Comparative trial of oltipraz versus praziquantel in the treatment of urinary schistosomiasis in the Gabon

The efficacy of oltipraz as a schistosomicidal drug was investigated in Gabonese children suffering from urinary schistosomiasis in the dosages of 1 X 25 mg/kg body weight, 1 X 35 mg/kg body weight, and 2 X 20 mg/kg body weight and compared to praziquantel, 2 X 30 mg/kg body weight. The study was undertaken in 165 patients, and follow-up investigations were carried out 6 weeks and 12 weeks after treatment. Oltipraz showed less efficacy compared to praziquantel when dosages of 1 X 25 and 1 X 35 mg/kg body weight were given. However, oltipraz 2 X 20 mg/kg body weight was equivalent to praziquantel 2 X 30 mg/kg body weight. Parasitological cure was obtained in 79% of patients treated by oltipraz and 81% of patients treated by praziquantel. Side effects were insignificant in both treatment groups. Thus, the same parasitological cure could be achieved by oltipraz as well as by praziquantel, but with a lower dosage of oltipraz.     

Pharmacotherapy of pediatric lung disease: differences between children and adults

Drug dosages for infants and children differ significantly from those used in adults (Table 5). This is due to normal developmental physiologic differences that affect absorption, distribution, and clearance. In general, infants and children require higher dosages of many therapeutic agents on a weight basis. Parenteral drug administration difficulties are complicated by the slow fluid infusion rates often used in infants and young children. The use of syringe infusion pump devices is critical for accurate therapeutic drug monitoring and dosage adjustment in pediatrics than in adults. Aerosol administration in pediatrics is more complicated and is poorly studied. Difficulty with coordinating metered-dose aerosols with inhalation and drug raining out on small endotracheal tubes of ventilated patients are two significant problems. Chronic and acute pulmonary disease can significantly affect drug disposition and metabolism, but has been poorly studied in children. The pharmacokinetics of a number of drugs have been evaluated in cystic fibrosis and may provide insight into the effect of disease states on drug disposition.     

Predicting body composition from anthropometry in pre-adolescent children

The objectives of this paper were to: a) evaluate the accuracy and precision of previously published pediatric body composition prediction equations and b) develop additional prediction equations from a large, heterogeneous group of Caucasian (n = 133) and African-American (n = 69) children. The combined cohort of 202 children included a wide range of ages (4.0-10.9 y), weights (14.0-70.8 kg), fat mass (FM: 1.2-28.5 kg) and percent body fat (% body fat: 6.2-49.6%). Skinfold measurements were obtained using a Lange caliper and body fat was measured with a Lunar DPX-L densitometer. The previously published equations of Slaughter et al and Goran et al did not accurately predict body fat. The entire cohort was randomly divided into two sub-groups for purposes of deriving and cross-validating a new prediction equation. In stepwise regression analysis in the development group (n = 135), weight, triceps skinfold, gender, ethnicity and abdominal skinfold estimated FM measured by dual energy x-ray absorptiometry (DEXA) with a model R2 of 0.95. The new prediction equation was cross-validated in the control group (n = 67) and each ethnic and gender subgroup. We conclude that a) the equations of Slaughter et al and Goran et al did not accurately predict FM in a heterogeneous group of children and b) a new anthropometric prediction equation is proposed that may provide accurate estimates of FM in both Caucasian and African-American children aged 4-10 y with a wide range of FM and body composition.     

