Age-based Dosing Research Articles

An approach to using pharmacokinetics and electroencephalography for propofol anesthesia for surgery in infants

Safe and effective techniques for propofol total intravenous anesthesia (TIVA) in infants are not well imbedded into clinical practice, resulting in practitioner unfamiliarity and potential for over- and under-dosing. In this education article, we describe our approach to TIVA dosing in infants and toddlers (birth to 36months) which combines the use of pharmacokinetic models with EEG multi-parameter analysis. Pharmacokinetic models describe propofol and remifentanil effect site concentrations (Ce) over time in different age groups for a given dosing regimen. These models display substantial biological variability between individuals within age groups, impeding their application to clinical practice. Nevertheless, they reveal that younger infants require a higher propofol loading dose, a lower propofol maintenance dose, and a higher remifentanil dose compared with older infants. Proprietary EEG indices (eg, Bispectral Index) can serve as a biomarker of propofol Ce in adults and children to guide dosing to the individual patient; however, they are not recommended for infants as their validity remains uncertain this population. In our experience, EEG waveforms and processed parameters can reflect propofol Ce in infants, reflected by spectral edge frequency (SEF), density spectral array (DSA), and waveform patterns. In our practice, we use a "lookup table" of age-based dosing regimens or target-controlled infusion (TCI) based on the pharmacokinetic models to deliver a target propofol Ce and co-administer remifentanil and/or regional technique for analgesia. We analyze Electroencephalogram (EEG) waveforms, SEF, and DSA to adjust the propofol dose or TCI target concentration to the individual infant. EEG analysis mitigates against biological variability inherent in the pharmacokinetic models and has improved our experience with TIVA for infants.

Doses of primaquine administered to children with Plasmodium vivax according to an age-based dose regimen

ABSTRACT Primaquine is still the first-line drug to eliminate hypnozoites of Plasmodium vivax. The therapeutic efficacy is related to the total dose administered. In several endemic areas, the drug is administered for children in an age-based regimen, which can lead to inadequate exposure, increasing the rates of recurrence of the infection. The present study aims to describe the mg/kg total dose of primaquine administered to children for treatment for vivax malaria when an age-based regimen is used and to measure the plasma concentrations of primaquine and carboxyprimaquine. A total of 85 children were included in the study. The total dose of primaquine administered based on mg/kg had a median value of 3.22 mg/kg. The percentage of patients with a total dose below the required dose of 3.5 mg/kg was 55.75%. The median primaquine maximum concentration was 94 ng/ml. For carboxy-primaquine, the median maximum concentration was 375 ng/ml. The results suggest that age-based dosing regimens likely lead to substantial under-dosing of primaquine, which is evident in the youngest children and is reflected in decreased levels of primaquine and carboxy-primaquine in plasma samples 13.

Evaluation of Efficacy and Safety of Age-Based Intrathecal Dosing of 0.5% Hyperbaric Bupivacaine in the Paediatric Age Group

Introduction: Spinal anaesthesia in the paediatric population is a safe and reliable method of anaesthesia for infraumbilical surgical procedures. As there is greater variation in intrathecal dosing using a conventional weight-based schedule, a prospective cohort study was designed to administer an age-based intrathecal dosing schedule using 0.5% hyperbaric bupivacaine for infraumbilical surgeries in paediatric patients. Aim: To find the efficacy of age-based intrathecal dosing in terms of level of sensory blockade, success rate and adequacy of blockade for infraumbilical surgery in the paediatric age group. Materials and Methods: One hundred and thirty paediatric patients, aged between 2-12 years, posted for elective infraumbilical surgeries were given spinal anaesthesia at a dose of Age/5 (Partha formula) using 0.5% hyperbaric bupivacaine. Sedation during the procedure was provided using a combination of effective doses of pentazocine, midazolam, and atropine. The number of attempts, the success rate, the level of sensory blockade, the duration of anaesthesia and cardio-respiratory complications if any were noted. Results: The mean age of the children was 8±2.55 years. The mean dose of 0.5% hyperbaric bupivacaine used in this study was 8±2.55 milligrams. The desired sensory level of T10 was achieved in the first attempt in all the cases (100%) within 10 minutes of the subarachnoid block. The mean duration of anaesthesia was 73.42±18.6 minutes. In all the patients, the surgical procedures were completed within this anaesthetic time and none of the cases had any conversion to general anaesthesia. No complications were found in any of the patients. Conclusion: Administration of intrathecal dosing of 0.5% hyperbaric bupivacaine using Partha formula (Age/5) is a safe and successful method to provide subarachnoid blockade for infraumbilical surgeries in the Indian paediatric population.

