A strategy to improve treatment‐related mortality and abandonment of therapy for childhood ALL in a developing country reveals the impact of treatment delays

Background

Treatment‐related mortality and abandonment of therapy are major barriers to successful treatment of childhood acute lymphoblastic leukemia (ALL) in the developing world.

Procedure

A collaboration was undertaken between Instituto Nacional de Cancerologia (Bogota, Colombia), which serves a poor patient population in an upper‐middle income country, and Dana‐Farber/Boston Children's Cancer and Blood Disorders Center (Boston, USA). Several interventions aimed at reducing toxic deaths and abandonment were implemented, including a reduced‐intensity treatment regimen and a psychosocial effort targeting abandonment. We performed a cohort study to assess impact.

Results

The Study Population comprised 99 children with ALL diagnosed between 2007 and 2010, and the Historic Cohort comprised 181 children treated prior to the study interventions (1995–2004). Significant improvements were achieved in the rate of deaths in complete remission (13% to 3%; P = 0.005), abandonment (32% to 9%; P < 0.001), and event‐free survival with abandonment considered an event (47% to 65% at 2 years; P = 0.016). However, relapse rate did not improve. Medically unnecessary treatment delays were common, and landmark analysis revealed that initiating the PIII phase of therapy ≥4 weeks delayed predicted markedly inferior disease‐free survival (P = 0.016). Conversely, patients who received therapy without excessive delays had outcomes approaching those achieved in high‐income countries.

Conclusions

Implementation of a twinning program was followed by reductions in abandonment and toxic deaths, but relapse rate did not improve. Inappropriate treatment delays were common and strongly predicted treatment failure. These findings highlight the importance of adherence to treatment schedule for effective therapy of ALL. Pediatr Blood Cancer 2015;62:1395–1402. © 2015 Wiley Periodicals, Inc.     

Evaluation of a new equation for LDL-c estimation and prediction of death by cardiovascular related events in a German population-based study cohort

A simple equation established by Cordova &; Cordova (LDL-COR) was developed to provide an improved estimation of LDL-cholesterol in a large Brazilian laboratory database. We evaluated this new equation in a general population cohort in Pomerania, north-eastern Germany (SHIP Study) compared to other existing formulas (Anandaraja, Teerakanchana, Chen, Hattori, Martin, Friedewald and Ahmadi), and its power in the prediction of death by atherosclerosis related events as the primary outcome. Analysis was conducted on a cohort of 4075 individuals considering age, gender, use of lipid lowering therapy and associated co-morbidities such as diabetes, hepatic, kidney and thyroid disease. LDL-COR values had a lower standard deviation compared to the previously published equations: 0.92 versus 1.02, 1.02, 1.03, 1.04, 1.09, 1.10 and 1.74?mmol/L, respectively. All of the factors known to affect the results obtained by the Friedewald’s equation (LDL-FW), except fibrate use, were associated with the difference between LDL-COR and LDL-FW (p?p?=?.06). LDL-COR determined a higher hazard ratio (1.23 versus 1.12, 1.19, 1.21, 1.19, 1.21 and 1.19) for cardiovascular disease related mortality, incident stroke or myocardial infarction compared to the other evaluated formulas, except for Ahmadi’s (1.24), and the same adjusted predictive power considering all confounding factors. The proposed simple equation was demonstrated to be suitable for a more precise LDL-c estimation in the studied population. Since LDL-c is a parameter frequently requested by medical laboratories in clinical routine, and will probably remain so, precise methods for its estimation are needed when direct measurement is not available.     

Imaging of dental infections

Emergency Radiology - Dental infections are a common presentation in the emergency department (ED). To help guide clinical management for these infections, the radiologist must be familiar with the...     

