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Biomedical subjects

Elizabeth Molyneux

Publications and source records attributed to Elizabeth Molyneux.

11 recordsLinked to original sources
PubMed2006

Efficacy and safety of intranasal lorazepam versus intramuscular paraldehyde for protracted convulsions in children: an open randomised trial.

BACKGROUND: In sub-Saharan Africa, rectal diazepam or intramuscular paraldehyde are commonly used as first-line anticonvulsant agents in the emergency treatment of seizures in children. These treatments can be expensive and sometimes toxic. We aimed to assess a drug and delivery system that is potentially more effective, safer, and easier to administer than those presently in use. METHODS: We did an open randomised trial in a paediatric emergency department of a tertiary hospital in Malawi. 160 children aged over 2 months with seizures persisting for more than 5 min were randomly assigned to receive either intranasal lorazepam (100 microg/kg, n=80) or intramuscular paraldehyde (0.2 mL/kg, n=80). The primary outcome measure was whether the presenting seizure stopped with one dose of assigned anticonvulsant agent within 10 min of administration. The primary analysis was by intention-to-treat. This study is registered with ClinicalTrials.gov, number NCT00116064. FINDINGS: Intranasal lorazepam stopped convulsions within 10 min in 60 (75%) episodes treated (absolute risk 0.75, 95% CI 0.64-0.84), and intramuscular paraldehyde in 49 (61.3%; absolute risk 0.61, 95% CI 0.49-0.72). No clinically important cardiorespiratory events were seen in either group (95% binomial exact CI 0-4.5%), and all children finished the trial. INTERPRETATION: Intranasal lorazepam is effective, safe, and provides a less invasive alternative to intramuscular paraldehyde in children with protracted convulsions. The ease of use of this drug makes it an attractive and preferable prehospital treatment option.

Administration, Intranasal↗
PubMed2006

Improved triage and emergency care for children reduces inpatient mortality in a resource-constrained setting.

PROBLEM: Early assessment, prioritization for treatment and management of sick children attending a health service are critical to achieving good outcomes. Many hospitals in developing countries see large numbers of patients and have few staff, so patients often have to wait before being assessed and treated. APPROACH: We present the example of a busy Under-Fives Clinic that provided outpatient services, immunizations and treatment for medical emergencies. The clinic was providing an inadequate service resulting in some inappropriate admissions and a high case-fatality rate. We assessed the deficiencies and sought resources to improve services. LOCAL SETTING: A busy paediatric outpatient clinic in a public tertiary care hospital in Blantyre, Malawi. RELEVANT CHANGES: The main changes we made were to train staff in emergency care and triage, improve patient flow through the department and to develop close cooperation between inpatient and outpatient services. Training coincided with a restructuring of the physical layout of the department. The changes were put in place when the department reopened in January 2001. LESSONS LEARNED: Improvements in the process and delivery of care and the ability to prioritize clinical management are essential to good practice. Making the changes described above has streamlined the delivery of care and led to a reduction in inpatient mortality from 10-18% before the changes were made (before 2001) to 6-8% after.

Ambulatory Care↗
PubMed2006

Acute bacterial meningitis in children presenting to the Royal Liverpool Children's Hospital, Liverpool, UK and the Queen Elizabeth Central Hospital in Blantyre, Malawi: a world of difference.

BACKGROUND: Bacterial meningitis is a serious childhood illness worldwide. Children can now be immunised against meningitis with conjugate vaccines. The outcome of bacterial meningitis in British and Malawian children before the introduction of these vaccines was compared. METHODS: All children with culture-positive bacterial meningitis treated in the Royal Liverpool Children's Hospital (RLCH), UK during 1984-1991 (n=197) and in the Children's Unit, Queen Elizabeth Central Hospital (QECH), Blantyre, Malawi during 1996-1997 (n=175) were studied. RESULTS: Children at QECH presented later and were more often comatose and malnourished. Mortality was 7% in RLCH compared with 41% in QECH. Three organisms caused most cases of meningitis: N. meningitidis 56% vs 4%, H. influenzae b 27% vs 25%, and S. pneumoniae 11% vs 35% in RLCH and QECH, respectively. Mortality was lower in RLCH for each organism: N. meningitidis 10% vs 28%, H. influenzae b 6% vs 43%, S. pneumoniae 0% vs 46%. CONCLUSIONS: Mortality from bacterial meningitis in Malawian children is much higher than in British children, even when infected with the same organisms. This might be owing to delay in presentation, malnutrition and HIV infection. Immunisation of Malawian children with conjugate vaccines should continue to develop since their risk of dying from meningitis is five times greater than that of British children.

