Long Term Outcome of Severe Anaemia in Malawian Children

Severe anaemia is a common, frequently fatal, condition in African children admitted to hospital, but its long term outcome is unknown. Early reports that survivors may be at risk of additional late morbidity and mortality may have significant implications for child survival in Africa. We assessed the short and long term outcome of severe anaemia in Malawian children and identified potential risk factors for death and further severe anaemia. For 18 months, we followed up children (6-60 months old) presenting to hospital with severe anaemia (haemoglobin <or=5 g/dl) and their hospital and community controls with the aim to compare all cause mortality and severe anaemia recurrence rates between the groups, and to identify risk factors for these adverse outcomes. A total of 377 cases, 377 hospital controls and 380 community controls were recruited. Among cases, the in-hospital mortality was 6.4% and post-discharge all cause mortality was 12.6%, which was significantly greater than in hospital controls (2.9%) or community controls (1.4%) (Log rank test, p <0.001). The incidence of recurrence of severe anaemia among the cases was 0.102 per child-year (95% Confidence Interval 0.075-0.138), and was significantly higher than the 0.007 per child-year (95% CI 0.003-0.015) in the combined controls (p <0.0001). HIV was the most important risk factor both for post-discharge mortality (Hazard Ratio 10.5, 95% CI 4.0-27.2) and for recurrence of severe anaemia (HR 5.6, 95% CI 1.6-20.1). Severe anaemia carries a high 'hidden' morbidity and mortality occurring in the months after initial diagnosis and treatment. Because severe anaemia is very common, this is likely to contribute importantly to overall under-five mortality. If not adequately addressed, severe anaemia may be an obstacle to achievement of the Millennium development goal No.4 on child survival. Strategies to diagnose and properly treat HIV infected children early most likely will reduce the high post-discharge mortality in severe anaemi

Pathophysiological Mechanisms of Severe Anaemia in Malawian Children

BACKGROUND: Severe anaemia is a major cause of morbidity and mortality in African children. The aetiology is multi-factorial, but interventions have often targeted only one or a few causal factors, with limited success. METHODS AND FINDINGS: We assessed the contribution of different pathophysiological mechanisms (red cell production failure [RCPF], haemolysis and blood loss) to severe anaemia in Malawian children in whom etiological factors have been described previously. More complex associations between etiological factors and the mechanisms were explored using structural equation modelling. In 235 children with severe anaemia (haemoglobin<3.2 mMol/L [5.0 g/dl]) studied, RCPF, haemolysis and blood loss were found in 48.1%, 21.7% and 6.9%, respectively. The RCPF figure increased to 86% when a less stringent definition of RCPF was applied. RCPF was the most common mechanism in each of the major etiological subgroups (39.7-59.7%). Multiple aetiologies were common in children with severe anaemia. In the final model, nutritional and infectious factors, including malaria, were directly or indirectly associated with RCPF, but not with haemolysis. CONCLUSION: RCPF was the most common pathway leading to severe anaemia, from a variety of etiological factors, often found in combination. Unlike haemolysis or blood loss, RCPF is a defect that is likely to persist to a significant degree unless all of its contributing aetiologies are corrected. This provides a further explanation for the limited success of the single factor interventions that have commonly been applied to the prevention or treatment of severe anaemia. Our findings underline the need for a package of measures directed against all of the local aetiologies of this often fatal paediatric syndrome

An update of malaria infection and anaemia in adults in Buea, Cameroon

<p>Abstract</p> <p>Background</p> <p>Anaemia is caused by many factors in developing countries including malaria. We compared anaemia rates in patients with malaria parasitaemia to that of patients without malaria parasitaemia.</p> <p>Findings</p> <p>A cross-sectional study was carried out from November 2007 to July 2008 in health units in Buea, Cameroon. Adult patients with fever or history of fever were included in the study. Information on socio-demographic variables and other variables was collected using a questionnaire. Malaria parasitaemia status was determined by microscopy using Giemsa stained thick blood smears. Haemoglobin levels were determined by the microhaematocrit technique.</p> <p>The study population consisted of 250 adult patients with a mean age of 29.31 years (SD = 10.63) and 59.44% were females. 25.60% of the patients had malaria parasitaemia while 14.80% had anaemia (haemoglobin < 11 g/dl). Logistic regression revealed that those with malaria parasitaemia had more anaemia compared to those without malaria parasitaemia(OR = 4.33, 95%CI = 1.21-15.43, p = 0.02) after adjusting for age, sex, rural residence, socioeconomic status, use of antimalarials, use of insecticide treated nets(ITN) and white blood cell count.</p> <p>Conclusions</p> <p>In adult patients with fever in this setting, malaria parasitaemia contributes to anaemia and is of public health impact. Our results also provide a baseline prevalence for malaria parasitaemia in febrile adults in health units in this setting.</p