Doses of chloroquine in the treatment of malaria by Plasmodium vivax in patients between 2 and 14\xa0years of age from the Brazilian Amazon basin

BackgroundA total dose of chloroquine of 25 mg/kg is recommended by the World Health Organization (WHO) to treat malaria by Plasmodium vivax. In several endemic areas, including the Brazilian Amazon basin, anti-malarial drugs are dispensed in small plastic bags at a dosing regimen based on age. This practice can lead to suboptimal dosing of the drug, which can impact treatment outcomes. The aim of the present study was to estimate the extent of sub-dosing of chloroquine in children and adolescents with vivax malaria using an age-based dose regimen, in addition to investigating the influence of age on the plasma concentrations of chloroquine and desethylchloroquine.MethodsA study of cases was conducted with male patients with a confirmed infection by P. vivax, ages 2 to 14 years, using a combined regimen of chloroquine and primaquine. Height, weight and body surface area were determined at admission on the study. The total dose of chloroquine administered was estimated based on the weight and on the body surface area of the study patients. Chloroquine and desethylchloroquine were measured on Day 7 in each patient included in the study by a high-performance liquid chromatographic method with fluorescence detection.ResultsA total of 81 patients were enrolled and completed the study. The median age was 9 years (2–14 years). All patients presented negative blood smears at 42 days follow-up. The total dose of chloroquine ranged from 13.1 to 38.1 mg/kg. The percentage of patients with a total dose of the drug below 25 mg/kg ranged from 29.4 to 63.6%. The total dose of chloroquine administered based on BSA ranged from 387 to 1079 mg/m2, increasing with age. Plasma chloroquine concentrations ranged from 107 to 420 ng/ml, increasing with age. For desethylchloroquine, the plasma concentrations ranged from 167 to 390 ng/ml, with similar values among age-groups.ConclusionThe data demonstrated the widespread exposure of children and adolescents to suboptimal doses of chloroquine in the endemic area investigated.

Electroconvulsive practice in Singapore: a cross-sectional national survey

The use of electroconvulsive therapy (ECT) in Singapore dates back to 1947. However, there is little local information on the clinical practice of ECT and its standards. We aimed to conduct a comprehensive national survey of ECT practice in Singapore. A cross-sectional structured questionnaire assessing the types of ECT (e.g. electrode placement, stimulus parameters), indications, anaesthetic technique, dosing methods, monitoring of outcomes and credentialing was sent in 2015 to all ECT centres in Singapore via email to collect qualitative and quantitative data regarding ECT. Data was obtained from all ECT centres (n = 6), which represented that ECT was available in 23.1% of all hospitals and 50.0% of all psychiatric specialist centres. The rate of ECT was 5.89 treatments per 10,000 residents per year, and each patient received an average of 5.4 ECT per course. Only 7.0% of ECT was administered for continuation/maintenance ECT. The most common indication for ECT was depression in 5 (83.3%) out of six centres, with schizophrenia being the second most common. In 5 (83.3%) out of six centres, ECT was brief (0.5 ms) bitemporal ECT with age-based dosing, and 93.0% of the sessions were conducted in an inpatient setting. All ECT was conducted under general anaesthesia, with propofol (66.7%) being the most common type of anaesthetic used. The practice of ECT in Singapore was highly uniform. The rates and indications for ECT were consistent with those of other developed countries, with greater use of ECT for schizophrenia. Future advances for ECT in Singapore include the use of individualised dosing based on empirical seizure threshold titration, expanded electrode placements and increased utilisation of continuation/maintenance ECT.

Reduced Exposure to Piperaquine, Compared to Adults, in Young Children Receiving Dihydroartemisinin-Piperaquine as Malaria Chemoprevention.

