Development and validation of a set of patient reported outcome measures to assess effectiveness of asthma prophylaxis.

BACKGROUND: In the local setting, asthma control is assessed by symptoms and signs elicited by clinicians because of the limited availability of spirometry. Hence, we intended to develop a patient reported outcome measure (PROM) with more holistic interpretation that could also serve as a tool to measure the asthma control in resource limited settings. Therefore, this study was carried out in Northern Sri Lanka to develop and validate the Asthma Control PROM (AC-PROM) Tamil to measure the effectiveness of asthma prophylaxis based on symptoms, exacerbation and limitation of activity which could also serve as an easy measure of asthma control to the provider. METHODS: The AC-PROM Tamil was developed in 3 steps: item generation, item reduction and psychometric evaluation. Items were generated through thematic analysis from focus group discussions among patients with asthma. Items were converted to an interviewer administered questionnaire in Tamil in the format of 5-point Likert scale. Item reduction was done by two rounds of online Delphi surveys among 10 experts and an exploratory factor analysis among 200 patients with asthma. The face and content validity were assessed by a panel of experts during Delphi survey and patients during the pre-test of the tool. Criterion validity of the tool was assessed against the forced expiratory volume in one second of 187 patients with asthma. The cut-off value to assess the asthma control was determined by receiver operating characteristic curve. Reliability was verified by Cronbach's alpha coefficient. RESULTS: From thematic analysis of focus group discussions 10 items were generated. One item was removed during Delphi survey. Exploratory factor analysis indicated removal of another item with 8 items categorised into two factors. Cronbach's alpha coefficient of factors 1 and 2 were 0.821 and 0.903 respectively, indicating good reliability. Observations made by experts and responses made by patients were incorporated to improve the clarity and relevance of the items. Criterion validity was demonstrated by significant correlation between the AC-PROM Tamil and forced expiratory volume in one second (r = 0.66, p = 0.001). The cut-off value of the AC-PROM Tamil to detect asthma control was 28.5 with 79% (95% CI 71.3-86.9) sensitivity and 71% (95% CI 61.9-79.6) specificity. The AC-PROM Tamil showed moderate accuracy (the area under the receiver operating characteristic curve = 0.796; 95% CI 0.73-0.86). Response rate of the AC-PROM Tamil was 100% and time taken to complete was 3-4 min. CONCLUSION: The AC-PROM Tamil is a simple, feasible and reasonably accurate tool to assesses the effectiveness of asthma prophylaxis, particularly in resource limited settings.

Rational dispensing of oral dosage forms of medicines to children at a teaching hospital in Sri Lanka.

BACKGROUND: Good dispensing practice is vital for rational use of medicines. There are many paediatric specific challenges when maintaining good dispensing practices to children. Lack of age appropriate dosage forms, lack of medicines in strengths suitable for children, lack of palatable medicines, lack of expertise in paediatric pharmacy are few challenges faced when maintaining good dispensing practices to children. These challenges contribute to poor dispensing practices. Hence there is an urgent need to investigate whether oral dosage forms of medicines are dispensed rationally to children. The objective of this study was to describe the rational dispensing practice of oral dosage forms of medicines to children in a Teaching Hospital in Sri Lanka. METHODS: A descriptive cross sectional study was conducted to assess the dispensing practice of 1800 oral dosage forms of medicines dispensed to children under the age of 12 years in two outdoor pharmacies over a period of 1 year using validated indicators. Required data were extracted from the prescriptions and by observation using a structured pre-tested observation sheet. Descriptive statistics and wherever relevant, chi square test were used in analysing the data. RESULTS: Information on 1800 oral dosage forms was obtained from 1889 medicines dispensed to 727 children. Liquids were 52% [95% CI: 50-55%] of these oral dosage forms. Of the solid dosage forms, about one quarter required manipulation prior to administration such as splitting and dissolving or crushing the adult dosage form. None of the medicine packs or bottles had the patient name on the label. CONCLUSION: Dispensing practice of oral dosage forms of medicines to children has room for improvement.

Developmental profile at initial presentation in children with infantile spasms.

