The analgesic effects of intrathecal morphine in comparison with ultrasound-guided transversus abdominis plane block after caesarean section: a randomised controlled trial at a Ugandan regional referral hospital.

Both transversus abdominis plane block and intrathecal morphine may produce prolonged postoperative analgesia, but the respective clinical outcomes of these anaesthetic techniques in resource-limited settings are not well described. We randomly assigned patients undergoing caesarean section to receive a hyperbaric bupivacaine (10 mg) spinal anaesthetic followed by an ultrasound-guided transversus abdominis plane block, or a hyperbaric bupivacaine (10 mg) spinal anaesthetic with 100 mcg intrathecal morphine, followed by a postoperative sham block. Supplemental postoperative analgesia included self-administered oral diclofenac 50 mg and paracetamol 1 g every 8 h. Numerical pain rating scores, the need for rescue medication, side-effects and patient satisfaction were recorded at 8, 16 and 24 h. We enrolled a total of 130 patients, with 65 women in each group. The mean numerical rating score for intrathecal morphine vs. transversus abdominis plane blocks at 8 h were: at rest, 2.5 vs. 3.1 (p = 0.04); with coughing, 4.3 vs. 4.8 (p = 0.07); and with movement, 3.6 vs. 4.2 (p = 0.06). At 16 h, respective scores were: 2.9 vs. 3.1 (p = 0.40) at rest; 4.0 vs. 4.3 (p = 0.19) with coughing; and 4.8 vs. 5.0 (p = 0.33) with movement. At 24 h, the respective scores were: 2.9 vs. 2.3 (p = 0.01); 4.6 vs. 4.2 (p = 0.04) with coughing; and 3.9 vs. 3.4 (p = 0.02) with movement. The need for rescue medication and the incidence of pruritis, sedation and nausea and vomiting were similar in both groups. Patient satisfaction with pain control was similar in both groups, with the majority of patients reporting satisfaction as good or excellent. Intrathecal morphine and transversus abdominis plane block provided clinically similar outcomes for pain relief after caesarean section.

Prospective cohort study of the feasibility and yield of household child tuberculosis contact screening in Uganda.

SETTING: Screening and isoniazid preventive therapy (IPT) of child contacts of tuberculosis (TB) patients is poorly implemented in resource-limited countries, in part due to difficulties in TB diagnosis in children. OBJECTIVE: To assess the feasibility and yield of hospital-based screening and IPT in Uganda, and to evaluate the utility of symptom-based screening. DESIGN: Household child (age <5 years) contacts of adults with pulmonary TB were assessed for TB or latent tuberculous infection (LTBI). Children classified as 'LTBI' or 'uninfected' were prescribed IPT and followed for 9 months. Screening algorithms based on combinations of symptoms associated with TB were constructed post hoc, and their performance evaluated against a radiological-based reference standard. RESULTS: Of 281 contacts (median age 33 months), 44 (15.7%) started anti-tuberculosis treatment and 234 (83.3%) received IPT, 80.3% of whom completed a 6-month course. After adjustment for age and human immunodeficiency virus status, cough (aOR 4.10, 95%CI 1.39-12.11) and reduced playfulness (aOR 7.79, 95%CI 2.12-25.18) were associated with radiological TB. Screening based on cough or reduced playfulness had a sensitivity of 81.8% and a negative predictive value of 97.6%. CONCLUSION: Hospital-based screening appears to be feasible, and confirms the potential utility of symptom-based screening to select children for IPT and those for further investigations.

Implementation of the WHO Surgical Safety Checklist and surgical swab and instrument counts at a regional referral hospital in Uganda - a quality improvement project.

The World Health Organization (WHO) Surgical Safety Checklist is a cost-effective tool that has been shown to improve patient safety. We explored the applicability and effectiveness of quality improvement methodology to implement the WHO checklist and surgical counts at Mbarara Regional Referral Hospital in Uganda between October 2012 and September 2013. Compliance rates were evaluated prospectively and monthly structured feedback sessions were held. Checklist and surgical count compliance rates increased from a baseline median (IQR [range]) of 29.5% (0-63.5 [0-67.0]) to 85.0% (82.8-87.5 [79.0-93.0]) and from 25.5% (0-52.5 [0-60.0]) to 83.0% (80.8-85.5 [69.0-89.0]), respectively. The mean all-or-none completion rate of the checklist was 69.3% (SD 7.7, 95% CI [64.8-73.9]). Use of the checklist was associated with performance of surgical counts (p value < 0.001; r(2) = 0.91). Pareto analysis showed that understaffing, malfunctioning and lack of equipment were the main challenges. A carefully designed quality improvement project, including stepwise incremental change and standardisation of practice, can be an effective way of improving clinical practice in low-income settings.

