The lived experience by patients and family members of extracorporeal membrane oxygenation: A qualitative study.

OBJECTIVE: To examine the lived experience of extracorporeal membrane oxygenation (ECMO) by patients and their families, and their relationship with intensive care clinicians. RESEARCH METHODOLOGY: Semi-structured interviews were conducted with six patients who had received ECMO and with four of their family members. The data were analysed narratively using a constant comparative method. SETTING: Patients were treated at a major acute care hospital in British Columbia between 2014 and 2021. ECMO was used either as a bridge to recovery or to organ transplant. Four had family members bedside throughout, while two had virtual visits due to COVID-19 infection control measures. FINDINGS: ECMO was experienced through a triad of relationships between the patient, key family members and key clinicians. The strength, directionality and focus of these relationships shifted during therapy and realigned once ECMO was removed. The largest shift involved family members. Post-ECMO, patients relied almost entirely on spouses, adult children and clinical team members to reconstruct their experience. The connection between families and clinical team members was limited and changed little. CONCLUSIONS: The lived experience of ECMO was complex in ways yet to be comprehensively reported in the literature. This technology had particular impact on family members when ECMO was used as a bridge to transplant and where run times extended to multiple weeks. COVID-19 infection control restrictions further complicated how this technology was experienced. Findings from this study highlight the importance of intensive care nurses recognising the critical role family members play as witnesses whose experiences later allow patients to make sense of their journey post-discharge.

The effectiveness of person-centred quality improvement strategies on the management and control of hypertension in primary care: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the effectiveness of person-centred quality improvement strategies on the management and control of adults with hypertension in primary care. METHODS: A systematic review and meta-analysis was conducted using the Medline, Cochrane Central Register for Controlled Trials, Embase, Cumulative Index to Nursing and Allied Health Literature, and APA PsycINFO databases (January 1980 to March 2020). Randomized controlled trials that evaluated person-centred quality improvement strategies for the management and control of essential hypertension among adults ( ≥ 18 years) in primary care were included. Random effects models were used to estimate weighted mean differences (WMD) for the change in systolic and diastolic blood pressures (SBP, DBP) from baseline; risk ratios (RR) were calculated for the proportion of participants achieving target blood pressures, for each quality improvement strategy assessed. A qualitative review of the implementation details of the interventions was conducted to identify common components of interventions that were effective in improving blood pressure outcomes. RESULTS: Eight studies were included (total of 5654 patients). Findings favour use of person-centred quality improvement interventions over usual care (RR = 1.23 [95% CI: 1.01; 1.48]) for improving blood pressure outcomes. Self-management (RR = 1.43 [95% CI: 1.23; 1.65]) had the greatest effects on blood pressure targets. Clinician education resulted in the greatest SBP reduction (WMD:6.09 mmHg [95% CI: 2.32; 9.85]), while patient education and patient reminder systems (both WMD:4.86 mmHg [95% CI: 0.88; 8.83]) saw the most improvements in DBP. While interventions varied in their strategy implementation, common features of effective interventions included tailored communication with patients, use of health information technology, and multidisciplinary collaboration. CONCLUSION: Person-centred quality improvement strategies were effective in improving blood pressure outcomes. Further research is needed regarding the context of implementing interventions to provide greater insight into the components of a person-centred quality improvement intervention most effective in improving hypertension outcomes.

A Qualitative Systematic Review of Facilitators of and Barriers to Community Pharmacists-Led Anticoagulation Management Service.

