Changing trends in blood transfusion in children and neonates admitted in Kilifi District Hospital, Kenya

<p>Abstract</p> <p>Background</p> <p>Severe anaemia is a common cause for hospitalization in children in sub-Saharan Africa. Malaria plays an important aetiological role, resulting in a substantial burden of paediatric transfusion in hospitals. A decline in malaria and paediatric admissions to the Kilifi District Hospital has been reported recently. This study aimed to investigate whether this trend affected clinical burden, clinical severity of anaemia and requirements for paediatric transfusion.</p> <p>Methods</p> <p>Eight-year retrospective review of paediatric admissions to Kilifi District Hospital, Kenya describing the frequency of moderate and severe anaemia, blood transfusion and case fatality over time. Definitions for severe anaemia were Hb <8 g/dl for newborns and <5 g/dl for other age groups and for moderate anaemia was Hb 8 to <11 g/dl for newborns and 5 to <9.3 g/dl for other age groups. Life threatening anaemia was defined as severe anaemia (Hb <5 g/dl) complicated by either deep breathing or prostration or profound anaemia (Hb <4 g/dl) alone.</p> <p>Results</p> <p>Of the 35,139 admissions 13,037 (37%) had moderate anaemia and 2,265 (6%) had severe anaemia; respiratory distress complicated 35% of cases with Hb <5 g/dl. Concurrent with the decline in malaria there was a marked decline in the prevalence of severe anaemia between 2002 (8%) and 2009 (< 4%) (chi²for trend = 134, P < 0.0001). The number and proportion of admissions transfused also declined significantly over this time (chi2 for trend = 152, P < 0.0001). Of the 2,265 children with severe anaemia 191 (8%) died. Case fatality remained unchanged during this period (P < 0.26) and was largely explained by the unchanged proportion with life-threatening anaemia, present in 58-65% of cases throughout the study period.</p> <p>Conclusion</p> <p>The impact of reduced malaria transmission on child morbidity has positive public benefits on the demand and use of blood for paediatric transfusion. Despite an overall reduction in paediatric transfusion requirement, case fatality of severe anaemia remained unchanged over this decade. Further research is required to improve outcome from severe anaemia, particularly in the high-risk group with life threatening features.</p

Anaemia and blood transfusion in African children presenting to hospital with severe febrile illness

BACKGROUND: Severe anaemia in children is a leading cause of hospital admission and a major cause of mortality in sub-Saharan Africa, yet there are limited published data on blood transfusion in this vulnerable group. METHODS: We present data from a large controlled trial of fluid resuscitation (Fluid Expansion As Supportive Therapy (FEAST) trial) on the prevalence, clinical features, and transfusion management of anaemia in children presenting to hospitals in three East African countries with serious febrile illness (predominantly malaria and/or sepsis) and impaired peripheral perfusion. RESULTS: Of 3,170 children in the FEAST trial, 3,082 (97%) had baseline haemoglobin (Hb) measurement, 2,346/3,082 (76%) were anaemic (Hb <10 g/dL), and 33% severely anaemic (Hb <5 g/dL). Prevalence of severe anaemia varied from 12% in Kenya to 41% in eastern Uganda. 1,387/3,082 (45%) children were transfused (81% within 8 hours). Adherence to WHO transfusion guidelines was poor. Among severely anaemic children who were not transfused, 52% (54/103) died within 8 hours, and 90% of these deaths occurred within 2.5 hours of randomisation. By 24 hours, 128/1,002 (13%) severely anaemic children had died, compared to 36/501 (7%) and 71/843 (8%) of those with moderate and mild anaemia, respectively. Among children without severe hypotension who were randomised to receive fluid boluses of 0.9% saline or albumin, mortality was increased (10.6% and 10.5%, respectively) compared to controls (7.2%), regardless of admission Hb level. Repeat transfusion varied from ≤2% in Kenya/Tanzania to 6 to 13% at the four Ugandan centres. Adverse reactions to blood were rare (0.4%). CONCLUSIONS: Severe anaemia complicates one third of childhood admissions with serious febrile illness to hospitals in East Africa, and is associated with increased mortality. A high proportion of deaths occurred within 2.5 hours of admission, emphasizing the need for rapid recognition and prompt blood transfusion. Adherence to current WHO transfusion guidelines was poor. The high rates of re-transfusion suggest that 20 mL/kg whole blood or 10 mL/kg packed cells may undertreat a significant proportion of anaemic children. Future evaluation of the impact of a larger volume of transfused blood and optimum transfusion management of children with Hb of <6 g/dL is warranted. Please see related article: http://dx.doi.org/10.1186/s12916-014-0248-5. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12916-014-0246-7) contains supplementary material, which is available to authorized users

WHO guidelines on fluid resuscitation in children: missing the FEAST data.

