'Working outside the box'-an interview study regarding manipulation of medicines with registered nurses and pharmacists at a Swedish paediatric hospital.

AIM: Studies on frequencies of manipulated medicines in paediatric care are common, but there is little knowledge of experiences of pharmacists and registered nurses in this area. The aim of this study was to explore registered nurses' and pharmacists' reasoning in the manipulation of medicines to paediatric inpatients. METHODS: Semistructured interviews with twelve registered nurses and seven pharmacists were performed at a Swedish paediatric university hospital. The interviews were transcribed verbatim and analysed using content analysis. RESULTS: Four major categories emerged from the analysis of the interviews: medicines management, knowledge, consulting others and organisation. Medicines management involved the process of drug handling, which is prescribing, reconstitution or manipulation and administration. Knowledge concerned both the knowledge base and how healthcare personnel seek information. Consulting others involved colleagues, registered nurses and pharmacists, between registered nurses, pharmacists and physicians and between registered nurses, pharmacists and caregivers. Organisation covered documentation, time and working environment. CONCLUSION: Both pharmacists and registered nurses stated that manipulation of medicines to paediatric patients was often necessary but felt unsafe due to lack of supporting guidelines. Pharmacists were natural members of the ward team, contributing with specific knowledge about medicines and formulations.

Frequency of paediatric patients administered extemporaneous preparations at a Swedish university hospital: a registry-based study comparing two study-years, 10 years apart.

BACKGROUND: Lack of child-friendly dosage forms and strengths often leads to manipulation of medicines at hospital units or by caregivers in the home setting. One alternative to manipulating dosage forms is the use of extemporaneous preparations. In Sweden, these are produced according to good manufacturing practice by a few extemporaneous pharmacies. OBJECTIVES: To compare frequencies of patients administered extemporaneous preparations in two separate years, 10 years apart. METHODS: This registry-based study describes and compares the frequency of extemporaneous oral preparations administered to paediatric patients in 2009 and 2019 at a Swedish university hospital.The study included 117 023 oral administrations (to 4905 patients) and 128 638 oral administrations (to 4718 patients) from 2009 and 2019, respectively. RESULTS: The frequency of inpatients administered one or more extemporaneous preparations increased from 22% in 2009 to 40% in 2019 (p<0.0001). The increase was observed in all age groups. The use of some active pharmaceutical ingredients increased (eg, captopril, clonidine, hydrocortisone, melatonin and propranolol), and some active pharmaceutical ingredients decreased between the study years (eg, midazolam and sildenafil). CONCLUSIONS: The introduction of new authorised products has decreased the need for manipulation or extemporaneous preparations in some therapeutic groups. There remains, however, a pronounced lack of commercially available child-friendly dosage forms and suitable strengths enabling safe administration of medicines to children, indicated by the large percentage of patients receiving at least one extemporaneous preparation.

Identifying neonatal adverse events in preterm and term infants using a paediatric trigger tool.

AIM: To explore the incidence and characteristics of inpatient neonatal adverse events in a Swedish setting. METHODS: A retrospective record review, using a trigger tool, performed by registered nurses and a neonatologist, at a University Hospital. The identified adverse events were categorised by, for example, preventability, severity and time of occurrence. RESULTS: A random selection of 150 admissions representing 3531 patient days were reviewed (mean [SD] birthweight 2620 [1120]g). Three hundred and sixty adverse events were identified in 78 (52.0%) infants, and 305 (84.7%) of these were assessed as being preventable. The overall adverse event rate was 240 per 100 admissions and 102.0 per 1000 patient days. Preterm infants had a higher rate than term infants (353 versus 79 per 100 admissions, p = 0.001); however, with regard to the length of stay, the rates were similar. Most adverse events were temporary and less severe (n = 338/360, 93.9%) and the most common type involved harm to skin, tissue or blood vessels (n = 163/360, 45.3%). Forty percent (n = 145) of adverse events occurred within the first week of admission. CONCLUSION: Adverse events were common in neonatal care, and many occurred during the first days of treatment. Characterisation of adverse events may provide focus areas for improvements in patient safety.

Improved home management of oral pediatric anticancer drugs as a result of an intervention comprising practical training, written instructions and movie clips: A pilot study.

