Properties and clinical performance of vaccines containing outer membrane vesicles from Neisseria meningitidis.

Background 
Adverse drug reactions in children are an important public health problem. We have undertaken a systematic review of observational studies in children in three settings: causing admission to hospital, occurring during hospital stay and occurring in the community. We were particularly interested in understanding how ADRs might be better detected, assessed and avoided.


Methods and Findings 
We searched nineteen electronic databases using a comprehensive search strategy. In total, 102 studies were included. The primary outcome was any clinical event described as an adverse drug reaction to one or more drugs. Additional information relating to the ADR was collected: associated drug classification; clinical presentation; associated risk factors; methods used for assessing causality, severity, and avoidability. Seventy one percent (72/102) of studies assessed causality, and thirty four percent (34/102) performed a severity assessment. Only nineteen studies (19%) assessed avoidability. Incidence rates for ADRs causing hospital admission ranged from 0.4% to 10.3% of all children (pooled estimate of 2.9% (2.6%, 3.1%)) and from 0.6% to 16.8% of all children exposed to a drug during hospital stay. Anti-infectives and anti-epileptics were the most frequently reported therapeutic class associated with ADRs in children admitted to hospital (17 studies; 12 studies respectively) and children in hospital (24 studies; 14 studies respectively), while anti-infectives and non-steroidal anti-inflammatory drugs (NSAIDs) were frequently reported as associated with ADRs in outpatient children (13 studies; 6 studies respectively). Fourteen studies reported rates ranging from 7%–98% of ADRs being either definitely/possibly avoidable.


Conclusions 
There is extensive literature which investigates ADRs in children. Although these studies provide estimates of incidence in different settings and some indication of the therapeutic classes most frequently associated with ADRs, further work is needed to address how such ADRs may be prevented.

Adverse Drug Reactions in Children—A Systematic Review

The utility of wild-type outer membrane vesicle (wtOMV) vaccines against serogroup B (MenB) meningococcal disease has been explored since the 1970s. Public health interventions in Cuba, Norway and New Zealand have demonstrated that these protein-based vaccines can prevent MenB disease. Data from large clinical studies and retrospective statistical analyses in New Zealand give effectiveness estimates of at least 70%. A consistent pattern of moderately reactogenic and safe vaccines has been seen with the use of approximately 60 million doses of three different wtOMV vaccine formulations. The key limitation of conventional wtOMV vaccines is their lack of broad protective activity against the large diversity of MenB strains circulating globally. The public health intervention in New Zealand (between 2004–2008) when MeNZB was used to control a clonal MenB epidemic, provided a number of new insights regarding international and public-private collaboration, vaccine safety surveillance, vaccine effectiveness esti...

https://www.tandfonline.com/doi/pdf/10.4161/hv.24129

Vaccines against meningococcal serogroup B disease containing outer membrane vesicles (OMV): Lessons from past programs and implications for the future

Objectives: To estimate the extent, nature and consequences of adverse events in a large National Health Service (NHS) hospital, and to evaluate the reliability of a two-stage casenote review method in identifying adverse events.

Design: A two-stage structured retrospective patient casenote review.

Setting: A large NHS hospital in England.

Population: A random sample of 1006 hospital admissions between January and May 2004: surgery (n = 311), general medicine (n = 251), elderly (n = 184), orthopaedics (n = 131), urology (n = 61) and three other specialties (n = 68).

Main outcome measures: Proportion of admissions with adverse events, the proportion of preventable adverse events, and the types and consequences of adverse events.

Results: 8.7% (n = 87) of the 1006 admissions had at least one adverse event (95% CI 7.0% to 10.4%), of which 31% (n = 27) were preventable. 15% of adverse events led to impairment or disability which lasted more than 6 months and another 10% contributed to patient death. Adverse events led to a mean increased length of stay of 8 days (95% CI 6.5 to 9). The sensitivity of the screening criteria in identifying adverse events was 92% (95% CI 87% to 96%) and the specificity was 62% (95% CI 53% to 71%). Inter-rater reliability for determination of adverse events was good (κ = 0.64), but for the assessment of preventability it was only moderate (κ = 0.44).

