A novel pre-clinical strategy to deliver antimicrobial doses of inhaled nitric oxide.

Effective treatment of respiratory infections continues to be a major challenge. In high doses (≥160 ppm), inhaled Nitric Oxide (iNO) has been shown to act as a broad-spectrum antimicrobial agent, including its efficacy in vitro for coronavirus family. However, the safety of prolonged in vivo implementation of high-dose iNO therapy has not been studied. Herein we aim to explore the feasibility and safety of delivering continuous high-dose iNO over an extended period of time using an in vivo animal model. Yorkshire pigs were randomized to one of the following two groups: group 1, standard ventilation; and group 2, standard ventilation + continuous iNO 160 ppm + methylene blue (MB) as intravenous bolus, whenever required, to maintain metHb <6%. Both groups were ventilated continuously for 6 hours, then the animals were weaned from sedation, mechanical ventilation and followed for 3 days. During treatment, and on the third post-operative day, physiologic assessments were performed to monitor lung function and other significative markers were assessed for potential pulmonary or systemic injury. No significant change in lung function, or inflammatory markers were observed during the study period. Both gas exchange function, lung tissue cytokine analysis and histology were similar between treated and control animals. During treatment, levels of metHb were maintained <6% by administration of MB, and NO2 remained <5 ppm. Additionally, considering extrapulmonary effects, no significant changes were observed in biochemistry markers. Our findings showed that high-dose iNO delivered continuously over 6 hours with adjuvant MB is clinically feasible and safe. These findings support the development of investigations of continuous high-dose iNO treatment of respiratory tract infections, including SARS-CoV-2.

Umbilical Cord Management at Term and Late Preterm Birth: A Meta-analysis.

CONTEXT: The International Liaison Committee on Resuscitation prioritized scientific review of umbilical cord management at term and late preterm birth. OBJECTIVE: To assess effects of umbilical cord management strategies (clamping timing and cord milking) in infants ≥34 weeks' gestational age. DATA SOURCES: Cochrane Central Register of Controlled Trials, Medline, PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, and trial registries searched July 2019. STUDY SELECTION: Two authors independently assessed eligibility of randomized controlled trials. DATA EXTRACTION: Two authors independently extracted data and assessed evidence certainty (Grading of Recommendations Assessment, Development and Evaluations). RESULTS: We identified 46 studies (9159 women and their infants) investigating 7 comparisons. Compared with early cord clamping (ECC) <30 seconds, delayed cord clamping (DCC) ≥30 seconds (33 studies), intact-cord milking (1 study), and cut-cord milking (2 studies) probably improve hematologic measures but may not affect survival without neurodisability, anemia in early infancy, or maternal postpartum hemorrhage. No differences in major neonatal morbidities are seen in studies comparing methods of optimizing placental transfusion (DCC versus cut-cord milking [3 studies], longer delays in clamping [7 studies], or physiologic parameters [3 studies]). Strategies that promote increased placental transfusion may be associated with greater phototherapy use. Evidence for all outcomes was low or very low certainty. LIMITATIONS: Incompleteness and low certainty of findings limit applicability. CONCLUSIONS: Compared with ECC, DCC or cord milking increases hemoglobin and hematocrit immediately after birth in infants ≥34 weeks' gestational age. The uncertain effects of DCC and cord milking compared with ECC on major morbidities limit usefulness of available evidence for policy and practice.

Wheat flour fortification with iron and other micronutrients for reducing anaemia and improving iron status in populations.

BACKGROUND: Anaemia is a condition where the number of red blood cells (and consequently their oxygen-carrying capacity) is insufficient to meet the body's physiological needs. Fortification of wheat flour is deemed a useful strategy to reduce anaemia in populations. OBJECTIVES: To determine the benefits and harms of wheat flour fortification with iron alone or with other vitamins and minerals on anaemia, iron status and health-related outcomes in populations over two years of age. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, 21 other databases and two trials registers up to 21 July 2020, together with contacting key organisations to identify additional studies. SELECTION CRITERIA: We included cluster- or individually-randomised controlled trials (RCTs) carried out among the general population from any country, aged two years and above. The interventions were fortification of wheat flour with iron alone or in combination with other micronutrients. We included trials comparing any type of food item prepared from flour fortified with iron of any variety of wheat DATA COLLECTION AND ANALYSIS: Two review authors independently screened the search results and assessed the eligibility of studies for inclusion, extracted data from included studies and assessed risks of bias. We followed Cochrane methods in this review. MAIN RESULTS: Our search identified 3538 records, after removing duplicates. We included 10 trials, involving 3319 participants, carried out in Bangladesh, Brazil, India, Kuwait, Philippines, South Africa and Sri Lanka. We identified two ongoing studies and one study is awaiting classification. The duration of interventions varied from 3 to 24 months. One study was carried out among adult women and one trial among both children and nonpregnant women. Most of the included trials were assessed as low or unclear risk of bias for key elements of selection, performance or reporting bias. Three trials used 41 mg to 60 mg iron/kg flour, three trials used less than 40 mg iron/kg and three trials used more than 60 mg iron/kg flour. One trial used various iron levels based on type of iron used: 80 mg/kg for electrolytic and reduced iron and 40 mg/kg for ferrous fumarate. All included studies contributed data for the meta-analyses. Iron-fortified wheat flour with or without other micronutrients added versus wheat flour (no added iron) with the same other micronutrients added Iron-fortified wheat flour with or without other micronutrients added versus wheat flour (no added iron) with the same other micronutrients added may reduce by 27% the risk of anaemia in populations (risk ratio (RR) 0.73, 95% confidence interval (CI) 0.55 to 0.97; 5 studies, 2315 participants; low-certainty evidence). It is uncertain whether iron-fortified wheat flour with or without other micronutrients reduces iron deficiency (RR 0.46, 95% CI 0.20 to 1.04; 3 studies, 748 participants; very low-certainty evidence) or increases haemoglobin concentrations (in g/L) (mean difference MD 2.75, 95% CI 0.71 to 4.80; 8 studies, 2831 participants; very low-certainty evidence). No trials reported data on adverse effects in children (including constipation, nausea, vomiting, heartburn or diarrhoea), except for risk of infection or inflammation at the individual level. The intervention probably makes little or no difference to the risk of Infection or inflammation at individual level as measured by C-reactive protein (CRP) (mean difference (MD) 0.04, 95% CI -0.02 to 0.11; 2 studies, 558 participants; moderate-certainty evidence). Iron-fortified wheat flour with other micronutrients added versus unfortified wheat flour (nil micronutrients added) It is unclear whether wheat flour fortified with iron, in combination with other micronutrients decreases anaemia (RR 0.77, 95% CI 0.41 to 1.46; 2 studies, 317 participants; very low-certainty evidence). The intervention probably reduces the risk of iron deficiency (RR 0.73, 95% CI 0.54 to 0.99; 3 studies, 382 participants; moderate-certainty evidence) and it is unclear whether it increases average haemoglobin concentrations (MD 2.53, 95% CI -0.39 to 5.45; 4 studies, 532 participants; very low-certainty evidence). No trials reported data on adverse effects in children. Nine out of 10 trials reported sources of funding, with most having multiple sources. Funding source does not appear to have distorted the results in any of the assessed trials. AUTHORS' CONCLUSIONS: Fortification of wheat flour with iron (in comparison to unfortified flour, or where both groups received the same other micronutrients) may reduce anaemia in the general population above two years of age, but its effects on other outcomes are uncertain. Iron-fortified wheat flour in combination with other micronutrients, in comparison with unfortified flour, probably reduces iron deficiency, but its effects on other outcomes are uncertain. None of the included trials reported data on adverse side effects except for risk of infection or inflammation at the individual level. The effects of this intervention on other health outcomes are unclear. Future studies at low risk of bias should aim to measure all important outcomes, and to further investigate which variants of fortification, including the role of other micronutrients as well as types of iron fortification, are more effective, and for whom.

