The effects of vitamin C supplementation on pre-eclampsia in Mulago Hospital, Kampala, Uganda: a randomized placebo controlled clinical trial.

BACKGROUND: Oxidative stress plays a role in the pathogenesis of pre-eclampsia. Supplementing women with antioxidants during pregnancy may reduce oxidative stress and thereby prevent or delay the onset pre-eclampsia. The objective of this study was to evaluate the effect of supplementing vitamin C in pregnancy on the incidence of pre-eclampsia, at Mulago hospital, Kampala, Uganda. METHODS: This was a (parallel, balanced randomization, 1:1) placebo randomized controlled trial conducted at Mulago hospital, Department of Obstetrics and Gynecology. Participants included in this study were pregnant women aged 15-42 years, who lived 15 km or less from the hospital with gestational ages between 12-22 weeks. The women were randomized to take 1000mg of vitamin C (as ascorbic acid) or a placebo daily until they delivered. The primary outcome was pre-eclamsia. Secondary outcomes were: severe pre-eclampsia, gestational hypertension, preterm delivery, low birth weight and still birth delivery. Participants were 932 pregnant women randomized into one of the two treatment arms in a ratio of 1:1. The participants, the care providers and those assessing the outcomes were blinded to the study allocation. RESULTS: Of the 932 women recruited; 466 were randomized to the vitamin and 466 to the placebo group. Recruitment of participants was from November 2011 to June 2012 and follow up was up to January 2013. Outcome data was available 415 women in the vitamin group and 418 women in the placebo group.There were no differences in vitamin and placebo groups in the incidence of pre-eclampsia (3.1% versus 4.1%; RR 0.77; 95% CI: 0.37-1.56), severe pre-eclampsia (1.2% versus 1.0%; RR 1.25; 95% CI: 0.34-4.65), gestational hypertension(7.7% versus 11.5%; RR 0.67; 95% CI: 0.43-1.03), preterm delivery (11.3% versus 12.2%; RR 0.92; 95% CI: 0.63-1.34), low birth weight (11.1% versus 10.3%; RR 1.07; 95% CI: 0.72-1.59) and still birth delivery (4.6% versus 4.5%; RR 1.01; 95% CI: 0.54-1.87). CONCLUSIONS: Supplementation with vitamin C did not reduce the incidence of pre-eclampsia nor did it reduce the adverse maternal or neonatal outcomes. We do not recommend the use of vitamin C in pregnancy to prevent pre-eclampsia. TRIAL REGISTRATION: This study was registered at the Pan African Clinical Trial Registry, PACTR201210000418271 on 25th October 2012.

Adverse neonatal outcomes in women with pre-eclampsia in Mulago Hospital, Kampala, Uganda: a cross-sectional study.

INTRODUCTION: Pre-eclampsia, which is more prevalent in resource-limited settings, contributes significantly to maternal, fetal and neonatal morbidity and mortality. However, the factors associated with these adverse outcomes are poorly understood in low resource settings. In this paper we examine the risk factors for adverse neonatal outcomes among women with pre-eclampsia at Mulago Hospital in Kampala, Uganda. METHODS: Pre-eclampsia, which is more prevalent in resource-limited settings, contributes significantly to maternal, fetal and neonatal morbidity and mortality. However, the factors associated with these adverse outcomes are poorly understood in low resource settings. In this paper we examine the risk factors for adverse neonatal outcomes among women with pre-eclampsia at Mulago Hospital in Kampala, Uganda. RESULTS: Predictors of adverse neonatal outcomes were: preterm delivery (OR 5.97, 95% CI: 2.97-12.7) and severe pre-eclampsia (OR 5.17, 95% CI: 2.36-11.3). CONCLUSION: Predictors of adverse neonatal outcomes among women with pre-eclampsia were preterm delivery and severe pre-eclampsia. Health workers need to identify women at risk, offer them counseling and, refer them if necessary to a hospital where they can be managed successfully. This may in turn reduce the neonatal morbidity and mortality associated with pre-eclampsia.

Zinc adjunct therapy reduces case fatality in severe childhood pneumonia: a randomized double blind placebo-controlled trial.