The pharmacokinetics and pharmacodynamics of rifampicin in adults and children in relation to the dosage recommended for children

The dosages of antituberculosis agents recommended for treatment of childhood tuberculosis often reflect those for adult patients with similar mg/kg body weight dosages and ranges advised. Literature relating to the pharmacokinetics and pharmacodynamics of rifampicin (RMP) is reviewed and the serum concentrations reached by adults, both patients and healthy volunteers and children, established or not established on RMP, compared. Straight line regression of maximum RMP serum concentrations (C(max)) on dosage, weighted for the number of individuals, found slopes (SE) of 1.025 (0.067) and 0.881 (0.046) respectively for adult volunteers not established and established on RMP (P = 0.076), and similarly 0.748 (0.057) and 0.684 (0.038) respectively for adult patients (P < 0.001) and 0.622 (0.050) and 0.368 (0.041) respectively for children (P < 0.001). These results indicate that for equivalent RMP dosages adult patients reach a lower C(max) than adult volunteers and that adults, both volunteers and patients established on RMP reach higher C(max) values than children; children established on RMP require approximately twice the mg/kg body weight dosage of RMP to reach serum concentrations equivalent to those of adults. It is noteworthy that many adult patients receiving currently recommended RMP dosages also do not reach the often recommended RMP 2 h serum concentration of 8 μg/mL.     

How reliable is eGFR when calculating drug dosage in acute medical admissions?

Background: The Modification of Diet in Renal Disease‐derived estimation of glomerular filtration rate (eGFR) is used widely. Although validated in stable chronic kidney disease (CKD) outpatients, it is not known how it performs in those presenting with acute medical illness. Aim: We aimed to compare eGFR with Cockroft Gault (CG) – the renal function assessment tool available prior to eGFR – to assess the difference in clinical outcome that would occur when one over another estimation is used in practice. In particular, we wished to assess whether use of eGFR would have resulted in a change of dose of commonly used acutely administered medications. Methods: Acute medical admissions presenting to a tertiary hospital between August and December 2008 were included. Serum creatinine concentration, age, sex, height and weight were collected. Renal function was estimated by both estimates. Movement from CKD class 3 to 4 or 5 was measured – a clinically used cut‐off point for changes in management. Results: A total of 54 patients was included. eGFR values were higher than those estimated by CG. Almost half of patients categorized as CKD stage 4–5 using CG were only categorized as CKD stage 3 using eGFR. Conclusion: Although we did not use a gold standard estimation of GFR, this study shows that estimates of renal function vary in a clinically significant manner. As estimates of GFR are used to adjust drug dosages and to stratify for many other treatments, it is imperative that we find a method of estimating kidney function that is readily available, consistent and accurate.     

Ethambutol in paediatric tuberculosis: aspects of ethambutol serum concentration, efficacy and toxicity in children.

SETTING: Ethambutol (EMB) is used as a fourth drug in paediatric anti-tuberculosis treatment. In current recommendations the dosage of EMB is calculated per kg body weight. OBJECTIVE: To present two studies investigating an appropriate EMB dosage in children, and observational data on its toxicity and efficacy. DESIGN: EMB serum levels in children of different age groups were determined after single oral administration of EMB alone as well as after EMB combined with rifampicin, and optimal dosages were established. The efficacy and toxicity of these EMB dosages were examined retrospectively. RESULTS: EMB serum levels were lower than those expected in adults receiving a similar oral dose, due to different pharmacokinetics and pharmacodynamics in childhood. Thereafter, children were treated with EMB doses calculated by body surface (867 mg/m2). Ocular toxicity occurred in 0.7% of cases and relapses in 0.8%. CONCLUSION: Current recommended EMB dosages in childhood tuberculosis lead to subtherapeutic serum levels. It appears to be more valid to calculate the EMB dosage on the basis of body surface rather than body weight, leading to higher dosages especially in younger children. With these dosages, therapeutic serum levels are reached in all age groups, leading to a high efficacy of anti-tuberculosis treatment without increased ocular toxicity.     