Dihydroartemisinin (DHA)-piperaquine is being evaluated as intermittent preventive therapy for malaria, but dosing has not been optimized for children. We assessed exposure to DHA and piperaquine in Ugandan children at two ages during infancy. Intensive sampling was performed in 32 children at 32weeks of age, 31 children at 104weeks, and 30 female adult controls. Compared with adults, DHA area under the concentration-time curve (AUC0-8 hr ) was 52% higher at 32weeks and comparable at 104weeks. Compared with adults, piperaquine AUC0-21 d was 35% lower at 32weeks and 53% lower at 104weeks. Terminal piperaquine concentrations on days 7, 14, and 21 were lower in children compared with adults and lower at 104 compared with 32weeks. Piperaquine exposure was lower in young children compared with adults, and lower at 104 compared with 32weeks of age, suggesting a need for age-based DHA-piperaquine dose optimization for chemoprevention.

Dosing pole recommendations for lymphatic filariasis elimination: A height-weight quantile regression modeling approach

BackgroundThe World Health Organization (WHO) currently recommends height or age-based dosing as alternatives to weight-based dosing for mass drug administration lymphatic filariasis (LF) elimination programs. The goals of our study were to compare these alternative dosing strategies to weight-based dosing and to develop and evaluate new height-based dosing pole scenarios.Methodology/Principal findingsAge, height and weight data were collected from >26,000 individuals in five countries during a cluster randomized LF clinical trial. Weight-based dosing for diethylcarbamazine (DEC; 6 mg/kg) and ivermectin (IVM; 200 ug/kg) with tablet numbers derived from a table of weight intervals was treated as the “gold standard” for this study. Following WHO recommended age-based dosing of DEC and height-based dosing of IVM would have resulted in 32% and 27% of individuals receiving treatment doses below those recommended by weight-based dosing for DEC and IVM, respectively. Underdosing would have been especially common in adult males, who tend to have the highest LF prevalence in many endemic areas. We used a 3-step modeling approach to develop and evaluate new dosing pole cutoffs. First, we analyzed the clinical trial data using quantile regression to predict weight from height. We then used weight predictions to develop new dosing pole cutoff values. Finally, we compared different dosing pole cutoffs and age and height-based WHO dosing recommendations to weight-based dosing. We considered hundreds of scenarios including country- and sex-specific dosing poles. A simple dosing pole with a 6-tablet maximum for both DEC and IVM reduced the underdosing rate by 30% and 21%, respectively, and was nearly as effective as more complex pole combinations for reducing underdosing.Conclusions/SignificanceUsing a novel modeling approach, we developed a simple dosing pole that would markedly reduce underdosing for DEC and IVM in MDA programs compared to current WHO recommended height or age-based dosing.

Electroconvulsive Therapy Practice in the Kingdom of Denmark: A Nationwide Register- and Questionnaire-Based Study.

The aim of this study was to survey and describe the contemporary practice of electroconvulsive therapy (ECT) in the Kingdom of Denmark (Denmark, Greenland, and the Faroe Islands). Data regarding number of ECTs and number of patients with different diagnoses treated with ECT were retrieved from the Danish National Patient Registry. In addition, a 45-item questionnaire was sent to all psychiatric departments practicing ECT in Denmark (n = 26), Greenland (n = 1), and the Faroe Islands (n = 1). According to the Danish National Patient Registry, a total of 21,730 ECTs were administered to 1891 unique patients in 2017. All departments responded to the survey. The psychiatric departments' attitude toward ECT was generally favorable and in accord with official guidelines. Maintenance ECT was used in all departments but one. Bilateral electrode placement was preferred. All departments used a preselected age-based dosing strategy. Involuntary ECT was performed in 96% of the psychiatric departments, but infrequently (3% of all treatments). All departments used a Thymatron (brief pulse) device, and in 71% of the departments, ECT was given in a specialized ECT unit and preanesthetic evaluation was carried out in all departments. The departments reported several different practices regarding documentation and monitoring of treatment effect, patient consent, screening for side effects (including cognitive side effects), and guidelines for the discharge of ECT patients. Electroconvulsive therapy is frequently used in Denmark, Greenland, and the Faroe Islands in a relatively uniform way in adherence with clinical guidelines.

Pertinence of Titration and Age-Based Dosing Methods for Electroconvulsive Therapy: An International Retrospective Multicenter Study.

