron group, there was an increase in the mean fecal calprotectin concentration (P < 0.01), which is a marker of gut inflammation, that correlated with the increase in fecal enterobacteria (P < 0.05). CONCLUSIONS: Anemic African children carry an unfavorable ratio of fecal enterobacteria to bifidobacteria and lactobacilli, which is increased by iron fortification. Thus, iron fortification in this population produces a potentially more pathogenic gut microbiota profile, and this profile is associated with increased gut inflammation. This trial was registered at controlled-trials.com as ISRCTN21782274

Intravenous Thrombolysis in Patients 90 years or Older with Moderate to Severe Acute Ischemic Stroke Increases Ambulation at Discharge and is Safe: A prospective cohort study from a single center in Santiago, Chile.

Introduction: The World Health Organization predicts that the global population aged 60 years and older will double by 2050, leading to a significant rise in the public health impact of acute ischemic stroke (AIS). Existing stroke guidelines do not specify an upper age limit for the administration of intravenous thrombolysis (IVT), although some suggest a relative exclusion criterion in patients aged ≥ 80 in the 3 – 4.5 hour window. Many physicians avoid treating these patients with IVT, argumenting high risk and little benefit. Our aim was to investigate the efficacy and safety of IVT treatment in patients with non-minor AIS aged ≥ 90, admitted to our institution. The primary efficacy endpoint was the ability to walk at discharge (mRS 0-3) and the primary safety endpoints were death and symptomatic intracerebral hemorrhagic transformation (sIHT) at discharge. Methods: Patients with AIS aged ≥ 90 admitted to our center from January 2003 to December 2022 were included. They were selected if had an NIHSS ≥ 5, were previously ambulatory (prestroke mRS score 3 or less) and arrived within 6 hours from symptom onset. Those treated or not with IVT were compared with univariate analysis. Results: The mean age was 93.2 (2.4) years and 51 (73.9%) were female. The admission mRS and NIHSS were 1 (IQR 0 – 2) and 14 (IQR 7 – 22), respectively. Thrombolysed patients had a shorter time from symptom onset to door and lower glycemia on admission. IVT was associated with a higher proportion of patients achieving mRS 0 – 3 at discharge (p=0.03) and at 90 days (p=0.04). There were no differences between groups in the risk of death (p=0.55) or sIHT (p=0.38). Conclusion: In this small sample, ambulatory patients aged ≥ 90 with moderate or severe AIS treated with IVT, had increased odds of being able to walk independently at discharge than those not treated, without safety concerns

No benefit of flat head positioning in early moderate-severe acute ischemic stroke: HeadPoST study subgroup analysis

Background Although the Head Positioning in acute Stroke Trial (HeadPoST) showed no effect of the flat head position (FP; vs sitting up head position (SUP)) on functional outcome, we hypothesised that it could still offer benefits if commenced early in those with acute ischaemic stroke (AIS) of at least moderate severity. Methods Subgroup analysis of HeadPoST in participants with National Institutes of Health Stroke Scale (NIHSS) scores ≥7, ≥10 and ≥14, randomised to FP or SUP <4.5 hours of AIS onset on functional outcomes defined by a shift in scores on the modified Rankin scale (mRS) and death/disability (mRS scores 3–6), and any cardiovascular serious adverse event. Logistic regression analyses were undertaken adjusted for study design and baseline risk factors. Results There was no significant differential treatment effect in patient subgroups defined by increasing baseline NIHSS scores: adjusted OR and 95% CI for ordinal shift and binary (3–6) mRS scores: for NIHSS ≥7 (n=867) 0.92 (0.67 to 1.25) and 0.74 (0.52 to 1.04); NIHSS ≥ 10 (n=606) 0.80 (0.58 to 1.10) and 0.77 (0.49 to 1.19); NIHSS ≥14 (n=378) 0.82 (0.54 to 1.24) and 1.22 (0.69 to 2.14). Conclusions Early FP had no significant effect in patients with moderate–severe AI

Short-Term Effect of Prebiotics Administration on Stool Characteristics and Serum Cytokines Dynamics in Very Young Children with Acute Diarrhea