Pharmacokinetics of amphotericin B in infants and children

The pharmacokinetics of amphotericin B (AmB) have not previously been evaluated in children. Five very small, premature infants and five older children received 0.25-1.0 mg of AmB/kg per 24 hr for Candida infections. Serum concentrations of AmB, measured by bioassay, were used to determine various pharmacokinetic parameters of AmB. A one-compartment model of drug distribution was most consistent with the data. The volume of AmB distributed per kilogram of body weight was smaller and the elimination clearance more rapid than those previously reported for adults. Serum levels were approximately one-half those seen in adults given comparable doses. The mean concentrations of AmB after various doses were as follows: at 0.25 mg/kg, 0.08 microgram/ml; at 0.50 mg/kg, 0.20 microgram/ml; at 0.75 mg/kg, 0.42 microgram/ml; and at 1.0 mg/kg, 0.54 microgram/ml. Interpatient variability was, however, marked, especially among the premature infants. AmB pharmacokinetics are different in infants and children than in adults; these differences may have implications for determining optimal pediatric dosing regimens.     

Safety and effectiveness of terbutaline in children with chronic asthma.

The bronchodilator and cardiovascular effects of orally administered tablets containing 2.5 mg of terbutaline and 25 mg of ephedrine were compared in a double-blind parallel manner in children (ages, 7 to 14 years) weighing 25 to 50 kg (44 to 110 lb). Both drugs produced bronchodilation within one-half hour, and this effect was maintained up to six hours, with a peak between two and three hours. Small increases in the pulse rate were measured within an hour following administration of both drugs. No significant variation was noted in blood pressure. No adverse effects (including tachyphylaxis and tremor) were observed for either drug during a three-month period. Both bronchodilator agents were shown to be equally effective in the dosages used. Terbutaline is a safe bronchodilator drug when administered orally in 2.5-mg doses for children with chronic asthma in this range of ages and weights, with minimal cardiovascular side effects and effective bronchodilation.     

Ethambutol dosage for the treatment of children: literature review and recommendations.

The currently recommended daily dose of ethambutol (EMB) for the treatment of tuberculosis (TB) in children varies from a maximum daily dose of 15 mg/kg body weight daily (without a range) to 15-20 mg/kg and 20 mg/ kg (range 15-25 mg/kg). Published evidence relating to the dosage, toxicity and pharmacokinetics of EMB in children and adults is reviewed and a dose of EMB for use in childhood is recommended. Using key words 'ethambutol', 'childhood', 'TB', 'pharmacokinetics', 'bioavailability' and 'toxicity', Medline searches were conducted; cross-references were sought from original papers, books and conference proceedings dating from 1961. When English summaries were available, data were extracted from papers in languages other than English. EMB has a dose-related efficacy best seen when given to adults alone or with a single other drug. Together with isoniazid (INH), a dose of 15 mg/kg EMB gave better results than 6 mg/kg, and 25 mg/kg better than 15 mg/kg. The occurrence of ocular toxicity was also dose-related; >40% of adults developed toxicity at doses of >50 mg/ kg, and 0-3% at a dose of 15 mg/kg/daily. Peak serum EMB concentrations increase in relation to dose, but are significantly lower in children receiving the same dosage. In only 2 of 3811 children (0.05%) receiving EMB doses of 15-30 mg/kg was EMB stopped due to possible ocular toxicity; children of all ages can be given EMB in daily doses of 20 mg/kg (range 15-25 mg/kg) and three times weekly intermittent doses of 30 mg/kg body weight without undue concern.     

Safety and efficacy of allogeneic PBSC collection in normal pediatric donors: the pediatric blood and marrow transplant consortium experience (PBMTC) 1996-2003

The use of peripheral blood stem cells (PBSC) for allogeneic transplants in adults has greatly increased. This trend is reflected in pediatrics, where healthy children increasingly are donating PBSC or donor lymphocyte infusion (DLI) via apheresis for use by ill siblings. There is a potential concern that the risks of PBSC collection may differ for pediatric donors. However, no large studies have assessed safety issues in this population. To address this need, we reviewed 218 (213 PBSC, five DLI) collections in 201 normal pediatric donors (8 months to 17 years, median 11.8 years) at 22 institutions in the Pediatric Blood and Marrow Transplant Consortium. Donors received a median of 4 days of growth factor, and mean collection yield was 9.1 x 10(6) CD34+ cells/kg recipient weight. Younger age, days of apheresis, and male gender predicted increased yield of CD34+ cells/kg donor weight. Growth factor-induced pain was mild and reported in less than 15% of patients. Most donors <20 kg (23/25, 92%) required PRBC priming of the apheresis machine. This experience with over 200 collections demonstrates that PBSC collection is safe in normal pediatric donors and desired CD34 cell yields are easily achieved. Younger children utilize more medical resources and children <20 kg usually require a single blood product exposure.     