BACKGROUND: Long term treatment of pediatric patients with oral anticancer drugs (OADs) requires the parents/caregivers to prepare the drug at home. The handling procedures in the home setting are, however, not regulated by Swedish law and the parents are often left without guidance on how to handle OADs in a safe way. AIM: The aim of this study was to increase understanding of how OADs are handled by parents/caregivers in the home setting before and after an intervention. METHODS: Parents of pediatric cancer patients were observed and videotaped during their handling of OADs in the home setting before and after the intervention. During the intervention, the parents were provided with written instructions, movie clips and practical training on handling the OADs. Four checklists were used to compare and score the four handling procedures (measuring an oral suspension, cutting tablets, dissolving tablets, and opening capsules) for each parent before and after the intervention. RESULTS: The intervention significantly improved the OAD handling procedures among the studied parents. The median score for correct handling was 19% (IQR: 3.6 to 30%) before the intervention and 89.5% (IQR: 71.5 to 94.5%) after the intervention (p < 0.0001). CONCLUSIONS: An intervention comprising practical training and information presented in different forms improved the handling of OADs at home by parents. There is an urgent need to implement this method in all oncology centers in Sweden, educate HCPs to standardize the presentation of information. There is also a great need to provide parents with age-appropriate oral drug formulations from the local hospital pharmacies in Sweden.

Parents' experiences of handling oral anticancer drugs at home: 'It all falls on me '.

AIM: The aim of this study was to describe the experiences of parents handling oral anticancer drugs in a home setting. METHODS: Parents of children with cancer were recruited from a paediatric oncology ward in Sweden to participate in an interview. The interviews were transcribed verbatim and subjected to qualitative content analysis. RESULTS: We found the following categories and subcategories: parents' views on the provided information-lack of, too little or contradictory information, and parents' preferences for information delivery; safety over time; correct drug dose; and drug administration. As time passed, most parents adapted to their child's illness, felt safer and found it easier to take in and process any given information. Parents preferred information in different formats (written, movie clips and orally) and in their mother tongue. Many parents were aware of the importance of giving an accurate dose to their child and described the process of drug administration as overwhelming. CONCLUSION: Parents need to be provided with accurate, timely, nonconflicting and repeated information-in different forms and in their mother tongue-on how to handle oral anticancer drugs at home.

Manipulated Oral and Rectal Drugs in a Paediatric Swedish University Hospital, a Registry-Based Study Comparing Two Study-Years, Ten Years Apart.

This is a registry-based study with the aim of describing and comparing the frequency of manipulations of solid oral and rectal medicines in 2009 and 2019 at inpatient units and an emergency department in a paediatric hospital within a Swedish university hospital. All patients aged 1 month−18 years with oral or rectal administrations were included. In total, 140,791 oral and rectal administrations were included in 2009, and 167,945 oral and rectal administrations were included in 2019. The frequency of patients receiving at least one manipulated oral medicine decreased between the study years, both in inpatient units and in the emergency department (from 19% to 17%, p = 0.0029 and from 11% to 5%, p < 0.0001, respectively). The frequency of patients receiving a manipulated rectal medicine also decreased between the study years, both in inpatient units and in the emergency department (from 22% to 10%, p < 0.0001 and from 35% to 7% 2019, p < 0.0001, respectively). The results show a decrease in the manipulation of both oral and rectal medicines to paediatric patients in 2019 compared to 2009. Even though this implies a safer practice, there is still a pronounced lack of child-friendly dosage forms and suitable strengths enabling the safe administration of medicines to sick children.

Estimation of body surface area in neonates, infants, and children using body weight alone.

