Anaemia in chronic kidney disease (CKD) mostly results from a decrease in the production of erythropoietin (EPO) by the failing kidney. CKD progression requires treatment with erythropoiesis-stimulating agents and iron supplementation to ensure sufficient erythrocyte production. Best clinical practice guidelines should be adhered to in managing CKD to reduce morbidity and mortality related to anaemia associated cardiovascular disease. Likewise, guideline deviations create an increased strain on the resources of the treatment facility. It is uncertain to which extent these guidelines are followed by Nephrology Units in the public healthcare sector, or whether the documented international trends are prevalent locally due to the paucity of local data, and therefore further investigation is warranted. This study aimed to assess treatment trends in managing anaemia in CKD patients at the Steve Biko Academic Hospital (SBAH). Files of patients receiving treatment at the SBAH Nephrology Unit between 2 January 2018 - 31 August 2018 were reviewed. Only individuals with stage 5 CKD receiving either haemodialysis, or peritoneal dialysis were included, while those with less than three months’ treatment were excluded. Measured variables included demographical information, current EPO treatment and/or iron supplementation regimens versus serum haemoglobin/iron levels and quantity of administered blood products. Ninety-seven patients met the inclusion criteria. Haemodialysis accounted for 43% (n = 42), and peritoneal dialysis 57% (n = 55). Intergroup comparison between the number of results where both haemoglobin and iron were within the target range versus the number of results where both parameters fell outside the target range yielded a significant difference (p = 0.0031). Patients receiving peritoneal dialysis reached serum haemoglobin and iron levels closer to normal target values compared to those receiving haemodialysis. Managing anaemia in CKD is a complex process. More stringent iron control, especially for patients receiving haemodialysis, including the administration of long-acting EPO preparations once a month, is proposed. The latter will contribute to the improvement of clinical outcomes of patients with CKD. Keywords: Chronic kidney disease, anaemia, erythropoiesis stimulating agent, haemoglobin, iron / Dissertation (MSc (Pharmacology))--University of Pretoria, 2020. / Pharmacology / MSc (Pharmacology) / Unrestricted

El texto completo de este trabajo no está disponible en el Repositorio Académico UPC por restricciones de la casa editorial donde ha sido publicado. / Introduction: Approximately, one in three Peruvian children aged 6 to 59 months old have anaemia. Maternal depression, which may be disabling and affect the proper care of children, is associated with chronic malnutrition in their offspring. Therefore, the aim of this study is to evaluate if there is an association between depressive symptoms of mothers with the presence of anaemia in their children. Methods: Analytical cross-sectional study of the Peruvian Demographic Health Survey 2015, which is nationally representative. Depressive symptoms were measured with the Patient Health Questionnaire-9 (PHQ-9) using a score of 10 as cut-off. The presence of anaemia was measured using HemoCue® and was considered positive when the haemoglobin was less than 11 g/dl. Results: Crude and adjusted prevalence ratios (PR and aPR) were calculated with 95% confidence interval (CI), using generalized linear models of the Poisson family. We analysed 6683 mother–child binomials. The prevalence of anaemia in the children and depressive symptoms in women were 28.7% (95% CI: 27.3–30.2) and 6.9% (95% CI: 6.1–7.9), respectively. We found no statistically significant association between these variables in the bivariable analysis or in the different multivariable models (aPR: 1.05, 95% CI: 0.85–1.30). The sample did not have moderate or severe malnutrition. Conclusions: There is no statistically significant difference between the prevalence of anaemia in children of mothers with or without depressive symptoms. We recommend continuing research in this field to determine more associate factors to childhood anaemia in order to improve primary prevention interventions. Ideally, conducting longitudinal studies such as prospectives cohorts to determine risk factors should be done. / Revisión por pares