Although the dosage of electroconvulsive therapy (ECT) stimulus has a major impact on the efficacy and safety of this treatment, the method used to determine an optimal dosage remains a matter of debate. We investigated factors influencing the seizure threshold (ST) in a large-sample study and compared age-based and titration dosing methods in terms of charge. A retrospective study examined data from 503 patients across France and Canada. The patients underwent right unilateral (RUL) or bitemporal (BT) ECT during a titration session before undergoing ECT. Seizure threshold and charge differences between age-based and titration-predicted methods were derived for each RUL and BT patient and compared according to sex, age, and anesthetic agents. Based on our results, ST is a function of electrode placement, sex, age, and anesthetic agents. Titration and age-based methods led to completely different patterns of charges for the same electrode placement, especially in elderly and in women in the RUL group. Regression models showed that differences between the age-based and titration methods varied with respect to age, sex, and anesthetic agent. Specifically, significant effects of sex and age were observed for RUL ECT and of sex and anesthetics for BT ECT. This study revealed that several factors significantly influence the prediction of ECT dose, depending on individuals and treatment modalities. Caution should be exercised when using nonindividualized methods to calculate ST.

Analgesic efficacy and safety of non-prescription doses of naproxen sodium in the management of moderate osteoarthritis of the knee or hip

Objectives: Current osteoarthritis therapies aim to alleviate pain and maintain joint function. Non-prescription oral non-steroidal anti-inflammatory drugs are frequently used alone for pain relief in osteoarthritis. This post-hoc pooled analysis evaluated the analgesic efficacy and safety of two non-prescription doses of naproxen sodium for short-term use in patients with osteoarthritis of the knee or hip. A separate sub-group analysis of older patients who were administered a lower dose of naproxen sodium was performed.Methods: In four multi-center, multi-dose, randomized, parallel, double-blind, placebo-controlled studies, oral naproxen sodium (age-based dosing regimen: <65 years, 660 mg/day; ≥65 years, 440 mg/day) or placebo was administered over 7 days. Data at baseline and after 7 days in 818 patients who received naproxen sodium or placebo (n = 409 in each group) was pooled and analyzed. Five-point rating scales were used to assess knee or hip joint pain, stiffness after rest, day and night pain, and patient and investigator assessment of treatment, while function was evaluated using a timed 50-foot walk test.Results: Compared with placebo, there were significant improvements in pain and physical function with naproxen sodium (p < .05), and treatment was rated “good” to “excellent” significantly more often (p < .001) by investigators and patients. Efficacy results were similar among younger and older patients. There were no significant differences in adverse events between groups, regardless of age.Conclusions: For the acute management of underlying pain in patients with moderate osteoarthritis of the hip or knee, non-prescription naproxen sodium is effective and well tolerated in patients of all ages.

The NICE-GUT trial protocol: a randomised, placebo controlled trial of oral nitazoxanide for the empiric treatment of acute gastroenteritis among Australian Aboriginal children

IntroductionDiarrhoeal disease is the second leading cause of death in children under 5 years globally, killing 525 000 annually. Australian Aboriginal and Torres Strait Islander (hereafter Aboriginal) children suffer a...

Single low-dose primaquine for blocking transmission of Plasmodium falciparum malaria \u2013 a proposed model-derived age-based regimen for sub-Saharan Africa