BACKGROUND: Pneumonia is a leading cause of children's deaths in developing countries and hinders achievement of the fourth Millennium Development Goal. This goal aims to reduce the under-five mortality rate, by two thirds, between 1990 and 2015.Few studies have examined the impact of zinc adjunct therapy on the outcome of childhood pneumonia. We determined the effect of zinc as adjunct therapy on time to normalization of respiratory rate, temperature and oxygen saturation. We also studied the effect of zinc adjunct therapy on case fatality of severe childhood pneumonia (as a secondary outcome) in Mulago Hospital, Uganda. METHODS: In this double blind, randomized, placebo-controlled clinical trial, 352 children aged 6 to 59 months, with severe pneumonia were randomized to zinc (20 mg for children ≥ 12 months, and 10 mg for those < 12 months) or a placebo once daily for seven days, in addition to standard antibiotics for severe pneumonia. Children were assessed every six hours. Oxygen saturation was normal if it was above 92% (breathing room air) for more than 15 minutes. The respiratory rate was normal if it was consistently (more than 24 hours) below 50 breaths per minute in infants and 40 breaths per minute in children above 12 months of age. Temperature was normal if consistently below 37.5°C. The difference in case fatality was expressed by the risk ratio between the two groups. RESULTS: Time to normalization of the respiratory rate, temperature and oxygen saturation was not significantly different between the two arms.Case fatality was 7/176 (4.0%) in the zinc group and 21/176 (11.9%) in the placebo group: Relative Risk 0.33 (95% CI 0.15 to 0.76). Relative Risk Reduction was 0.67 (95% CI 0.24 to 0.85), while the number needed to treat was 13. Among HIV infected children, case fatality was higher in the placebo (7/27) than in the zinc (0/28) group; RR 0.1 (95% CI 0.0, 1.0).Among 127 HIV uninfected children receiving the placebo, case fatality was 7/127 (5.5%); versus 5/129 (3.9%) among HIV uninfected group receiving zinc: RR 0.7 (95% CI 0.2, 2.2). The excess risk of death attributable to the placebo arm (Absolute Risk Reduction or ARR) was 8/100 (95% CI: 2/100, 14/100) children. This excess risk was substantially greater among HIV positive children than in HIV negative children (ARR: 26 (95% CI: 9, 42) per 100 versus 2 (95% CI: -4, 7) per 100); P-value for homogeneity of risk differences = 0.006. CONCLUSION: Zinc adjunct therapy for severe pneumonia had no significant effect on time to normalization of the respiratory rate, temperature and oxygen saturation. However, zinc supplementation in these children significantly decreased case fatality.The difference in case fatality attributable to the protective effect of zinc therapy was greater among HIV infected than HIV uninfected children. Given these results, zinc could be considered for use as adjunct therapy for severe pneumonia, especially among Highly Active Antiretroviral Therapynaïve HIV infected children in our environment. CLINICAL TRIALS REGISTRATION NUMBER: clinicaltrials.gov NCT00373100.

Plasma vitamin C assay in women of reproductive age in Kampala, Uganda, using a colorimetric method.

OBJECTIVE: Vitamin C alone or in combination with vitamin E has been proposed to prevent pre-eclampsia. In this study, we assayed the plasma vitamin C in women of reproductive age in Kampala and assessed its association with pre-eclampsia. METHODS: Participants in this study were 215 women with pre-eclampsia, 400 women with normal pregnancy attending antenatal clinic and 200 non-pregnant women attending family planning clinic at Mulago Hospital's Department of Obstetrics and Gynaecology from 1st May 2008 to 1st May 2009. Plasma vitamin C was assayed using the acid phosphotungstate method; differences in the means of plasma vitamin C were determined by ANOVA. RESULTS: Mean plasma vitamin C levels were 1.72 (SD 0.68)×10(3)µg/l in women with pre-eclampsia, 1.89 (SD 0.73)×10(3)µg/l in women with normal pregnancy and 2.64 (SD 0.97)×10(3)µg/l in non-pregnant women. Plasma vitamin C was lower in women with pre-eclampsia than in women with normal pregnancy (P=0.005) and non-pregnant women (P<0.001). CONCLUSION: Health workers need to advise women of reproductive age on foods that are rich in vitamin C, as this may improve the vitamin status and possibly reduce the occurrence of pre-eclampsia.

Risk factors for pre-eclampsia in Mulago Hospital, Kampala, Uganda.

OBJECTIVE: Pre-eclampsia contributes significantly to maternal, foetal and neonatal morbidity and mortality. The risk factors for pre-eclampsia have not been well documented in Uganda. In this paper, we describe the risk factors for pre-eclampsia in women attending antenatal clinics at Mulago Hospital, Kampala. METHODS: This casecontrol study was conducted from 1st May 2008 to 1st May 2009. 207 women with pre-eclampsia were the cases, and 352 women with normal pregnancy were the controls. The women were 15-39 years old, and their gestational ages were 20 weeks or more. They were interviewed about their socio-demographic characteristics, past medical history and, their past and present obstetric performances. RESULTS: The risk factors were low plasma vitamin C (OR 3.19, 95% CI: 1.54-6.61), low education level (OR 1.67, 95% CI: 1.12-2.48), chronic hypertension (OR 2.29, 95% CI 1.12-4.66), family history of hypertension (OR 2.25, 95% CI: 1.53-3.31) and primiparity (OR 2.76, 95% CI: 1.84-4.15) and para≥5 (3.71, 95% CI:1.84-7.45). CONCLUSION: The risk factors identified are similar to what has been found elsewhere. Health workers need to identify women at risk of pre-eclampsia and manage them appropriately so as to prevent the maternal and neonatal morbidity and mortality associated with this condition.