Acute Disease↗
PubMed2005

The 2000 Burkitt lymphoma trial in Malawi.

BACKGROUND: We previously reported 57% 12-month event free survival (EFS) in Malawian children with stage I to III Burkitt lymphoma (BL) with an intermediate dose chemotherapy protocol lasting 77 days. This protocol was shortened to 42 days and evaluated in children with stage I to IV disease for EFS and toxicity. METHODS: All Malawian children admitted to Queen Elizabeth Central Hospital, from 03/08/2000 to 12/03/2002 with confirmed BL were eligible. A fine needle aspirate, bone marrow aspirate, cerebrospinal fluid cytology, haemoglobin (Hb), white cell count (WCC), malaria smear, ELISA for HIV, and abdominal ultrasound were performed routinely. Murphy staging was used. The first dose of chemotherapy (COP1) consisted of 300 mg cyclophosphamide (CPM), 1 mg vincristine, and 60 mg prednisone given on day 1 and followed by COP2 on day 8 (only for patients with larger tumour volumes, stage III or IV disease). The vincristine dose in COP2 was 2 mg. COMP1 and 2 given on days 22 and 36 consisted of 500 mg CPM, 2 mg vincristine, 60 mg prednisone, and 2 g methotrexate. All doses were calculated per body surface area. Intrathecal methotrexate and hydrocortisone were given with COP1 and 2. RESULTS: Forty-two patients, 30 boys and 12 girls median ages 6 and 7.5 years, respectively, had Murphy stage I(n5), II(n8), III(n21), and IV(n8) disease. The face was involved in 74%, abdomen in 55%, bone marrow in 14%, kidneys in 24%, and 12% had paraplegia. Fourteen children died during or shortly after completion of chemotherapy. Three of these were disease related. Twelve patients suffered a local relapse after 57-328 days, and one a CNS relapse at 76 days. The projected EFS at 12 months is 50% in stage I, 50% in stage II, 24% in stage III, 25% in stage IV, and 33% for all patients. The cumulative mean dose of CPM was 62 mg/kg in survivors and 64 mg/kg in children who relapsed. One third of patients experienced significant marrow suppression, and infections after COMP1. CONCLUSIONS: Thirty-three percent of children are in first remission at 12 months. The morbidity and mortality of treatment was high. The high relapse rate in all stages may be due to the low cumulative dose of CPM.

Adolescent↗
PubMed2005

Human immunodeficiency virus infection and pediatric bacterial meningitis in developing countries.

Over a million children are infected by the human immunodeficiency virus (HIV); most of whom live in the developing world. Bacterial meningitis is a serious infection of childhood that is 10 times more common in resource-constrained settings than well-resourced countries, and the outcome is worse. This paper reviews the relationship of bacterial meningitis to HIV infection and also the effect of HIV status on antibiotic sensitivity to common causes of childhood meningitis. The combined effects on outcome and long-term sequelae of meningitis are discussed and illustrated with results from Malawi and Southern Africa.

Anti-Bacterial Agents↗
PubMed2004

Bacterial infections in children with HIV/AIDS.