BackgroundIn 2012, the World Health Organization recommended blocking the transmission of Plasmodium falciparum with single low-dose primaquine (SLDPQ, target dose 0.25 mg base/kg body weight), without testing for glucose-6-phosphate dehydrogenase deficiency (G6PDd), when treating patients with uncomplicated falciparum malaria. We sought to develop an age-based SLDPQ regimen that would be suitable for sub-Saharan Africa.MethodsUsing data on the anti-infectivity efficacy and tolerability of primaquine (PQ), the epidemiology of anaemia, and the risks of PQ-induced acute haemolytic anaemia (AHA) and clinically significant anaemia (CSA), we prospectively defined therapeutic-dose ranges of 0.15–0.4 mg PQ base/kg for children aged 1–5 years and 0.15–0.5 mg PQ base/kg for individuals aged ≥6 years (therapeutic indices 2.7 and 3.3, respectively). We chose 1.25 mg PQ base for infants aged 6–11 months because they have the highest rate of baseline anaemia and the highest risks of AHA and CSA. We modelled an anthropometric database of 661,979 African individuals aged ≥6 months (549,127 healthy individuals, 28,466 malaria patients and 84,386 individuals with other infections/illnesses) by the Box–Cox transformation power exponential and tested PQ doses of 1–15 mg base, selecting dosing groups based on calculated mg/kg PQ doses.ResultsFrom the Box–Cox transformation power exponential model, five age categories were selected: (i) 6–11 months (n = 39,886, 6.03%), (ii) 1–5 years (n = 261,036, 45.46%), (iii) 6–9 years (n = 20,770, 3.14%), (iv) 10–14 years (n = 12,155, 1.84%) and (v) ≥15 years (n = 328,132, 49.57%) to receive 1.25, 2.5, 5, 7.5 and 15 mg PQ base for corresponding median (1st and 99th centiles) mg/kg PQ base of: (i) 0.16 (0.12–0.25), (ii) 0.21 (0.13–0.37), (iii) 0.25 (0.16–0.38), (iv) 0.26 (0.15–0.38) and (v) 0.27 (0.17–0.40). The proportions of individuals predicted to receive optimal therapeutic PQ doses were: 73.2 (29,180/39,886), 93.7 (244,537/261,036), 99.6 (20,690/20,770), 99.4 (12,086/12,155) and 99.8% (327,620/328,132), respectively.ConclusionsWe plan to test the safety of this age-based dosing regimen in a large randomised placebo-controlled trial (ISRCTN11594437) of uncomplicated falciparum malaria in G6PDd African children aged 0.5 − 11 years. If the regimen is safe and demonstrates adequate pharmacokinetics, it should be used to support malaria elimination.

Switching From Age-Based Stimulus Dosing to Dose Titration Protocols in Electroconvulsive Therapy: Empirical Evidence for Better Patient Outcomes With Lower Peak and Cumulative Energy Doses.

The aim of this study was to test the proposition that adoption of a dose titration protocol may be associated with better patient outcomes, at lower treatment dose, and with comparable cumulative dose to that in patients treated using an age-based stimulus dosing protocol. This was an analysis of data assembled from archived records and based on cohorts of patients treated respectively on an age-based stimulus dosing protocol and on a dose titration protocol in the National Health Service in England. We demonstrated a significantly better response in the patient cohort treated with dose titration than with age-based stimulus dosing. Peak doses were less and the total cumulative dose was less in the dose titration group than in the age-based stimulus dosing group. Our findings are consistent with superior outcomes in patients treated using a dose titration protocol when compared with age-based stimulus dosing in a similar cohort of patients.

Modelling the therapeutic dose range of single low dose primaquine to reduce malaria transmission through age-based dosing

BackgroundLow-dose primaquine is a key candidate for use in malaria transmission reduction and elimination campaigns such as mass drug administration (MDA). Uncertainty about the therapeutic dose range (TDR) required for general and paediatric populations challenge the implementation of the World Health Organisation’s recommendation to add 0.25 mg/kg to current standard antimalarial treatment in such settings. Modelling work shows that for low-dose primaquine to have an impact, high efficacy and extensive population coverage are needed. In practice, age-based dose regimens, often used in MDA, could lead to safety concerns and a different effectiveness profile. We aimed to define TDRs for primaquine and to assess dosing accuracy of age-based dose regimens.MethodsOptimised regional age-based dosing regimens for low-dose primaquine were developed in steps. First, we identified potential TDR options based on suggested published efficacy and safety thresholds (i.e. 0.1–0.4, 0.125–0.375, 0.15–0.35 mg/kg). We then used our previously defined weight-for-age growth references and age-based dose optimisation tool to model predicted regimen accuracies for Africa, Asia and Latin America based on low-dose primaquine tablets (3.75 mg and 7.5 mg) currently under development by Sanofi while employing the identified dose range options and pre-specified regimen characteristics.ResultsDose regimens employing TDRs of 0.1–0.4 and 0.125–0.375 mg/kg had the highest average predicted dose accuracies in all regions with the widest dose range of 0.1–0.4 mg/kg resulting in ≥99% dose accuracy in all three regions. The narrower 0.15–0.35 mg/kg range was on average predicted to correctly dose 91.4% of the population in Africa, 93.2% in Asia and 92.6% in Latin America. This range would prescribe ≥20% of 3-year-olds doses below 0.15 mg/kg and ≥20% of 11-year-olds doses above 0.35 mg/kg. Widening the TDR from 0.15–0.35 to 0.1–0.4 mg/kg increased the dose accuracy by ≥20% in Africa, ≥15% in Asia and ≥10% in Latin America.ConclusionOptimised age-based dose regimens derived from wider TDRs are predicted to attain the dose accuracies required for effective MDA in malaria transmission reduction and elimination settings. We highlight the need for a clearly defined TDR and for safety and efficacy trials to focus on doses compatible with age-based dosing often employed in such settings.