Intraoperative transesophageal echocardiography using high resolution imaging in infants and children with congenital heart disease

A transesophageal probe recently has been developed for use in pediatric patients, which incorporates 48 rather than 26 elements, and permits continuous-wave Doppler, and pulsed and color Doppler flow modalities. This probe potentially offers significantly enhanced image quality. To evaluate its capabilities, we tested the probe intraoperatively in 53 infants and children undergoing surgical repair of congenital heart disease, and found that clear echocardiographic images with good detail were provided, including the ability to image coronary arteries in patients weighing as little as 2.7 kg. Imaging detail transesophageally is commensurate with the performance of this system from a transthoracic route. This probe also has the capacity for accurate estimates of high velocity jets using continuous-wave Doppler, which is a relatively new development.     

Children's weights: guess or measure by tape?

Children's doses of drugs are prescribed according to bodyweight but in resource-poor countries weighing scales may be unavailable, inaccurate, or broken. We designed a length/weight tape for use in our community and found it reasonably accurate for weights of 4-16 kg and better than a clinician's guess.     

Fasting respiratory exchange ratio and resting metabolic rate as predictors of weight gain: the Baltimore Longitudinal Study on Aging.

The authors followed 775 men (aged 18-98 years) participating in the Baltimore Longitudinal Study in Aging for an average of ten years. Resting metabolic rate and fasting respiratory exchange ratio (RER) were measured by indirect calorimetry on their first visit and related to subsequent weight change. Deviations from the predicted value of resting metabolic rates (predicted from their estimated fat-free mass) were calculated. Average weight change was 0.07 kg (s.d. 6.4 kg); 122 men (15.3%) gained more than 5 kg and 40 (5.2%) more than 10 kg during the follow-up. After adjustment for initial age, body mass index, fat-free mass, and duration of follow-up, RER, but not RMR or deviations from predicted RMR, was positively related to weight change (P less than 0.001). Major weight gain (from at least 5 kg to at least 15 kg) was related to initial RER in non-obese men only (initial body mass index less than 25 kg/m2). From Cox proportional hazard regression analyses the adjusted relative risk of gaining 5 kg or more in initially non-obese men with a fasting RER of 0.85 or more was calculated to be 2.42 (95% confidence interval: 1.10-5.32) compared to men with a fasting RER less than 0.76. It was concluded that a relatively high fasting RER is a weak but significant predictor of substantial weight gain in non-obese white men.     

Effect of size and disease on estimated deposition of drugs administered using jet nebulization in children with cystic fibrosis

STUDY OBJECTIVES: To develop a model that quantified the nebulizer output that was inhaled by subjects with cystic fibrosis (CF) in order to predict the amount of drug likely to enter the upper airway contained in particles small enough to be deposited in the lower respiratory tract of individual patients. DESIGN: Forty-three patients (age, 6 to 18 years) with CF, with FEV(1) of 26 to 124% of predicted, breathed through a nebulizer circuit with a pneumotachograph in place at the distal end. Algorithms were developed from the measured flows through the pneumotachograph, allowing partitioning of inspiration into undiluted aerosol and fresh gas. In order to validate the algorithms, argon was added to the nebulizing gas flow and then its concentration was analyzed at the mouth by mass spectrometry. RESULTS: Predictions of the concentration of argon at the mouth were concordant with that measured by mass spectrometry, thus validating the model. Combining data from the model with in vitro nebulizer performance data, predictions for estimates for lung deposition for individuals were possible. Total estimate was independent of patient size or FEV(1). The respiratory duty cycle was 0.44 +/- 0.05 (mean +/- SD) and correlated (r = 0.91, p < 0.001) with estimated deposition and minute ventilation (r = 0.60, p < 0.01). However, when expressed in milligrams per kilogram of body weight, the estimated deposition in smaller children was fourfold higher than in larger children. CONCLUSIONS: If the effect of patient size and pattern of breathing on estimated drug deposition are not considered when prescribing drugs given by nebulization, the result may be overdosing younger children, underdosing older children, or both.     