The World Health Organization recommendations on management of common childhood illnesses affect the lives of millions of children admitted to hospital worldwide. Its latest guidelines,1 released in May 2013, continue to recommend rapid fluid resuscitation for septic shock, even though the only large controlled trial of this treatment (Fluid Expansion as a Supportive Treatment (FEAST) found that it increased the risk of death in African children.2 A subsequent systematic review of bolus resuscitation in children with shock resulting from severe infection also did not support its use.3 Failure to take this evidence into account is not consistent with WHO’s commitment to systematically and transparently assess evidence using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) process when producing guidelines and could endanger the lives of children

A microRNA/Runx1/Runx2 network regulates prostate tumor progression from onset to adenocarcinoma in TRAMP mice

While decades of research have identified molecular pathways inducing and promoting stages of prostate cancer malignancy, studies addressing dynamic changes of cancer-related regulatory factors in a prostate tumor progression model are limited. Using the TRAMP mouse model of human prostate cancer, we address mechanisms of deregulation for the cancer-associated transcription factors, Runx1 and Runx2 by identifying microRNAs with reciprocal expression changes at six time points during 33 weeks of tumorigenesis. We molecularly define transition stages from PIN lesions to hyperplasia/neoplasia and progression to adenocarcinoma by temporal changes in expression of human prostate cancer markers, including the androgen receptor and tumor suppressors, Nkx3.1 and PTEN. Concomitant activation of PTEN, AR, and Runx factors occurs at early stages. At late stages, PTEN and AR are downregulated, while Runx1 and Runx2 remain elevated. Loss of Runx-targeting microRNAs, miR-23b-5p, miR-139-5p, miR-205-5p, miR-221-3p, miR-375-3p, miR-382-5p, and miR-384-5p, contribute to aberrant Runx expression in prostate tumors. Our studies reveal a Runx/miRNA interaction axis centered on PTEN-PI3K-AKT signaling. This regulatory network translates to mechanistic understanding of prostate tumorigenesis that can be developed for diagnosis and directed therapy

Magnitude and pattern of improvement in processes of care for hospitalised children with diarrhoea and dehydration in Kenyan hospitals participating in a clinical network

Objective WHO recommends optimisation of available interventions to reduce deaths of under‐five children with diarrhoea and dehydration (DD). Clinical networks may help improve practice across many hospitals but experience with such networks is scarce. We describe magnitude and patterns of changes in processes of care for children with DD over the first 3 years of a clinical network. Methods Observational study involving children aged 2–59 months with DD admitted to 13 hospitals participating in the clinical network. Processes of individual patient care including agreement of assessment, diagnosis and treatment according to WHO guidelines were combined using the composite Paediatric Admission Quality of Care (PAQC) score (range 0–6). Results Data from 7657 children were analysed and improvements in PAQC scores were observed. Predicted mean PAQC score for all the hospitals at enrolment was 59.8% (95% CI: 54.7, 64.9) but showed a wide variation (variance 10.7%, 95% CI: 5.8, 19.6). Overall mean PAQC score increased by 13.8% (95% CI: 8.7–18.9, SD between hospitals: ±8.2) in the first 12 months, with an average 0.9% (95% CI: 0.3–1.5, SD ± 1.0) increase per month and plateaued thereafter, and changes were similar in two groups of hospitals joining the network at different times. Conclusion Adherence to guidelines for children admitted with DD can be improved through participation in a clinical network but improvement is limited, not uniform for all aspects of care and contexts and occurs early. Future research should address these issues

Should colloid boluses be prioritized over crystalloid boluses for the management of dengue shock syndrome in the presence of ascites and pleural effusions?

<p>Abstract</p> <p>Background</p> <p>Although the WHO guideline for the management of dengue fever considers the presence of ascites or pleural effusions in the diagnosis of DSS, it does not emphasize the importance of their presence when selecting fluids for resuscitation.</p> <p>Case presentation</p> <p>We highlight three patients with DSS who received boluses of crystalloids on priority basis as recommended by WHO guidelines during resuscitation. All three patients had varying degrees of third space fluid loss (ascites and pleural effusions) at the time of development of DSS. Ascites and pleural effusions were detected in all 3 patients at the time of shock irrespective of whether iv fluids were given or not. All three patients had documented liver involvement at the time of shock evidenced by elevation of AST (4800 iu/L, 5000 iu/L and 1960 iu/L). One patient who had profound shock died 6 hours after admission with evidence of acute pulmonary oedema in the convalescence phase. All of them needed CPAP ventilator support and potent diuretics.</p> <p>Conclusions</p> <p>We therefore feel that resuscitation of patients with DSS who already have third space fluid accumulation with crystalloid boluses on priority basis may contribute to recovery phase pulmonary oedema.</p

Sustained reduction in vaccine-type invasive pneumococcal disease despite waning effects of a catch-up campaign in Kilifi, Kenya: A mathematical model based on pre-vaccination data