BACKGROUND: The aim of this study was to use Body Surface Area (BSA) data calculated with the Mosteller equation to test potential new equations that estimate BSA using Body Weight (BW) alone in children aged 0-18 years.Mosteller's equation, the golden standard at our hospital, was used to calculate the BSA in infants and children aged 0-18 years using BW and height data from 27,440 hospital visits by 20,635 patients over one year. METHODS: The best fit of three nonlinear regression equations (third-order polynomial, Meeh-type, and modified Boyd self-adjusting-type) to a plot of the calculated Mosteller BSA values versus BW was then investigated. The correlation between the BSA values estimated by these equations and the Mosteller BSA values was established by the Spearman rank correlation test. Bias and precision were evaluated as outlined by Sheiner and Beal. Measured and estimated BSA values were compared using the Eksborg plot. RESULTS: The estimated BSA values from all three equations and the BSA values from the Mosteller equation were closely correlated (P < .0001). The third-order polynomial and Meeh-type equations overestimated BSA by 0.13% and 0.40%, respectively, while the Boyd self-adjusted-type equation underestimated BSA by 0.060%. For the entire pediatric population, the best fit was obtained with the Meeh-type equation: 99.2% of the Meeh/Mosteller BSA ratios were within the range of 0.9-1.1 when compared with 98.3% and 97.2% for the polynomial and Boyd-type equations, respectively. CONCLUSION: A single Meeh-type equation can be used to predict the results of Mosteller equation when H is not available with high precision and accuracy in children aged 0-18 years, including term neonates. We now plan to include the results of this study in CPOE systems in Sweden to improve drug dosage in all children.

Cross-sectional study identifying high-alert substances in medication error reporting among Swedish paediatric inpatients.

AIM: The aims were to characterise paediatric medication errors and to identify the prevalence of known high-alert substances in these errors. METHODS: All paediatric drug-related incident reports and complaints nationally reported to the Health and Social Care Inspectorate in Sweden 2011-2017 regarding inpatients were characterised by context and modal details. In addition, drug use at a university hospital was matched to local incident reports. Drug substances were classified using three high-alert lists. RESULTS: On a national level, there were 160 reports (2.5 per 10 000 patients) in which the three high-alert lists were found in different degrees (17/35/47%). Morphine (n = 12), vancomycin (n = 11) and potassium (n = 7) were most frequently involved. Eighty per cent of the reports concerned patients aged 0-6 years. Intravenous was the most common route of administration (66%). On a university hospital level, the prevalence of all types of drug incidents reports was 1.7% among all inpatients. The prevalence of local incident reports involving high-alert substances was almost double that of non-alert substances. CONCLUSION: Existing high-alert drug lists are relevant for paediatric inpatients. A higher awareness and usage of such lists among hospital staff prescribing, dispensing and administering drugs to children may have the potential to reduce medication errors.

Drug Use and Type of Adverse Drug Events-Identified by a Trigger Tool in Different Units in a Swedish Pediatric Hospital.

PURPOSE: The objectives of our study were to determine drug use, type and incidence of all adverse event associated with drug or drug-related processes (Adverse Drug Events, ADE) among pediatric inpatients in relation to hospital unit and length of stay. PATIENTS AND METHODS: 600 pediatric (0-18 years) admissions at a Swedish university hospital during one year were included and stratified in blocks to 150 neonatal, surgical/orthopedic, medicine and emergency-medicine unit admissions, respectively. Adverse events were identified from medical records using a pediatric trigger tool. All triggers identifying an adverse event related to drugs and drug-related devices were included. Data on drug use were extracted from the hospital drug-data warehouse. RESULTS: In total, 17794 daily drug orders were administrated to 486 (81.0% exposed) admissions. Parental nutrition, potassium salts and morphine constituted half of all high-risk drugs prescribed. Two-thirds of intravenous irritating drug doses consisted of vancomycin, esomeprazole and meropenem. In 129 (21.5%) admissions, at least one ADE was identified, out of which 21 ADE were classified as more severe (National Coordinating Council Medication Error Reporting Prevention-Index, NCCMERP≥F). The ADE incidence was 47.4 (95% confidence interval: 39.4-57.3) per 1000 admission days and varied by unit category. In neonatal units, 56.9 (49.5-65.4) ADEs/1000 admission days were detected, in surgery/orthopedic 54.2 (40.3-72.8), in medicine 44.1 (33.1-58.7), and in emergency-medicine 14.3 (7.7-26.7) ADEs/1000 admission days were found. The most common types of ADEs were identified by triggers that were not directly aiming at drugs including insufficiently treated pain (incidence peaking already in the first days), skin, tissue or vascular harm (peaking at the end of the first week) and hospital-acquired infections (peaking in later admission days). CONCLUSION: Adverse drug events are common in pediatric patients. The incidence of ADEs and type of ADE varies by hospital unit and length of hospital stay.

Evaluation of Electronic Prescribing Decision Support System at a Tertiary Care Pediatric Hospital: The User Acceptance Perspective.