OBJECTIVE: To identify the facilitators of and barriers to the implementation of Community Pharmacists-Led Anticoagulation Management Services (CPAMS). DATA SOURCES: MEDLINE, EMBASE, CINAHL, Cochrane Database of Systematic Reviews, and Cochrane CENTRAL Register of Controlled Trials were searched from inception until August 20, 2021. STUDY SELECTION AND DATA EXTRACTION: All abstracts proceeded to full-text review, which was completed by 2 reviewers. Data extraction was completed by a single reviewer and verified. Analysis was completed using best-fit framework synthesis. DATA SYNTHESIS: A total of 17 articles reporting on CPAMS from 6 jurisdictions were included: 2 Canadian provincial programs (Nova Scotia, Alberta), a national program (New Zealand), and 3 cities in the United Kingdom (Whittington and Brighton and Hove) and Australia (Sydney). Facilitators of CPAMS included convenience for patients, accessibility for patients, professional satisfaction for pharmacists, increased efficiency in anticoagulation management, improved outcomes, enhanced collaboration, and scalability. Barriers included perceived poor quality of care by patients, resistance by general practitioners, organizational limits, capping of the number of eligible patients, and cost. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: The barriers and facilitators identified in this review will inform health policy makers on the implementation and improvement of CPAMS for patients and health care practitioners. CONCLUSION AND RELEVANCE: CPAMS has been implemented in 6 jurisdictions across 4 countries, with reported benefits and challenges. The programs were structurally similar in most jurisdictions, with minor variations in implementation. New anticoagulation management programs should consider adapting existing frameworks to local needs.

A scoping review of opioid harm reduction interventions for equity-deserving populations.

Background: Morbidity and mortality associated with opioid use has become a North American crisis. Harm reduction is an evidence-based approach to substance use. Targeted harm reduction strategies that consider the needs of specific populations are required. The objective of this scoping review was to document the range of opioid harm reduction interventions across equity-deserving populations including racialized groups, Indigenous peoples, LGBTQIA2S+, people with disabilities, and women. Methods: Ten databases were searched from inception to July 5th, 2021. Terms for harm reduction and opioid use formed the central concepts of the search. We included studies that: (1) assessed the development, implementation, and/or evaluation of harm reduction interventions for opioid use, and (2) reported health-related outcomes or presented perspectives that directly related to experiences receiving or administering harm reduction interventions, (3) were completed within an equity-deserving population and (4) were completed in New Zealand, Australia, Canada or the US. A knowledge map was developed a-priori based on literature outlining different types of harm reduction interventions and supplemented by the expertise of the research team. Findings: 12,958 citations were identified and screened, with 1373 reviewed in full-text screening. Of these, 15 studies were included in the final dataset. The most common harm reduction program was opioid agonist treatment (OAT) (n = 11, 73%). The remaining four studies included: overdose prevention; drug testing equipment; and outreach, peer support, and educational programs for safer use. Nine studies focused on women, primarily pregnant/post-partum women, three focused on Indigenous peoples, and three studies included racialized groups. No studies were identified that provided any information on persons with a disability or members of the LGBTQIA2S+ population. Interpretation: The scant opioid specific harm reduction literature on equity-deserving populations to date has primarily focused on OAT programs and is focused primarily on women. There is a need for more targeted research to address the diverse social experiences of people who use drugs and the spectrum of harm reduction interventions that are needed. There is also a need to acknowledge the history of harm reduction as a drug-user activist movement aimed at challenging bio-medical paradigms of drug use. Further, there is a need to recognize that academic research may be contributing to health inequity by not prioritizing research with this lens. Funding: This research was funded by the Canadian Institutes of Health Research.

Skin and soft tissue infections in hospitalized cancer patients: A retrospective study.

OBJECTIVES: To assess the clinical and epidemiological characteristics of hospitalized cancer patients with skin and soft-tissue infections (SSTIs). METHODS: An observational retrospective study was conducted between March 2016 and December 2020 at the Oncology Department of King Saudi Medical City, Riyadh, Saudi Arabia. Patients with complicated and uncomplicated SSTIs were included. RESULTS: A total of 204 cancer patients with SSTIs were evaluated. The incidence of SSTIs was 1.67% (204/12,203). Breast cancer (39%) was the most common solid tumor in all patients with SSTIs. Exit site infection (n=84, 41.2%) was the most common SSTI in cancer patients, followed by wound infection (n=72, 35.3%), and cellulitis (n=44, 21.5%). The majority of patients received appropriate antimicrobial therapy (n=150, 73.5%). CONCLUSION: This study has shown a modest incidence of SSTIs in hospitalized cancer patients, with many of the patients received appropriate antimicrobial therapy.