AIM: To describe the baseline developmental profile and influence of clinical and demographic factors on the developmental skills of infants diagnosed with infantile spasms. METHOD: Ninety-five infants (55 males, 40 females) newly diagnosed with infantile spasms were recruited for a cross-sectional, longitudinal study. All infants underwent Bayley Scales of Infant and Toddler Development assessments in the cognitive, receptive communication, expressive communication, and fine and gross motor developmental domains; they also underwent visual, auditory, and social behaviour assessments. Infants were categorized as 'early' (<6mo) or 'late' (≥6mo) presenters; if presented within 28 days, this was considered as 'early presentation', whereas a delay greater than 28 days was considered as a 'delay in presentation'. Antenatal, perinatal, and postnatal risk factors were identified. RESULTS: Over 90% of infants showed impairment in all domains, with the majority having severe delay; 99% showed cognitive impairment. Delayed presentation was significantly associated with receptive communication delay (odds ratio [OR]=5.35; 95% confidence interval [CI]=1.05-27.32). Onset at 6 months or less influenced auditory (OR=2.8; 95% CI=1.16-6.8) and visual (OR=3.03; 95% CI=1.22-7.57) behaviours. Neonatal infections impacted both receptive (OR=1.12; 95% CI=1.04-1.2) and expressive communication (OR=1.08; 95% CI=1.02-1.14) delay. Neonatal seizures significantly influenced visual, auditory, and social impairments. Expressive communication and gross motor development shared common perinatal risk factors. INTERPRETATION: Adverse developmental status at presentation, associated with delayed presentation and neonatal risk factors should alert clinicians to the surveillance of at-risk infants and seek out timely interventions. WHAT THIS PAPER ADDS: Ninety per cent of infants showed impaired cognitive, communication, and motor skills at presentation. Visual, auditory, and social behaviour impairments were significantly associated with perinatal risks. Visual, auditory, and social behaviour impairments were significantly associated with neonatal seizures.

PERFIL DE DESARROLLO DURANTE LA PRESENTACIÓN INICIAL DE LOS ESPASMOS INFANTILES EN NIÑOS: OBJETIVO: Describir el perfil de desarrollo basal y la influencia de factores clínicos y demográficos sobre las habilidades de desarrollo en niños diagnosticados con espasmos infantiles. METODO: Se reclutaron 95 niños recientemente diagnosticados con espasmos infantiles en una corte transversal, de un estudio longitudinal. Se realizaron Escalas de Bayley (Bayley Scales of Infant and Toddler Development) para el desarrollo de lactantes y preescolares a todos los niños, evaluando cognición, comunicación receptiva, comunicación expresiva, y los dominios del desarrollo motor, grueso y fino; también se sometieron a evaluaciones visuales, auditivas y de comportamiento social. Los niños fueron clasificados como presentación Temprana'(< 6 meses) o Tardía (≥ 6 meses); si los espasmos se presentaron dentro de los primeros 28 días, se consideró como presentación temprana, mientras que un retraso mayor de 28 días fue considerado como un retraso en la presentación. Se identificaron los factores de riesgo prenatales, perinatales y postnatales. RESULTADOS: Más del 90% de los lactantes mostró discapacidad en todos los dominios, la mayoría con retraso severo; 99% mostró deterioro cognitivo. El retraso en la presentación está significativamente asociado con retraso en la comunicación receptiva (razón de probabilidades [OR]= 5,35; 95% intervalo de confianza [CI]= 1,05-27,32). El inicio a los 6 meses o menos influenció en el comportamiento auditivo (OR = 2,8; 95% CI = 1,16-6,8) y visual (OR = 3,03; 95% CI = 1,22-7,57). Las infecciones neonatales impactaron tanto en el retraso de la comunicación receptiva (OR = 1,12; 95% CI=1,04-1,2) como en la expresiva (OR =1,08; 95% CI = 1,02-1,14). Las convulsiones neonatales influenciaron significativamente en discapacidades visuales, auditivas, y sociales. La comunicación expresiva y el desarrollo motor grueso tuvieron factores de riesgo perinatales comunes. INTERPRETACIÓN: Un estado de desarrollo adverso al momento de la presentación de espasmos infantiles, asociado con un retraso en la presentación y los factores de riesgo neonatal deben alertar a los clínicos a la vigilancia de niños en riesgo y buscar intervenciones oportunas.