HIV/AIDS affects over 850,000 children in Africa. Bacterial infections are frequent in this group of children. Pneumonia, meningitis and septicaemia are especially common, recurrent and most often caused by Streptococcus pneumoniae. Salmonella spp are the most frequently isolated causative agent of septicaemia in malarial areas. Soft tissue, eye and oral infections have a higher incidence in HIV-infected than uninfected children. In all instances the causative agents are not dissimilar from those that cause disease in HIV-uninfected children, but the mortality is greater. Increased bacterial resistance to first line antibiotics has been reported and the use of cotrimoxazole prophylaxis may further influence the resistance pattern of common bacteria.

AIDS-Related Opportunistic Infections↗
PubMed2003

Malawi pilot study of Burkitt lymphoma treatment.

BACKGROUND: Burkitt lymphoma (BL) accounts for 50% of childhood cancer in Malawi. Lack of resources precludes the use of new successful treatment approaches such as the LMB 89 group B protocol, which cures >80% of children with stage III BL with high dose chemotherapy and matching supportive care. Our objective was to achieve a good cure rate in Murphy stage I-III BL with manageable toxicity in Malawi at a drug cost of <1000 US dollars per patient. PROCEDURE: The intensity and toxicity of the LMB 89 group B protocol was reduced and adapted to Malawi realities. All stages received the same treatment. Children with suspected BL in the period July 1997-November 1999 were subjected to abdominal ultrasound, a tumor biopsy and/or fine needle aspirate (FNA) and bone marrow (BM), cerebrospinal fluid (CSF), and peripheral blood examination. HIV seropositive children were excluded. Endpoints are projected event free survival (EFS) at minimum 1 year, blood and gastro-intestinal tract toxicity, and risk for and severity of infections. RESULTS: Forty-four children were eligible for treatment and analysis. Their median age was 7.2 years, M:F ratio 1.4:1 with 10 stage I, 5 stage II, and 29 stage III patients. Projected Kaplan-Meier EFS for all was 57% (CI 41-73) at 1 year with 90% EFS in stage I and 52% EFS in stage III. The survival curve remained stable at 500 days. Toxicity and delays in appropriate supportive care contributed to ten deaths during treatment. Local recurrent tumor caused five and CNS recurrence one death. Two children died from progressive disease. The incidence of severe (grade 3 and/or 4) hematologic toxicity varied from 13% to 36%, gastro-intestinal toxicity (GIT) from 2% to 17%, and infections from 7% to 41% per chemotherapy module. CONCLUSIONS: It is possible to administer less intense and less costly multiagent chemotherapy to children with BL in a developing society with acceptable EFS rates. Adequate supportive care of the at-times associated severe toxicity must be made available to better the results.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

Promiscuous expression of Epstein-Barr virus genes in Burkitt's lymphoma from the central African country Malawi.

Primary BL in Malawian children has a very high frequency association, approaching 100%, with the human herpesvirus EBV. A detailed study carried out on viral gene expression in these tumours, using both fresh material and methanol-fixed FNAs, showed, contrary to prediction, that most belong to a variant "class II" latency category, with lytic cycle-related genes also expressed. That is, in addition to EBNA1 expression, membrane proteins (LMP1/2A), immediate early (BZLF1) and early (IR2 and IR4) genes, a putative viral oncogene (BARF1), CST (BART) antisense transcripts and the viral bcl-2 homologue are expressed in a high proportion of the BLs. Most, but not all, express the small viral (EBER) RNAs. Two other significant observations were made: (i) in addition to expression of cellular cytokine (IL-10) transcripts in all tumours investigated, the normally silent viral IL-10 homologue was expressed in some tumours; (ii) whereas EBNA1 expression from its restricted Qp promoter was generally observed, the nonrestricted Cp/Wp promoter was also active in some tumours. Viral gene expression in the Malawian [endemic (e)] BLs appears to be more promiscuous than predicted from other studies, but expression accords with the cytopathologic picture of eBLs as a rapidly proliferating cell population accompanied by considerable necrosis, and a clinically diverse disease. A small-scale study of relapse Malawian BLs revealed a different picture of viral association, more akin to systemic BL than eBL, where EBV appears to be absent or present only at very low levels. The significance of these findings is considered.

Antigens, Viral↗