The effect of interventions targeting gut microbiota on depressive symptoms: a systematic review and meta-analysis.

BACKGROUND: Despite their popularity, the efficacy of interventions targeting gut microbiota to improve depressive symptoms is unknown. Our objective is to summarize the effect of microbiome-targeting interventions on depressive symptoms. METHODS: We conducted a systematic review and meta-analysis. We searched MEDLINE, Embase, PsycINFO, Database of Abstracts of Reviews of Effects, Cochrane Database of Systematic Reviews and the Cochrane Controlled Register of Trials from inception to Mar. 5, 2021. We included studies that evaluated probiotic, prebiotic, synbiotic, paraprobiotic or fecal microbiota transplant interventions in an adult population (age ≥ 18 yr) with an inactive or placebo comparator (defined by the absence of active intervention). Studies must have measured depressive symptoms with a validated scale, and used a randomized controlled trial study design. We conducted a random effects meta-analysis of change scores, using standardized mean difference as the measure of effect. RESULTS: Sixty-two studies formed the final data set, with 50 included in the meta-analysis. Probiotic, prebiotic, and synbiotic interventions on depressive symptoms showed statistically significant benefits. In the single studies evaluating each of fecal microbiota transplant and paraprobiotic interventions, neither showed a statistically significant benefit. INTERPRETATION: Despite promising findings of benefit of probiotic, prebiotic and synbiotic interventions for depressive symptoms in study populations, there is not yet strong enough evidence to favour inclusion of these interventions in treatment guidelines for depression. Critical questions about species administered, dosage and timing relative to other antidepressant medications remain to be answered. STUDY REGISTRATION: PROSPERO no. 143178.

Medication Misadventures Among COVID-19 Patients in Saudi Arabia.

BACKGROUND: Due to the need for early and effective medications for coronavirus disease (COVID-19), less attention may have been paid to medication safety during this pandemic. OBJECTIVES: This study aimed to examine the incidence, nature, and seriousness of medication errors (MEs) and adverse drug reactions (ADRs) among hospitalized patients with COVID-19. MATERIALS AND METHODS: This is a retrospective study of MEs and ADRs reported at the King Saud Medical City (KSMC) between April 2020 and September 2020. RESULTS: A total of 343 MEs and 416 ADRs were reported during the study period. The incidence of MEs was 19% (19/100). Seventy-five MEs (21.5%) reached the patient but did not cause any harm. Wrong dose (n=101, 29.4%) was the most common type of MEs. Physicians were the most common source of MEs (87.5%). Antibiotics (32%) and antineoplastics (25%) were the most common drug categories involved in MEs and ADRs, respectively. Thirty-nine percent (n=163) of the ADRs were of serious nature. 24% (n=100) required hospitalization, 5% (n=21) were life-threatening, 16 (3.8%) required intervention to prevent permanent impairment or damage, and 6.2% (n=26) resulted in the discontinuation of treatment. CONCLUSION: The reporting of MEs appears to be high among COVID-19 patients in a large tertiary care setting in the Kingdom of Saudi Arabia (KSA). The majority of MEs were caused by dosing errors and errors in drug frequency, mostly ascribed to physicians, which may be indicative of burnout or stress among them. The reporting of MEs and ADRs can be improved by providing incentives to healthcare professionals (HCPs) and promoting a non-punitive culture. Further studies should explore the clinical consequences of medication misadventures in hospitalized COVID-19 patients.

A Retrospective Study of Pediatric Medication Errors in Saudi Arabia.