Postdischarge mortality in children with acute infectious diseases: derivation of postdischarge mortality prediction models.

OBJECTIVES: To derive a model of paediatric postdischarge mortality following acute infectious illness. DESIGN: Prospective cohort study. SETTING: 2 hospitals in South-western Uganda. PARTICIPANTS: 1307 children of 6 months to 5 years of age were admitted with a proven or suspected infection. 1242 children were discharged alive and followed up 6 months following discharge. The 6-month follow-up rate was 98.3%. INTERVENTIONS: None. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was postdischarge mortality within 6 months following the initial hospital discharge. RESULTS: 64 children died during admission (5.0%) and 61 died within 6 months of discharge (4.9%). Of those who died following discharge, 31 (51%) occurred within the first 30 days. The final adjusted model for the prediction of postdischarge mortality included the variables mid-upper arm circumference (OR 0.95, 95% CI 0.94 to 0.97, per 1 mm increase), time since last hospitalisation (OR 0.76, 95% CI 0.61 to 0.93, for each increased period of no hospitalisation), oxygen saturation (OR 0.96, 95% CI 0.93 to 0·99, per 1% increase), abnormal Blantyre Coma Scale score (OR 2.39, 95% CI 1·18 to 4.83), and HIV-positive status (OR 2.98, 95% CI 1.36 to 6.53). This model produced a receiver operating characteristic curve with an area under the curve of 0.82. With sensitivity of 80%, our model had a specificity of 66%. Approximately 35% of children would be identified as high risk (11.1% mortality risk) and the remaining would be classified as low risk (1.4% mortality risk), in a similar cohort. CONCLUSIONS: Mortality following discharge is a poorly recognised contributor to child mortality. Identification of at-risk children is critical in developing postdischarge interventions. A simple prediction tool that uses 5 easily collected variables can be used to identify children at high risk of death after discharge. Improved discharge planning and care could be provided for high-risk children.

Synchronous distance anesthesia education by Internet videoconference between Uganda and the United States.

STUDY OBJECTIVE: We evaluated the effectiveness of anesthesia education delivered via Internet videoconferencing between the Massachusetts General Hospital, Boston, MA, and Mbarara Regional Referral Hospital, Uganda. DESIGN: This is a prospective educational study. SETTING: The setting is the education in 2 hospitals in Uganda and the United States. SUBJECTS: The subjects are anesthesia residents. INTERVENTIONS: The interventions are anesthesia education lectures delivered in person and via Internet videoconferencing. MEASUREMENTS: The average pre-lecture and post-lecture scores of the local, remote, and combined audiences were compared. MAIN RESULTS: Post-lecture test scores improved over pre-lecture scores: local audience, 59% ± 22% to 81% ± 16%, P = .0002, g = 1.144; remote audience, 51% ± 19% to 81% ± 8%, P < .0001, g = 2.058; and combined scores, 56% ± 14% to 82% ± 8%, P < .0001, g = 2.069). CONCLUSIONS: Transfer of anesthetic knowledge occurs via small group lectures delivered both in person and remotely via synchronous Internet videoconferencing. This technique may be useful to expand educational capacity and international cooperation between academic institutions, a particular priority in the growing field of global health.

Evaluation of a large-scale donation of Lifebox pulse oximeters to non-physician anaesthetists in Uganda.

Pulse oximetry is widely accepted as essential monitoring for safe anaesthesia, yet is frequently unavailable in resource-limited settings. The Lifebox pulse oximeter, and associated management training programme, was delivered to 79 non-physician anaesthetists attending the 2011 Uganda Society of Anaesthesia Annual Conference. Using a standardised assessment, recipients were tested for their knowledge of oximetry use and hypoxia management before, immediately following and 3-5 months after the training. Before the course, the median (IQR [range]) test score for the anaesthetists was 36 (34-39 [26-44]) out of a maximum of 50 points. Immediately following the course, the test score increased to 41 (38-43 [25-47]); p < 0.0001 and at the follow-up visit at 3-5 months it was 41 (39-44 [33-49]); p = 0.001 compared with immediate post-training test scores, and 75/79 (95%) oximeters were in routine clinical use. This method of introduction resulted in a high rate of uptake of oximeters into clinical practice and a demonstrable retention of knowledge in a resource-limited setting.

Needle-stick injuries in an Ugandan teaching hospital.