Assessment of the quality of measures of child oral health-related quality of life

Background Several measures of oral health-related quality of life have been developed for children. The most frequently used are the Child Perceptions Questionnaire (CPQ), the Child Oral Impacts on Daily Performances (C-OIDP) and the Child Oral Health Impact Profile (COHIP). The aim of this study was to assess the methodological quality of the development and testing of these three measures. Methods A systematic search strategy was used to identify eligible studies published up to December 2012, using both MEDLINE and Web of Science. Titles and abstracts were read independently by two investigators and full papers retrieved where the inclusion criteria were met. Data were extracted by two teams of two investigators using a piloted protocol. The data were used to describe the development of the measures and their use against existing criteria. The methodological quality and measurement properties of the measures were assessed using standards proposed by the Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) group. Results The search strategy yielded 653 papers, of which 417 were duplicates. Following analysis of the abstracts, 119 papers met the inclusion criteria. The majority of papers reported cross-sectional studies (n = 117) with three of longitudinal design. Fifteen studies which had used the original version of the measures in their original language were included in the COSMIN analysis. The most frequently used measure was the CPQ. Reliability and construct validity appear to be adequate for all three measures. Children were not fully involved in item generation which may compromise their content validity. Internal consistency was measured using classic test theory with no evidence of modern psychometric techniques being used to test unidimensionality of the measures included in the COSMIN analysis. Conclusion The three measures evaluated appear to be able to discriminate between groups. CPQ has been most widely tested and several versions are available. COHIP employed a rigorous development strategy but has been tested in fewer populations. C-OIDP is shorter and has been used successfully in epidemiological studies. Further testing using modern psychometric techniques such as item response theory is recommended. Future developments should also focus on the development of measures which can evaluate longitudinal change

A pharmacokinetic and pharmacodynamic study of delayed- and extended-release hydrocortisone (ChronocortTM) vs. conventional hydrocortisone (CortefTM) in the treatment of congenital adrenal hyperplasia

SUMMARY: OBJECTIVE: Existing glucocorticoid treatment for congenital adrenal hyperplasia (CAH) is suboptimal and nonphysiological. We compared hormonal profiles during therapy with a new modified-release hydrocortisone (MR-HC), Chronocort™, to conventional hydrocortisone (HC), Cortef™, in patients with CAH. DESIGN AND PATIENTS: We conducted a Phase 2, open-label, crossover pharmacokinetic and pharmacodynamic study in 14 patients (7 males, ages 17 to 55) with classic 21-hydroxylase deficiency. One week of thrice daily HC (10 mg, 5 mg, 15 mg) was followed by one month of once daily MR-HC (30 mg at 2200 h). Twenty-four hour sampling of cortisol, 17-hydroxyprogesterone (17-OHP), androstenedione, and ACTH was performed at steady state. MEASUREMENTS: The primary outcome measures were 8- and 24-hour area under the curve (AUC) hormones and 0800 h 17-OHP. RESULTS: HC therapy resulted in three cortisol peaks. A single cortisol peak occurred at approximately 0600 h on MR-HC. MR-HC resulted in significantly (P<0.001) lower 24-hour, afternoon (1200 h to 2000 h), and night-time (2000 h to 0400 h) cortisol compared to HC. From 0400 h to 1200 h, when physiological cortisol is highest, cortisol was higher on MR-HC than HC (P<0.001). Patients on MR-HC had significantly (P<0.05) higher afternoon (1200 h to 2000 h) 17-OHP, androstenedione and ACTH, but significantly (P=0.025) lower 0800 h 17-OHP. No serious adverse events occurred. CONCLUSIONS: MR-HC represents a promising new treatment for CAH. Overnight adrenal androgens were well-controlled, but rose in the afternoon with once daily dosing suggesting that a morning dose of glucocorticoid is needed. Further studies are needed to determine the optimal dosing regimen and long-term clinical outcome