Background: The peculiarities of medication errors (MEs) among the pediatric population in the Middle East have not been adequately explored. In this study, we describe the MEs reported at the largest tertiary hospital in Saudi Arabia. Methods: This study is a retrospective analysis of MEs reported by health care professionals at a large tertiary hospital in Saudi Arabia between 2015 and 2016. Results: There were a total of 9123 MEs involving 84 different medications. In total, 109 382 drugs were ordered. Thus, 8.3 MEs per 100 prescriptions were reported during the study period. Thirty-nine errors (0.4%) reached the patient, but did not cause any harm. Transcribing errors accounted for more than half of the MEs (n = 4856, 53.2%). Physicians were the least likely to report an ME (n = 159, 1.7%), whereas pharmacists reported more MEs than any other health care professional (n = 4924, 54%). The most common drug causes of MEs were paracetamol, salbutamol, and amoxicillin, which accounted for 21.0%, 16.6%, and 12.4% of MEs, respectively, over the study period. Conclusions: Medication errors are common in pediatric care, especially for drugs such as paracetamol and amoxicillin that are frequently prescribed. Transcription error was common in this study and is more likely to be reported by pharmacists.

Diabetic Retinopathy Screening: A Systematic Review of Qualitative Literature.

OBJECTIVES: Diabetic retinopathy is a common microvascular complication that leads to vision loss. Despite national and international organizations developing guidelines for diabetic retinopathy screening, patients with diabetes remain unscreened. Our aim was to understand facilitators and barriers influencing diabetic retinopathy screening attendance and to examine factors that promote program success. METHODS: MEDLINE, Embase, PsycINFO and CINAHL from inception until September 23, 2019, were used for data collection. Studies were included if they were original qualitative research articles, included adults >18 years of age and assessed diabetic retinopathy screening programs or retinopathy screening as a component of a general diabetes care program. A "best-fit" framework synthesis methodology was used for this analysis. RESULTS: Twenty-nine articles involving 1,433 participants were identified. Six themes of barriers to, and facilitators of, diabetic retinopathy screening were identified, including access to screening, knowledge and information sharing, training and skills competency, service delivery, cultural competency and psychological factors. Cost and competing interests were common barriers to access; lack of knowledge about screening services was also a frequently reported barrier. Both patients and providers identified the need for improved service delivery, especially the referral and follow-up process. Providers recognized the need for additional training, patients enumerated several psychological barriers to screening uptake and cultural considerations were believed to be important, particularly among Indigenous communities. CONCLUSIONS: To improve screening uptake, the identified challenges must be addressed while also reinforcing the facilitators. Furthermore, program administrators could model new and unsuccessful screening programs after the successful ones while also considering local peculiarities.

Immunogenicity and Safety of Reduced-Dose Intradermal vs Intramuscular Influenza Vaccines: A Systematic Review and Meta-analysis.