The on-going HIV epidemic has generally increased fear of needle-stick injuries (NSI) and renewed interest in the problem such injuries pose in Africa. The aims of the present study were to evaluate the frequency of NSI, explore the circumstances surrounding each injury and estimate the corresponding infection risk, among healthcare workers (HCW) in Uganda. Questionnaires, asking the recipients how many NSI they had suffered in the past year, how each of these NSI had occurred, what (perceived) risk of infection was associated with each injury, and what their practical and psychological reactions were, were sent to the HCW associated with the Mbarara Teaching Hospital in Uganda. Of the 280 individuals who received questionnaires, 180 (64%) responded and 100 (55% of the respondents) each reported suffering at least one NSI in the previous year. The total number of NSI reported (336) represented an incidence of 1.86 NSI/HCW-year. Interns suffered more NSI (annual mean=4.8) than any other occupational group. Most NSI occurred when patients moved during procedures, when HCW re-sheathed needles, or during suturing (each reported by 55 HCW--30% of those responding). Following NSI, 60 HCW said they squeezed the site of the injury and washed it with bleach, 43 believed they had a 10% risk of HIV infection, 87 felt anxious, 54 felt depressed, 40 prayed, 24 had an HIV test, and four were counselled. To estimate actual infection risk, 435 patients were screened for antibody to HIV (1 and 2) and for the surface antigen of the hepatitis B virus (HBSAg); 26% and 2.8% were found seropositive, respectively. These seroprevalences were multiplied by previously determined probabilities of transmission to give estimated risks of infection (following a single NSI) of 0.08% for HIV and 0.135% for hepatitis B. During 3 years of training as a clinician (i.e. 2 years as a medical student and 1 year as an intern), more than six in 1000 individuals would be infected with HIV as a result of NSI and almost 10 in 1000 would be infected with hepatitis B virus by the same route. NSI are common, preventable sources of infection and stress for HCW in Africa.

Diagnosis of pulmonary tuberculosis in children in an HIV-endemic area, Malawi.

The diagnosis of pulmonary tuberculosis (PTB) in young children is particularly complex in resource-poor regions where HIV infection is common. This study examines the impact of HIV infection on diagnosis in children with suspected PTB attending Queen Elizabeth Central Hospital, Blantyre. A total of 110 children (4 months-14 years) were studied over a 4-month period. Clinical data were recorded and investigations included Mantoux test, chest X-ray, HIV status (HIV-PCR when younger than 18 months) and sputum, if available. Laryngeal swabs were compared with sputa or gastric aspirates in a subgroup of 60 children. All children were commenced on anti-TB therapy and followed for treatment response. Aware of the clinical overlap between HIV and TB infection, we used more limited criteria than recommended to allocate a final diagnosis following review of all data except HIV status. Final diagnosis included confirmed PTB (n = 8), probable PTB (n = 41), lymphocytic interstitial pneumonitis (n = 10), pulmonary Kaposi sarcoma (n = 3) and bronchiectasis (n = 5). Culture rates of M. tuberculosis were: five (27.8%) of 18 sputa, three (7.1%) of 42 gastric aspirates and four (6.6%) of 60 laryngeal swabs. The HIV infection rate was 70.6% overall and 57.8% in 45 children with confirmed or probable PTB. Although a positive contact history was more common in HIV-infected children, a final diagnosis of confirmed or probable PTB was less common than in HIV-uninfected children (36% vs 63%; p = 0.02). The Mantoux test was positive in 14 (19%) of 72 HIV-infected compared with 15 (50%) of 30 HIV-uninfected children (p < 0.01). A final diagnosis could not be made in 43 (39%) of the study children with suspected PTB, the majority of whom were HIV-infected. HIV-infected children had a significantly poorer response to TB treatment and higher lost-to-follow-up rates.

Childhood bacterial meningitis in Mbarara Hospital, Uganda: antimicrobial susceptibility and outcome of treatment.

BACKGROUND: The recommended antibiotic treatment of bacterial meningitis has come under scrutiny following frequent reports of in-vitro resistance by the common causative organisms to penicillin and chloramphenicol. OBJECTIVE: The study recorded the causative organisms, antibiotic sensitivity patterns and outcome of treatment of bacterial meningitis in children and examined the impact of various factors on the recorded outcome. DESIGN: This was a retrospective review of all case records of patients treated for bacterial meningitis over a one year period. SETTING: The study was set in the paediatric wards of Mbarara University Teaching Hospital, in south western Uganda. RESULTS: A total of 77 patients were treated. Among 56 patients with available CSF results the frequency of bacterial causes was as follows: H. influenzae 13(23.2%), coliforms 7(12.5%), uncultured Gram-negative bacilli 7(12.5%), S. pneumoniae 5(8.9%) and N. meningitidis 3(5.4%). Most isolates tested were resistant to both penicillin and chloramphenicol, but all were sensitive to ciprofloxacin and perfloxacin. Twenty eight(36.8%) patients died, 22(28.9%) survived with sequelae and 15(19.7%) improved without sequelae. 14/18 who received perfloxacin and/or ciprofloxacin survived compared with 23/47 who did not: p=0.04). CONCLUSIONS: The high case-fatality rates and the high frequency of resistance to penicillin and chloramphenicol make a case for a review of the currently recommended antibiotic treatment of bacterial meningitis in this region. Fluoroquinolones need further evaluation as potential alternatives to chloramphenicol in the treatment of bacterial meningitis.