PERFIL DE DESENVOLVIMENTO NA APRESENTAÇÃO INICIAL EM CRIANÇAS COM ESPASMOS INFANTIS: Xxx. OBJETIVO: Descrever o perfil de desenvolvimento inicial e a influência de fatores clínicos e demográficos nas habilidades do desenvolvimento de crianças diagnosticadas com espasmos infantis. MÉTODO: Noventa e cinco lactentes diagnosticados com espasmos infantis foram recrutados para um estudo transversal longitudinal. Todas as crianças foram submetidas a avaliações pela Escala Bayley de Desenvolvimento para bebes e crianças nos domínios Cognitivo, comunicação receptiva e expressiva, e desenvolvimento motor fino e grosso; eles também foram submetidos a avaliações: visual, auditivo e comportamento social. Os bebês foram categorizados como "precoces" (<6 m) ou "atrasados" (≥6 m); se apresentada no prazo de 28 dias, foi considerado como "precoces", enquanto que superior a 28 dias foi considerado como "atrasados". Fatores de risco pré-natais, perinatais e pós-natais foram identificados. RESULTADOS: Mais de 90% dos lactentes apresentaram comprometimento em todos os domínios, sendo a maioria com atraso grave; 99% apresentaram comprometimento cognitivo. A apresentação tardia foi significativamente associada ao atraso na comunicação receptiva (odds ratio [OR] = 5,35; intervalo de confiança de 95% [IC] = 1,05-27,32). O início aos 6 meses ou menos influenciou os comportamentos auditivos (OR = 2,8; 95% IC = 1,16-6,8) e visuais (OR = 3,03; IC95% = 1,22-7,57). As infecções neonatais impactaram no atraso na comunicação receptiva (OR = 1,12; 95% IC = 1,04-1,2) e expressiva (OR = 1,08; 95% IC = 1,02-1,14). As convulsões neonatais comprometeram significativamente as áreas: visual, auditiva e social. Comunicação expressiva e desenvolvimento motor grosso ambos demostraram fatores de risco perinatais comuns. INTERPRETAÇÃO: O estado de desenvolvimento adverso, associado à atraso na apresentação e fatores de risco neonatais devem alertar os clínicos para a vigilância de bebês de risco e buscar intervenções oportunas.

What information and the extent of information research participants need in informed consent forms: a multi-country survey.

BACKGROUND: The use of lengthy, detailed, and complex informed consent forms (ICFs) is of paramount concern in biomedical research as it may not truly promote the rights and interests of research participants. The extent of information in ICFs has been the subject of debates for decades; however, no clear guidance is given. Thus, the objective of this study was to determine the perspectives of research participants about the type and extent of information they need when they are invited to participate in biomedical research. METHODS: This multi-center, cross-sectional, descriptive survey was conducted at 54 study sites in seven Asia-Pacific countries. A modified Likert-scale questionnaire was used to determine the importance of each element in the ICF among research participants of a biomedical study, with an anchored rating scale from 1 (not important) to 5 (very important). RESULTS: Of the 2484 questionnaires distributed, 2113 (85.1%) were returned. The majority of respondents considered most elements required in the ICF to be 'moderately important' to 'very important' for their decision making (mean score, ranging from 3.58 to 4.47). Major foreseeable risk, direct benefit, and common adverse effects of the intervention were considered to be of most concerned elements in the ICF (mean score = 4.47, 4.47, and 4.45, respectively). CONCLUSIONS: Research participants would like to be informed of the ICF elements required by ethical guidelines and regulations; however, the importance of each element varied, e.g., risk and benefit associated with research participants were considered to be more important than the general nature or technical details of research. Using a participant-oriented approach by providing more details of the participant-interested elements while avoiding unnecessarily lengthy details of other less important elements would enhance the quality of the ICF.

Quality of measuring devices enclosed with paediatric oral liquid dosage forms of medicines registered in Sri Lanka.