Weekly Vitamin D3 supplementation improves aerobic performance in combat sport athletes.

AbstractVitamin D3 supplementation can affect the strength and power of an athlete, however the effect on endurance performance remains unclear. Twenty-seven recreational male combat athletes with at least 12 months experience within combat sports were recruited (age: 24 ± 4 years, stature: 176 ± 6 cm, weight: 77 ± 14 kg). Participants completed baseline testing for blood haemoglobin and haematocrit, upper and lower body VO2peak and upper and lower body Wingate. Following testing participants were stratified to 50,000IU (D1), 80,000IU (D2) or 110,000IU (D3) of vitamin D3 per week. They then completed a 6-week placebo period followed by a 6-week supplementation period. Retesting was carried out after the placebo and supplementation period. There was a significant effect for time for haemoglobin and haematocrit, upper and lower body VO2peak and upper body Wingate power (P < 0.01) but no effect for dose of vitamin D given. Performance data were normalised to vitamin D intake and there was a moderate effect size between D1 and D2 for lower body VO2peak (d = 0.6), upper body VO2peak (d = 0.13) and upper body average power (d = 0.75), with a large effect size between D1 and D2 for haemoglobin (d = 1.19), haematocrit (d = 0.93) and upper body peak power (d = 0.95). There was a large effect size for D1 compared to D3 for all variables (d > 0.8). Therefore, there is no additional benefit to increasing dose above 50,000IU vitamin D per week. Given the endurance adaptations from vitamin D supplementation and the importance of endurance for combat performance, recreational combat athletes should supplement at 50,000IU per week for six weeks.

Prevalence of iron deficiency among university kendo practitioners in Japan: an observational cohort study.

BACKGROUND: Iron deficiency is widely recognized as being the cause of anemia in athletes, although iron status in athletes of Kendo, a traditional Japanese martial art based on swordsmanship and practiced as an educational sport, has not been widely investigated. METHODS: We performed a health assessment on anemia and serum ferritin levels, along with nutrient intake evaluation, for Kendo practitioners in a university in Japan. RESULTS: A total of 56 Kendo practitioners (39 male and 17 female) aged between 18 and 23 years participated in the study. No individuals exhibited WHO-defined anemia (less than 13 or 12 g/dL of hemoglobin levels in male or female), while hypoferritinemia (less than 30 ng/mL) was found in seven (41%) females but not in males. Significantly higher body mass index was found in the female athletes with hypoferritinemia compared to females with normo-ferritinemia in sub-analysis (median [interquartile range]; 25.6 [24.2, 26.9] versus 22.6 [21.7, 24.1], respectively. p < 0.05). No significant differences in the intake of iron were registered between males and females (with and without hypoferritinemia) using data from a food-frequency questionnaire survey. CONCLUSION: No apparent anemia was found in adolescent Kendo practitioners, although this study confirmed the presence of hypoferritinemia in several female athletes. Careful follow-up, involving both clinical and nutritional assessment, will be necessary for them to prevent progression into anemia. A future study with larger cohorts in multiple sites is warranted to assess the prevalence of iron deficiency for validation and, if necessary, to devise a strategy for improving the iron status in Kendo athletes.

Wheat flour fortification with iron for reducing anaemia and improving iron status in populations.

