Alan Ruttenberg
Melanie Courtot
The Adverse Event Reporting Ontology (AERO) is designed to facilitate the representation of adverse event reports and their evaluation in relation to clinical guidelines written by various authorities. We take a realist approach in which findings in reports are information artifacts and are related to instances or types that represent patient, symptoms, diseases, etc. We intend that use of this ontology will result in data that interoperates well with OBO Foundry ontologies as we directly use terms from OBO ontologies wherever appropriate. The initial domain for this work are reports of adverse events following immunization (AEFIs). We represent the Brighton case definitions as our guidelines, show how findings can be assessed in terms of Brighton criteria and how diagnoses of adverse events with different levels of certainty can be obtained by use of the OWL reasoner.
BrightonFormula
An annotation property reflecting the string used by Brighton in their ABC tool to encode the term
AngEdGenLoc - angioedema, localized or generalized
PHAC definition
The definition of the term as formalized in the PHAC user guide, http://www.phac-aspc.gc.ca/im/pdf/AEFI-ug-gu-eng.pdf. Those definitions are often very specific to adverse event following immunization and are intended for reporting personel.
found to exhibit
A funny kind of relation, as there is a sense in which this is really a made up relation so we can speak from a patient centric point of view. Really, the relation is established in the inverse direction - a process in which a patient or information about the patient is assessed leads to a finding about the patient.
if something is 'found to exhibit' a clinical finding, then there is a clinical finding 'that 'is clinical finding about' that something.
has component
a VAERS report has_component MedDRA term 12345
indicates the constitutive elements of a document/guideline/specification.
involves
20101115, MC: one difiiculty in defining this relation is how to "cut" the chain at the first system involved. Example (from AR): a patient has a stroke in a nexk artery, which causes brain damage. We would still say "stroke involves cardiovascular system" and NOT "stroke involves nervous system"
A relation between a clinical finding and the anatomical system or entity in which it takes place, at least partly.
is clinical finding about
A clinician records a finding that the patient has nausea
Relates a clinical finding to the patient or part about which the finding was made.
a finding is made that the heart has a malfunctioning valve
realizes
begins to exist during
located at
diagnosis guideline
A directive information entity that specifies how to establish a diagnosis based on clinical findings
disorder resulting from an AEFI process
MC, 20110120: AR mentioned that the use of is_specified_output is not appropriate, as this would indicate that the adverse event process is a planned process - specified output are things that are specified in the plan to realize a process. Adverse events are not planned process but processual entities, and therefore this should be updated. AR mentioned that BFO will include an appropriate relation.
MC, 20110120: This class should have a different label for OBO Foundry unique label. "adverse event following immunization" is a term in use by the clinician community, however in the context if the Foundry it may be confusing to associate the word "event" which seem to refer to a process with the hierarchical position under continuant. Proposed OBO Foundry label: disorder resulting from an AEFI
MC, 20110126: class renamed from "adverse event following immunization continuant" following AR suggestion
Brighton case definition
A diagnosis guideline specifying how to establish a diagnosis of adverse event with an associated degree of certainty, as developed by the Brighton Collaboration, http://www.brightoncollaboration.org/
MC, 20110126: this should be linked to the different adverse events reported. AR suggests using a new relation to appear in BFO2, maybe "ascription"
Brighton diagnosis of generalized convulsive seizure as an adverse event following immunization
PMID:14741144#Generalized convulsive seizure as an adverse event following immunization: case definition and guidelines for data collection, analysis, and presentation.
20121115, MC: originally "a categorical measurement datum whose instances are used to classify adverse events according to whether or not they have some likelihood of being a seizure and if so, to what degree"
disorder resulting from an adverse event process
MC, 20110120: This class was initially labeled "adverse event continuant". After discussion with AR, and due to the fact that the word "event" implicitely refers to a process, we renamed this class.
adverse event
ICH Topic E 2 A Clinical Safety Data Management: Definitions and Standards for Expedited Reporting
An adverse event is an undesirable, unfavorable and unintended medical occurrence presenting in a predetermined time frame following administration of a compound or usage of a device
I initialy made adverse event a defined class: is_a sign and preceded by administration. However, by doing so, and as the range of preceded by is processual entities, I was implicitely making adverse event a subclass of processual entity, therfore making adverse event rash (a continuant) inconsistent.