Diagnostic yield of capillary compared to venous glucose in the diagnosis of hypoglycorrhachia in children: A prospective,observational study

IntroductionThe ratio of cerebrospinal fluid (CSF) glucose and blood glucose is of major relevance, conducting to the diagnosis of hypoglycorrhachia, which is a sign of neuroinfection, as well as a number of neurological diseases of genetic or neoplastic etiology. Glucose in capillary sample (glucometry) is a low cost, readily available technique, as compared to venous glucose. This study aims to compare glucometry to venous glucose in the diagnosis of hypoglycorrhachia in pediatric population.MethodsProspective cross-sectional study based on data obtained from lumbar punctures in the period from February 2017 to January 2019 in a specialized pediatric institution in Colombia.Results97 patients were analyzed, aged 1 month to 17 years old, mean 7.67 years, 52 (53.61%) were female. 26 (26.8%) were diagnosed with hypoglycorrhachia. Pearson correlation coefficient for absolute venous and capillary glucose was 0.54, and 0.55 for the ratios of CSF glucose/venous glucose and CSF glucose/glucometry, which support a linear correlation between the variables in both, absolute values and ratios. Intraclass correlation coefficient was calculated for both, the venous glucose and glucometry ratios, which was 0.52, revealing a moderate agreement among the tests. Sensitivity and specificity of CSF glucose/glucometry, as compared to gold standard are 73.1% and 60.6% respectively; whereas predictive positive value (PPV) and negative predictive value (NPV), were 40.4% and 86.0%.ConclusionGlucometry cannot replace the glucose in venous sample in the diagnosis of hypoglycorrhachia in children.     

Sex-specific environmental influences affecting MS development

Vitamin D status, smoking, and Epstein–Barr virus infection (EBV) may all contribute to explain differences in disease prevalence and incidence of Multiple Sclerosis (MS). MS affects women more often than men, and recent cross-sectional study assessments provide evidence of increased female to male prevalence in relapsing remitting MS patients, suggesting that sex hormones may exert an active role in disease pathogenesis. Studies in both humans and animal disease models demonstrate a functional synergy for the immunomodulatory effects of Vitamin D3 and 17-β estradiol. Both smoking and EBV infection clearly increase MS risk, and smoking history has also been associated with poorer disease prognosis. However, neither factor can explain the recent trend indicating greater female prevalence. Therefore, large population-based case–control studies from well defined geographic areas with homogeneous populations should be performed, in order to define environmental factor effects, and sex hormone influences, to better understand prevalence and incidence gender differences observed.     

Trimetazidine improves left ventricular function and quality of life in elderly patients with coronary artery disease.

AIM: Elderly patients have an increased incidence of ischaemic dilated cardiomyopathy often related to diffuse coronary artery disease. Trimetazidine protects ischaemic myocardium by improving the myocardial energy utilisation during myocardial ischaemia. Aim of the present study was to evaluate the effects of trimetazidine on left ventricular (LV) function in elderly patients with ischaemic heart disease and reduced LV function. METHODS: Forty seven elderly patients (40 males and 7 females, mean age 78+/-3 years) were randomised to receive, in addition to standard therapy, either trimetazidine or placebo and were evaluated by echocardiography at baseline and after 6 months. RESULTS: Trimetazidine and placebo had no effect on either blood pressure or heart rate (SBP 2+/-5 vs 4+/-6 mmHg, DBP -1+/-6 vs 3+/-4 mmHg, HR -3+/-7 vs 5+/-9 bpm, trimetazidine and placebo compared to baseline, respectively). At the end of the study patients randomised to trimetazidine showed a significant greater left ventricular function and smaller left ventricular diastolic and systolic diameters and volume indices compared to patients receiving placebo (LVEF: 34.4+/-2.3% vs 27+/-2.8%, p<0.0001; LVEDD: 58.6+/-1.9 mm vs 64+/-1.7 mm, p<0.0001; LVESD: 44.5+/-1.1 vs 50+/-0.8 mm, p<0.0001). A significant smaller wall motion score index was detected in trimetazidine-treated patients compared to those allocated to placebo (1.24+/-0.12 vs 1.45+/-0.19, p<0.01), the percentage change in LVEF compared to baseline was also significantly greater in trimetazidine-treated patients. Diastolic function significantly improved in the trimetazidine group while it remained unchanged in the placebo group. At follow-up evaluation, patients receiving trimetazidine showed a greater improvement in angina and NYHA class than patients allocated to placebo. Quality of life significantly improved in all patients treated with trimetazidine while remained unchanged in those allocated to placebo. CONCLUSION: In elderly patients with ischaemic cardiomyopathy trimetazidine in addition to standard medical therapy has a beneficial effect on LV systolic and diastolic function, and improves quality of life.