Symptom-based screening tool for asthma syndrome among young children in Uganda

Under-diagnosis of asthma in ‘under-fives’ may be alleviated by improved inquiry into disease history. We assessed a questionnaire-based screening tool for asthma among 614 ‘under-fives’ with severe respiratory illness in Uganda. The questionnaire responses were compared to post hoc consensus diagnoses by three pediatricians who were guided by study definitions that were based on medical history, physical examination findings, laboratory and radiological tests, and response to bronchodilators. Children with asthma or bronchiolitis were categorized as “asthma syndrome”. Using this approach, 253 (41.2%) had asthma syndrome. History of and present breathing difficulties and present cough and wheezing was the best performing combination of four questionnaire items [sensitivity 80.8% (95% CI 77.6–84.0); specificity 84.7% (95% CI 81.8–87.6)]. The screening tool for asthma syndrome in ‘under-fives’ may provide a simple, cheap and quick method of identifying children with possible asthma. The validity and reliability of this tool in primary care settings should be tested

EPHB4 kinase-inactivating mutations cause autosomal dominant lymphatic-related hydrops fetalis.

Hydrops fetalis describes fluid accumulation in at least 2 fetal compartments, including abdominal cavities, pleura, and pericardium, or in body tissue. The majority of hydrops fetalis cases are nonimmune conditions that present with generalized edema of the fetus, and approximately 15% of these nonimmune cases result from a lymphatic abnormality. Here, we have identified an autosomal dominant, inherited form of lymphatic-related (nonimmune) hydrops fetalis (LRHF). Independent exome sequencing projects on 2 families with a history of in utero and neonatal deaths associated with nonimmune hydrops fetalis uncovered 2 heterozygous missense variants in the gene encoding Eph receptor B4 (EPHB4). Biochemical analysis determined that the mutant EPHB4 proteins are devoid of tyrosine kinase activity, indicating that loss of EPHB4 signaling contributes to LRHF pathogenesis. Further, inactivation of Ephb4 in lymphatic endothelial cells of developing mouse embryos led to defective lymphovenous valve formation and consequent subcutaneous edema. Together, these findings identify EPHB4 as a critical regulator of early lymphatic vascular development and demonstrate that mutations in the gene can cause an autosomal dominant form of LRHF that is associated with a high mortality rate

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Factors associated with asthma among under-fives in Mulago hospital, Kampala Uganda:a cross sectional study

BACKGROUND: Asthma is the most common chronic childhood illness, with rapidly increasing prevalence in low-income countries. Among young children, asthma is often under-diagnosed. We investigated the factors associated with asthma among under-fives presenting with acute respiratory symptoms at Mulago hospital, Uganda. METHODS: A hospital-based cross sectional study of 614 children with cough and/or difficult breathing, and fast breathing, was conducted between August 2011 and June 2012. A questionnaire focusing on clinical history of the child was administered to the caretakers. A physical examination and, laboratory and radiological investigations were done. Asthma was defined according to GINA (Global Initiative for Asthma) guidelines which were modified by excluding the symptom of “chest tightness”, spirometry/peak expiratory flow measurements and by adding chest x-ray findings to distinguish asthma from pneumonia. A panel of three paediatricians reviewed the participants’ case reports and, guided by the study definitions, made a diagnosis of asthma or other. Multivariable logistic regression analysis was done to determine factors independently associated with asthma. RESULTS: Of the 614 children, 128 (20.8%) had asthma, 125 (20.4%) bronchiolitis, 167 (27.2%) bacterial pneumonia only, 163 (26.5%) viral pneumonia while 31 (5.1%) had other diagnoses including pulmonary tuberculosis. The majority (71.1%) of children with asthma were aged ≥ 12 months. Factors associated with asthma included maternal asthma (AOR 2.4, 95% CI 1.2, 4.6), a history of allergy in the patient (AOR 2.6, 95% CI 1.2, 5.4,), use of gas for cooking (AOR 3.8, 95% CI 1.2, 13.3), prematurity (AOR 9.3, 95% CI 1.2, 83.3) and high level of education of caretaker (AOR 9.1, 95% CI 1.1, 72.8). CONCLUSION: Maternal asthma, a history of allergy in the patient, use of gas for cooking, prematurity and high level of education of caretaker were significantly associated with asthma. There is need for studies to explore the role of the above factors in development and exacerbation of childhood asthma to provide information that can be used to design strategies for asthma prevention and control

Asthma and pneumonia among children less than five years with acute respiratory symptoms in Mulago Hospital, Uganda:evidence of under-diagnosis of asthma

BACKGROUND: Pneumonia is considered the major cause of mortality among children with acute respiratory disease in low-income countries but may be over-diagnosed at the cost of under-diagnosing asthma. We report the magnitude of asthma and pneumonia among "under-fives" with cough and difficulty breathing, based on stringent clinical criteria. We also describe the treatment for children with acute respiratory symptoms in Mulago Hospital. METHODS: We enrolled 614 children aged 2-59 months with cough and difficulty breathing. Interviews, physical examination, blood and radiological investigations were done. We defined asthma according to Global Initiative for Asthma guidelines. Pneumonia was defined according to World Health Organization guidelines, which were modified by including fever and white cell count, C-reactive protein, blood culture and chest x-ray. Children with asthma or bronchiolitis were collectively referred to as "asthma syndrome" due to challenges of differentiating the two conditions in young children. Three pediatricians reviewed each participant's case report post hoc and made a diagnosis according to the study criteria. RESULTS: Of the 614 children, 41.2% (95% CI: 37.3-45.2) had asthma syndrome, 27.2% (95% CI: 23.7-30.9) had bacterial pneumonia, 26.5% (95% CI: 23.1-30.2) had viral pneumonia, while 5.1% (95% CI: 3.5-7.1) had other diagnoses including tuberculosis. Only 9.5% of the children with asthma syndrome had been previously diagnosed as asthma. Of the 253 children with asthma syndrome, 95.3% (95% CI: 91.9-97.5) had a prescription for antibiotics, 87.7% (95% CI: 83.1-91.5) for bronchodilators and 43.1% (95% CI: 36.9-49.4) for steroids. CONCLUSION: Although reports indicate that acute respiratory symptoms in children are predominantly due to pneumonia, asthma syndrome contributes a significant proportion. Antibiotics are used irrationally due to misdiagnosis of asthma as pneumonia. There is need for better diagnostic tools for childhood asthma and pneumonia in Uganda

Magnitude of asthma syndrome and pneumonia among ‘under-fives’ in Mulago hospital Uganda.

<p>Magnitude of asthma syndrome and pneumonia among ‘under-fives’ in Mulago hospital Uganda.</p