adverse event following immunization
Adapted from ICH Topic E 2 A Clinical Safety Data Management: Definitions and Standards for Expedited Reporting
An adverse event is an undesirable, unfavorable and unintended medical occurrence presenting in a predetermined time frame following administration of a vaccine
_manifestations
temporary placeholder - to be removed This class just helps me group some terms during development of the structure
AEFI idiopathic thrombocytopenic purpura according to Brighton
Idiopathic thrombocytopenic purpura (ITP) is the condition of having a low platelet count (thrombocytopenia) of no known cause (idiopathic).v
AEFI encephalitis according to Brighton
Encephalitis is an inflammation of the brain. It may be caused by a number of different factors. One of the most common causes is direct infection of the brain by a virus or bacterium. Inflammation can also occur as a complication of some other disorder, such as mumps (see mumps entry) or herpes simplex (see herpes infections entry).
motor manifestation
A _manifestation involving the motor system
adverse event process
An adverse event process is a processual entity occurring in a pre determined time frame following administration of a compound or usage of a device
I included the usage of a device into the definition of adverse event as I am aiming at being inclusive, and cover cases such as those described by MAUDE - Manufacturer and User Facility Device Experience. See for example http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfMAUDE/detail.cfm?mdrfoi__id=1942591 - a patient get fitted with bioprosthetic heart valves and dies within the following 4 months.
Note that this definition of adverse event doesn't imply any type of causality between the sign observed and the coumpond administration/device utilization. For our purposes, we consider any type of sign presenting within a specific time frame after the coumpound administration/device utilization to be an adverse event.
adverse event following immunization process
seizure level 1 of certainty according to the Brighton criteria
MC, 20110126: this needs to be linked to the Brighton guideline defined under directive information entity
witnessed sudden loss of consciousness AND generalized, tonic, clonic, tonic–clonic, or atonic motor manifestations. (atonic In the absence of: hypotonic hyporesponsive episode (as deﬁned by the Brighton Collaboration), syncope, and myoclonic jerks.
seizure level 2 of certainty according to the Brighton criteria
history of unconsciousness AND generalized, tonic, clonic, tonic–clonic, or atonic motor manifestations. (atonic In the absence of: hypotonic hyporesponsive episode (as deﬁned by the Brighton Collaboration), syncope, and myoclonic jerks.
seizure level 3 of certainty according to the Brighton criteria
history of unconsciousness AND other generalized motor manifestations.
atonic motor manifestation finding
A sudden loss of tone in postural muscle, often preceded by a myoclonic jerk and precipitated by hyperventilation
Brighton Collaboration, http://www.brightoncollaboration.org/
generalized atonic motor manifestation finding
clonic motor manifestation finding
Sudden, brief (100ms) involuntary contractions of the same muscle groups, regularly repetitive at a frequency of about two to three contractions per second.
generalized motor manifestation finding
bilateral motor manifestation, more than minimal muscle involvement
generalized clonic motor manifestation finding
generalized tonic motor manifestation finding
generalized tonic-clonic motor manifestation finding
AEFI hypotonic-hyporesponsive episode according to Brighton
HHE
HHE is characterized by sudde onset of reduced muscle tone, hyporesponsiveness (i.e., less responsive than usual to verbal or other sensorial stimuli) and change of skin color (pallor or cyanosis)
performing a diagnosis of generalized convulsive seizure according to Brighton guidelines
performing a diagnosis specified by the Brighton case definition for convulsive seizure as an adverse event following immunization
Brighton case definition of generalized convulsive seizure as an adverse event following immunization
A Brighton case definition of generalized convulsive seizure as an adverse event following immunization
shaking finding
quivering
repetitive, cyclical movements of the body or a body part; usually involuntary, but can also manifest in response to an attempt at movement
shivering
trembling
tremor
bilateral shaking finding
A shaking process which unfolds in both sides of an organism
syncope finding
MC, 20110126: The Brighton guideline on which this is based needs to be checked. Email correspondance with Brighton: [MC] One thing is unclear to me: Level 1 of diagnostic certainty is defined as "witnessed sudden loss of consciousness AND generalized, tonic, clonic, tonicâclonic, or atonic motor manifestations." A footnote adds: atonic in the absence of: hypotonic hyporesponsive episode (as deï¬ned by the Brighton Collaboration), syncope, and myoclonic jerks. If we define syncope as being a loss of consciousness, how can I have a witnessed sudden loss of consciousness and a generalized atonic motor manifestation in the absence of syncope? [Brighton] Thank you for your question. You are right, that there is an overlap between the clinical presentation of an atonic seizure and a Syncope. This is also true for HHE. This is the very reasonf or the footnote to alert the user of the definition to this differential diagnosis. If you are working on a database and only have the clinical criteria vailable, you may have some false positives for the atonic seizure cases, unless you obtain additional information, e.g. that the Syncope was vasovagal or orthostatic, or arrhythmic, etc.