Population Pharmacokinetics of Nusinersen in the Cerebral Spinal Fluid and Plasma of Pediatric Patients With Spinal Muscular Atrophy Following Intrathecal Administrations.

Nusinersen is an antisense oligonucleotide intended for the treatment of spinal muscular atrophy. The pharmacokinetics of nusinersen, following intrathecal administrations, in the cerebrospinal fluid (CSF) and plasma of 72 pediatric patients (3 months to 17 years) with spinal muscular atrophy across 5 clinical trials was analyzed via population-based modeling. With sparse data in the CSF and profile data in the plasma, a linear 4-compartment model simultaneously described the time-concentration profiles in both matrices. The typical population parameters were: Qp = 0.572 L/h, QCSF = 0.069 L/h, CLp = 2.50 L/h, CLCSF = 0.133 L/hr, VCSF = 0.441 L, Vp = 32.0 L, Vsystemic_tissue = 429 L, and VCNS_tissue = 258 L. A full covariate modeling approach identified baseline body weight to be a statistically and clinically relevant covariate on VCSF , Vp , and CLp . The model predicted that the CSF volume of distribution increased steadily with age from 0 to 2 years but became relatively steady for children >2 years. Simulations from the final model showed that age-based dosing in children under 2 years ensured a more comparable exposure (peak concentration and area under the concentration-time curve) across subjects in the population relative to a fixed dosing scheme. However, because no dose-limiting toxicity has been reported in any of the trials, a fixed-dose scheme (12 mg across all age groups) was recommended. The median terminal half-life of nusinersen in the CSF was determined from the model to be 163 days, which supported infrequent dosing, once every 4 to 6 months in pediatric patients with spinal muscular atrophy.

Loratadine in combination with desloratadine for the treatment of chronic spontaneous urticaria in children: a clinical observation

Objective To evaluate clinical efficacy and safety of loratadine combined with desloratadine in the treatment of chronic spontaneous urticaria (CSU) in children. Methods A total of 177 children with CSU were enrolled into this study, and randomly and equally divided into 3 groups: combination group treated with an age-based dose of desloratadine tablet every morning and a weight-based dose of loratadine tablet before sleep every night for consecutive 28 days, loratadine group treated with a half tablet of placebo (starch tablet) every morning and oral loratadine tablet before sleep every night for consecutive 28 days, and desloratadine group treated with a half tablet of placebo (starch tablet) every morning and oral desloratadine tablet before sleep every night for 28 consecutive days. Possible adverse reactions were observed and recorded after the start of treatment, and therapeutic effects were evaluated at the end of treatment. Results A total of 166 patients completed the trial, including 55 in the combination group, 56 in the loratadine group and 55 in the desloratadine group. After 28-day treatment, the total response rate was significantly higher in the combination group (90.9%, 50/55) than in the loratadine group (71.4% [40/56], χ2 = 6.865, P 0.05). Conclusion Combination of loratadine and desloratadine was superior to loratadine or desloratadine alone in the treatment of childhood CSU, and there was no significant difference in the incidence of adverse reactions among the 3 treatment groups. Key words: Urticaria; Loratadine; Randomized controlled trials; Child; Desloratadine

Age-based Local Anesthetic Dosing in Pediatric Spinal Anesthesia: Evaluation of a New Formula - A Pilot Study in Indian Patients.