INTRODUCTION: Oral liquid dosage forms remain popular in several middle income countries. The accuracy of liquid dosage form dosing depends on the accuracy and availability of measuring devices. Lack of quality oral liquid measuring devices will lead to medication errors. Hence there is an urgent need to describe the quality of manufacturer supplied measuring devices enclosed with paediatric oral liquid dosage forms currently registered in Sri Lanka. METHODOLOGY: Standards for measuring devices were developed after a detailed literature search. Multidisciplinary panel rated each standard for the necessity criteria on a 9 point Likert scale. Standards with overall panel median score of ≥ 7 with agreement were selected. A cross-sectional study was done. All the measuring devices, labels and instructions enclosed with the registered products were assessed against the standards developed. Three volumes of liquid antibacterials were measured using the enclosed measuring device. Accuracy of the volumes was measured. RESULTS: Of the total products (n = 202) only 126 were packed with a dosing device. Around quarter of the oral liquid dosage forms (n = 36) did not have a measuring device. More than half of the measuring devices aligned with all the standards developed. Out of 44 oral liquid paediatric antimicrobials measuring cups (n = 25, 56.8%, 95% CI: 41%-72%) were enclosed more and less error was seen with measuring cups. CONCLUSION: The quality of oral liquid measuring devices were not satisfactory. Quality could be further improved if the regulatory body request the manufactures/importers to adhere to the standards developed. Correct volumes were not measured using the measuring devices provided with the liquid antimicrobial agents.

Price and affordability of key essential medicines for children in Sri Lanka, a lower-middle-income country: comparison of two national cross-sectional surveys done 8 years apart.

OBJECTIVE: To describe the price and affordability of key essential medicines for children in the private sector in Sri Lanka in 2017/2018, and compare the findings with 2009 data. DESIGN: National cross-sectional descriptive survey using the WHO/Health Action International medicine price methodology. SETTING AND PARTICIPANTS: Data were collected from a representative sample of 54 private sector pharmacies selected from all 9 provinces in Sri Lanka using a multistage clustered approach. MAIN OUTCOMES: Median price ratio (MPR) and affordability of originator brand (OB) and lowest priced generics (LPG) of 25 key essential medicines for children. RESULTS: The median MPR was 2.69 for OBs and 1.45 for LPGs compared with 3.7 and 1.35 in 2009. MPR of OB of all but one (chlorphenamine syrup) were higher than that of the LPG. MPR-OB>5 was observed for ceftriaxone injection, amoxicillin capsule, mebendazole chewable tablet and metronidazole tablet. This was documented in 2009 as well except for amoxicillin capsule. Prices of LPGs of seven medicines (amoxicillin capsule, amoxicillin suspension, clotrimazole cream, mebendazole chewable tablet, metronidazole tablet) were estimated as excessive (MPR ≥2.5) compared with chlorphenamine syrup, clotrimazole topical cream, ibuprofen syrup and paracetamol syrup in 2009. Compared with 2009, MPRs of OBs of 8 medicines and LPGs of 12 medicines were higher in 2017/2018. Compared with 2009, no change in affordability was noted except for asthma, which has been assessed as affordable in 2017/2018. Standard drug therapy for mild lower respiratory tract infections and acute gastroenteritis remained affordable, and treating epilepsy with carbamazepine syrup remained unaffordable. CONCLUSION: Economic access to key essential medicines for children has not improved in Sri Lanka in the 8 years' time since the initial survey in 2009.

The status of paediatric medicines initiatives around the world--What has happened and what has not?