loss of consciousness, fainting
myoclonic jerk finding
A myoclonic jerk is the brief, involuntary twitching of a muscle or group of muscles. It may be caused either by a sudden muscle contraction, or a sudden lapse of contraction. This happens when a person is on the verge of falling asleep, and suddenly have a sensation or feeling that they are free falling through the air. Contractions are called positive myoclonus; relaxations are called negative myoclonus. When falling asleep, it is common for people to experience a type of myoclonic jerk known as a hypnic jerk. Hiccups are also a kind of myoclonic jerk specifically affecting the diaphragm.
tonic motor manifestation finding
A sustained increase in muscle contraction lasting a few seconds to minutes
loss of consciousness finding
Total suspension of conscious relationship with the outside world demonstrated by the inability to perceive and to respond to verbal, visual, and painful stimulus
history of unconsciousness
MC, 20110126: AR suggest that "history of consciousness is not a process. definition reads "the sudden loss of consciousness was not observed, but the patient was found unconscious", so maybe updating the label would be better : "unwitnessed loss of consciousness with history of unconsciousness" would help
the sudden loss of consciousness was not observed, but the patient was found unconscious
witnessed sudden loss of consciousness finding
bilateral site
witness role
A role inhering in a person that is realized when the bearer sees an event and reports what happened
adapted from http://golovchenko.org/cgi-bin/wnsearch?q=witness
adverse side effect
side effect is an adverse event of a type that has been determined by a review board to be causally related to the intervention.
while in some cases the particular may not be actually caused by the intervention, it is an adverse side effect nonetheless.
device malfunction
A process in which the device doesn't perform as expected
adverse event report
A report as submitted in an adverse event reporting system
MC, 20110719: not all adverse event report are about adverse event. See for example cases in MAUDE database that are about potential adverse events such as device malfunctions.
reporting process
The process of creating documentation about something and adding it to a system allowing further analysis of the reported entity
sudden onset
Anaphylaxis: Case definition and guidelines for data collection, analysis, and presentation of immunization safety data. Vaccine 25 (2007) 5675–5684
The term sudden onsets refers to an event that occurred unexpectedly and without warning leading to a marked change in a subjects previously stable condition
rapid progression
The term rapid progression is a conventional clinical term. An exact timeframe sould not be offered since it would have to refer to a wide range of signs and symptoms without a scientific evidence base. Using an arbitrarily restrictive setpoint might bias future data collection unnecessarily.
respiratory distress diagnosis
respiratory distress—2 or more of the following: • tachypnoea • increased use of accessory respiratory muscles (sternocleidomastoid, intercostals, etc.) • recession • cyanosis • grunting
performing a diagnosis according to a Brighton case definition
Brighton diagnosis result
The diagnosis performed upon review of an adverse event report according to the Brighton case definitions
adverse event reporting process
The process of creating documentation about an adverse event and adding it to a system allowing further analysis of the event
clinical diagnosis of uncompensated shock
combination of at least 3 of the following: - tachycardia - capillary refill time > 3s - reduced central pulse volume - decreased level of consciousness or loss of consciousness
dermatologic or mucosal sign
A clinical finding that involves the dermatological-mucosal system
token
respiratory-distress-token
uncompensated-shock-token
Brighton case definition of anaphylaxis as an adverse event following immunization
PMID:17448577#Anaphylaxis: case definition and guidelines for data collection, analysis, and presentation of immunization safety data.
performing a diagnosis of anaphylaxis according to Brighton guidelines
major dermatological criterion for anaphylaxis according to Brighton
generalized urticaria or generalized erythema finding
angioedema finding
20130423, MC: in the anaphylaxis case definition, angioedeme can be localized or generalized. There was no need as of today to create specialized subclasses representing those.
AngEdGenLoc
Areas of deeper swelling of the skin and/or mucosal tissues in either single or multiple sites which may not be well circumscribed and is usually not itchy. Reported symptoms of ‘swelling of the lip’ or ‘swelling of the tongue or throat’ should not be documented as angioedema unless there is visible skin or mucosal swelling.
generalized pruritus with skin rash finding
_anaphylaxis according to Brighton criteria set of clinical findings
20120821, MC: placeholder for development
the set of clinical findings that are classified as being relevant for the anaphylaxis diagnosis
major cardiovascular criterion for anaphylaxis according to Brighton
major respiratory criterion for anaphylaxis according to Brighton
measured hypotension finding
An abnormally low blood pressure and documented by appropriate measurement. Infants and children: age specific systolic BP of <3-5%percentile or greater than a 30% decrease from that person’s baseline; Adults: systolic BP of <90mm Hg or greater than 30% decrease from that person’s baseline.