Background:Spinal anesthesia is a safe alternative to general anesthesia and often the anesthetic technique of choice in many lower abdominal and lower limb surgeries in children. As the vertebral column and spinal cord grows variedly with age and not weight, we planned to administer an age-based dosing schedule of hyperbaric bupivacaine in the intra-thecal space in select infra umbilical surgeries in children. The aim was to find out the efficacy and complications associated with this dosage.Methodology:Twenty-five pediatric patients between 2 and 12 years, posted for elective infra umbilical surgeries were given a sedation as a combination of effective doses of pentazocine, midazolam, and atropine. In all those patients, spinal anesthesia was administered at a dose of age/5 of hyperbaric bupivacaine. The number of attempts, the onset of blockade, the mean sensory level, and the duration of anesthesia were noted. Any other complications were also noted.Results:The mean and standard deviation of age is 7.68 ± 2.49 years. Intra-thecal anesthesia was administered successfully in the first attempt in 88% of cases whereas the remaining needed the second attempt. Three patients needed intravenous ketamine of 0.25 mg/kg additionally for preoperative sedation. The sensory level was between T6 and T10 with a mean of T8.5. There were no intra-operative complications. In all patients, surgery was finished within the duration of anesthesia of approximately 60 min. There was no conversion to general anesthesia in any case, but a three patients required dose of 0.25 mg/kg of intravenous ketamine as a calming dose.Conclusion:Administration of age-based local anesthetic dosing of hyperbaric bupivacaine in the intra-thecal space by utilizing a new formula of age/5 (Partha formula) is successful in a pilot study in Indian children for infra-umbilical surgeries. There were no observed complications.

Erratum to: An optimised age-based dosing regimen for single low-dose primaquine for blocking malaria transmission in Cambodia.

In 2012, the World Health Organization recommended the addition of single low-dose primaquine (SLDPQ, 0.25 mg base/kg body weight) to artemisinin combination therapies to block the transmission of Plasmodium falciparum without testing for glucose-6-phosphate dehydrogenase deficiency. The targeted group was non-pregnant patients aged ≥ 1 year (later changed to ≥ 6 months) with acute uncomplicated falciparum malaria, primarily in countries with artemisinin-resistant P. falciparum (ARPf). No dosing regimen was suggested, leaving malaria control programmes and clinicians in limbo. Therefore, we designed a user-friendly, age-based SLDPQ regimen for Cambodia, the country most affected by ARPf. By reviewing primaquine’s pharmacology, we defined a therapeutic dose range of 0.15–0.38 mg base/kg (9–22.5 mg in a 60-kg adult) for a therapeutic index of 2.5. Primaquine doses (1–20 mg) were tested using a modelled, anthropometric database of 28,138 Cambodian individuals (22,772 healthy, 4119 with malaria and 1247 with other infections); age distributions were: 0.5–4 years (20.0 %, n = 5640), 5–12 years (9.1 %, n = 2559), 13–17 years (9.1 %, n = 2550), and ≥ 18 years (61.8 %, n = 17,389). Optimal age-dosing groups were selected according to calculated mg base/kg doses and proportions of individuals receiving a therapeutic dose. Four age-dosing bands were defined: (1) 0.5–4 years, (2) 5–9 years, (3) 10–14 years, and (4) ≥15 years to receive 2.5, 5, 7.5, and 15 mg of primaquine base, resulting in therapeutic doses in 97.4 % (5494/5640), 90.5 % (1511/1669), 97.7 % (1473/1508), and 95.7 % (18,489/19,321) of individuals, respectively. Corresponding median (1st–99th centiles) mg base/kg doses of primaquine were (1) 0.23 (0.15–0.38), (2) 0.29 (0.18–0.45), (3) 0.27 (0.15–0.39), and (4) 0.29 (0.20–0.42). This age-based SLDPQ regimen could contribute substantially to malaria elimination and requires urgent evaluation in Cambodia and other countries with similar anthropometric characteristics. It guides primaquine manufacturers on suitable tablet strengths and doses for paediatric-friendly formulations. Development of similar age-based dosing recommendations for Africa is needed.

An optimised age-based dosing regimen for single low-dose primaquine for blocking malaria transmission in Cambodia.