Heterotransplantation of human Burkitt's lymphoma cell lines in athymic nude mice: tumor-host relationships.

We have explored the factors which influence tumorigenicity of Burkitt's lymphoma (BL) cell lines in athymic nude mice. Four cell lines, Namalwa, CA46, JD38, and ST486 revealed tumor incidence of 63.5, 69.0, 45.5 and 10.0%, respectively, in nude mice, but there was no correlation between tumor incidence and growth rate in vivo. Thus, growth rate and tumorigenicity are dependent upon different biochemical pathways. Evidence of tumor cell heterogeneity was demonstrated in the CA46 parent cell line. Five subclones derived from CA46 revealed varying degrees of tumor incidence (but very similar growth rates) that were consistently less than the parent CA46 line. Line 5, for example, produced 5.7-fold less tumors than the parent line. None of the BL cell lines or clones produced any metastatic lesions in liver, lung, brain, bone marrow or spleen in athymic nude mice. Northern blot analysis of c-myc mRNA levels in different BL cell lines revealed a possible relationship between percent tumor takes (but not growth rates) and the level of c-myc oncogene expression. However, no correlation was observed between c-myc mRNA levels and tumor incidence or growth rates among the CA46 clones. There was no correlation between the ability of the cell lines and the subclones to either secrete growth factors or to respond to growth factors secreted by Epstein-Barr virus-induced lymphoblastoid cells or lipopolysaccharide-activated monocytes, and their growth rates or percent tumor takes in mice. Comparison of tumor incidence and growth rates in irradiated and unirradiated mice showed that host factors influenced the growth of BL in nude mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of sample type on the interpretation of the oral glucose tolerance test for gestational diabetes mellitus.

The World Health Organization (1985) criteria allow evaluation of the oral glucose tolerance test using venous or capillary whole blood or plasma glucose measurements. However, the empirical factors used for interconversion may not reflect observed differences, especially during pregnancy, causing inconsistent classification. To investigate how choice of sample would influence the interpretation of results, venous and capillary blood was taken during oral glucose tolerance tests in 36 pregnant women at risk of gestational diabetes and in 21 non-pregnant control subjects. Glucose was measured on whole blood and plasma by a glucose oxidase method. No cases of gestational diabetes were identified. Eight subjects had gestational Impaired Glucose Tolerance using either venous plasma or venous whole blood results, but only five were similarly classified with capillary whole blood and only four using capillary plasma. Plasma-whole blood differences (venous 0.6 +/- 0.2 (+/- SD) mmol l-1, capillary 0.7 +/- 0.3 mmol l-1) and capillary-venous differences (plasma 0.5 +/- 0.4, whole blood 0.4 +/- 0.5 mmol l-1) at 2 h were lower (all p less than 0.05) than in the WHO criteria (1.1 mmol l-1). When compared with venous plasma, capillary measurements may give a lower incidence and venous whole blood measurements a higher incidence of Impaired Glucose Tolerance in pregnancy.

Autoimmune neutropenia and Hodgkin's disease: successful treatment with intravenous gammaglobulin.

We describe a child with Hodgkin's disease (HD) who presented with profound neutropenia, secondary to an antineutrophil antibody. The patient responded to intravenous immunoglobulin (IVIG), with prompt and sustained improvement in total white blood cell count (WBC) and absolute neutrophil count (ANC). The literature pertaining to autoimmune cytopenias complicating HD is reviewed, as well as the role of IVIG in management of these disorders.

Immunoglobulin delta expression in Burkitt's lymphoma cell lines.