BACKGROUND: Anaemia is a condition where the number of red blood cells (and consequently their oxygen-carrying capacity) is insufficient to meet the body's physiologic needs. Fortification of wheat flour is deemed a useful strategy to reduce anaemia in populations. OBJECTIVES: To determine the benefits and harms of wheat flour fortification with iron alone or with other vitamins and minerals on anaemia, iron status and health-related outcomes in populations over two years of age. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, and other databases up to 4 September 2019. SELECTION CRITERIA: We included cluster- or individually randomised controlled trials (RCT) carried out among the general population from any country aged two years and above. The interventions were fortification of wheat flour with iron alone or in combination with other micronutrients. Trials comparing any type of food item prepared from flour fortified with iron of any variety of wheat were included. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the search results and assessed the eligibility of studies for inclusion, extracted data from included studies and assessed risk of bias. We followed Cochrane methods in this review. MAIN RESULTS: Our search identified 3048 records, after removing duplicates. We included nine trials, involving 3166 participants, carried out in Bangladesh, Brazil, India, Kuwait, Phillipines, Sri Lanka and South Africa. The duration of interventions varied from 3 to 24 months. One study was carried out among adult women and one trial among both children and nonpregnant women. Most of the included trials were assessed as low or unclear risk of bias for key elements of selection, performance or reporting bias. Three trials used 41 mg to 60 mg iron/kg flour, two trials used less than 40 mg iron/kg and three trials used more than 60 mg iron/kg flour. One trial employed various iron levels based on type of iron used: 80 mg/kg for electrolytic and reduced iron and 40 mg/kg for ferrous fumarate. All included studies contributed data for the meta-analyses. Seven studies compared wheat flour fortified with iron alone versus unfortified wheat flour, three studies compared wheat flour fortified with iron in combination with other micronutrients versus unfortified wheat flour and two studies compared wheat flour fortified with iron in combination with other micronutrients versus fortified wheat flour with the same micronutrients (but not iron). No studies included a 'no intervention' comparison arm. None of the included trials reported any other adverse side effects (including constipation, nausea, vomiting, heartburn or diarrhoea). Wheat flour fortified with iron alone versus unfortified wheat flour (no micronutrients added) Wheat flour fortification with iron alone may have little or no effect on anaemia (risk ratio (RR) 0.81, 95% confidence interval (CI) 0.61 to 1.07; 5 studies; 2200 participants; low-certainty evidence). It probably makes little or no difference on iron deficiency (RR 0.43, 95% CI 0.17 to 1.07; 3 studies; 633 participants; moderate-certainty evidence) and we are uncertain about whether wheat flour fortified with iron increases haemoglobin concentrations by an average 3.30 (g/L) (95% CI 0.86 to 5.74; 7 studies; 2355 participants; very low-certainty evidence). No trials reported data on adverse effects in children, except for risk of infection or inflammation at the individual level. The intervention probably makes little or no difference to risk of Infection or inflammation at individual level as measured by C-reactive protein (CRP) (moderate-certainty evidence). Wheat flour fortified with iron in combination with other micronutrients versus unfortified wheat flour (no micronutrients added) Wheat flour fortified with iron, in combination with other micronutrients, may or may not decrease anaemia (RR 0.95, 95% CI 0.69 to 1.31; 2 studies; 322 participants; low-certainty evidence). It makes little or no difference to average risk of iron deficiency (RR 0.74, 95% CI 0.54 to 1.00; 3 studies; 387 participants; moderate-certainty evidence) and may or may not increase average haemoglobin concentrations (mean difference (MD) 3.29, 95% CI -0.78 to 7.36; 3 studies; 384 participants; low-certainty evidence). No trials reported data on adverse effects in children. Wheat flour fortified with iron in combination with other micronutrients versus fortified wheat flour with same micronutrients (but not iron) Given the very low certainty of the evidence, the review authors are uncertain about the effects of wheat flour fortified with iron in combination with other micronutrients versus fortified wheat flour with same micronutrients (but not iron) in reducing anaemia (RR 0.24, 95% CI 0.08 to 0.71; 1 study; 127 participants; very low-certainty evidence) and in reducing iron deficiency (RR 0.42, 95% CI 0.18 to 0.97; 1 study; 127 participants; very low-certainty evidence). The intervention may make little or no difference to the average haemoglobin concentration (MD 0.81, 95% CI -1.28 to 2.89; 2 studies; 488 participants; low-certainty evidence). No trials reported data on the adverse effects in children. Eight out of nine trials reported source of funding with most having multiple sources. Funding source does not appear to have distorted the results in any of the assessed trials. AUTHORS' CONCLUSIONS: Eating food items containing wheat flour fortified with iron alone may have little or no effect on anaemia and probably makes little or no difference in iron deficiency. We are uncertain on whether the intervention with wheat flour fortified with iron increases haemoglobin concentrations improve blood haemoglobin concentrations. Consuming food items prepared from wheat flour fortified with iron, in combination with other micronutrients, has little or no effect on anaemia, makes little or no difference to iron deficiency and may or may not improve haemoglobin concentrations. In comparison to fortified flour with micronutrients but no iron, wheat flour fortified with iron with other micronutrients, the effects on anaemia and iron deficiency are uncertain as certainty of the evidence has been assessed as very low. The intervention may make little or no difference to the average haemoglobin concentrations in the population. None of the included trials reported any other adverse side effects. The effects of this intervention on other health outcomes are unclear.

The effect of anaemia on normal tissue toxicity and survival outcomes in prostate cancer treated with radical radiotherapy and neo-adjuvant androgen deprivation.

OBJECTIVE: It has been established that survival and toxicity outcomes in some cancer types could be influenced by haemoglobin (Hb) levels. This study aims to determine if pre-treatment Hb is associated with late toxicity or survival outcomes in prostate cancer. METHODS: Data from one Phase III randomised controlled trial and one single arm translational trial were analysed. Patients had localized prostate cancer and received ≥70 Gy radiotherapy and neo-adjuvant androgen deprivation between 1997 and 2013. RESULTS: 302 males were included. Median follow-up was 6.8 years for toxicity and 10.3 years for survival outcomes. Patients with Hb below the reference range were more likely to experience Grade 2-3 late gastrointestinal toxicity than patients with Hb within the range (p = 0.050). Neither late genitourinary toxicity, erectile function toxicity, prostate-specific antigen relapse free survival nor overall survival of patients were statistically significantly different between groups. CONCLUSION: Anaemia in prostate cancer is found in the minority of patients and is usually mild. Prostate cancer patients undergoing radiotherapy with low Hb were more likely to experience Grade 2-3 late gastrointestinal toxicity. ADVANCES IN KNOWLEDGE: This study is one of the first in the published literature to investigate the role of Hb in prostate cancer toxicity and survival. We have found an association between Hb below the reference range and late GI toxicity. Consideration should be given to further investigating patients with iron deficiency anaemia to guide management options and outrule underlying GI pathology before proceeding with radiotherapy treatment.

Association of independent risk factors with post-extubation failure in patients undergoing mechanical ventilation weaning.

