Asia N. Rashed

Simple evaluation of the wound healing activity of a crude extract of Portulaca oleracea L. (growing in Jordan) in Mus musculus JVI-1.

The preliminary wound healing activity of Portulaca oleracea was studied using Mus musculus JVI-1. For this purpose fresh homogenized crude aerial parts of Portulaca oleracea were applied topically on the excision wound surface as single and two doses in different amounts. Wound contraction and tensile strength measurements were used to evaluate the effect of Portulaca oleracea on wound healing. The results obtained indicated that Portulaca oleracea accelerates the wound healing process by decreasing the surface area of the wound and increasing the tensile strength. The greatest contraction was obtained at a single dose of 50mg and the second greatest by two doses of 25mg. Measurements of tensile strength and healed area were in agreement.

Risk factors associated with adverse drug reactions in hospitalised children: international multicentre study

BackgroundUnderstanding the epidemiology and risk factors of adverse drug reactions (ADRs) is important in order to develop appropriate prevention strategies. This study aimed to identify risk factors associated with ADRs in hospitalised children and recommend strategies to minimise ADRs.MethodsA prospective multicentre cohort study was conducted on paediatric general medical wards in five European and non-European hospitals. ADRs were identified by intensive chart review. Multivariable logistic regression was used to investigate risk factors associated with ADRs. For the risk factor analysis, prescribed drugs were divided into high-risk and low-risk drug groups. Analgesics, anti-epileptics, antibacterials and antimycotics for systemic use, corticosteroids for systemic use and immunosuppressant agents were considered as high-risk groups whereas the remaining drug classes were defined as low-risk drug groups.ResultsA total of 1,253 paediatric patients were identified [Australia (n = 145), Germany (n = 372), Hong Kong (n = 138), Malaysia (n = 291), UK (n = 307)]. A total of 328 ADRs were observed in 16.7% of patients (186/1,115). Use of five or more low-risk drugs per patient or  three or more high-risk drugs was a strong predictor for ADRs (OR 4.7, 95% CI 2.4–9.3; OR 6.5, 95% CI 2.7–16.0 respectively; p < 0.001). Older children were more likely to experience ADRs; gender was not significantly associated.ConclusionTo reduce the risk of ADRs in children, clinicians and pharmacists should aim to minimise polypharmacy and be aware of higher ADR risks associated with some drug groups.

Adverse Drug Reactions in Children--International Surveillance and Evaluation (ADVISE): a multicentre cohort study

AbstractBackground: A previous meta-analysis reported that 9.5% of hospitalized children suffered from an adverse drug reaction (ADR); however, reported incidences among studies varied. Objective: To enhance the knowledge of ADRs in paediatric hospitalized patients at a global level we investigated the incidence and characteristics of ADRs in hospitalized children in European and non-European countries. Methods: A prospective observational cohort study was conducted in academic and non-academic hospitals in five countries: Australia, Germany, Hong Kong, Malaysia and the UK. Children aged 0–18 years admitted during a 3-month period (between 1 October 2008 and 31 December 2009) were recruited. The main outcome measures were incidence, causality and outcome of ADRs. Results: A total of 1278 patients (1340 admissions) were included [Australia n = 146 (149 admissions), Germany n = 376 (407), Hong Kong n = 143 (149), Malaysia n = 300 (314) and the UK n = 313 (321)]. The median age was 2 years (interquartile range [IQR] 0–7). Patients received a total of 5367 drugs (median 3; IQR 2–5) and median length of hospital stay was 4 days (IQR 3–7). A total of 380 ADRs were identified in 211 patients. The resultant ADR incidence of 16.5% (95% CI 14.5, 18.7) varied significantly between countries (p < 0.001). The highest incidences were observed in Malaysia and the UK. 65.3%(n = 248) of ADRs were found to be probable, and 24% of the ADRs were serious, with one being fatal. Conclusions: By comparing data from five countries in Europe, Asia and Australia we have shown that the incidence of ADRs in hospitalized children is at least as high as incidences published in adults. However, the variation between countries was mainly due to different populations and treatment strategies. Particular attention should be given to opioid use in hospitalized children.

Adverse drug reactions in hospitalised children in Germany are decreasing: results of a nine year cohort-based comparison.

