George Swingler

Induced sputum versus gastric lavage for microbiological confirmation of pulmonary tuberculosis in infants and young children: a prospective study

BACKGROUND For microbiological confirmation of diagnosis of pulmonary tuberculosis in young children, sequential gastric lavages are recommended; sputum induction has not been regarded as feasible or useful. We aimed to compare the yield of Mycobacterium tuberculosis from repeated induced sputum with that from gastric lavage in young children from an area with a high rate of HIV and tuberculosis. METHODS We studied 250 children aged 1 month to 5 years who were admitted for suspected pulmonary tuberculosis in Cape Town, South Africa. Sputum induction and gastric lavage were done on three consecutive days according to a standard procedure. Specimens were stained for acid-fast bacilli; each sample was cultured singly for M tuberculosis. FINDINGS Median age of children was 13 months (IQR 6-24). A positive smear or culture for M tuberculosis was obtained from 62 (25%) children; of these, 58 (94%) were positive by culture, whereas almost half (29 [47%]) were smear positive. Samples from induced sputum and gastric lavage were positive in 54 (87%) and 40 (65%) children, respectively (difference in yield 5.6% [1.4-9.8%], p=0.018). The yield from one sample from induced sputum was similar to that from three gastric lavages (p=1.0). Microbiological yield did not differ between HIV-infected and HIV-uninfected children (p=0.17, odds ratio 0.7 [95% CI 0.3-1.3]). All sputum induction procedures were well tolerated; minor side-effects were increased coughing, epistaxis, vomiting, or wheezing. INTERPRETATION Sputum induction is safe and useful for microbiological confirmation of tuberculosis in young children. This technique is preferable to gastric lavage for diagnosis of pulmonary tuberculosis in both HIV-infected and HIV-uninfected infants and children.

Diagnostic accuracy of chest radiography in detecting mediastinal lymphadenopathy in suspected pulmonary tuberculosis

Objective: To estimate the diagnostic accuracy of chest radiography in the detection of chest lymphadenopathy in children with clinically suspected pulmonary tuberculosis. Methods: Design: Prospective cross sectional study. Setting: A short stay ward in a children’s hospital in South Africa. Patients: Consecutive children under 14 years of age admitted with suspected pulmonary tuberculosis. Diagnostic test: Antero-posterior and/or lateral chest x rays interpreted independently and blind to the reference standard by three primary care clinicians and three paediatricians, all with a special interest in tuberculosis. Reference standard: Spiral chest computed tomography (CT) with contrast injection. Results: One hundred children (median age 21.5 months) were enrolled. Lymphadenopathy was present in 46 of 100 reference CT scans and judged to be present in 47.1% of x ray assessments. Overall sensitivity was 67% and specificity 59%. Primary care clinicians were more sensitive (71.5% v 63.3%, p = 0.047) and less specific (49.8% v 68.9%, p<0.001) than paediatricians. Overall accuracy was higher for the paediatricians (diagnostic odds ratio 3.83 v 2.49, p = 0.008). The addition of a lateral to an antero-posterior view did not significantly increase accuracy (diagnostic odds ratio 3.09 v 3.73, p = 0.16). Chance adjusted inter-observer agreement (κ) varied widely between viewer pairs, but was around 30%. Conclusions: Detection of mediastinal lymphadenopathy on chest x ray to diagnose pulmonary tuberculosis in children must be interpreted with caution. Diagnostic accuracy might be improved by refining radiological criteria for lymphadenopathy.

Relation between burden of disease and randomised evidence in sub-Saharan Africa: survey of research.

Abstract Objective: To evaluate whether the amount of randomised clinical research on various medical conditions is related to the burden of disease and health needs of the local populations in sub-Saharan Africa. Design: Construction and analysis of comprehensive database of randomised controlled trials in sub-Saharan Africa based on Medline, the Cochrane Controlled Trials Register, and several African databases. Setting: Sub-Saharan Africa. Main outcome measures: Number of trials and randomised subjects for each category of disease in the global burden of disease taxonomy; ratios of disability adjusted life years (DALYs) per amount of randomised evidence. Results: 1179 eligible randomised controlled trials were identified. The number of trials published each year increased over time. Almost half of the trials (n=565) had been done in South Africa. There was relatively good correlation between the estimated burden of disease at year 2000 and the number of trials performed (r=0.53, P=0.024) and the number of participants randomised (r=0.68, P=0.002). However,some conditions—for example, injuries (over 20 000 DALYs per patient ever randomised)—were more neglected than others. Conclusion: Despite recent improvements, few clinical trials are done in sub-Saharan Africa. Clinical research in this part of the world should focus more evenly on the major contributors to burden of disease. What is already known on this topic Sub-Saharan Africa has a large burden of disease Little clinical research is conducted for problems affecting sub-Saharan Africa What this study adds Only 1179 randomised controlled trials conducted in sub-Saharan Africa in the past 50 years were identified Correlation between the amount of randomised evidence and the estimated burden of disease was fairly good However, some disease categories were more neglected than others, with the worst being injuries