Importance: Low-dose intradermal influenza vaccines could be a suitable alternative to full intramuscular dose during vaccine shortages. Objective: To compare the immunogenicity and safety of the influenza vaccine at reduced or full intradermal doses with full intramuscular doses to inform policy design in the event of vaccine shortages. Data Sources: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched for studies published from 2010 until June 5, 2020. Study Selection: All comparative studies across all ages assessing the immunogenicity or safety of intradermal and intramuscular influenza vaccinations were included. Data Extraction and Synthesis: Data were extracted by a single reviewer and verified by a second reviewer. Discrepancies between reviewers were resolved through consensus. Random-effects meta-analysis was conducted. Main Outcomes and Measures: Primary outcomes included geometric mean titer, seroconversion, seroprotection, and adverse events. Results: A total of 30 relevant studies were included; 29 studies were randomized clinical trials with 13 759 total participants, and 1 study was a cohort study of 164 021 participants. There was no statistically significant difference in seroconversion rates between the 3-µg, 6-µg, 7.5-µg, and 9-µg intradermal vaccine doses and the 15-µg intramuscular vaccine dose for each of the H1N1, H3N2, and B strains, but rates were significantly higher with the 15-µg intradermal dose compared with the 15-µg intramuscular dose for the H1N1 strain (rate ratio [RR], 1.10; 95% CI, 1.01-1.20) and B strain (RR, 1.40; 95% CI, 1.13-1.73). Seroprotection rates for the 9-µg and 15-µg intradermal doses did not vary significantly compared with the 15-µg intramuscular dose for all the 3 strains, except for the 15-µg intradermal dose for the H1N1 strain, for which rates were significantly higher (RR, 1.05; 95% CI, 1.01-1.09). Local adverse events were significantly higher with intradermal doses than with the 15-µg intramuscular dose, particularly erythema (3-µg dose: RR, 9.62; 95% CI, 1.07-86.56; 6-µg dose: RR, 23.79; 95% CI, 14.42-39.23; 9-µg dose: RR, 4.56; 95% CI, 3.05-6.82; 15-µg dose: RR, 3.68; 95% CI, 3.19-4.25) and swelling (3-µg dose: RR, 20.16; 95% CI, 4.68-86.82; 9-µg dose: RR, 5.23; 95% CI, 3.58-7.62; 15-µg dose: RR, 3.47 ; 95% CI, 2.21-5.45). Fever and chills were significantly more common with the 9-µg intradermal dose than the 15-µg intramuscular dose (fever: RR, 1.36; 95% CI, 1.03-1.80; chills: RR, 1.24; 95% CI, 1.03-1.50) while all other systemic adverse events were not statistically significant for all other doses. Conclusions and Relevance: These findings suggest that reduced-dose intradermal influenza vaccination could be a reasonable alternative to standard dose intramuscular vaccination.

Clinical trials in Asia: A World Health Organization database study.

BACKGROUND AND OBJECTIVE: The Asian continent appears to be a growing destination for conducting cost-effective clinical trials, utilizing the available pool of treatment naïve subjects. This study aims to determine the growth rate of clinical trials in Asia. METHODS: A database review was conducted. Registered clinical trials conducted in selected countries in Asia, Europe, Australia, and North America between 2008 and 2017 were searched from the International Clinical Trial Registry Platform. Compound Annual Growth Rate was determined for registered clinical trials. RESULTS: During the 10-year period, a total of 125,918 registered clinical trials were conducted in Asia. There was a 7-fold increase in the number of registered clinical trials in Asia. More trials were registered in Japan than any other Asian country (30.8%). The average annual increase in the number of registered trials was generally higher in Asia than the United States of America, Canada, EU countries, or Australia. Iran recorded the highest average annual increase in the number of all clinical trials in Asia (41.9%). The number of pediatric clinical trials in Iran also increased annually by an average of 30.4%, more than any other country included in this study. CONCLUSIONS: Clinical trials recruitment in Asia is increasing faster than Europe, North America, and Australia. Lower trial cost and large patient pool may be contributory to this increase.

Variability in the burden of disease estimates with or without age weighting and discounting: a methodological study.

OBJECTIVES: This study examines the impact of the type of method used on the estimation of the burden of diseases. DESIGN: Comparison of methods of estimating disease burden. SETTING: Four metrics of burden of disease estimation, namely, years of potential life lost (YPLL), non-age weighted years of life lost (YLL) without discounting and YLL with uniform or non-uniform age weighting and discounting were used to calculate the burden of selected diseases in three countries: Australia, USA and South Africa. PARTICIPANTS: Mortality data for all individuals from birth were obtained from the WHO database. OUTCOMES: The burden of 10 common diseases with four metrices, and the relative contribution of each disease to the overall national burden when each metric is used. RESULTS: There were variations in the burden of disease estimates with the four methods. The standardised YPLL estimates were higher than other methods of calculation for diseases common among young adults and lower for diseases common among the elderly. In the three countries, discounting decreased the contributions of diseases common among younger adults to the total burden of disease, while the contributions of diseases of the elderly increased. After discounting with age weighting, there were no distinct patterns for diseases of the elderly and young adults in the three countries. CONCLUSIONS: Given the variability in the estimates of the burden of disease with different approaches, there should be transparency regarding the type of metric used and a generally acceptable method that incorporates all the relevant social values should be developed.