Background In recent years, efforts have been made to improve paediatric drug therapy. The aim of this research was to investigate any changes regarding the frequency and nature of adverse drug reactions (ADRs) in hospitalized children in one paediatric general medical ward over a 9-year period. Methodology Two prospective observational cohort studies were conducted at a large University hospital in Germany in 1999 and 2008, respectively. Children aged 0–18 years admitted to the study ward during the study periods were included. ADRs were identified using intensive chart review. Uni- and multivariable regression has been used for data analysis. Results A total of 520 patients (574 admissions) were included [1999: n = 144 (167); 2008: n = 376 (407)]. Patients received a total of 2053 drugs [median 3, interquartile range (IQR) 2–5]. 19% of patients did not receive any medication. Median length of stay was 4 days (IQR 3–7; range 1–190 days) with a significantly longer length of stay in 1999. The overall ADR incidence was 13.1% (95% CI, 9.8–16.3) varying significantly between the two study cohorts [1999: 21.9%, 95% CI, 14.7–29.0; 2008: 9.2%, 95% CI, 5.9–12.5 (p<0.001)]. Antibacterials and corticosteroids for systemic use caused most of the ADRs in both cohorts (1999; 2008). Exposure to systemic antibacterials decreased from 62.9% to 43.5% whereas exposure to analgesics and anti-inflammatory drugs increased from 17.4% to 45.2%, respectively. The use of high risk drugs decreased from 75% to 62.2%. In 1999, 45.7% and in 2008 96.2% of ADRs were identified by treating clinicians (p<0.001). Conclusions Between 1999 and 2008, the incidence of ADRs decreased significantly. Improved treatment strategies and an increased awareness of ADRs by physicians are most likely to be the cause for this positive development. Nevertheless further research on ADRs particularly in primary care and the establishment of prospective pharmacovigilance systems are still needed.

Trends and patterns of hormonal contraceptive prescribing for adolescents in primary care in the UK

Background Hormonal contraceptives are the most common method used worldwide by teenagers to prevent unwanted pregnancies. To date there are limited data about such use by teenagers in the UK. This study investigated trends and patterns of hormonal contraceptive prescribing to adolescents aged 12–18 years in UK primary care between 2002 and 2011. Methods A retrospective cohort study using the IMS Disease Analyzer database was conducted. All females aged 12–18 years with ≥1 prescription for a contraceptive drug between 1 January 2002 and 31 December 2011 were included. Annual prevalence of contraceptive drug prescribing was calculated, and indications for prescribing, and types of contraceptive drug prescribed, were examined. Results In 2002, 13.7% (6135/44 532) of female adolescents received prescriptions for hormonal contraceptives, compared to 19.0% (6597/34 676) in 2011. The majority of female adolescents [2002: 76.2% (4676/6135); 2011: 65.7% (4334/6597)] received a contraceptive drug for ‘contraceptive management’. The combined oral contraceptive (COC), ‘progestogen+estrogen’, was the most commonly prescribed. Although use of progestogen-only contraceptives was lower than COCs, the number of patients who received desogestrel pills and etonogestrel implants increased during the study period; levonorgestrel pill use declined. Only one injectable progestogen, long-acting depot medroxyprogesterone acetate, was prescribed. Conclusions Use of hormonal contraceptives among adolescents increased between 2002 and 2011, and COC usage was dominant. The increasing use of hormonal contraceptives in adolescents, especially in younger adolescents, warrants further investigation, including research into the long-term safety of these medicines in this age group.

The feasibility of using dose-banded syringes to improve the safety and availability of patient-controlled opioid analgesic infusions in children

Opioid infusions are essential therapy for children in severe pain. Patient controlled analgesia (PCA) is an attractive treatment option because of the multiple benefits it provides: immediate and effective pain relief, titration of analgesia and empowerment of the patient (or nurse) to have a degree of control over their pain which helps to retain autonomy and decrease anxiety. However, opioid infusions for children carry a high risk of medication error. Risks include the complexity in calculating dosages, the manipulation of small volumes to prepare individual infusions and the necessity to deliver the infusion with precision at low flow rates (down to 0.1 mL/h). During PCA additional boluses on top of the baseline infusion rate add to the pharmaceutical and therapeutic complexity. The severe side effects of opioids, including hypoventilation, hypotension and sedation, exacerbate the risk and raise great concern in hospitals, plus limiting the use of PCA in community and hospice settings. At present there is no international standard practice or guideline on the way that PCA is administered. This commentary highlights problems with current practices of preparing and administering PCA in hospitalised children in the UK. Additionally, we advocate a system management approach which we are piloting to address the problems of opioid-based PCA for children in a large (200-bed) hospital, the Evelina London Childrens Hospital, in the hope of developing safer practices for the delivery of opioid analgesia. Intravenous infusions are an important means of administering therapy, yet the technical process is complex with multiple error-prone steps. The errors associated with preparing and administering intravenous infusions in paediatrics (eg, low volume at low flow rate) make drug delivery by infusion a particularly high risk,1 but continuous infusions of opioid are crucial to achieve effective analgesia and avoid uncontrolled pain in neonates and children with conditions such as sickle …

Current practice of preparing morphine infusions for nurse/patient-controlled analgesia in a UK paediatric hospital: healthcare professionals’ views and experiences

Objective To explore the views and experiences of healthcare professionals (HCPs) regarding the preparation of morphine infusions for nurse/patient-controlled analgesia (N/PCA). Methods Three focus groups were conducted with HCPs (anaesthetists, nurses in theatres and wards) at one UK childrens hospital. Focus groups were transcribed verbatim and content analysis was used to identify themes. Results A variety of approaches are used to prepare morphine infusions. A lack of appreciation of the excess volume present in morphine ampoules that nominally contain 1 or 2 mL was identified. Other sources of error were miscalculation, complexity of the multistep procedure, distractions and time pressure. Participants suggested that ‘ready-to-use’ prefilled syringes and preprogrammed syringe pumps would improve practice and minimise the risk of error. Conclusions Risks associated with the preparation of infusions for paediatric N/PCA, in particular non-appreciation of the overage (excess volume) in morphine ampoules, raise concerns about the accuracy of current practices.