Cervical spine stabilization in pediatric patients: evaluation of current techniques

We evaluated the performance of commercially available infant and pediatric cervical collars, both alone and in combination with commonly used supplemental devices (eg, Kendrick Extrication Device, half-spine board). One infant and 11 pediatric-sized collars were tested on mannequins representing an infant and a 5-year old child. Maximum forces generated by cooperative children were measured, then applied to the mannequins to reproduce head and neck flexion, extension, rotation, and lateral motion. Limitation of motion was measured in each direction for each collar and combination method. In general, collars of rigid plastic construction performed better than did foam types. However, when used alone none of the collars provided acceptable immobilization, with even the best allowing 17 degrees flexion, 19 degrees extension, 4 degrees rotation, and 6 degrees lateral motion. When combined with supplemental devices, immobilization to 3 degrees or less in any direction could be achieved. Findings were verified using cooperative children and selected collars. Overall, combination methods were more effective than cervical collars alone (P less than .001) or supplemental devices alone (P less than .05). The modified half-spine board used with a rigid collar and tape was the most effective combination method. We conclude that prehospital cervical spine stabilization in pediatric patients is best accomplished using a rigid-type cervical collar in combination with supplemental devices as described.     

Hanging leg weight--a rapid technique for estimating total body weight in pediatric resuscitation

The accuracy of two methods of rapidly estimating total body weight in children was assessed. The first method correlated patient length to known total body weight, and the second correlated the weight of both legs weighted together to known total body weight. One hundred children undergoing general anesthesia in the operating rooms of Childrens Hospital of Los Angeles were entered into the study. Each child had a known preoperative body weight. After induction of anesthesia, each child's supine length was measured and hanging (inert) legs were weighted. There was excellent linear correlation between hanging leg weight and total body weight (correlation coefficient [r2], 0.95) for all patients, and good linear correlation between supine length and total body weight, r2, 0.86). Range restriction analysis for both techniques showed poor correlation for total body weights of less than 10 kg and poor correlation for the supine length technique when total body weight was more than 25 kg. The hanging leg weight of an inert child has excellent correlation to total body weight for children weighing more than 10 kg.     

Physical activity and fitness in obese children

Daily physical activity and physical fitness were studied in 31 obese and 31 normal-weight children matched for age and sex. The ages of the children ranged from 5.7 to 16.1 years. The history of their physical activity was examined using a questionnaire completed by the child and the parents. Physical fitness was measured using a two-stage exercise test on a bicycle ergometer. There were no significant differences in daily activities between the obese and the non-obese children, while the sports grades at school were lower and participation in the training teams of sports clubs was less frequent among obese than normal-weight subjects. The obese children were physically less fit than the normal-weight subjects as judged from the pedalling time in exercise test (P less than 0.05) and from the maximum oxygen consumption (VO2 max) related to lean body mass (LBM) (P less than 0.001). Twenty-seven children participated for 1 year in a weight-reduction programme which comprised individual nutrition counselling, guidance on physical activities and supportive therapy. The reduction in weight was successful in 25 out of 27 children and VO2 max increased on average from 44.2 to 47.1 ml/min/kg of LBM (P less than 0.025). There was no change in the time used for physical activities during the weight reduction period although the children's participation in the training teams of sports clubs increased. It was concluded that obese children are less fit than their non-obese counterparts. Weight reduction results, however, in an improvement of the maximum oxygen consumption towards normal.     