Background: Fanconi anaemia (FA) is a rare genetic disorder associated with bone marrow failure (BMF), congenital anomalies and cancer susceptibility. Stem cell transplantation (SCT) offers a potential cure for BMF or leukaemia, but incurs substantial risks. Little is known about factors influencing SCT decision making. Objective: The study objective was to explore factors influencing patients' with FA and family members' decision making about SCT. Design: Using a mixed-methods exploratory design, we surveyed US and Canadian patients with FA and family members who were offered SCT. Main variables studied: Closed-ended survey items measured respondents' beliefs about the necessity, risks and concerns regarding SCT; multivariable logistic regression was used to examine the association between these factors and the decision to undergo SCT. Open-ended survey items measured respondents' perceptions of factors important to the SCT decision; qualitative analysis was used to identify emergent themes. Results: The decision to undergo SCT was significantly associated with greater perceived necessity (OR = 2.81, P = 0.004) and lower concern about harms of SCT (OR = 0.31, P = 0.03). Qualitative analysis revealed a perceived lack of choice among respondents regarding the use of SCT, which was related to physician influence and respondent concerns about patients' quality of life. Conclusions: Overall, study results emphasize the importance of the delicate interplay between provider recommendation of a medical procedure and patient/parental perceptions and decision making. Findings can help providers understand the need to acknowledge family members' perceptions of SCT decision making and offer a comprehensive discussion of the necessity, risks, benefits and potential outcomes.

Objective To reduce prevalence of anaemia in low-income postpartum women.Design A randomised, non-blind clinical trial was conducted among 959 low-income, postpartum women in eleven clinics in Mississippi. The clinics were randomised to one of three treatment groups: (i) selective anaemia screening of high-risk women as recommended currently (control); (ii) universal anaemia screening and treatment of anaemic women (group I); and (iii) universal Fe supplementation of 65 mg/d for two months to all low-income women (group II). All study participants within each clinic received the same treatment. Women were followed up at 6 months after delivery. Hb was measured at baseline and at follow-up. The primary outcome variable was the proportion of women with anaemia after treatment.Setting Eleven health clinics in Mississippi.Subjects Low-income, postpartum women.Results Baseline characteristics of the three study groups were compared using one-way ANOVA and an appropriate post hoc test for continuous variables and the χ 2 test for categorical variables. Fifty-two per cent of postpartum women were anaemic (Hb < 12.0 g/dl) and the rate decreased to 33 % at 6 months after the intervention. Group II women, who received universal Fe supplementation, improved their Hb status significantly (P < 0.001) at 6 months postpartum compared with the other groups. Prevalence of anaemia was also significantly lower among group II women (22.5 %) compared with controls (34 %) and group I women (43 %; P < 0.001).Conclusions A universal Fe supplementation strategy was effective in reducing the prevalence of anaemia among low-income postpartum women.

This study compared uncomplicated canine babesiosis (CB) with various grades of experimentally induced normovolaemic anaemia (EA) and the physiological state (controls) in the dog using Doppler variables of the abdominal aorta and splanchnic vessels. There were 14 cases of uncomplicated CB, and each EA and control group had 11 Beagles. There were significant increases in the abdominal aorta, cranial mesenteric artery, coeliac artery and main portal vein blood flow velocities, and in portal blood flow during EA when compared with the physiological state. There were significant reductions in resistance indices of the same vessels, and those of the hilar splenic artery. Changes were most notable during severe EA and less consistent during lower grades of anaemia. Significant changes in renal haemodynamics were found only during severe acute EA. In contrast to other abdominal vessels, left renal artery pulsatility and resistive indices increased significantly during EA while those of the interlobar artery remained unchanged. There was a significant increase in peak systolic velocity and significant decrease in end diastolic velocity. Renal artery time-averaged mean velocity (TAVmean) (P < 0.008) and end diastolic velocity (P = 0.041) were significantly lower than the corresponding variables of the aorta, cranial mesenteric and coeliac arteries during the EA but not the physiological state. The TAVmean ratio was significantly (P< 0.014) lower during EA when compared to the physiological state, and significantly (P< 0.004) lower than the corresponding variables of cranial mesenteric or coeliac artery during the EA but not the physiological state. There was a striking similarity between CB and EA regarding haemodynamic change patterns of Doppler variables in all vessels. In spite of this, renal resistive indices during CB were significantly higher than during EA and the physiological state. The similarity between CB and EA haemodynamic patterns is attributed to anaemia while significant differences between them may be attributable to pathophysiological factors peculiar to CB. This observation supports the view that CB impairs renal circulation through certain mechanisms such as capillary blockage with sequestered red blood cells. Doppler ultrasonography is a useful technique for clinical investigation of haemodynamics in CB and related diseases. / Thesis (PhD (Veterinary Science))--University of Pretoria, 2005. / Companion Animal Clinical Studies / unrestricted