INTRODUCTION: Even with an adequate mechanical ventilation weaning (MVW) protocol, the procedure fails in 15 to 30 % of cases. OBJECTIVE: To assess the association between independent risk factors (IRFs) and post-extubation failure in patients undergoing MVW in an intensive care unit. METHOD: Longitudinal, prospective, analytical cohort study in patients on mechanical ventilation for more than 24 hours and who were extubated. Pre-extubation reports of hemoglobin, albumin, phosphorus, waist-hip ratio and SOFA score were obtained. Extubation failure was defined as resumption of mechanical ventilation within 48 hours or less. RESULTS: 123 patients were extubated, out of whom 74 were males (60 %); average age was 50 ± 18 years. Extubation failure occurred in 37 (30 %). Hypoalbuminemia was associated as an independent risk factor in 29 (23.8 %, RR = 1.43, 95 % CI = 1.11-1.85) and hypophosphatemia was in 18 (14.6 %, RR = 2.98, 95 % CI = 1.66-5.35); two or more IRFs were observed in 22.7 % (RR = 1.51, 95 % CI = 1.14-2.00). CONCLUSIONS: Identifying independent risk factors prior to MVW can help reduce the risk of extubation failure and associated morbidity and mortality. INTRODUCCIÓN: Aun con adecuado protocolo de desconexión de la ventilación mecánica (DVM), el procedimiento falla en 15 a 30 % de los casos. OBJETIVO: Evaluar la asociación entre factores de riesgo independientes y fracaso posextubación en pacientes con DVM en una unidad de cuidados intensivos. MÉTODO: Estudio de cohorte, longitudinal, prospectivo, analítico, que incluyó pacientes sometidos a ventilación mecánica por más de 24 horas y que fueron extubados. Se obtuvieron reportes preextubación de hemoglobina, albúmina, fósforo, índice cintura-cadera y puntuación SOFA. Se definió como fracaso de extubación al reinicio de la ventilación mecánica en 48 horas o menos. RESULTADOS: Se extubaron 123 pacientes, 74 hombres (60 %); la edad promedio fue de 50 ± 18 años. Ocurrió fracaso de extubación en 37 (30 %). Como factores de riesgo independentes se asoció hipoalbuminemia en 29 (23.8 %, RR = 1.43, IC 95 % = 1.11-1.85) e hipofosfatemia en 18 (14.6 %, RR = 2.98, IC 95 % = 1.66-5.35); se observaron dos o más factores de riesgo independientes en 22.7 % (RR = 1.51, IC 95 % = 1.14-2.00). CONCLUSIONES: Identificar los factores de riesgo independentes antes de la DVM puede ayudar a reducir el fracaso de la extubación y la morbimortalidad asociada.

[Off-pump Coronary Artery Bypass Grafting in Jehovah's Witness Patient on Hemodialysis;Report of a Case].

Cardiac surgery in Jehovah's witnesses is challenging due to their refusal of blood transfusion. Furthermore, dialysis patients often suffer from anemia and are also prone to bleeding. We performed offpump coronary artery bypass grafting (CABG) [OPCAB] on a Jehovah's witness male patient on hemodialysis. His preoperative hemoglobin level was around 10.0 g/dl. We used cell saver-collected blood as much as possible during operation. His postoperative course was uneventful with the lowest hemoglobin level of 7.2 g/dl using iron supplements and erythropoietin. This case indicates that intraoperative blood salvage and perioperative management of anemia make OPCAB without blood transfusion possible even in Jehovah's witness hemodialysis patients, when their preoperative hemoglobin levels are maintained greater than 10.0 g/dl.

Fortification of maize flour with iron for controlling anaemia and iron deficiency in populations.

BACKGROUND: Approximately 800 million women and children have anaemia, a condition thought to cause almost 9% of the global burden of years lived with disability. Around half this burden could be amenable to interventions that involve the provision of iron. Maize (corn) is one of the world's most important cereal grains and is cultivated across most of the globe. Several programmes around the world have fortified maize flour and other maize-derived foodstuffs with iron and other vitamins and minerals to combat anaemia and iron deficiency. OBJECTIVES: To assess the effects of iron fortification of maize flour, corn meal and fortified maize flour products for anaemia and iron status in the general population. SEARCH METHODS: We searched the following international and regional sources in December 2017 and January 2018: Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; MEDLINE (R) In Process; Embase; Web of Science (both the Social Science Citation Index and the Science Citation Index); CINAHL Ebsco; POPLINE; AGRICOLA (agricola.nal.usda.gov); BIOSIS (ISI); Bibliomap and TRoPHI; IBECS; Scielo; Global Index Medicus - AFRO (includes African Index Medicus); EMRO (includes Index Medicus for the Eastern Mediterranean Region); LILACS; PAHO (Pan American Health Library); WHOLIS (WHO Library); WPRO (includes Western Pacific Region Index Medicus); IMSEAR, Index Medicus for the South-East Asian Region; IndMED, Indian medical journals; and the Native Health Research Database. We searched clinicaltrials.gov and the International Clinical Trials Registry Platform (ICTRP) for any ongoing or planned studies on 17 January 2018 and contacted authors of such studies to obtain further information or eligible data if available.For assistance in identifying ongoing or unpublished studies, we also contacted relevant international organisations and agencies working in food fortification on 9 August 2016. SELECTION CRITERIA: We included cluster- or individually randomised controlled trials and observational studies. Interventions included (central/industrial) fortification of maize flour or corn meal with iron alone or with other vitamins and minerals and provided to individuals over 2 years of age (including pregnant and lactating women) from any country. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the eligibility of studies for inclusion, extracted data from included studies and assessed the risk of bias of the included studies. Trial designs with a comparison group were included to assess the effects of interventions. Trial designs without a control or comparison group (uncontrolled before-and-after studies) were included for completeness but were not considered in assessments of the overall effectiveness of interventions or used to draw conclusions regarding the effects of interventions in the review. MAIN RESULTS: Our search yielded 4529 records. After initial screening of titles and abstracts, we reviewed the full text of 75 studies (80 records). We included 5 studies and excluded 70. All the included studies assessed the effects of providing maize products fortified with iron plus other vitamins and minerals versus unfortified maize flour. No studies compared this intervention to no intervention or looked at the relative effect of flour and products fortified with iron alone (without other vitamins and minerals). Three were randomised trials involving 2610 participants, and two were uncontrolled before-and-after studies involving 849 participants.Only three studies contributed data for the meta-analysis and included children aged 2 to 11.9 years and women. Compared to unfortified maize flour, it is uncertain whether fortifying maize flour or corn meal with iron and other vitamins and minerals has any effect on anaemia (risk ratio (RR) 0.90, 95% confidence interval (CI) 0.58 to 1.40; 2 studies; 1027 participants; very low-certainty evidence), or on the risk of iron deficiency (RR 0.75, 95% CI 0.49 to 1.15; 2 studies; 1102 participants; very low-certainty evidence), haemoglobin concentration (mean difference (MD) 1.25 g/L, 95% CI -2.36 to 4.86 g/L; 3 studies; 1144 participants; very low-certainty evidence) or ferritin concentrations (MD 0.48 µg/L, 95% CI -0.37 to 1.33 µg/L; 1 study; 584 participants; very low-certainty evidence).None of the studies reported on any adverse effects. We judged the certainty of the evidence to be very low based on GRADE, so we are uncertain whether the results reflect the true effect of the intervention. We downgraded evidence due to high risk of selection bias and unclear risk of performance bias in one of two included studies, high heterogeneity and wide CIs crossing the line of no effect for anaemia prevalence and haemoglobin concentration. AUTHORS' CONCLUSIONS: It is uncertain whether fortifying maize flour with iron and other vitamins and minerals reduces the risk of anaemia or iron deficiency in children aged over 2 years or in adults. Moreover, the evidence is too uncertain to conclude whether iron-fortified maize flour, corn meal or fortified maize flour products have any effect on reducing the risk of anaemia or on improving haemoglobin concentration in the population.We are uncertain whether fortification of maize flour with iron reduces anaemia among the general population, as the certainty of the evidence is very low. No studies reported on any adverse effects.Public organisations funded three of the five included studies, while the private sector gave grants to universities to perform the other two. The presence of industry funding for some of these trials did not appear to positively influence results from these studies.The reduced number of studies, including only two age groups (children and women of reproductive age), as well as the limited number of comparisons (only one out of the four planned) constitute the main limitations of this review.