This study aims to evaluate pediatrician's acceptance, perception and use of Electronic Prescribing Decision Support Systems (EPDSS) at a tertiary care using Extended Technology Acceptance Model (TAM2). Qualitative research methodology was applied. Semi-structured questions were developed according to TAM2 model. Pediatricians perceived that the EPDSS is useful and they showed a favorable attitude. However, perceived ease of use and output quality appeared to affect use of EPDSS. Concerns were expressed about complicated screens, difficulty to read and view medication overview of the patient, the navigation requires many clicks and medication system don't meet their need. End users have difficulty of ordering drugs for ploy-clinical patients and they were unable to cancel or stop medications. Junior pediatricians were influenced by senior colleague since they can get better advice about medication order than the system. Applying TAM2 framework has revealed that pediatrician's attitude and acceptance of electronic prescribing system. This study has identified factors that are important for end user acceptance as well as suggestions for system improvement. Although pediatricians are positive to the usefulness of EPDSS, it appears there are some acceptance problems due to ease of use concern and usability issues of the system.

Pediatricians' Understanding and Experiences of an Electronic Clinical-Decision-Support-System.

OBJECTIVES: Subsequent dosing errors after implementing an Electronic Medical Record (EMR) at a pediatric hospital in Sweden led to the development, in close collaboration with the clinical profession, of a Clinical Decision Support System (CDSS) with Dose Range Check and Weight Based Dose Calculation integrated directly in the EMR. The aim of this study was to explore the understanding and experiences of the CDSS among Swedish pediatricians after one year of practice. METHODS: Semi-structured interviews with physicians at different levels of the health care system were performed with seventeen pediatricians working at three different pediatrics wards in Stockholm County Council. The interviews were analysed with a thematic analysis without pre-determined categories. RESULTS: Six categories and fourteen subcategories emerged from the analysis. The categories included the use, the benefit, the confidence, the situations of disregards, the misgivings/risks and finally the development potential of the implemented CDSS with Weight Based Dose Calculation and Dose Range Check. CONCLUSIONS: A need for CDSS in the prescribing for children is evident to support the prevention of medication errors. After implementing a CDSS, organized efforts are crucial to understand the need for further development based on the practical knowledge of the clinical profession. Different contextual settings of health care organisations do affect the way how physicians think and act in work. When implementing a CDSS in practice we need to describe and analyse the context where the CDSS should be used as well as the prescribers' needs in work.

[Careful medical history taking is worthwhile in child sleep disorders]. / Noggrann anamnes lönar sig vid sömnstörningar hos barn - Läkemedel avråds som förstahandsbehandling.

Sleeping disturbances are common in children and adolescents and in rare cases signal underlying disease. Complete history and diagnosis are mandatory for treatment. The basis for pharmacologic treatment is unsatisfactory but phenotiazides and benzodiazepines should not be used because of lack of documented effects and potentially serious side effects. Melatonin may be used in selected cases.

Validation of triggers and development of a pediatric trigger tool to identify adverse events.

BACKGROUND: Little is known about adverse events (AEs) in pediatric patients. Record review is a common methodology for identifying AEs, but in pediatrics the record review tools generally have limited focus. The aim of the present study was to develop a broadly applicable record review tool to identify AEs in pediatric inpatients. METHODS: Using a broad literature review and expert opinion with a modified Delphi process, a pediatric trigger tool with 88 triggers, definitions, and descriptions including AE preventability decision support was developed and tested in a random sample of 600 hospitalized pediatric patients admitted in 2010 to a single university children's hospital. Four registered nurse-physician teams performed complete two-stage retrospective reviews of 150 records each from either neonatal, surgical/orthopedic, medicine, or emergency medicine units. RESULTS: Registered nurse review identified 296 of 600 records with triggers indicating potential AEs. Records (n = 121) with only false positive triggers not indicating any potential AEs were not forwarded to the next review stage. On subsequent physician review, 204 (34.0%) of patients were found to have had 563 AEs, range 1-27 AEs/patient. A total of 442 preventable AEs were found in 161 patients (26.8%), range 1-22. Overall, triggers were found 3,598 times in 417 (69.5%) records, with a mean of 6 (median 1, range 0-176) triggers per patient. The overall positive predictive value of the triggers was 22.9%, (range 0.0-100.0%). The final pediatric trigger tool, developed with a second Delphi round, required 29 triggers. CONCLUSIONS: AEs are common in pediatric patients and most are preventable. The main contributions of this study are to further develop and adapt trigger definitions, including AE preventability decision support, to introduce new triggers in pediatric care, as well as to apply pediatric triggers in different clinical specialties. Our findings resulted in a national pediatric trigger tool, and might also be adapted internationally. The pediatric trigger tool can help healthcare organizations to measure and analyze the AEs occurring in hospitalized children in order to improve patient safety.