京都大学 / 0048 / 新制・課程博士 / 博士(社会健康医学) / 甲第21033号 / 社医博第87号 / 新制||社医||10(附属図書館) / 京都大学大学院医学研究科社会健康医学系専攻 / (主査)教授 中山 健夫, 教授 木原 正博, 教授 西渕 光昭 / 学位規則第4条第1項該当 / Doctor of Public Health / Kyoto University / DFAM

Yes / Recombinant human erythropoietin (rHuEPO) is an effective treatment for anaemia but concerns that it causes disease progression in cancer patients by activation of EPO receptors (EPOR) in tumour tissue have been contro- versial and have restricted its clinical use. Initial clinical studies were flawed because they used polyclonal antibodies, later shown to lack specificity for EPOR. Moreover, multiple isoforms of EPOR caused by differential splicing have been reported in cancer cell lines at the mRNA level but investigations of these variants and their potential impact on tumour progression, have been hampered by lack of suitable antibodies. The EpoCan consortium seeks to promote improved pathological testing of EPOR, leading to safer clinical use of rHuEPO, by producing well characterized EPOR antibodies. Using novel genetic and traditional peptide immunization protocols, we have produced mouse and rat monoclonal antibodies, and show that sev- eral of these specifically recognize EPOR by Western blot, immunoprecipi- tation, immunofluorescence, flow cytometry and immunohistochemistry in cell lines and clinical material. Widespread availability of these antibodies should enable the research community to gain a better understanding of the role of EPOR in cancer, and eventually to distinguish patients who can be treated safely by rHuEPO from those at increased risk from treatment. / Study was supported by the FP7-Health European commission EpoCan grant (282551).

Background: The Zanzibar Infant Nutrition Campaign is a large-scale randomised control trial investigating the effects of iron and zinc supplementation on the morbidity and mortality of infants and young children on Pemba Island, Zanzibar, Tanzania. The Child Development Study is a substudy of the larger ZINC control trial assessing the effects of 12 months of iron and zinc supplementation on motor and language development. The Caregiver-Infant Interaction Study is a substudy of the Child Development Study, assessing the effects of 1 to 3 months of iron and zinc supplementation on caregiver-infant interaction among 9-month-old dyads. This thesis reports on the dyads enrolled in the Caregiver-Infant Interaction Study. While not examining treatment effects1 • Formulate behavioural and developmental hypotheses specific to a population of 9-month-old caregiver-infant dyads affected by a history of IDA , hypothesised disturbances in the behaviour and development of infants affected by a history of iron deficiency anaemia (IDA) are examined. Objectives: • Develop a hypothesis-driven observational coding system and establish the psychometric properties of this measure • Test hypotheses about the relationship between a history of IDA and the behaviour and development of 9-month-old caregiver-infant dyads Rationale: Iron deficiency anaemia is the most common nutritional disorder in the world. Prevalence is especially high among women, young children and infants in developing countries. As a public health concern, the effects of IDA are various and insidious, however the relationship between IDA and infant behaviour and development is not known. The majority of studies concerned with the impact of IDA in infancy have relied on global developmental scales, such as the Bayley Scales of Infant Development (Bayley, 1969, 1993). While infants with IDA consistently score worse than non-anaemic comparisons on mental and motor subscales, the value of this form of assessment is known to be limited. Apart from being of questionable validity as indices of abilities or functions (e.g., Fagan & Singer, 1983), the scores and ratings produced by traditional developmental scales are not designed to assess the specific functions hypothesised to be affected by IDA (Lozoff, De Andraca, Castillo, Smith, Walter & Pino, 2003). Over-reliance on this kind of measure thus rules out meaningful hypothesis-driven research. Recently, malnutrition researchers have begun to made use of systematic behavioural observation as a means of assessment. While a promising approach, extant research is limited to only two studies (see Footnote 6), and both of these have been conducted by the same research group. Moreover, these studies have relied on fairly rudimentary behavioural coding to examine a version of the ‘Functional Isolation Hypothesis', originally proposed some time ago in the infrahuman literature (Levitsky & Barns, 1972, 1973). More sophisticated hypotheses are available, especially given the ready availability of insights from developmental psychobiology and cognitive science. Design: A correlational design was used to examine the behaviour and development of 9-month old caregiver-infant dyads with a history of IDA. Setting: Wete District, Pemba Island, Zanzibar, Tanzania. Participants: 160 Caregiver-infant dyads assessed observationally at 9-month of age. Main Outcome Measure: Systematic observational coding. Main Findings: Infants with a history of more severe IDA spent significantly less time in high energy states during free play, and their caregivers made less physically demanding requests. A history of IDA also correlated with developmental disturbances in postural control. Affectively, IDA infants were hypo-responsive, and caregivers showed more (overt) positive affect for healthy males, but not females. Caregivers coordinated actions and vocalizations less often during interaction with infants affected by a history of IDA. Conclusion: A history of IDA among 9-month old infants is related to behavioural and developmental disturbances in both motor and socio-cognitive domains. Note to reader: The present research was first submitted as a Masters dissertation in 2008. The author was subsequently offered the opportunity rather to upgrade to a Doctoral thesis and resubmit the work as PhD. Chronologically then, studies which did not inform the design and development of the coding system used for data collection, or which published findings after the first submission of the present work, are discussed in the final chapter. / Thesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2009.