Anemia ferropénica en niños menores de un año usuarios de CASMU-IAMPP: prevalencia y factores asociados / Iron deficiency anemia in children younger than 1 year old users of CASMU-IAMPP: prevalence and associated factors

Resumen Introducción: la anemia ferropénica es un problema de salud nacional. Existen recomendaciones para su prevención. Para su diagnóstico temprano se incorporó a partir de 2014 la medición de la hemoglobina por punción digital entre los 8-12 meses de edad. Objetivo: determinar la prevalencia de anemia en lactantes usuarios de CASMU-IAMPP e identificar factores asociados. Material y métodos: se estudiaron lactantes entre 8-12 meses, a quienes se realizó medición de hemoglobina por punción digital, entre julio-diciembre 2014. Se describió la prevalencia de anemia. Se describieron las características de los niños con anemia y se compararon con las de un grupo control de niños sin anemia. Resultados: en el período evaluado se realizó hemoglobina digital a 95% de los lactantes entre 8-12 meses, 18,3% presentaba anemia. El 65,9% incorporó carne a la alimentación en forma tardía, 28,6% recibía dosis incorrecta de hierro suplementario y 23,4% no adhería al tratamiento. Los niños con anemia, en comparación con el grupo control, no presentaron mayor prevalencia de prematurez, peso al nacer menor a 3000 g, embarazo gemelar, anemia en el embarazo, suplementación con hierro en el embarazo, pecho directo exclusivo durante 6 meses, o inicio adecuado de alimentación complementaria. En los niños con anemia se detectó una falla en el inicio oportuno de la suplementación con hierro en dosis adecuada así como una mala adherencia al tratamiento. Discusión: debe alertar un 20% de niños con anemia en una población seleccionada en general con recursos económicos adecuados. Se debe insistir en la incorporación temprana de carne a la alimentación e inicio adecuado de la suplementación con hierro en dosis adecuada recomendando una buena adherencia al tratamiento.

Summary Introduction: iron deficiency anemia is a health problem in Uruguay. In 2014, hemoglobin measurement by digital puncture in infants between 8 and 12 months was introduced as a screening method for early diagnosis. Objective: to determine anemia prevalence in infants between 8 and 12 months in the institution (CASMU-IAMPP), and to identify associated factors. Method: infants between 8 and 12 months were studied with hemoglobin measurement by digital puncture from July to December of 2014. The characteristics of the children with anemia were described and compared with the control group. The data were obtained from the medical record and by means of a telephone survey. Results: 804 children were evaluated with hemoglobin measurement by digital puncture, 145 presented anemia (18.03%). The characteristics presented by children with anemia (n=143) were compared with the control group of children without anemia (n=143). There was no significant difference in the distribution by sex, prematurity prevalence, weight under 3.000 g, twin pregnancy, exclusive breastfeeding, and adequate initiation of replacement treatment. Children with anemia presented problems in the initiation of iron supplementation, doses of supplementary iron were adequate, although adherence to treatment was bad (p<0.05). Discussion: the fact that 20% of children from a socio-economic sector with adequate resources have anemia is rather alarming. Early consumption of meat and adequate initiation of iron supplementation in the right doses must be encouraged, as well as a good adherence to treatment.

Effect of hyperbaric oxygen therapy on complete blood count.