PURPOSE: This review was conducted to examine the current status of paediatric medicines initiatives across the globe. METHODS: The authors made a non-systematic descriptive review of current world situation. RESULTS: Two regions, the United States (US) and the European Union (EU), and the World Health Organization (WHO) have introduced strong paediatric initiatives to improve children's health through improving access to better paediatric medicines. The experience from the US initiative indicates that it is possible to stimulate development and study of paediatric medicines and provide important new information for improvement of paediatric therapy. The early results from the EU initiative are similarly encouraging. In Canada, Japan, Australia and other developed countries, specific paediatric medicines initiatives have been less extensive and weaker, with modest results. Disappointingly, current evidence suggests that results from clinical trials outside the US often do not benefit children in the country in which the trials were largely conducted. Pharmaceutical companies that have derived a financial benefit commensurate with the cost of doing the paediatric trials in one country do not seem to be making the results of these trials available to all countries if there is no financial incentive to the company. The WHO campaign 'make medicines child size' has produced substantive accomplishments in building improved foundations to improve mechanisms that will enhance children's access to critical medicines in resource-limited settings. However, practically all of this work has been performed using an amalgamation of short-term funding from a variety of sources as opposed to a sustained, programmatic commitment. CONCLUSIONS: Although much still needs to be done, it's clear that with concerted efforts and appropriate resources, change is possible but slow. Retaining and fostering public and political interest in paediatric medicines is challenging, but pivotal for success.

A cost effectiveness analysis of the preferred antidotes for acute paracetamol poisoning patients in Sri Lanka.

BACKGROUND: Acute paracetamol poisoning is a rapidly increasing problem in Sri Lanka. The antidotes are expensive and yet no health economic evaluation has been done on the therapy for acute paracetamol poisoning in the developing world. The aim of this study is to determine the cost effectiveness of using N-acetylcysteine over methionine in the management of acute paracetamol poisoning in Sri Lanka. METHODS: Economic analysis was applied using public healthcare system payer perspective. Costs were obtained from a series of patients admitted to the National Hospital of Sri Lanka with a history of acute paracetamol overdose. Evidence on effectiveness was obtained from a systematic review of the literature. Death due to hepatotoxicity was used as the primary outcome of interest. Analysis and development of decision tree models was done using Tree Age Pro 2008. RESULTS: An affordable treatment threshold of Sri Lankan rupees 1,537,120/death prevented was set from the expected years of productive life gained and the average contribution to GDP. A cost-minimisation analysis was appropriate for patients presenting within 10 hours and methionine was the least costly antidote. For patients presenting 10-24 hours after poisoning, n-acetylcysteine was more effective and the incremental cost effectiveness ratio of Sri Lankan rupees 316,182/life saved was well under the threshold. One-way and multi-way sensitivity analysis also supported methionine for patients treated within 10 hours and n-acetylcysteine for patients treated within 10-24 hours as preferred antidotes. CONCLUSIONS: Post ingestion time is an important determinant of preferred antidotal therapy for acute paracetamol poisoning patients in Sri Lanka. Using n-acetylcysteine in all patients is not cost effective. On economic grounds, methionine should become the preferred antidote for Sri Lankan patients treated within 10 hours of the acute ingestion and n-acetylcysteine should continue to be given to patients treated within 10-24 hours.

Administration of oral dosage forms of medicines to children in a resource limited setting.

BACKGROUND: There are many paediatric specific challenges such as lack of age-appropriate dosage forms, inability of young children to swallow tablets and capsules and poor acceptability, during administration of oral dosage forms of medications to children. Parents adopt various methods which they consider best to circumvent this problem. The objective of this study was to describe the administration practice by parents when giving oral dosage forms of medications to children. METHODS: A descriptive cross-sectional study was conducted to assess the administration practice of 1800 oral dosage forms of medications administered to children under the age of 12 years using validated indicators. A pre-tested interviewer-administered questionnaire given to parents or caregivers was used to collect the necessary data. The data were analysed using descriptive statistics. RESULTS: Data from 1800 oral dosage forms was obtained from 663 children. Of the 1287 solid dosage forms, almost one-third were manipulated by parents at the time of giving the medications to children. They were crushed and dissolved in water given to children. In about 17% of instances safety of water was questionable. In 92% of instances, measuring device was found to be inappropriate. CONCLUSION: Administration of oral dosage forms of medications to children is far from ideal and hinders successful use of medications in children.

Effect of intramuscular ACTH versus oral prednisolone on the developmental trajectories of children with West syndrome over 24 months: A randomised control study.