Informed consent in blood transfusion: knowledge and administrative issues in Uganda hospitals.

Blood as a transplant is not free of risks. Clinicians and patients ought to know the parameters of a transfusion informed consent. A mixed methodology to explore patients' and clinicians' knowledge and opinions of administration and strategies to improve the transfusion informed consent process was conducted. The clinicians' level of knowledge was limited to provision of information about and the right to consent to a transfusion. They disagreed on administrative issues but had acceptable opinions on improving the process. Patients perceived this process as a way of assurance of blood safety. This process is important and should not be omitted.

Quantitative assessment of the sensitivity of various commercial reverse transcriptases based on armored HIV RNA.

BACKGROUND: The in-vitro reverse transcription of RNA to its complementary DNA, catalyzed by the enzyme reverse transcriptase, is the most fundamental step in the quantitative RNA detection in genomic studies. As such, this step should be as analytically sensitive, efficient and reproducible as possible, especially when dealing with degraded or low copy RNA samples. While there are many reverse transcriptases in the market, all claiming to be highly sensitive, there is need for a systematic independent comparison of their applicability in quantification of rare RNA transcripts or low copy RNA, such as those obtained from archival tissues. METHODOLOGY/PRINCIPAL FINDINGS: We performed RT-qPCR to assess the sensitivity and reproducibility of 11 commercially available reverse transcriptases in cDNA synthesis from low copy number RNA levels. As target RNA, we used a serially known number of Armored HIV RNA molecules, and observed that 9 enzymes we tested were consistently sensitive to ∼1,000 copies, seven of which were sensitive to ∼100 copies, while only 5 were sensitive to ∼10 RNA template copies across all replicates tested. Despite their demonstrated sensitivity, these five best performing enzymes (Accuscript, HIV-RT, M-MLV, Superscript III and Thermoscript) showed considerable variation in their reproducibility as well as their overall amplification efficiency. Accuscript and Superscript III were the most sensitive and consistent within runs, with Accuscript and Superscript II ranking as the most reproducible enzymes between assays. CONCLUSIONS/SIGNIFICANCE: We therefore recommend the use of Accuscript or Superscript III when dealing with low copy number RNA levels, and suggest purification of the RT reactions prior to downstream applications (eg qPCR) to augment detection. Although the results presented in this study were based on a viral RNA surrogate, and applied to nucleic acid lysates derived from archival formalin-fixed paraffin embedded tissue, their relative performance on RNA obtained from other tissue types may vary, and needs future evaluation.

Comparison of methods in the recovery of nucleic acids from archival formalin-fixed paraffin-embedded autopsy tissues.

Archival formalin-fixed paraffin-embedded (FFPE) human tissue collections are typically in poor states of storage across the developing world. With advances in biomolecular techniques, these extraordinary and virtually untapped resources have become an essential part of retrospective epidemiological studies. To successfully use such tissues in genomic studies, scientists require high nucleic acid yields and purity. In spite of the increasing number of FFPE tissue kits available, few studies have analyzed their applicability in recovering high-quality nucleic acids from archived human autopsy samples. Here we provide a study involving 10 major extraction methods used to isolate total nucleic acid from FFPE tissues ranging in age from 3 to 13years. Although all 10 methods recovered quantifiable amounts of DNA, only 6 recovered quantifiable RNA, varying considerably and generally yielding lower DNA concentrations. Overall, we show quantitatively that TrimGen's WaxFree method and our in-house phenol-chloroform extraction method recovered the highest yields of amplifiable DNA, with considerable polymerase chain reaction (PCR) inhibition, whereas Ambion's RecoverAll method recovered the most amplifiable RNA.

The accuracy of self monitoring blood glucose meter systems in Kampala Uganda.