Complete blood count (CBC) is a routine diagnostic procedure for patients and a part of routine health inspection for healthy individuals. The effect of hyperbaric oxygen (HBO2) on CBC is not known. The objective of this study was to determine the effects of HBO2 on blood parameters in CBC with long-term HBO2 therapy. In this study, patients received HBO2 at the department of Underwater and Hyperbaric Clinical Medicine. CBC results were obtained at specific time points during HBO2 therapy. The study recruited a total of 140 patients who met the research inclusion criteria. Patients were treated for 55.5 ± 41 days. During the treatment period, they underwent HBO2 sessions for an average of 35.9 ± 24.9 times. Five groups were created as follows: before the treatment; between 1-20 sessions; between 21-40 sessions; between 41-60 sessions; and more than 60 sessions. The results of the present study showed that a number of alterations occurred in CBC values in patients who received HBO2. HBO2 reduces the number of platelets, but this was not clinically significant. According to the results, HBO2 does not have any effect on hemoglobin, hematocrit, red blood cells, mean corpuscular volume, mean corpuscular hemoglobin, red blood cell distribution width, mean corpuscular hemoglobin concentration, platelet count, platelet distribution width and mean platelet volume. Except for a temporary reduction in platelet count, HBO2 has no effect on CBC parameters. Medical professionals may use the outcome of this study in their routine examinations, as it suggests that the changes in CBC driven by HBO2 are not statistically significant, and could be disregarded. More research is needed to examine the effects of HBO2 on other blood parameters.

Association between Vitamin D Deficiency and Anemia in Patients with End-Stage Renal Disease: A Cross-Sectional Study.

PURPOSE: Despite new treatment strategies, anemia remains the most prevalent complication in patients with end-stage renal disease (ESRD). We investigated whether 25-hydroxyvitamin D [25(OH)D3] deficiency was associated with anemia in ESRD patients. MATERIALS AND METHODS: We reviewed the medical records of 410 ESRD patients who had undergone renal transplantation (RTx) at Yonsei University Health System and who had 25(OH)D3 levels measured at the time of RTx. Patients were divided into two groups based on baseline 25(OH)D3 concentrations: group 1, 25(OH)D3 levels <10 ng/mL; and group 2, 25(OH)D3 levels ≥10 ng/mL. RESULTS: Using multivariate regression models, 25(OH)D3, age, and erythrocyte-stimulating agent (ESA) dose were found to be significantly associated with hemoglobin (Hb) levels [25(OH)D3: ß=0.263, p<0.001; age: ß=0.122, p=0.010; ESA dose: ß=-0.069, p=0.005]. In addition, logistic regression analysis revealed that patients in group 1 had a significantly higher risk for developing anemia (Hb level <10 g/dL) compared to group 2 patients, even after adjusting for potential risk factors for anemia (odds ratio=3.857; confidence interval=1.091-13.632; p=0.036). CONCLUSION: 25(OH)D3 deficiency was significantly associated with anemia in patients with ESRD. Randomized controlled trials are needed to determine whether vitamin D supplementation can improve anemia in these patients.

Blood Loss Management in Primary Hip Surgery: Is Reinfusion drain A Feasible Option in Maintaining Hemoglobin Levels?

The management of blood loss in primary hip arthroplasty is a controversial topic. Aim: To evaluate the efficacy of reinfusion drains in terms of hemoglobin levels and volume of red blood cell transfused postoperatively. Material and Methods: 295 patients who underwent primary hip arthroplasty were retrospectively assessed. After applying the exclusion criteria, 94 patients were included in the study and were divided into two groups: 45 patients received a reinfusion drain and 49 a suction drain. The following were analyzed: demographic characteristics of patients, preoperative hemoglobin level, 12-h and 24-h postoperative hemoglobin levels and their variations, number of transfused units of packed red blood cells, and postoperative complications. Results: Kruskal Wallis analysis revealed the homogeneity of the study groups (Chi-square=2.40, df=2, p=0.301). A statistically significant lower decline in mean Hb24 was found in suction drain group (p=0.001). Kruskal Wallis test revealed a significantly more frequent postoperative use of a higher number of packed red blood cell units in the suction drain group (Chi-square=28.70, df=2, p=0.001) compared to reinfusion drain group. Conclusions: We failed to demonstrate the superiority of reinfusion drains versus suction drains in maintaining hemoglobin levels.

Association between Vitamin D Deficiency and Anemia in Patients with End-Stage Renal Disease: A Cross-Sectional Study

PURPOSE: Despite new treatment strategies, anemia remains the most prevalent complication in patients with end-stage renal disease (ESRD). We investigated whether 25-hydroxyvitamin D [25(OH)D3] deficiency was associated with anemia in ESRD patients. MATERIALS AND METHODS: We reviewed the medical records of 410 ESRD patients who had undergone renal transplantation (RTx) at Yonsei University Health System and who had 25(OH)D3 levels measured at the time of RTx. Patients were divided into two groups based on baseline 25(OH)D3 concentrations: group 1, 25(OH)D3 levels <10 ng/mL; and group 2, 25(OH)D3 levels ≥10 ng/mL. RESULTS: Using multivariate regression models, 25(OH)D3, age, and erythrocyte-stimulating agent (ESA) dose were found to be significantly associated with hemoglobin (Hb) levels [25(OH)D3: β=0.263, p<0.001; age: β=0.122, p=0.010; ESA dose: β=-0.069, p=0.005]. In addition, logistic regression analysis revealed that patients in group 1 had a significantly higher risk for developing anemia (Hb level <10 g/dL) compared to group 2 patients, even after adjusting for potential risk factors for anemia (odds ratio=3.857; confidence interval=1.091-13.632; p=0.036). CONCLUSION: 25(OH)D3 deficiency was significantly associated with anemia in patients with ESRD. Randomized controlled trials are needed to determine whether vitamin D supplementation can improve anemia in these patients.

Iron therapy for pre-operative anaemia.