OBJECTIVE: To assess the developmental progression and compare the developmental attainments of children treated with two hormonal therapies for infantile spasms (IS) over two years (seizure and EEG outcomes of this RCT published previously). METHODS: Newly diagnosed infants with IS were randomised to receive adrenocorticotrophin (ACTH) or prednisolone for 14 days. All underwent Bayley III Infant and Toddler Assessments in cognitive (Cog), receptive (RC) and expressive (EC) communication, fine (FM) and gross (GM) motor developmental subsets at baseline (T0), one-year (T1) and two-years (T2). RESULTS: 95 infants randomised to prednisolone (n = 48) and ACTH (n = 47) groups were eligible for developmental assessments. Mean age at initial assessment was 8.75 months (SD = 6.37, range 1.46-34.4 months). 48 children presented for all three assessments. Mean composite scores of each developmental domain improved across the three time points; but the progression was significant only in relation to motor development (p = 0.04). When comparing the treatment outcomes at 2-years, mean composite scores of children treated with ACTH were significantly lower in motor domain (p = 0.023). As for developmental delay, the ACTH group (n = 32) showed significant delay in expressive communication (adjusted OR 5.46, 95% CI: 1.1, 28.57; p = 0.04) and fine motor (adjusted OR 9.4, 95% CI: 1.1, 83.3; p = 0.04) at T2 compared to the prednisolone (n = 30) in a regression analysis. CONCLUSION: The number of children with delay at the 2 year follow up were significantly higher in two domains in the ACTH group compared to the prednisolone group. Overall results do not show a significant advantage of ACTH over prednisolone for developmental outcomes at two years, but further comparative studies over longer periods are required for more definitive conclusions.

A national survey of antibacterial consumption in Sri Lanka.

INTRODUCTION: Optimizing the use of antibacterial medicines is an accepted strategy to combat the antibacterial resistance. Availability of reliable antibacterial consumption (ABC) data is a prerequisite to implement this strategy. OBJECTIVES: To quantify and describe the national ABC in Sri Lanka and to examine any differences in the consumption between public and private sector. METHODS: The methodology for this survey was adapted from World Health Organization (WHO) methodology for a global programme on surveillance of antimicrobial consumption. Aggregate data on national consumption of systemic antibacterials (J01- Anatomical Therapeutic Chemical Classification (ATC) for 2017 were retrospectively extracted from all available data sources and classified using ATC classification. Quantity of consumption was converted to Defined Daily Doses (DDDs). Data are presented as total consumption and comparison between the public and private sector. Selected key quality indicators of ABC were compared between these two sectors. FINDINGS: From the available data sources, the total ABC in 2017 was 343.46 million DDDs. Private sector consumption accounted for 246.76 million DDDs compared to 97.96 million DDDs distributed to entire public sector by the Ministry of Health. Beta-lactam-penicillins antibacterial group accounted for 58.79% in public sector compared to 27.48% in private sector while macrolides, quinolones and other beta-lactam antibacterials accounted for 60.51% in the private compared to 28.41% in public sector. Consumption of Reserve group antibacterials was negligible, and limited to private sector. Watch category antibacterials accounted for 46%, 24% and 54% of the total, public and private sector consumption, respectively. CONCLUSIONS: A disproportionately higher use of broad spectrum and Watch category antibacterials was observed in the private sector which needs further study. This national consumption survey highlights the need and provides the opening for establishment of ABC surveillance in Sri Lanka.

Pharmacovigilance through consumer feedback (reporting) in the mass treatment of lymphatic filariasis using diethylcarbamazine and albendazole in two districts of Sri Lanka.