BACKGROUND: Many blood glucose self monitoring systems are privately and publicly used by people in Uganda and technical and human errors may occur during their operation. Many patients were referred to Kololo polyclinic laboratory to have their blood glucose checked because the values obtained on the patients' glucose meter systems did not tally with familiar clinical signs and symptoms. This prompted an experimental set up to check glucose meter systems using a larger number of patients. OBJECTIVE: The objective was to collate the technical conditions and standing operational procedures of four common glucose meter systems; observe the time, ambient temperature and humidity at which the meter systems operate locally; and compare the performance of three meter systems A, B, and C with the Sensorex glucose meter system on a number of capillary blood samples. SETTING: Kololo polyclinic laboratory--a privately run facility in Kampala, Uganda. DESIGN: An experimental set up to compare four glucose meter systems. METHODS: Instruction manuals of the four glucose monitoring systems were studied and used to familiarize with the meter operations. One hundred and fourteen capillary blood specimens were assayed for blood glucose. Blood glucose values were instantly read off the four randomly set meter systems A, B, C, and Sensorex, noting the time, ambient temperature and humidity. Results from meter systems A, B, and C were regressed against those of Sensorex using Epi-Info computer program. RESULTS: Blood glucose concentration levels on meter system A tallied with those on Sensorex meter system. However, those on meter system B and C were significantly lower and different. Temperature and humidity adversely affected the analytical performance of meter systems B and C in the Kampala environ. CONCLUSION: Some of the blood glucose monitoring systems in Kampala, Uganda are poor performers and may lead to the mismanagement of patients. There is need for a system to ensure national quality control of blood glucose monitoring systems.

Monitoring the severity of iodine deficiency disorders in Uganda.

BACKGROUND: Iodine deficiency disorders (IDD) cover a variety of pathological conditions including goitre, mental retardation and perinatal mortality in millions of individuals globally. IDD was initially identified as a problem in 1970 and was confirmed in 1991. In 1993, the Uganda government introduced a policy of Universal Salt Iodization (USI) requiring all household salt to be iodized. After 5 years this study evaluates the USI programme. OBJECTIVES: To determine goitre prevalence rate, establish the proportion of household consuming iodized salt and determine the levels of iodine intake in the sample districts. METHODS: A sample of 2880 school children aged 6-12 years from 72 Primary schools in 6 districts of Uganda was studied in October 1999. Goitre was established by palpation, salt iodine was analysed by thiosulphate titration, while urinary iodine was analyzed using ICCIDD recommended method F in which iodine is detected colorimetrically at 410 nm. RESULTS: The over all total goitre rate was 60.2% down from 74.3 in 1991 and visible goitre was 30% down from 39.2% in 1991. The proportion of households taking adequately iodized salt was 63.8% and the median urinary iodine was 310 microg/L. Whereas 36% of 95 urine samples analysed in 1991 had urinary iodine below 50 microg/L, only 5% of the 293 urine samples studied in 1999 had the same urine levels. This represents a considerable improvement in iodine intake, which is confirmed by the fact that 63.8% of the study households consume adequately iodized salt. If maintained and evenly spread, this will enable Uganda to control IDD. CONCLUSION: USI has improved iodine intake in Uganda. However, iodine malnutrition is still a severe public health problem because some communities in this study such as in Kisoro still have low iodine consumption, while others such as Luwero now have iodine excess. The latter is likely to predispose to hyperthyroidism. RECOMMENDATION: The national set standard of household salt iodine of 100 ppm be revised. Locally produced salt be iodized, and a national iodine monitoring programme be instituted to ensure evenly spread consumption of adequately iodized salt by all communities in the country.

Monitoring the severity of iodine deficiency disorders in Uganda

Iodine deficiency disorders (IDD) cover a variety of pathological conditions including goitre; mental retardation and perinatal mortality in millions of individuals globally. IDD was initially identified as a problem in 1970 and was confirmed in 1991. In 1993; the Ugandan government introduced a policy of Universal Salt Iodization (USI) requiring all household salt to be iodized. After 5 years this study evaluates the USI programme. Objectives: To determine goitre prevalence rate; establish the proportion of household consuming iodized salt and determine the levels of iodine intake in the sample districts. Methods: A sample of 28880 school children aged 6-12 years from 72 primary school in 6 districts of Uganda was studied in October 1999. Goitre was established by palpation; salt iodine was analysed by thiosulphate titration; while urinary iodine was analyzed using ICCIDD recommended method F in which iodine is detected colorimetrically at 410nm. Results: The over all total goitre rate was 60.2down from 74.3 in 1991 and visible goitre was 30down from 39.2in 1991. The proportion of households taking adequately iodized salt was 63.8and the median urinary iodine was 310ug/L. Whereas 36of 95 urine samples analyzed in 1991 had urinary iodine below 50ug/L; only 5of the 293 urine samples studied in 1999 had the same urine levels. This represents a considerable improvement in iodine intake which is confirmed by the fact that 63.8of the study households consume adequately iodized salt. If maintained and evenly spread; this will enable Uganda to control IDD. Conclusion: USI has improved iodine intake in Uganda. However; iodine malnutrition is still a severe public health problem because some communities in this study such as in Kisoro still have low iodine consumption; while others such as Luwero now have iodine excess. The latter is likely to predispose to hypertthyroidism. Recommendation: The national set standard of household salt iodine of 100ppm be revised. Locally produced salt be iodized; and a national iodine monitoring programme be instituted to ensure evenly spread consumption of adequately iodized salt by all communities in the country