Estimation of body surface area in various childhood ages--validation of the Mosteller formula.

AIM: The aim of the present study was to validate the Mosteller formula for the estimation of body surface area (BSA) in various childhood ages. Many physiological processes including drug metabolism correlate with values for BSA. In addition, dosing of many drugs, especially drugs with low therapeutic index, for example, anti-neoplastics, are based on estimated values of BSA. METHODS: Published data from measured BSA in 268 children and infants (median age: 8 month; range: 0-18 years) were compared with BSA values estimated by the Mosteller formula. Correlation between estimated and measured BSA values was performed by the Spearman rank correlation. Bias and precision were evaluated as outlined by Sheiner and Beal. Measured and estimated BSA values were compared by the Eksborg's plot. RESULTS: Measured values of BSA and BSA values estimated by the Mosteller formula were closely correlated (r(s) = 0.973; p < 0.0001). The formula of Mosteller had with a precision of 9.38% and underestimated BSA by 4.06%. The quotients Estimated/Measured BSA were within the range 0.9-1.1 in 71.3% of the observations, but deviation up to 35% occurred. CONCLUSION: The Mosteller formula underestimates BSA in the paediatric population and must be used with precautions because of low precision, most pronounced in neonates and infants.

Recent drug history in children visiting a pediatric emergency room and documentation in medical records.

AIMS: We performed a systematic analysis of which drugs, prescribed, over the counter (OTC), and/or natural remedies, children had used prior to visiting a pediatric emergency room (ER), and to compare this information with the documentation of drug use in the medical records. METHODS: A questionnaire study was performed at a pediatric ER in a Swedish university hospital during 3 weeks in April 2008. The questionnaire was validated through an interview with a subgroup of participants. Only drug use associated with the time of that hospital visit was requested. Information was compared with information in medical records related to the same visit. RESULTS: Two hundred and seventy-four children aged 0-18 (median 2) years were enrolled, representing 28% of the total number of patients visiting the ER within the time frame. Forty% (n = 109) of participants reported use of prescribed drugs, 65% (n = 172) OTC drugs, and 8% (n = 17) natural remedies prior to the ER visit. The most common drugs in the three groups were salbutamol, paracetamol, and omega fatty acids, respectively. In the medical records, no more than 50% of the reported drug intake could be found, representing 74% of prescribed drugs but only 34% of OTC drugs and 27% of natural remedies. CONCLUSIONS: The majority of children had used drugs, both prescribed and OTC, before coming to the ER , but this drug intake, and especially that of nonprescribed drugs, was often not documented in the medical records.

Off-label drug use evaluation in paediatrics--applied to ciprofloxacin when used as treatment of cholangitis.

PURPOSE: To evaluate drug and indication specific off-label use in paediatrics, applied to ciprofloxacin (CPFX) in cholangitis. METHODS: We collected four different sets of data for an off-label drug use evaluation. (1) Literature review from medical journals, (2) the use and safety profile from the whole Swedish paediatric population by extracting data from national registers, (3) locally performed retrospective drug chart reviews, and (4) interviews regarding paediatric patients with CPFX treated cholangitis. RESULTS: The literature reviews show a lack of information for paediatric use of CPFX in cholangitis. The prescribing of CPFX to Swedish children has grown over the last decade and generated a small number of reports for adverse drug reactions. In our local biliary atresia population 32 patients had suffered from at least one episode of cholangitis and 13 patients had been prescribed CPFX. The dosing strategy had an empirical prescribing approach, since monitoring of bacterial resistance and efficacy is difficult in the biliary ducts. No clear relationship was seen between dosing and age/weight. Reports of suspected side effects could not be found in the retrospective chart reviews. The interviews show that the existing dosage forms are well accepted. CONCLUSIONS: This drug use evaluation creates awareness of the off-label situation. The international and national data are sparse for the paediatric use of CPFX in cholangitis. Locally we have highlighted a heterogeneous dosing strategy of CPFX, drug/drug interactions, and the need to monitor and report the risk of short- and long-term adverse drug reactions.