Pyrazinamide pharmacokinetics and efficacy in adults and children

Pyrazinamide (PZA) is an essential sterilizing drug and with rifampicin enables six-month short-course antituberculosis chemotherapy. Despite routine use for nearly forty years uncertainty remains regarding the most appropriate PZA dosage for children. In view of this uncertainty literature relating to the efficacy and pharmacokinetics of PZA in children treated for tuberculosis and in adult volunteers and patients was reviewed. Making use of the PZA maximum concentration (C(max)) following various PZA dosages in different groups straight line regression of concentration on dosage was fitted through the origin by least squares and weighted for the numbers of subjects. The fitted line offers an approximation of the likely PZA C(max) that would result from a particular dosage. The slopes of C(max)/dosage of the fitted lines are 1.32 (SE 0.099) for paediatric patients, 1.36 (SE 0.051) for adult volunteers and 1.35 (SE 0.037) for adult patients; there is little difference between the C(max) concentrations achieved in children and adults, whether patients or healthy volunteers, following various mg/kg body weight dosages, suggesting that children and adults receiving the same mg/kg body weight PZA dosage will reach a similar C(max). Children can receive the same mg/kg body weight PZA dosage as adults.     

Converting enzyme inhibition in hypertensive emergencies.

The diagnostic and therapeutic value of the angiotensin converting enzyme inhibitor teprotide (SQ 20881) was assessed in 18 patients with hypertensive emergencies. Mean blood pressure fell 31 +/- 18 mm Hg in the 10 subjects who responded to 1 mg/kg body weight administered intravenously, whereas it fell 5 +/- 3 mm Hg in the eight nonresponders. In patients who had received no previous drug treatment, log baseline plasma renin activity and change in mean blood pressure after SQ 20881 correlated significantly (r = 0.651, P less than 0.05). After acute therapy with SQ 20881, the patients who had a satisfactory response to the drug were treated with propranolol and a relatively normal sodium intake (88 meq/day). Nonresponders were treated with diuretics and sodium restriction (10 meq/day), and intermediate responders were given combination therapy. Mean blood pressure responded favorably within 24 h to the chosen regimen for each group from 152 +/- 47 to 102 +/- 31 mm Hg. SQ 20881 allows prompt evaluation of the role of renin in hypertensive emergencies and permits early choice of appropriate therapy based on the prevailing mechanism.     

Energy requirements are not greater in elderly patients suffering from pressure ulcers

OBJECTIVES: To estimate energy requirements in diseased elderly patients with pressure ulcers (PUs). DESIGN: Open, case-control study. SETTING: University Hospital of Angers (France). PARTICIPANTS: Twenty-nine patients with PUs (Norton index risk=14.3+/-3.3) and 27 controls hospitalized for various diseases (Norton=13.9+/-3.3). MEASUREMENTS: Energy requirements were estimated using measured resting metabolic rate (RMR) and multiplied by 1.26 and 1.5 to range between minimal World Health Organization (WHO) requirements and those of adults undergoing light physical activity. Energy intakes were estimated using 3-day food weight records. Measured RMR was compared with the prediction equations of Harris-Benedict, WHO, and Schofield. RESULTS: Measured RMR did not differ between the two groups (P=.48), and was not related to grade or size of the PUs. The WHO equation (82 kcal/d, P=.006) and the Schofield formula (57 kcal/d, P=.05) slightly underestimated calculated RMR, but the Harris-Benedict equation (40 kcal/d, P=.13) accurately estimated it. Energy requirements therefore ranged between 1,536+/-340 kcal/d and 1,828+/-405 kcal/d, (25-30 kcal/kg body weight per day). Energy intake was lower than energy requirements by 176 to 479 kcal/d. CONCLUSION: Diseased elderly patients with PUs do not have greater energy expenditure, with their requirements suggested to range between 25 and 30 kcal/kg body weight per day. Malnutrition within this population is most likely the result of low energy intake.