BackgroundIn 2012, the World Health Organization recommended the addition of single low-dose primaquine (SLDPQ, 0.25 mg base/kg body weight) to artemisinin combination therapies to block the transmission of Plasmodium falciparum without testing for glucose-6-phosphate dehydrogenase deficiency. The targeted group was non-pregnant patients aged ≥ 1 year (later changed to ≥ 6 months) with acute uncomplicated falciparum malaria, primarily in countries with artemisinin-resistant P. falciparum (ARPf). No dosing regimen was suggested, leaving malaria control programmes and clinicians in limbo. Therefore, we designed a user-friendly, age-based SLDPQ regimen for Cambodia, the country most affected by ARPf.MethodsBy reviewing primaquine’s pharmacology, we defined a therapeutic dose range of 0.15–0.38 mg base/kg (9–22.5 mg in a 60-kg adult) for a therapeutic index of 2.5. Primaquine doses (1–20 mg) were tested using a modelled, anthropometric database of 28,138 Cambodian individuals (22,772 healthy, 4119 with malaria and 1247 with other infections); age distributions were: 0.5–4 years (20.0 %, n = 5640), 5–12 years (9.1 %, n = 2559), 13–17 years (9.1 %, n = 2550), and ≥ 18 years (61.8 %, n = 17,389). Optimal age-dosing groups were selected according to calculated mg base/kg doses and proportions of individuals receiving a therapeutic dose.ResultsFour age-dosing bands were defined: (1) 0.5–4 years, (2) 5–9 years, (3) 10–14 years, and (4) ≥15 years to receive 2.5, 5, 7.5, and 15 mg of primaquine base, resulting in therapeutic doses in 97.4 % (5494/5640), 90.5 % (1511/1669), 97.7 % (1473/1508), and 95.7 % (18,489/19,321) of individuals, respectively. Corresponding median (1st–99th centiles) mg base/kg doses of primaquine were (1) 0.23 (0.15–0.38), (2) 0.29 (0.18–0.45), (3) 0.27 (0.15–0.39), and (4) 0.29 (0.20–0.42).ConclusionsThis age-based SLDPQ regimen could contribute substantially to malaria elimination and requires urgent evaluation in Cambodia and other countries with similar anthropometric characteristics. It guides primaquine manufacturers on suitable tablet strengths and doses for paediatric-friendly formulations. Development of similar age-based dosing recommendations for Africa is needed.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-016-0701-8) contains supplementary material, which is available to authorized users.

Weight-based dosing in medication use: what should we know?

BackgroundWeight-based dosing strategy is still challenging due to poor awareness and adherence. It is necessary to let clinicians know of the latest developments in this respect and the correct circumstances in which weight-based dosing is of clinical relevance.MethodsA literature search was conducted using PubMed.ResultsClinical indications, physiological factors, and types of medication may determine the applicability of weight-based dosing. In some cases, the weight effect may be minimal or the proper dosage can only be determined when weight is combined with other factors. Medications within similar therapeutic or structural class (eg, anticoagulants, antitumor necrosis factor medications, P2Y12-receptor antagonists, and anti-epidermal growth factor receptor antibodies) may exhibit differences in requirements on weight-based dosing. In some cases, weight-based dosing is superior to currently recommended fixed-dose regimen in adult patients (eg, hydrocortisone, vancomycin, linezolid, and aprotinin). On the contrary, fixed dosing is noninferior to or even better than currently recommended weight-based regimen in adult patients in some cases (eg, cyclosporine microemulsion, recombinant activated Factor VII, and epoetin α). Ideal body-weight-based dosing may be superior to the currently recommended total body-weight-based regimen (eg, atracurium and rocuronium). For dosing in pediatrics, whether weight-based dosing is better than body surface-area-based dosing is dependent on the particular medication (eg, methotrexate, prednisone, prednisolone, zidovudine, didanosine, growth hormone, and 13-cis-retinoic acid). Age-based dosing strategy is better than weight-based dosing in some cases (eg, intravenous busulfan and dalteparin). Dosing guided by pharmacogenetic testing did not show pharmacoeconomic advantage over weight-adjusted dosing of 6-mercaptopurine. The common viewpoint (ie, pediatric patients should be dosed on the basis of body weight) is not always correct. Effective weight-based dosing interventions include standardization of weight estimation, documentation and dosing determination, dosing chart, dosing protocol, order set, pharmacist participation, technological information, and educational measures.ConclusionAlthough dosing methods are specified in prescribing information for each drug and there are no principal pros and cons to be elaborated, this review of weight-based dosing strategy will enrich the knowledge of medication administration from the perspectives of safety, efficacy, and pharmacoeconomics, and will also provide research opportunities in clinical practice. Clinicians should be familiar with dosage and administration of the medication to be prescribed as well as the latest developments.