A Neonatal Unit Experience with Empiric Antibiotics for Late-onset Neonatal Sepsis: A Retrospective Study.

Neonatal sepsis remains a major cause of morbidity and mortality and warrants the immediate start of appropriate empiric treatment. Thus, this study compared the effectiveness of the 2 antibiotic regimens (cloxacillin-amikacin or cefotaxime-ampicillin) among neonates with late-onset neonatal sepsis. METHODS: We conducted a retrospective cohort study comparing mortality between 2 treatment cohorts of very low birth weight neonates with late-onset sepsis, who had received amikacin-cloxacillin or cefotaxime-ampicillin between January 2014 and December 2017. There were 27 neonates in each treatment arm after 1:1 propensity score matching. Univariate analyses (Chi-square and independent t tests, where appropriate) were performed to determine the association between variables. We determined the hazard ratio for all-cause mortality using the Cox regression model. RESULTS: We identified a total of 132 neonates from the hospital's record. We included 27 neonates each in the amikacin-cloxacillin and cefotaxime-ampicillin groups. Intraventricular hemorrhage, necrotizing enterocolitis, birth weight, and gestational age were significantly associated with mortality (P < 0.05). The risk of mortality was significantly higher in neonates receiving empiric cefotaxime and ampicillin than those receiving amikacin and cloxacillin (hazard ratio: 2.91, 95% confidence interval: 1.17-7.30, P = 0.023). CONCLUSIONS: In our center, amikacin-cloxacillin combination therapy was associated with lower mortality in very low birth weight neonates with late-onset sepsis compared with cefotaxime-ampicillin therapy.

Systematic Review of the Efficacy and Safety of Gabapentin and Pregabalin for Pain in Children and Adolescents.

The barriers to opioid use in some countries necessitate the need to identify suitable alternatives or adjuncts for pain relief. The gabapentinoids (gabapentin and pregabalin) are approved for the management of persistent pain in adults, but not in children. Searches were conducted in Embase, Medline, Scopus, and Web of Science up until November 2017, for randomized controlled trials that investigated the analgesic effects of gabapentin or pregabalin in children and adolescents <18 years of age. A total of 7 publications were identified, 5 regarding gabapentin as prophylactic postsurgical pain relief for either adenotonsillectomy (n = 3) or scoliosis surgery (n = 2), and 1 for gabapentin treatment of chronic regional pain syndrome/neuropathic pain. One study investigated the efficacy of pregabalin as a treatment for fibromyalgia. Based on the studies' primary outcomes alone, neither of the chronic pain studies involving gabapentin and pregabalin showed significant efficacy compared with amitriptyline or placebo, respectively. Two of the prophylactic gabapentin studies for adenotonsillectomy and idiopathic scoliosis surgery reported significantly fewer children requiring analgesia and lower opioid requirement, respectively, compared with placebo. Two of the identified clinical trials (conducted by the same first author) on the efficacy of gabapentin for prophylactic postadenotonsillectomy pain relief were omitted from narrative synthesis due to clear evidence of fabricated data. Overall, this review identified a paucity of evidence for the analgesic effect and safety of gabapentinoids in children. We also suggest audit of any current evidence-based practice and clinical guidelines that have cited the research studies with fabricated data.

Adverse drug reaction reporting in a large tertiary hospital in Saudi Arabia: results of an incentive strategy.