OBJECTIVE: To document the types and severity of adverse drug reactions to diethylcarbamazine and albendazole in randomly selected urban populations from Colombo and rural populations from Gampaha, Sri Lanka. METHODS: Interviewers administered a pre-tested questionnaire to elicit information about the type and severity of adverse drug reactions experienced by recipients. Seeking medical treatment and requiring hospital admission for the adverse drug reactions were used as indicators for severity. The sample population was selected using the cluster sampling method. RESULTS: Two thousand three hundred and nineteen persons aged 10 to 90 years (median 40.0) responded to the questionnaire; 63.9% of them had received and ingested the drugs. 12.6% reported that they had experienced adverse drug reactions, the proportion being similar in urban and rural areas (chi2 = 0.05; p = 0.82). Commonly reported reactions were drowsiness (34.7%), headache (23.1%), gastrointestinal symptoms (18.7%) and dizziness or faintness (11.9%). However, most symptoms were mild (96.3%) and did not interfere with daily activities or require medical attention. 3.2% said that they sought medical advice for their symptoms; one person (0.5%) who had severe abdominal pain was hospitalized. CONCLUSIONS: Fewer people experienced adverse drug reactions than in previous years, possibly due to lower microfilariaemia prevalence after several rounds of mass drug administration against filariasis. Community awareness of adverse drug reactions is essential for improving compliance and for the success of the filariasis elimination programme.

Essential medicines for children.

Millions of children die every year before they reach the age of 5 years, of conditions largely treatable with existing medicines. The WHO Model List of Essential Medicines was launched in 1977 to make the most necessary drugs available to populations whose basic health needs could not be met by the existing supply system. During the first 30 years of the Model List of Essential Medicines, children's needs were not systematically considered. After adoption of the 'Better medicines for children' resolution by the World Health Assembly, things changed. The first WHO Model List of Essential Medicines for Children was drawn up by a Paediatric Expert Subcommittee and adopted in October 2007. The most recent, 4th Model List of Essential Medicines for Children was adopted in 2013. Data from country surveys show that access to essential medicines for children is still generally poor; much more work is needed.

Randomized, Single-Blind, Parallel Clinical Trial on Efficacy of Oral Prednisolone Versus Intramuscular Corticotropin on Immediate and Continued Spasm Control in West Syndrome.

OBJECTIVE: A single-center, single-blind, parallel-group, randomized clinical trial was performed to test the null hypothesis that adrenocorticotropic hormone is not superior to high-dose prednisolone for treatment of newly diagnosed West syndrome. METHODS: Newly diagnosed infants with West syndrome were randomized to receive 14 days of oral prednisolone (40-60 mg/day) or a synthetically prepared intramuscular long-acting adrenocorticotropic hormone (40-60 IU/every other day [0.5-0.75 mg]) according to the United Kingdom Infantile Spasm Study protocol. They were blindly evaluated for infantile spasm remission by day 14, electroclinical remission (spasm cessation + resolution of hypsarrhythmia on a 30-minute electroencephalograph) by day 14 and continued spasm freedom for 28 days. RESULTS: Ninety-seven patients were enrolled in the study, with 48 of them receiving prednisolone and 49 receiving ACTH. There was no significant difference in the baseline characteristics or risk factors for the two treatment groups. By day 14, cessation of infantile spasms occurred in 28/48 (58.3%) infants on prednisolone compared with only 18/49 (36.7%) infants given adrenocorticotropic hormone (P = 0.03) and electroclinical remission in 21 on prednisolone compared with nine on adrenocorticotropic hormone (P = 0.007). Sustained spasm control for 28 consecutive days following electroclinical remission occurred in 15 children on prednisolone compared with six on adrenocorticotropic hormone (P = 0.008). The total number of days required for spasm cessation was significantly less in those treated with prednisolone (3.85 days ± 2.4) compared with adrenocorticotropic hormone (8.65 days ± 3.7) (P = 0.001). Among patients who did not achieve remission, there was a non-significant trend toward greater quantitative reduction of spasms with prednisolone than with adrenocorticotropic hormone (P = 0.079). CONCLUSION: Synthetic adrenocorticotropic hormone of 40-60 IU/every other day did not yield superior rates of electroencephalographic or clinical remission when compared with prednisolone of 40-60 mg/day. Significantly, more patients achieved electroclinical remission when treated with prednisolone than with adrenocorticotropic hormone.

A national survey of price and affordability of key essential medicines for children in Sri Lanka.