Eighteen Burkitt's lymphoma (BL) cell lines were analyzed for rearrangement and expression of the delta gene. None had rearrangement of the delta gene locus within the 9.0-kb BamHI restriction fragment. Cell lines that expressed the delta gene contained both mu alleles, with at least one productively rearranged. Thirteen of 18 cell lines had detectable transcripts hybridizing with the delta probe. In 10 of the 13 cell lines with delta transcripts, cytoplasmic delta chains were detected, but only two of these expressed delta chains strongly on the surface. All 13 lines made cytoplasmic mu chains, and all except one made cytoplasmic light chains. Surface IgM was detected in all except two of the 13 cell lines. Although BL has generally been considered not to express IgD, except in occasional cases, previous studies have been confined to examination of the cell surface. Many of the cell lines that we examined express delta mRNA transcripts as well as produce cytoplasmic delta chains but no detectable surface IgD. This suggests that delta chains are detectable in the cytoplasm prior to being apparent on the surface. Our findings argue against an origin of BL from germinal center cells since IgD is almost totally lacking in normal B cells present in germinal centers.

Antiimmunoglobulin inhibition of Burkitt's lymphoma cell proliferation and concurrent reduction of c-myc and mu heavy chain gene expression.

We have demonstrated that polyvalent antiimmunoglobulin antibodies directed at appropriate cell surface light (L) or heavy (H) immunoglobulin (Ig) chains will inhibit proliferation and the expression of c-myc and mu-Ig chain mRNA in Burkitt's lymphoma (BL) cell lines bearing 8;14 chromosomal translocations. This effect was not observed in BL cell lines bearing 8;22 translocations or in BL cell lines which did not express surface Ig or in karyotypically normal Epstein-Barr virus-transformed lymphoblastoid cell lines. The antiproliferative effect was reproducible and resulted in cell death in the most sensitive cell lines. The decrease in gene expression preceded the antiproliferative effect. The effect of anti-Ig on gene expression was relatively specific since the level of total (shown by Northern blots) and cytoplasmic (dot blots) mRNA of several other genes (beta-actin, G6PD, kappa-L chain) and the first exon of c-myc (in cell lines in which this exon is expressed separately from the second and third exons) was not changed in these same BL cell lines. Expression of both c-myc and mu was maximally inhibited between 3 and 6 h after the addition of anti-Ig. In the most sensitive BL cell line, concurrent reduction in c-myc and mu mRNA was noted as early as 1 h after anti-Ig and the nadir of expression of these genes occurred at 3 h. These results indicate that the deregulated high constitutive expression of c-myc in some BLs can be down-regulated by anti-Ig resulting in inhibition of proliferation and cell death. In addition these data are consistent with the possibility that in at least some 8;14 bearing BLs the malignant transformation occurs in an immature B-cell undergoing antigen-independent differentiation.

Soluble interleukin-2 receptor levels in patients with undifferentiated and lymphoblastic lymphomas: correlation with survival.

We have been able to detect soluble interleukin-2 receptors (IL-2R) in pretreatment sera from 80 patients with undifferentiated lymphoma (predominantly Burkitt's lymphoma) and lymphoblastic lymphoma. The demonstration of IL-2R in lymphoma-derived cell lines by immunoprecipitation and direct staining indicates that IL-2R is synthesized by the tumor cells. Comparisons were made with two other subject groups: 42 sarcoma patients and 17 normal individuals. The distribution of soluble IL-2R values for lymphoma patients (geometric mean, 1,132 U/mL) was significantly greater than that of sarcoma patients (geometric mean, 332 U/mL; P = .0001) or normal individuals (geometric mean, 238 U/mL; P = .0001). Patients with undifferentiated lymphoma stages B, C, and D had significantly higher soluble IL-2R values (geometric mean, 1,648 U/mL) than stages A and AR (geometric mean, 706 U/mL; P = .0001) or lymphoblastic lymphoma (geometric mean, 826 U/mL; P = .0002). Within the lymphoma group, the soluble IL-2R level was found to be the most significant prognostic indicator of disease-free interval and survival when compared with other previously recognized factors such as histology, stage, bone marrow involvement at presentation, lactic dehydrogenase (LDH), uric acid (UA), and age. No factor was significantly associated with response to therapy, ie, the initial achievement of complete remission (CR) status, although small numbers of patients with a partial response limit interpretation. Soluble IL-2R levels were measured serially in two patients and were found to be elevated at presentation or relapse and to decrease to normal levels during periods of disease remission. IL-2R appears to reflect tumor burden and may prove to be a useful and specific marker for lymphoid tumors.

Chronic ITP terminating in aplastic anemia.

A 14-year-old white male developed gastric anemia with normal chromosomes following a 6-year history of chronic ITP refractory to splenectomy. The disorder was partially responsive to oxymethalone which was discontinued because of hepatotoxicity. Antiplatelet and antigranulocyte antibodies were identified in the patient's sera. Absorbed sera suppressed normal marrow CFU-C and CFU-E. This case may represent a single-entity autoimmune mechanism characterized initially by thrombocytopenia followed by pancytopenia.