BACKGROUND: Pre-operative anaemia is common and occurs in up to 76% of patients. It is associated with increased peri-operative allogeneic blood transfusions, longer hospital lengths of stay and increased morbidity and mortality. Iron deficiency is one of the most common causes of this anaemia. Oral iron therapy has traditionally been used to treat anaemia but newer, safer parenteral iron preparations have been shown to be more effective in other conditions such as inflammatory bowel disease, chronic heart failure and post-partum haemorrhage. A limited number of studies look at iron therapy for the treatment of pre-operative anaemia. The aim of this Cochrane review is to summarise the evidence for use of iron supplementation, both enteral and parenteral, for the management of pre-operative anaemia. OBJECTIVES: The objective of this review is to evaluate the effects of pre-operative iron therapy (enteral or parenteral) in reducing the need for allogeneic blood transfusions in anaemic patients undergoing surgery. SEARCH METHODS: We ran the search on 25 March 2015. We searched the Cochrane Injuries Group's Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R), EMBASE Classic and EMBASE (Ovid), CINAHL Plus (EBSCO), PubMed, clinical trials registries, conference abstracts, and we screened reference lists. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) which compared pre-operative iron monotherapy to placebo, no treatment, standard of care or another form of iron therapy for anaemic adults undergoing surgery. Anaemia was defined by haemoglobin values less than 13 g/dL for males and 12 g/dL for non-pregnant females. DATA COLLECTION AND ANALYSIS: Data were collected by two authors on the proportion of patients who receive a blood transfusion, amount of blood transfused per patient (units) and haemoglobin measured as continuous variables at pre-determined time-points: pre-treatment, pre-operatively but post-treatment, and post-operatively. Statistical analysis was performed using the Cochrane statistical software, Review Manager 2014. Outcome data were summarised in tables and a forest plot. MAIN RESULTS: Three prospective randomised controlled studies evaluated pre-operative iron therapy to correct anaemia (two in colorectal and one in gynaecological surgery) and included 114 patients in total. One compared oral iron versus standard care (Lidder 2007); one intravenous iron versus control (Edwards 2009); and one study compared oral versus intravenous iron (Kim 2009). Both colorectal trials reported the primary outcome (proportion of patients who received allogeneic blood transfusions) and meta-analysis showed a reduction in blood transfusions with the administration of iron therapy, but the reduction was not statistically significant (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.27 to 1.18). All studies reported haemoglobin change but data for the anaemic patients were only available for two studies (Edwards 2009 and Kim 2009). Edwards 2009 showed no difference in haemoglobin at the end of treatment pre-operatively. The intravenous versus oral iron study showed an increase in haemoglobin with intravenous iron at the end of treatment pre-operatively (MD 1.90 g/dL, 95% CI 1.16 to 2.64; participants = 56), but the results are at high risk of bias because participants with less than 80% compliance with therapy were excluded from the analysis and compliance was lower in the oral iron group due to the side-effects of treatment (Kim 2009).None of the studies reported quality of life, short- or long-term mortality or post-operative morbidity. AUTHORS' CONCLUSIONS: The use of iron therapy for pre-operative anaemia does not show a statistically significant reduction in the proportion of patients who received an allogeneic blood transfusion compared to no iron therapy. However, the 38 patients in our analysis falls far short of the 819 patients our information size calculation recommended to detect a 30% reduction in blood transfusions. Intravenous iron may be more effective than oral iron at increasing haemoglobin. However, all these conclusions are drawn from only three small randomised controlled studies. Further well designed, adequately powered randomised controlled studies are required to determine the true effectiveness of iron therapy for pre-operative anaemia.

Effect of Daily Antenatal Iron Supplementation on Plasmodium Infection in Kenyan Women: A Randomized Clinical Trial.

IMPORTANCE: Anemia affects most pregnant African women and is predominantly due to iron deficiency, but antenatal iron supplementation has uncertain health benefits and can increase the malaria burden. OBJECTIVE: To measure the effect of antenatal iron supplementation on maternal Plasmodium infection risk, maternal iron status, and neonatal outcomes. DESIGN, SETTING, AND PARTICIPANTS: Randomized placebo-controlled trial conducted October 2011 through April 2013 in a malaria endemic area among 470 rural Kenyan women aged 15 to 45 years with singleton pregnancies, gestational age of 13 to 23 weeks, and hemoglobin concentration of 9 g/dL or greater. All women received 5.7 mg iron/day through flour fortification during intervention, and usual intermittent preventive treatment against malaria was given. INTERVENTIONS: Supervised daily supplementation with 60 mg of elemental iron (as ferrous fumarate, n = 237 women) or placebo (n = 233) from randomization until 1 month postpartum. MAIN OUTCOMES AND MEASURES: Primary outcome was maternal Plasmodium infection at birth. Predefined secondary outcomes were birth weight and gestational age at delivery, intrauterine growth, and maternal and infant iron status at 1 month after birth. RESULTS: Among the 470 participating women, 40 women (22 iron, 18 placebo) were lost to follow-up or excluded at birth; 12 mothers were lost to follow-up postpartum (5 iron, 7 placebo). At baseline, 190 of 318 women (59.7%) were iron-deficient. In intention-to-treat analysis, comparison of women who received iron vs placebo, respectively, yielded the following results at birth: Plasmodium infection risk: 50.9% vs 52.1% (crude difference, -1.2%, 95% CI, -11.8% to 9.5%; P = .83); birth weight: 3202 g vs 3053 g (crude difference, 150 g, 95% CI, 56 to 244; P = .002); birth-weight-for-gestational-age z score: 0.52 vs 0.31 (crude difference, 0.21, 95% CI, -0.11 to 0.52; P = .20); and at 1 month after birth: maternal hemoglobin concentration: 12.89 g/dL vs 11.99 g/dL (crude difference, 0.90 g/dL, 95% CI, 0.61 to 1.19; P < .001); geometric mean maternal plasma ferritin concentration: 32.1 µg/L vs 14.4 µg/L (crude difference, 123.4%, 95% CI, 85.5% to 169.1%; P < .001); geometric mean neonatal plasma ferritin concentration: 163.0 µg/L vs 138.7 µg/L (crude difference, 17.5%, 95% CI, 2.4% to 34.8%; P = .02). Serious adverse events were reported for 9 and 12 women who received iron and placebo, respectively. There was no evidence that intervention effects on Plasmodium infection risk were modified by intermittent preventive treatment use. CONCLUSIONS AND RELEVANCE: Among rural Kenyan women with singleton pregnancies, administration of daily iron supplementation, compared with administration of placebo, resulted in no significant differences in overall maternal Plasmodium infection risk. Iron supplementation led to increased birth weight. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01308112.

Oral or parenteral iron supplementation to reduce deferral, iron deficiency and/or anaemia in blood donors.