EVALUATION OF THE CURRENT PRACTICE OF DELIVERING INTRAVENOUS OPIOIDS INFUSIONS IN A UK PAEDIATRIC HOSPITAL

Introduction Opiate intravenous infusions are the therapy of choice in severe pain. However, administering infusions to children requires complex dosage calculations, rate adjustments and often multiple manipulations of injectable medicines to obtain the final “ready to use” solution for both continuous infusion and additional boluses; potentially putting children at high risk.1 2 Aim To investigate the practice and accuracy of healthcare professionals (HCPs) in hospital theatres and wards in preparing morphine infusions for nurse/patient controlled analgesia (N/PCA) use in a UK childrens hospital. Methods A mixed methods study in which direct observation of HCPs preparing paediatric morphine infusions for N/PCA in theatres and on wards, focus groups with HCPs and quantitative analysis of morphine concentration in the syringe using UV-Vis Spectrophotometer. The British Pharmacopoeia (BP) reference limits of ±7.5% were used to compare label strength (LS) of morphine infusion with measured concentration. Results The preparation of 153 syringes was observed which related to 128 paediatric patients [mean age (±sd) 7.5 years±5.6; 65.3% male]. 64% (98/153) were prepared by anaesthetists in theatres, 36% (55/153) by nurses at ward level. Major differences in preparation methods were identified. The final volume prepared was above the required volume (50 mL) in 35.9% (55/153) preparations. Wearing gloves during preparation was not followed in theatre for 83.7% (82/98) of syringes. No decontamination of morphine ampoules was undertaken during preparation of any syringe. Inconsistency in the appropriate syringe size used to withdraw drug from the ampoule was observed in both theatres and wards. Lack of appreciation of the overage in morphine ampoules by HCPs was identified. Of the syringes analysed 61.5% (48/78) had a concentration outside the BP reference limits (92.5–107.5% of LS), most were in excess (83.3%, 40/48). Of these 20.8% (10/48) deviated by more than +20%, with one deviated by 100%. Conclusion This study identified that variation in preparation techniques followed by HCPs may result in morphine N/PCA dosages that are significantly higher or lower than that prescribed. Also, lack of understanding of ampoule overage, accuracy of the syringe size used and the ability to measure small volumes led to inaccurate concentrations in prepared infusions.

Drug-related problems in hospitalised children in United Kingdom and Saudi Arabia

Objectives: Individual case safety reports (ICSRs) could be an important source in giving further information to characterize the risk situation and aid in the prevention, diagnosis, management and treatment of adverse drug reactions (ADRs). The aim was to determine whether and where on the ICSRs clinically useful information was specified for rare ADRs in the paediatric population. Methods: ICSR concerning rhabdomyolysis occurring during use of antipsychotic medicines for patients up to 17 years of age were retrieved from the WHO Global ICSR database, VigiBase. The original case reports were requested and received from the national pharmacovigilance centres. We focused on five areas of information specified in a recent guideline for publishing ADRs.[1] Results: Eighteen original cases with an age span from 5 to 17 years were reviewed with the following outcomes. Circumstances preceding the reaction: 9 reports included this information, consisting primarily of abdominal, muscle and back pain. In eight of these reports, the full account of the symptoms and sequence of events were only found in the narratives. Underlying risk factors for rhabdomyolysis: Recorded for four of five patients in the narrative: seizures (n = 1), strenuous physical activity (n = 2), diabetic ketoacidosis (n = 1), alcohol use (n = 1). Four patients had Neuroleptic Malignant Syndrome (NMS) co-reported. Physical examination and laboratory tests: All values for patient temperature and laboratory values were given in free text. Elevated creatine phosphokinase (CPK) or myoglobin values were recorded in 14 reports ranging from 1200 to 95 000 IU/L (CPK). Patient temperature was specified for 5 patients, of whom 3 patients were also reported to experience NMS. Drug-reaction time-to-onset: 13 reports included information on the duration from drug start to reaction onset, which ranged from 4 days to 1.5 years. 9 reports included dates in the structured data, so that time to onset could be calculated and in 4 reports the information was specified in the narratives. Treatment of the reaction: Apart from stopping the drug (n = 18) and hospitalization (n = 16), other actions of treatment, such as forced intravenous fluids or resolving spontaneously, was given for 5 cases in the narrative. Conclusions: This study showed that useful clinical information was available to characterize the risk situation for these patients in this subset of reports. This should be regarded in the context that ICSRs are generally considered to be of poor quality. However, access to the free text fields recorded by the reporter was crucial to capture this information. Reference 1. Kelly WN, Arellano FM, Barnes J, et al. Guidelines for submitting adverse event reports for publication. Drug Saf 2007; 30 (5): 367-73