Background: In 2011, Kenya introduced the 10-valent pneumococcal conjugate vaccine together with a catch-up campaign for children aged <5 years in Kilifi County. In a post-vaccination surveillance study based in Kilifi, there was a substantial decline in invasive pneumococcal disease (IPD). However, given the continued circulation of the vaccine serotypes, it is possible that vaccine-serotype disease may re-emerge once the effects of the catch-up campaign wear off.Methods: We developed, a compartmental, age-structured dynamic model of pneumococcal carriage and invasive disease for three serotype groups: the 10-valent vaccine serotypes and two groups of non vaccine serotypes based on their susceptibility to mutual competition. The model was calibrated to age- and serotype-specific data on carriage and IPD in the pre-vaccination era and used to predict carriage prevalence and IPD up to ten years post-vaccination in Kilifi. The model was validated against the observed carriage prevalence after vaccine introduction.Results: The model predicts a sustained reduction in vaccine-type pneumococcal carriage prevalence from 33% to 8% in infants and from 30% to 8% in 1-5 year olds over the 10-year period following vaccine introduction. The incidence of IPD is predicted to decline across all age groups resulting in an overall reduction of 56% in the population, corresponding to 10.4 cases per 100,000 per year. The vaccine-type IPD incidence is estimated to decline by 83% while non-vaccine-type IPD incidence is predicted to increase by 52%. The model's predictions of carriage prevalence agrees well with the observed data in the first five years post-vaccination.Conclusion: We predict a sustained and substantial decline in IPD through PCV vaccination and that the current regimen is insufficient to fully eliminate vaccine-serotype circulation in the model. We show that the observed impact is likely to be sustained despite waning effects of the catch-up campaign. (C) 2017 The Author(s). Published by Elsevier Ltd

Criteria for Pediatric Sepsis-A Systematic Review and Meta-Analysis by the Pediatric Sepsis Definition Taskforce

OBJECTIVE: To determine the associations of demographic, clinical, laboratory, organ dysfunction, and illness severity variable values with: 1) sepsis, severe sepsis, or septic shock in children with infection and 2) multiple organ dysfunction or death in children with sepsis, severe sepsis, or septic shock. DATA SOURCES: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched from January 1, 2004, and November 16, 2020. STUDY SELECTION: Case-control studies, cohort studies, and randomized controlled trials in children greater than or equal to 37-week-old postconception to 18 years with suspected or confirmed infection, which included the terms "sepsis," "septicemia," or "septic shock" in the title or abstract. DATA EXTRACTION: Study characteristics, patient demographics, clinical signs or interventions, laboratory values, organ dysfunction measures, and illness severity scores were extracted from eligible articles. Random-effects meta-analysis was performed. DATA SYNTHESIS: One hundred and six studies met eligibility criteria of which 81 were included in the meta-analysis. Sixteen studies (9,629 patients) provided data for the sepsis, severe sepsis, or septic shock outcome and 71 studies (154,674 patients) for the mortality outcome. In children with infection, decreased level of consciousness and higher Pediatric Risk of Mortality scores were associated with sepsis/severe sepsis. In children with sepsis/severe sepsis/septic shock, chronic conditions, oncologic diagnosis, use of vasoactive/inotropic agents, mechanical ventilation, serum lactate, platelet count, fibrinogen, procalcitonin, multi-organ dysfunction syndrome, Pediatric Logistic Organ Dysfunction score, Pediatric Index of Mortality-3, and Pediatric Risk of Mortality score each demonstrated significant and consistent associations with mortality. Pooled mortality rates varied among high-, upper middle-, and lower middle-income countries for patients with sepsis, severe sepsis, and septic shock (p < 0.0001). CONCLUSIONS: Strong associations of several markers of organ dysfunction with the outcomes of interest among infected and septic children support their inclusion in the data validation phase of the Pediatric Sepsis Definition Taskforce

Bicalutamide-induced hypoxia potentiates RUNX2-mediated Bcl-2 expression resulting in apoptosis resistance.

BACKGROUND: We have previously shown that hypoxia selects for more invasive, apoptosis-resistant LNCaP prostate cancer cells, with upregulation of the osteogenic transcription factor RUNX2 and the anti-apoptotic factor Bcl-2 detected in the hypoxia-selected cells. Following this observation, we questioned through what biological mechanism this occurs. METHODS: We examined the effect of hypoxia on RUNX2 expression and the role of RUNX2 in the regulation of Bcl-2 and apoptosis resistance in prostate cancer. RESULTS: Hypoxia increased RUNX2 expression in vitro, and bicalutamide-treated LNCaP tumours in mice (previously shown to have increased tumour hypoxia) exhibited increased RUNX2 expression. In addition, RUNX2-overexpressing LNCaP cells showed increased cell viability, following bicalutamide and docetaxel treatment, which was inhibited by RUNX2 siRNA; a range of assays demonstrated that this was due to resistance to apoptosis. RUNX2 expression was associated with increased Bcl-2 levels, and regulation of Bcl-2 by RUNX2 was confirmed through chromatin immunoprecipitation (ChIP) binding and reporter assays. Moreover, a Q-PCR array identified other apoptosis-associated genes upregulated in the RUNX2-overexpressing LNCaP cells. CONCLUSION: This study establishes a contributing mechanism for progression of prostate cancer cells to a more apoptosis-resistant and thus malignant phenotype, whereby increased expression of RUNX2 modulates the expression of apoptosis-associated factors, specifically Bcl-2