Student Number : 9807768F - MSc (Med) research report - Faculty of Health Sciences / Fanconi anaemia (FA) is an autosomal recessive disorder characterised by aplastic anaemia (AA) and a high risk of developing acute myeloid leukaemia (AML). It is unknown whether heterozygote carriers are also predisposed to developing these disorders. The black South African population group is ideal for FA mutation screening because the presence of a founder mutation, FANCG 637-643, makes screening relatively straight forward. Three individuals with AML (115 screened) and one with AA (78 screened) were found to be heterozygous for the black South African founder mutation. From our data it seems unlikely that this mutation places heterozygous carriers of the mutation at high risk of developing AML or AA. Three children with AA out of 26 screened, were homozygous for the mutation. This finding reiterates the importance of screening all children with AA for FA. The frequency of certain congenital abnormalities in black South African FA patients was compared to patients described by other research groups. The frequencies of the abnormalities were similar to other FANCG cohorts described but significant differences to a group of FA patients from unspecified complementation groups were found. This difference could be because different complementation groups are associated more or less strongly with specific abnormalities. It was found previously that particular congenital abnormalities in FA patients are associated with a poor haematological outcome. We concluded that black South African FANCG patients have a high risk of early development of AA even though they do not have a high frequency of congenital abnormalities.

Due to the action of endogenous and exogenous agents, DNA is subject up to 70,000 lesions per day, thus the existence of repair mechanisms and enzymes is more than necessary. We know basic mechanisms of several specific DNA repair pathways, of which the Fanconi anaemia (FA) repair pathway is one of the least explored. FA is a rare, autosomal recessive disorder characterized by early onset bone marrow failure, developmental defects, genomic instability and predisposition to acute myeloid leukaemia and solid tumours. The primary diagnosis of FA is a hypersensitivity to cross-linking agents of DNA due to inactivation of one of the 21 genes from the FA repair pathway, the so-called FANC genes (FA complementation group). The molecular defect in FA is an impaired repair of DNA interstrand cross-links (ICLs). The ICLs are cytotoxic lesions that inhibit the process of DNA replication and transcription. A crucial step in the FA pathway that initiates ICL repair is a monoubiquitination of FANCD2. FANCD2 monoubiquitination is a base for the recruitment of additional proteins that coordinate DNA repair. Ubiquitin is recruited via activating enzyme E1 (UBA1), ubiquitin-conjugating enzyme E2T (UBE2T) and transferred onto FANCD2 by multisubunit E3 ligase (FA core complex). There are up to 11 different proteins...