BACKGROUND: Iron deficiency is a significant cause of deferral in people wishing to donate blood. If iron removed from the body through blood donation is not replaced, then donors may become iron deficient. All donors are screened at each visit for low haemoglobin (Hb) levels. However, some deferred blood donors do not return to donate. Deferred first-time donors are even less likely to return. Interventions that reduce the risk of provoking iron deficiency and anaemia in blood donors will therefore increase the number of blood donations. Currently, iron supplementation for blood donors is not a standard of care in many blood services. A systematic review is required to answer specific questions regarding the efficacy and safety of iron supplementation in blood donors. OBJECTIVES: To assess the efficacy and safety of iron supplementation to reduce deferral, iron deficiency and/or anaemia in blood donors. SEARCH METHODS: We ran the search on 18 November 2013. We searched Cochrane Injuries Group Specialised Register, CENTRAL, PubMed, MEDLINE (OvidSP), EMBASE (OvidSP), CINAHL (EBSCO Host) and six other databases. We also searched clinical trials registers and screened guidelines reference lists. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing iron supplementation versus placebo or control, oral versus parenteral iron supplementation, iron supplementation versus iron-rich food supplements, and different doses, treatment durations and preparations of iron supplementation in healthy blood donors. Autologous blood donors were excluded. DATA COLLECTION AND ANALYSIS: We combined data using random-effects meta-analyses. We evaluated heterogeneity using the I(2) statistic; we explored considerable heterogeneity (I(2) > 75%) in subgroup analyses. We carried out sensitivity analyses to assess the impact of trial quality on the results. MAIN RESULTS: Thirty RCTs (4704 participants) met the eligibility criteria, including 19 comparisons of iron supplementation and placebo or control; one comparison of oral and parenteral iron supplementation; four comparisons of different doses of iron supplementation; one comparison of different treatment durations of iron supplementation; and 12 comparisons of different iron supplementation preparations.Many studies were of low or uncertain methodological quality and therefore at high or uncertain risk of bias. We therefore rated the quality of the evidence for our outcomes as moderate. There was a statistically significant reduction in deferral due to low haemoglobin in donors who received iron supplementation compared with donors who received no iron supplementation, both at the first donation visit after commencement of iron supplementation (risk ratio (RR) 0.34; 95% confidence interval (CI) 0.21 to 0.55; four studies; 1194 participants; P value < 0.0001) and at subsequent donations (RR 0.25; 95% CI 0.15 to 0.41; three studies; 793 participants; P value < 0.00001). Supplementation also resulted in significantly higher haemoglobin levels (mean difference (MD) 2.36 g/L; 95% CI 0.06 to 4.66; eight studies; 847 participants, P value =0.04), and iron stores, including serum ferritin (MD 13.98 ng/mL; 95% CI 8.92 to 19.03; five studies; 640 participants; P value < 0.00001) and transferrin saturation (MD 3.91%; 95% CI 2.02 to 5.80; four studies; 344 participants; P value < 0.0001) prior to further donation. The differences were maintained after subsequent donation(s).Adverse effects were widely reported and were more frequent in donors who received iron supplementation (RR 1.60; 95% CI 1.23 to 2.07; four studies; 1748 participants; P value = 0.0005). Adverse effects included constipation, diarrhoea, nausea, vomiting and taste disturbances, and some participants stopped treatment due to side effects. AUTHORS' CONCLUSIONS: There is moderate quality evidence that rates of donor deferral due to low haemoglobin are considerably less in those taking iron supplements compared with those without iron supplementation, both at the first donation visit and at subsequent donation. Iron-supplemented donors also show elevated haemoglobin and iron stores. These beneficial effects are balanced by more frequent adverse events in donors who receive iron supplementation than in those who do not; this is likely to limit acceptability and compliance. The long-term effects of iron supplementation without measurement of iron stores are unknown. These considerations are likely to preclude widespread use of iron supplementation by tablets. Blood services may consider targeted use of supplementation in those at greatest risk of iron deficiency, personalised donation intervals and providing dietary advice.

Trends in anemia care in older patients approaching end-stage renal disease in the United States (1995-2010).

IMPORTANCE: Anemia is common in patients with advanced chronic kidney disease. Whereas the treatment of anemia in patients with end-stage renal disease (ESRD) has attracted considerable attention, relatively little is known about patterns and trends in the anemia care received by patients before they start maintenance dialysis or undergo preemptive kidney transplantation. OBJECTIVE: To determine the trends in anemia treatment received by Medicare beneficiaries approaching ESRD. DESIGN, SETTING, AND PARTICIPANTS: Closed cohort study in the United States using national ESRD registry data (US Renal Data System) of patients 67 years or older who initiated maintenance dialysis or underwent preemptive kidney transplantation between 1995 and 2010. All eligible patients had uninterrupted Medicare (A+B) coverage for at least 2 years before ESRD. EXPOSURE: Time, defined as calendar year of incident ESRD. MAIN OUTCOMES AND MEASURES: Use of erythropoiesis-stimulating agents (ESA), intravenous iron supplements, and blood transfusions in the 2 years prior to ESRD; hemoglobin concentration at the time of ESRD. We used multivariable modified Poisson regression to estimate utilization prevalence ratios (PRs). RESULTS: Records of 466,803 patients were analyzed. The proportion of patients with incident ESRD receiving any ESA in the 2 years before increased from 3.2% in 1995 to a peak of 40.8% in 2007; thereafter, ESA use decreased modestly to 35.0% in 2010 (compared with 1995; PR, 9.85 [95% CI, 9.04-10.74]). Among patients who received an ESA, median time from first recorded ESA use to ESRD increased from 120 days in 1995 to 337 days in 2010. Intravenous iron administration increased from 1.2% (1995) to 12.3% (2010; PR, 9.20 [95% CI, 7.97-10.61]). The proportion of patients receiving any blood transfusions increased monotonically from 20.6% (1995) to 40.3% (2010; PR, 1.88 [95% CI, 1.82-1.95]). Mean hemoglobin concentrations were 9.5 g/dL in 1995, increased to a peak of 10.3 g/dL in 2006, and then decreased moderately to 9.9 g/dL in 2010. CONCLUSIONS AND RELEVANCE: Between 1995 and 2010, older adults approaching ESRD were increasingly more likely to be treated with ESAs and to receive intravenous iron supplementation, but also more likely to receive blood transfusions.