Cytochrome P450 3A activity in mothers and their neonates as determined by plasma 4ß-hydroxycholesterol.

PURPOSE: The purpose of this study was to determine the 4ß-hydroxycholesterol to cholesterol ratio in mothers and neonates at the time of birth and 4 months post-partum. METHOD: 21 mothers and 22 neonates were recruited at the delivery ward at Karolinska University Hospital, Huddinge, Sweden. Blood samples taken from mothers and neonates at birth and 4 months post-partum were analysed for 4ß-hydroxycholesterol and cholesterol. RESULTS: The median plasma concentration of 4ß-hydroxycholesterol was higher in mothers at delivery (50 ng/mL) compared to healthy non-pregnant women (29 ng/mL). The pregnant women had a higher median cholesterol concentration (6.2 mmol/L) compared to healthy non-pregnant women (4.6 mmol/L) but this could only partly explain the increased 4ß-hydroxycholesterol. The major cause is an increased CYP3A activity during pregnancy. The median 4ß-hydroxycholesterol/cholesterol ratio·10(4) was elevated in mothers at time of birth compared to non-pregnant women (0.19 and 0.15, respectively) but decreased to 0.15 4 months post-partum. Neonates had a median 4ß-hydroxycholesterol/cholesterol ratio·10(4) (0.19) comparable to adults already at birth, but lower 4ß-hydroxycholesterol (12 ng/mL) and cholesterol (1.8 mmol/L) concentrations. CONCLUSION: Pregnancy leads to increased CYP3A enzyme activity as determined by the 4ß-hydroxycholesterol/cholesterol ratio. Neonates have low 4ß-hydroxycholesterol and cholesterol concentrations but similar total CYP3A activity as adults already at birth.

Over-the-counter drug use--estimations within the Swedish paediatric population.

We have used three different sources to estimate the use of drugs sold over the counter (OTC) by the Swedish paediatric population during 2007-2008 as part of a European evaluation initiated by the European Medicines Agency. An estimation of the paediatric use from the total numbers of over-the-counter drugs (OTCD) packages sold by Swedish pharmacies and analyses of two separate questionnaires directed towards a population of 11- to 14-year-old children and another towards visitors to one of the paediatric emergency wards in Stockholm County were included in the study. In Sweden, 1.25 OTC packages are sold quarterly per child (0-18 years), and the children in both questionnaire studies use, on average, 0.9 OTC substances. Sixty-five percent of the children visiting an emergency ward and 67% of the 13-year-old Stockholm inhabitants had used at least one OTCD. OTCD use among children is common. Interpretation of OTCD data must be done carefully since questions with regard to OTCD use is subject to recall bias and the number of packages sold to children is hypothesised through a conversion factor.

Transfer of buprenorphine into breast milk and calculation of infant drug dose.

Little is known about the safety of buprenorphine (BUP) in breastfeeding. The aim of this work was to investigate the transfer of buprenorphine and its main active metabolite, norbuprenorphine (n-BUP), into human milk and to determine the drug dose and effects in exposed infants. Seven lactating women, who were maintained on BUP treatment because of previous opiate addiction, were studied in an open observational study. All mothers had a strong wish to breastfeed their newborn infants. Buprenorphine samples for analysis were collected from the urine of 6 infants together with breast milk, blood, and urine from their mothers during a 24-hour period in the week after birth. One mother-infant pair was studied at 9 months of age. Buprenorphine and n-BUP were analyzed by a liquid chromatography/mass spectrometry method suitable for handling different matrices. Buprenorphine and n-BUP were found in low levels in the infants' urine. Breastfed infants were exposed to a calculated BUP dose per kg bodyweight less than 1%, with an average milk/plasma area under the curve of 1.7 (range, 1.1-2.8) for BUP and 0.7 (range, 0.4-1.2) for n-BUP. These data support the use of BUP during breastfeeding. However, the authors recommend that infants be monitored closely.