BACKGROUND: Underreporting is a common problem with spontaneous adverse drug reaction (ADR) reporting. In this study, we aim to describe the reporting of ADRs in a tertiary hospital and determine the effect of incentives to healthcare professionals on ADR reporting. METHODS: In this interventional study, a time series analysis was used to determine the effect of incentives on ADR reporting in a tertiary hospital between 2015 and 2016. The incentive strategy included public commendation of health care providers and nomination for a monthly award. RESULTS: A total of 967 ADRs were reported over a 2-year period. After the introduction of incentives in January 2016, the number of ADR reports per month increased by 40.6 (95% confidence interval: 26.1-55.1). The proportion of serious ADRs reported was significantly higher in 2016 (39/800) than 2015 (0/167) (p < 0.001). In 2016, there was a significant association between profession and serious ADR reporting (p < 0.001). A total of 14/21 ADRs (66.7%) reported by physicians in 2016 were serious compared with 20/700 (2.9%) reported by clinical pharmacists and 5/72 (6.9%) by nurses. CONCLUSIONS: ADR reporting was improved by providing incentives, including commendation and reward, to healthcare professionals.

Discontinuities and disruptions in drug dosage guidelines for the paediatric population.

AIMS: This study investigates paediatric drug dosage guidelines with the aim of investigating their agreement with body surface area (BSA) scaling principles. METHODS: A total of 454 drug dosage guidelines listed in the AMH-CDC 2015 were examined. Data extracted included the administration, frequency and dose per age bracket from 0 to 18 years. Drug treatments were categorized as follows: (1) The same dose recommendation in milligrams per kilogram (mg kg-1 ) for all age/weights; (2) Change in the mg kg-1 dosing according to age/weight; (3) Change in dose in mg according to age/weight; (4) Change from mg kg-1 dosing to a dose in mg according to age/weight; (5) The same recommendation for all age/weight groups in mg; or (6) BSA dosing. Example drugs were selected to illustrate dose progression across ages. RESULTS: Most drug treatments (63%) have the same mg kg-1 dose for all age/weight groups, 14% are dosed in mg kg-1 across all ages with dose changes according to age/weight, 13% were dosed in mg across all ages with dose changes, 10% switched from mg kg-1 to a set dose in mg, 4.2% have the same dose in mg for all age and weight groups and 2.2% are dosed according to BSA. CONCLUSIONS: Paediatric dosage guidelines are based on weight-based formulas, available dosing formulations and prior patterns of use. Substantial variation from doses predicted by BSA scaling are common, as are large shifts in recommended doses at age thresholds. Further research is required to determine if better outcomes could be achieved by adopting biologically based scaling of paediatric doses.

Safety of antiepileptic drugs in children and young people: A prospective cohort study.

PURPOSE: This study aims to describe the incidence of adverse drug reactions (ADRs) in children receiving antiepileptic drugs (AEDs) and compare ADRs to the individual drugs when given as monotherapy. METHOD: Paediatric patients (≤18 years old) were enrolled for this prospective observational study over a 6-month period, between September 2015 and March 2016. Adverse reactions to antiepileptic drugs (AEDs) were elicited at the time of enrolment and after 3 months using the Paediatric Epilepsy Side Effects Questionnaire. RESULTS: A total of 1139 suspected ADRs were reported in 124 participants. Eighteen different AEDs were prescribed. Sixty-six children (53%) were receiving AED monotherapy at the time of recruitment; 34/66 (52%) of whom received new generation AEDs. Levetiracetam was the most frequently prescribed AED (62/124, 50%). When only children receiving AED monotherapy were considered, fatigue, drowsiness, weight gain, dizziness were less likely with levetiracetam (p < .01). Slow thinking and decreased concentration were less likely with levetiracetam or carbamazepine than valproic acid (p < .05). Five patients (four on polytherapy) discontinued AED treatment due to ADRs and 2 had a dose reduction. CONCLUSIONS: Levetiracetam and carbamazepine were better tolerated than sodium valproate.

Retrospective review of paediatric case reports of Stevens-Johnson syndrome and toxic epidermal necrolysis with lamotrigine from an international pharmacovigilance database.