Conclusion: This study confirms that adverse events are common, serious and potentially preventable source of harm to patients in NHS hospitals. The accuracy and reliability of a structured two-stage casenote review in identifying adverse events in the UK was confirmed.

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Extent, nature and consequences of adverse events: results of a retrospective casenote review in a large NHS hospital

Background: Pediatric inpatient settings are known for their high medication error rate. The aim of this study was to investigate whether the Health Care Failure Mode and Effect Analysis (HFMEA) is a valid proactive method to evaluate circumscribed health care processes like prescription up to and including administration of chemotherapy (vincristine) in the pediatric oncology inpatient setting.

Methods: A multidisciplinary team consisting of a team leader, pharmacy, nursing and medical staff and a patient’s parent was assembled in a pediatric oncology ward with a computerized physician order entry system. A flow diagram of the process was made and potential failure modes were identified and evaluated using a hazard scoring matrix. Using a decision tree, it was determined for which failure mode recommendations had to be made.

Results: The process was divided into three main parts: prescription, processing by the pharmacy, and administration. Fourteen out of 61 failure modes were classified as high risk, 10 of which were sufficiently covered by current protocols. For the other four failure modes, five recommendations were made. Four additional recommendations were made concerning non-high risk failure modes. Most of them were implemented by the hospital management. The whole process took seven meetings and a total of 140 man-hours.

Conclusions: The systematic approach of HFMEA by a multidisciplinary team is a useful method for detecting failure modes. A patient or a parent of a patient contributes to the multidisciplinarity of the team.

/pdf/health-care-failure-mode-and-effect-analysis-a-useful-3j2sjdmh4o.pdf

Health care failure mode and effect analysis: a useful proactive risk analysis in a pediatric oncology ward

Background: Adverse drug events (ADEs) are an important problem in all hospitalized patients as these events represent medication-related patient harm. Few epidemiologic data exist regarding ADEs in the pediatric inpatient setting and, in particular, the economic impact of such ADEs upon the healthcare sector.

Incidence, preventability, and impact of Adverse Drug Events (ADEs) and potential ADEs in hospitalized children in New Zealand: a prospective observational cohort study.

Background: Although neonates are reported to be at greater risk of medication error than infants and older children, little is known about the causes and characteristics of error in this patient group. Failure mode and effects analysis (FMEA) is a technique used in industry to evaluate system safety and identify potential hazards in advance. The aim of this study was to identify and prioritise potential failures in the neonatal intensive care unit (NICU) medication use process through application of FMEA. Methods: Using the FMEA framework and a systems-based approach, an eight-member multidisciplinary panel worked as a team to create a flow diagram of the neonatal unit medication use process. Then by brainstorming, the panel identified all potential failures, their causes and their effects at each step in the process. Each panel member independently rated failures based on occurrence, severity and likelihood of detection to allow calculation of a risk priority score (RPS). Results: The panel identified 72 failures, with 193 associated causes and effects. Vulnerabilities were found to be distributed across the entire process, but multiple failures and associated causes were possible when prescribing the medication and when preparing the drug for administration. The top ranking issue was a perceived lack of awareness of medication safety issues (RPS score 273), due to a lack of medication safety training. The next highest ranking issues were found to occur at the administration stage. Common potential failures related to errors in the dose, timing of administration, infusion pump settings and route of administration. Perceived causes were multiple, but were largely associated with unsafe systems for medication preparation and storage in the unit, variable staff skill level and lack of computerised technology. Conclusion: Interventions to decrease medication-related adverse events in the NICU should aim to increase staff awareness of medication safety issues and focus on medication administration processes.

Identification of priorities for medication safety in neonatal intensive care.

Background: In medication safety research studies medication related events are often classified by type, seriousness, and degree of preventability, but there is currently no universally reliable “gold standard” approach. The reliability (reproducibility) of this process is important as the targeting of prevention strategies is often based on specific categories of event. The aim of this study was to determine the reliability of reviewer judgements regarding classification of paediatric inpatient medication related events.

Methods: Three health professionals independently reviewed suspected medication related events and classified them by type (adverse drug event (ADE), potential ADE, medication error, rule violation, or other event). ADEs and potential ADEs were then rated according to seriousness of patient injury using a seven point scale and preventability using a decision algorithm and a six point scale. Inter- and intra-rater reliabilities were calculated using the kappa (κ) statistic.