OBJECTIVE: To investigate the price and affordability of key essential medicines for children in Sri Lanka. METHODS: This national survey investigated the prices and affordability of 25 key essential medicines for children in private sector pharmacies using the WHO/Health Action International (HAI) medicine price methodology. Data were collected from a representative sample of 48 private sector pharmacies selected from 8 Provinces using a multistage clustered approach. At each pharmacy prices of originator brand (OB) and lowest priced generics (LPG) of the selected medicines were collected. Medicine prices were compared with international reference prices to obtain a median price ratio (MPR). Income of the lowest paid unskilled government worker was used to establish the affordability. RESULTS: The median MPR of retail prices to patients was 3.7 for OB (range 0.23-20) and 1.35 for LPG (range 0.05-3.75). MPR >5 was observed for OBs of 5 medicines: ceftriaxone injection, diazepam injection, mebendazole syrup, mebendazole chewable tablet and metronidazole tablet whereas MPR >2.5 was observed only for LPGs of 3 medicines: chlorphenamine syrup, clotrimazole topical cream, and paracetamol syrup. Mean percent difference in price between OB and LPG products was 365 % (range -21, 2343). Rational treatment for acute infections such as mild lower respiratory tract infections and acute gastroenteritis seems to be affordable but treatment for chronic illnesses requiring liquid or inhaled dosage forms were largely unaffordable. CONCLUSIONS: Intervention is needed to improve the economic access to key essential medicines for children indicated in the treatment of chronic diseases.

The efficacy of moderate-to-high dose oral prednisolone versus low-to-moderate dose intramuscular corticotropin for improvement of hypsarrhythmia in West syndrome: a randomized, single-blind, parallel clinical trial.

BACKGROUND: The role of therapy on improvement of hypsarrhythmia has not been systematically assessed. This study was performed to assess the efficacy of oral prednisolone and intramuscular adrenocorticotrophin hormone in improving hypsarrhythmia in West syndrome. METHOD: Children (2 months-2 years), with previously untreated West syndrome, were randomized to receive 40-60 IU every other day of intramuscular adrenocorticotrophin hormone or 40-60 mg/day of oral prednisolone for 14 days. Children with tuberous sclerosis were excluded. Improvement of hypsarrhythmia was assessed blindly using a hypsarrhythmia severity scale before and after completion of therapy. Adverse effects were assessed on day 14 using symptom diary. (Clinical trial registry identifier: SLCTR/2010/010.) RESULTS: From 92 newly diagnosed West syndrome infants, 48 were randomized to receive prednisolone and 44 to receive adrenocorticotrophin hormone. Eighty infants completed the posttreatment evaluation according to specifications. The hypsarrhythmia severity score, significantly improved with hormonal therapy for 2 weeks (10.45 ± 2.65 vs 3.45 ± 2.67); P < 0.01. When individual treatment arms were compared using mean differences in the improvement of scores, improvement in prednisolone arm (7.95 ± 2.76) was significantly greater than that in the adrenocorticotrophin hormone arm (6.00 ± 2.61); P < 0.01. Both forms of therapy were tolerated well. Frequent crying, irritability, weight gain, increased appetite, and abdominal distension were more common (but not statistically significant) with prednisolone. CONCLUSIONS: Hypsarrhythmia severity score improved significantly with both hormonal therapies, but this improvement was significantly better with oral prednisolone than intramuscular adrenocorticotrophin hormone. This is the first ever documentation of a superior therapeutic role of oral steroids in West syndrome.

Realities of paediatric pharmacotherapy in the developing world.

Diseases causing high mortality in children under 5 years of age in resource limited settings (RLS) could be treated if children in these countries had access to existing medicines. It took 30 years before the WHO Essential Medicines List (EML) considered the issue of medicines for children, with the first EML for children being published in 2007. Recent data indicate that less than half of the key paediatric essential medicines are available in countries of sub-Saharan Africa. Problems include substandard medicines, irrational use of medicines, inefficiency and even possible corruption in pharmaceutical management systems. These are global issues which affect RLS most. Clinical trials in developing countries for the benefit of children are needed but challenging in several ways. In this review, the authors will consider the following areas where progress could improve paediatric pharmacotherapy in RLS: registration and regulation of medicines, rational use of medicines, clinical trials in children and restriction of corruption in pharmaceutical management systems.