OBJECTIVES: This study aims to characterise paediatric reports with lamotrigine (LTG) and Stevens-Johnson syndrome or toxic epidermal necrolysis (SJS/TEN), and to explore whether potential risk factors can be identified. DESIGN: This is a retrospective review of suspected adverse drug reaction (ADR) reports. Reported time from LTG start to SJS/TEN onset, indication for use and dose was explored. To identify potential risk groups, report features (eg, ages, patient sex, co-reported drugs) for LTG and SJS/TEN were contrasted with two reference groups in the same database, using shrinkage logOR. SETTING: Reports were retrieved from VigiBase, the WHO global database of individual case safety reports, in January 2015. PATIENTS: Data for patients aged ≤17 years old were extracted. RESULTS: There were 486 reports of SJS/TEN in LTG-treated paediatric patients. Ninety-seven per cent of the cases with complete information on time to onset of SJS/TEN occurred within 8 weeks of initiation of LTG therapy. The median time to onset was 15 days (IQR: 10-22 days). The proportion of SJS/TEN with LTG and valproic acid (VPA) co-reporting was significantly more than non-cutaneous ADRs (43% vs 19%, (logOR: 1.60 (99% CI: 1.33 to 1.84)). CONCLUSIONS: The results suggest that VPA co-medication with LTG therapy is a risk factor for SJS/TEN in the paediatric population. Although this relationship has been identified from individual case reports, this is the first supportive study from a large compilation of cases. SJS/TEN risk is highest in first 8 weeks of treatment with LTG in children and clinicians should be aware of this risk during this period.

Anti-epileptic drug utilisation in paediatrics: a systematic review.

OBJECTIVES: This study aims to determine global anti-epileptic drug (AED) utilisation prevalence and describe utilisation trends in different countries. METHODS: Databases Embase (1980-May 2017), Medline (1946-May 2017) and PubMed were searched for original research on AED utilisation. All paediatric national or regional database studies and surveys were included. RESULTS: Twenty-one studies were identified. Five were excluded from the analysis as the data were collected before 2005, leaving 16 studies. Monotherapy regimen varied between 58% and 94% in different countries. In several of the studies, sodium valproate was the most frequently prescribed AED. However, there is a trend towards increasing utilisation of new-generation AEDs, particularly levetiracetam, in some countries. CONCLUSION: Monotherapy was used in 58%-94%of patients. There is increasing utilisation of the new-generation AEDs, in particular lamotrigine, levetiracetam and topiramate. Old-generation AEDs are still used in the majority of patients. There is a need for up-to-date studies to determine the prevalence of AEDs in children.

Protocol for a prospective observational study of adverse drug reactions of anti-epileptic drugs in children in the UK.

BACKGROUND: Epilepsy is a common chronic disease of children that can be treated with anti-epileptic drugs (AEDs). AEDs, however, have significant side effects. Newer AEDs are thought to have fewer side effects. There have, however, been few comparative studies of AED toxicity. The aim is to compare the safety profile of the most frequently used AEDs by performing a multicentre prospective cohort study. This protocol describes the planned study. DESIGN: A multicentre prospective cohort study of children on AED treatment in hospitals across the UK. Ethical approval will be obtained. SAMPLE SIZE: Three thousand children on treatment for epilepsy will be recruited from paediatric clinics. It is expected that this sample size will have the potential to compare toxicity between the most frequently used AEDs. DURATION OF STUDY: 24 months. OUTCOME MEASURE: Adverse drug reactions (ADRs) to AEDs. These will be identified by the use of a validated questionnaire, the Paediatric Epilepsy Side Effect Questionnaire. They will be evaluated using the Naranjo algorithm. Preventability will be assessed using the Schumock and Thornton scale. DISCUSSION: Toxicity of individual AEDs when given as monotherapy and polytherapy will be determined. Additionally, discontinuation rates due to ADRs will be determined. The data will assist clinicians in choosing AEDs with the least toxicity.