Radiologic Differentiation Between Bacterial and Viral Lower Respiratory Infection in Children: A Systematic Literature Review:

A systematic literature review was performed to quantify the accuracy of chest radiography in differentiating bacterial from viral lower respiratory infection in children. Relevant studies were identified in a systematic literature search and were included in the review according to predetermined criteria. Five of 13 relevant identified studies met the inclusion criteria. No clinically useful degree of accuracy was demonstrated, but great caution is needed in interpreting the findings because of the suboptimal nature of the reference standards, even in included studies. It is recommended that future surveys of the microbial etiology of pneumonia that employ a credible reference standard (such as lung aspiration) be used as opportunities to perform studies of diagnostic accuracy.

Can lay health workers increase the uptake of childhood immunisation? Systematic review and typology.

Objectives  Lay health workers (LHWs) are used in many settings to increase immunisation uptake among children. However, little is known about the effectiveness of these interventions. The objective of this review was to assess the effects of LHW interventions on childhood immunisation uptake.

Children in reviews: Methodological issues in child-relevant evidence syntheses

BackgroundThe delivery of optimal medical care to children is dependent on the availability of child relevant research. Our objectives were to: i) systematically review and describe how children are handled in reviews of drug interventions published in the Cochrane Database of Systematic Reviews (CDSR); and ii) determine when effect sizes for the same drug interventions differ between children and adults.MethodsWe systematically identified all of the reviews relevant to child health in the CDSR 2002, Issue 4. Reviews were included if they investigated the efficacy or effectiveness of a drug intervention for a condition that occurs in both children and adults. Information was extracted on review characteristics including study methods, results, and conclusions.ResultsFrom 1496 systematic reviews, 408 (27%) were identified as relevant to both adult and child health; 52% (213) of these included data from children. No significant differences were found in effect sizes between adults and children for any of the drug interventions or conditions investigated. However, all of the comparisons lacked the power to detect a clinically significant difference and wide confidence intervals suggest important differences cannot be excluded. A large amount of data was unavailable due to inadequate reporting at the trial and systematic review level.ConclusionOverall, the findings of this study indicate there is a paucity of child-relevant and specific evidence generated from evidence syntheses of drug interventions. The results indicate a need for a higher standard of reporting for participant populations in studies of drug interventions.

Early clinical signs in neonates with hypoxic ischemic encephalopathy predict an abnormal amplitude-integrated electroencephalogram at age 6 hours

BackgroundAn early clinical score predicting an abnormal amplitude-integrated electroencephalogram (aEEG) or moderate-severe hypoxic ischemic encephalopathy (HIE) may allow rapid triage of infants for therapeutic hypothermia. We aimed to determine if early clinical examination could predict either an abnormal aEEG at age 6 hours or moderate-severe HIE presenting within 72 hours of birth.MethodsSixty infants ≥ 36 weeks gestational age were prospectively enrolled following suspected intrapartum hypoxia and signs of encephalopathy. Infants who were moribund, had congenital conditions that could contribute to the encephalopathy or had severe cardio-respiratory instability were excluded. Predictive values of the Thompson HIE score, modified Sarnat encephalopathy grade (MSEG) and specific individual signs at age 3–5 hours were calculated.ResultsAll of the 60 infants recruited had at least one abnormal primitive reflex. Visible seizures and hypotonia at 3–5 hours were strongly associated with an abnormal 6-hour aEEG (specificity 88% and 92%, respectively), but both had a low sensitivity (47% and 33%, respectively). Overall, 52% of the infants without hypotonia at 3–5 hours had an abnormal 6-hour aEEG. Twelve of the 29 infants (41%) without decreased level of consciousness at 3–5 hours had an abnormal 6-hour aEEG (sensitivity 67%; specificity 71%). A Thompson score ≥ 7 and moderate-severe MSEG at 3–5 hours, both predicted an abnormal 6-hour aEEG (sensitivity 100 vs. 97% and specificity 67 vs. 71% respectively). Both assessments predicted moderate-severe encephalopathy within 72 hours after birth (sensitivity 90%, vs. 88%, specificity 92% vs. 100%). The 6-hour aEEG predicted moderate-severe encephalopathy within 72 hours (sensitivity 75%, specificity 100%) but with lower sensitivity (p = 0.0156) than the Thompson score (sensitivity 90%, specificity 92%). However, all infants with a normal 3- and 6-hour aEEG with moderate-severe encephalopathy within 72 hours who were not cooled had a normal 24-hour aEEG.ConclusionsThe encephalopathy assessment described by the Thompson score at age 3–5 hours is a sensitive predictor of either an abnormal 6-hour aEEG or moderate-severe encephalopathy presenting within 72 hours after birth. An early Thompson score may be useful to assist with triage and selection of infants for therapeutic hypothermia.