Results: Agreement between all three reviewers regarding event type ranged from “slight” for potential ADEs (κ = 0.20, 95% CI 0.00 to 0.40) to “substantial” agreement for the presence of an ADE (κ = 0.73, 95% CI 0.69 to 0.77). Agreement ranged from “slight” (κ = 0.06, 95% CI 0.02 to 0.10) to “fair” (κ = 0.34, 95% CI 0.30 to 0.38) for seriousness classifications but, by collapsing the seven categories into serious versus not serious, “moderate” agreement was found (κ = 0.50, 95% CI 0.46 to 0.54). For preventability decision, overall agreement was “fair” (κ = 0.37, 95% CI 0.33 to 0.41) but “moderate” for not preventable events (κ = 0.47, 95% CI 0.43 to 0.51).

Conclusion: Trained reviewers can reliably assess paediatric inpatient medication related events for the presence of an ADE and for its seriousness. Assessments of preventability appeared to be a more difficult judgement in children and approaches that improve reliability would be useful.

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Inter- and intra-rater reliability for classification of medication related events in paediatric inpatients.

AIMS To evaluate the frequency and characteristics of preventable medication-related events in hospitalised children, to determine the yield of several methods for identifying them and to recommend priorities for prevention. METHODS A prospective observational cohort study was conducted over a 12-week period on the paediatric wards at a university-affiliated urban general hospital in New Zealand. For all admissions of greater than 24 hours, medication-related events were identified using a multifaceted approach and subsequently classified independently by three reviewers (using a standardised reviewer form) by event type, type of error, stage of the medication process, and preventability. RESULTS There were 495 eligible study patients, who had 520 admissions and 3037 patient days of admission, during which 3160 medication orders were written. Of 761 medication-related events reported during the study period, 630 (83.3%) were identified by chart review; 111 (14.6%) by a voluntary staff quality improvement reporting system; 16 (2.1%) by interview of parents; and 4 (0.53%) events via the concurrent routine hospital-incident reporting system. Excluding duplicate reports and practice-related issues, a total of 696 study patient-specific events were included in the analysis. Excluding the inconsequential events (trivial rule violation and 'other' categories), the majority [368/399 (92.2%)] of events were found to be preventable; comprising 38/67 (56.7%) ADEs, 75/77 (97.4%) potential ADEs, and all 255 (100%) harmless medication errors. Most commonly implicated in preventable ADEs and potential ADEs were, event rate (95%CI): improper dose and the prescribing stage-35 (29 to 42) and 74 (64 to 84) respectively per 1000 patient days; and antibacterial agents and the intravenous route of administration 21 (17 to 25) and 11 (10 to 13) respectively per 100 medication orders. CONCLUSIONS Preventable medication-related events occur commonly in the paediatric inpatient setting, and importantly over half of the events that caused patient harm were deemed preventable. Voluntary staff reporting in a quality improvement environment was found to be inferior to chart review for identifying events, but a vast improvement on the conventional incident reporting system. Most commonly implicated in the harmful or potentially harmful preventable events, and hence the best targets for prevention are dosing errors, particularly during the prescribing stage of the medication use process, and use of antibacterial agents, particularly when administered by the intravenous route.

Preventable medication-related events in hospitalised children in New Zealand.

The New Zealand Pharmacovigilance Centre (NZPhvC) is the national centre responsible for monitoring adverse reactions to therapeutic products in New Zealand(NZ). The NZPhvC operates three pharmacovigilance programmes and this article explains how each of these programmes operate, focuses on their strengths and limitations, and looks to the future for medicines safety monitoring in NZ.

Desireé L. Kunac

Papers

Incidence, preventability, and impact of Adverse Drug Events (ADEs) and potential ADEs in hospitalized children in New Zealand: a prospective observational cohort study.

Identification of priorities for medication safety in neonatal intensive care.

Inter- and intra-rater reliability for classification of medication related events in paediatric inpatients.

Preventable medication-related events in hospitalised children in New Zealand.

Pharmacovigilance in New Zealand: the role of the New Zealand Pharmacovigilance Centre in facilitating safer medicines use.