We investigated the effect of a mixture of long-chain fructo-oligosaccharides, galacto-oligosaccharides and acidic oligosaccharides on the number and consistency of stools and on immune system biomarkers in 104 supplemented and non-supplemented subjects (aged 9-24 months) with acute diarrhea. Interleukin-1 (IL-1), IL-1RA, IL-6, IL-8, IL-10, TNF-α and sIL-2R cytokine levels were determined. The significant decrease in number of stools and increase in stool consistency in the supplemented group was of little clinical relevance. The only significant change in pro- and anti-inflammatory cytokines was decreased TNF-α levels in the supplemented group. Prebiotic supplementation during acute diarrhea episodes did not influence the clinical course

Head Position in Stroke Trial (HeadPoST)- sitting-up vs lying-flat positioning of patients with acute stroke: study protocol for a cluster randomised controlled trial

Background Positioning a patient lying-flat in the acute phase of ischaemic stroke may improve recovery and reduce disability, but such a possibility has not been formally tested in a randomised trial. We therefore initiated the Head Position in Stroke Trial (HeadPoST) to determine the effects of lying-flat (0°) compared with sitting-up (≥30°) head positioning in the first 24 hours of hospital admission for patients with acute stroke. Methods/Design We plan to conduct an international, cluster randomised, crossover, open, blinded outcome-assessed clinical trial involving 140 study hospitals (clusters) with established acute stroke care programs. Each hospital will be randomly assigned to sequential policies of lying-flat (0°) or sitting-up (≥30°) head position as a ‘business as usual’ stroke care policy during the first 24 hours of admittance. Each hospital is required to recruit 60 consecutive patients with acute ischaemic stroke (AIS), and all patients with acute intracerebral haemorrhage (ICH) (an estimated average of 10), in the first randomised head position policy before crossing over to the second head position policy with a similar recruitment target. After collection of in-hospital clinical and management data and 7-day outcomes, central trained blinded assessors will conduct a telephone disability assessment with the modified Rankin Scale at 90 days. The primary outcome for analysis is a shift (defined as improvement) in death or disability on this scale. For a cluster size of 60 patients with AIS per intervention and with various assumptions including an intracluster correlation coefficient of 0.03, a sample size of 16,800 patients at 140 centres will provide 90 % power (α 0.05) to detect at least a 16 % relative improvement (shift) in an ordinal logistic regression analysis of the primary outcome. The treatment effect will also be assessed in all patients with ICH who are recruited during each treatment study period. Discussion HeadPoST is a large international clinical trial in which we will rigorously evaluate the effects of different head positioning in patients with acute stroke. Trial registration ClinicalTrials.gov identifier: NCT02162017 (date of registration: 27 April 2014); ANZCTR identifier: ACTRN12614000483651 (date of registration: 9 May 2014). Protocol version and date: version 2.2, 19 June 2014

Influence of including patients with pre-morbid disability in acute stroke trials : The HeadPoST experience

Background: Patients with premorbid functional impairment are generally excluded from acute stroke trials. We aimed to determine the impact of including such patients in the Head Positioning in acute Stroke Trial (HeadPoST) and early additional impairment on outcomes. Methods: Post hoc analyses of HeadPoST, an international, cluster-randomized crossover trial of lying-flat versus sitting-up head positioning in acute stroke. Associations of early additional impairment, defined as change in modified Rankin scale (mRS) scores from premorbid levels (estimated at baseline) to Day 7 (“early ΔmRS”), and poor outcome (mRS score 3–6) at Day 90 were determined with generalized linear mixed model. Heterogeneity of the trial treatment effect was tested according to premorbid mRS scores 0–1 versus 2–5. Results: Of 8,285 patients (38.9% female, mean age 68 ± 13 years) with complete data, there were 1,984 (23.9%) with premorbid functional impairment (mRS 2–5). A significant linear association was evident for early ∆mRS and poor outcome (per 1-point increase in ΔmRS, adjusted odds ratio 1.20, 95% confidence interval 1.14–1.27; p < 0.0001). Patients with greater premorbid functional impairment were less likely to develop additional impairment, but their risk of poor 90-day outcome significantly increased with increasing (worse) premorbid mRS scores (linear trend p < 0.0001). There was no heterogeneity of the trial treatment effect by level of premorbid function. Conclusions: Early poststroke functional impairment that exceeded premorbid levels was associated with worse 90-day outcome, and this association increased with greater premorbid functional impairment. Yet, including premorbid impaired patients in the HeadPoST did not materially affect the subsequent treatment effect. Clinical Trial Registration: HeadPoST is registered at http://www.ClinicalTrials.gov (NCT02162017)