Interobserver variability in the detection of mediastinal and hilar lymph nodes on CT in children with suspected pulmonary tuberculosis

Background: The presence of mediastinal or hilar adenopathy is critical for the diagnosis of pulmonary TB. Interobserver variability in the detection of lymphadenopathy on CT in children affects the usefulness of CT as a gold standard. Objective: To determine the interobserver variability for the detection of hilar and mediastinal adenopathy on CT in children. Materials and methods: One hundred children with clinically suspected pulmonary TB were prospectively recruited for CT scanning of the chest. Four observers reviewed the scans independently for the presence of lymphadenopathy at predetermined sites. Overall Kappa statistic was determined for each recognised site of mediastinal and hilar lymphadenopathy. Results: Kappa statistics showed that observers only agreed moderately in their detection of lymphadenopathy. The site of best agreement was the right hilum, followed by the subcarinal, right paratracheal and precarinal locations. Observers differed most at the anterior mediastinum and left hilum. The best Kappa statistic was for the overall presence of lymphadenopathy taking all sites into account. Conclusions: Imaging techniques that are considered the gold standard for particular diseases must be validated pathologically, and if this is not possible, interobserver variability should be evaluated. CT is considered the gold standard for detecting lymphadenopathy, but we have shown only moderate agreement between readers. Readers had difficulty in distinguishing lymphadenopathy from normal thymus and were unable to distinguish normal from pathological nodes without a predetermined size threshold for abnormality. The right hilum and the sites around the carina are the most reliable for the reported presence of lymphadenopathy.

An audit of the use of antibiotics in presumed viral meningitis in children.

The antibiotic management of 139 consecutive patients with presumed viral meningitis evaluated during a 6-month period was examined. The presumptive diagnosis of viral meningitis was made in retrospect by consensus among the authors, using clinical and routinely available laboratory information. Sixty-eight (51.9%) of 131 patients with complete records were treated with antibiotics after diagnosis, 25 for 2 days or less and 43 for longer than 2 days. Antibiotic treatment was retrospectively judged to be unjustified in 35 (81.4%) of the 43 patients treated for longer than 2 days. When compared with untreated patients antibiotic treatment was started in younger female children with lower cerebrospinal fluid glucose values and longer duration of symptoms. There was no difference between the two groups in other cerebrospinal fluid values, peripheral white blood cell count or history of preceding antibiotics. In contrast no associations were found with treatment beyond 2 days, compared with treatment for 2 days or less. Thus the decision to stop antibiotic treatment early did not appear to be made according to consistent clinical criteria. This apparent lack of consistent criteria suggests the need to develop clinical guidelines for such decisions, both to aid clinicians and to provide standards for medical audit.

Educational outreach to general practitioners reduces children's asthma symptoms: a cluster randomised controlled trial.

BackgroundChildhood asthma is common in Cape Town, a province of South Africa, but is underdiagnosed by general practitioners. Medications are often prescribed inappropriately, and care is episodic. The objective of this study is to assess the impact of educational outreach to general practitioners on asthma symptoms of children in their practice.MethodsThis is a cluster randomised trial with general practices as the unit of intervention, randomisation, and analysis. The setting is Mitchells Plain (population 300,000), a dormitory town near Cape Town. Solo general practitioners, without nurse support, operate from storefront practices. Caregiver-reported symptom data were collected for 318 eligible children (2 to 17 years) with moderate to severe asthma, who were attending general practitioners in Mitchells Plain. One year post-intervention follow-up data were collected for 271 (85%) of these children in all 43 practices.Practices randomised to intervention (21) received two 30-minute educational outreach visits by a trained pharmacist who left materials describing key interventions to improve asthma care. Intervention and control practices received the national childhood asthma guideline. Asthma severity was measured in a parent-completed survey administered through schools using a symptom frequency and severity scale. We compared intervention and control group children on the change in score from pre-to one-year post-intervention.ResultsSymptom scores declined an additional 0.84 points in the intervention vs. control group (on a nine-point scale. p = 0.03). For every 12 children with asthma exposed to a doctor allocated to the intervention, one extra child will have substantially reduced symptoms.ConclusionEducational outreach was accepted by general practitioners and was effective. It could be applied to other health care quality problems in this setting.