HypotensMeas
uncompensated shock sign finding
tachycardia finding
A heart rate that is abnormally high for age and circumstance (In beats per minute: <1year old: >160; 1 – 2 yrs: >150; 2-5 yrs: >140; 5-12 yrs: >120; >12 yrs: >100)
Citation for norms is Don & Roberton; Physical examination; in Practical Pediatrics 2007; 6th ed
TachyCard
capillary refill time > 3s finding
CapRefillOver3
Capillary refill time is the time required for the normal skin colour to reappear after a blanching pressure is applied. It is usually performed by pressing on the nail bed to cause blanching and then counting the time it takes for the blood to return to the tissue, indicated by a pink colour returning to the nail. Normally it is <3 seconds.
reduced central pulse volume finding
PulseVolRed
decreased level of consciousness or loss of consciousness finding
loss of counsciousness is a subclass of decreased consciousness, so saying "is about some decreased level of consciousness" I cover all cases
bilateral wheeze finding
WheezeBilat
bronchospasm finding
stridor finding
A harsh and continuous sound made on breathing in.
Stridor
upper airway swelling finding
SwellUpAirways
lip, tongue, throat, uvula or larynx
tachypnoea finding
Rapid breathing which is abnormally high for age and circumstance rapid breathing whichis abnormally high for age and circumstance (<1yr: >60; 1-2 yrs: >40; 2-5 yrs: >35; 5-12 yrs: >30: >12 yrs: >16)
TachyPnea
tachypnea finding
increased use of accessory respiratory muscles finding
RespMuscAccIncr
sternocleidomastoid, intercostals, etc
recession finding
Recess
cyanosis finding
A dark bluish or purplish discolouration of the skin and mucous membrane due to lack of oxygen in the blood.
grunting finding
A sudden and short noise with each breath when breathing out.
Grunting
respiratory distress sign finding
Brighton diagnosis of anaphylaxis as an adverse event following immunization
Level 1 of certainty of anaphylaxis according to Brighton
patient
generalized prickle sensation finding
PrickleSens
localized injection site urticaria finding
Localized redness of superficial layers of skin that is itchy, raised, sharply demarcated and transient (that is skin changes at any location are usually present for less than 12 hours).
UrticariaLOC
red and itchy eyes finding
EyeRedItch
reduced peripheral circulation finding
capillary refill time > 3s finding without hypotension
reduced peripheral circulation diagnosis
The reduced peripheral circulation diagnosis is the minor cardiovascular criterion for anaphylaxis according to Brighton. The diagnosis is established by observing the combination of at least 2 reduced peripheral circulation findings, but at most one of each type.
generalized pruritus without skin rash finding
persistent dry cough finding
CoughPersisDry
Rapid expulsion of air from the lungs to clear the lung airways and not accompanied by expectoration (a non-productive cough).
hoarse voice finding
An unnaturally harsh cry of infant or vocalization in a child or adult.
VoiceHoarse
sensation of throat closure finding
ThroatCloseSens
sneezing or rhinorrhea finding
diarrhoea finding
Diarrhea
Loose and/or watery stool which may occur more frequently than usual.
diarrhea finding
abdominal pain finding
AbdoPain
Sensation of discomfort or pain in the abdominal region.
nausea finding
An unpleasant sensation vaguely referred to the upper abdominal region and the abdomen, with a tendency to vomit.
Nausea
vomiting finding
The reflex act of ejecting the contents of the stomach through the mouth.
VomitUnspec
mast cell tryptase elevation > upper normal limit finding
MastCellTryp
minor dermatological criterion for anaphylaxis according to Brighton
minor cardiovascular criterion for anaphylaxis according to Brighton
minor respiratory criteria set for anaphylaxis according to Brighton
difficulty breathing without wheeze or stridor finding
20130319, MC: Here the ontology is more specific than Brighton formula which just states "DiffBreath" - we logically encode the restrictions mentioned in the guideline -> without wheeze or stridor
DiffBreath
minor gastrointestinal criterion for anaphylaxis according to Brighton
minor laboratory criteria set for anaphylaxis according to Brighton
Level 2 of certainty of anaphylaxis according to Brighton
Level 3 of certainty of anaphylaxis according to Brighton
cardiovascular sign
respiratory sign
gastrointestinal sign
Reported anaphylaxis with insufficient evidence to meet the case definition
not a case of anaphylaxis
dry cough finding
chest tightness finding
indrawing finding
rhinorrhea finding
Discharge of thin nasal mucus.
Rhinorrhea
sore throat finding
wheezing finding
erythema finding
generalized erythema finding
ErythemaGen
red eyes finding
itchy eyes finding
prickle sensation finding
Tingling or smarting (stinging) sensation.
pruritus finding
generalized pruritus finding
PruritusGen
rash finding
skin rash finding
SkinRash
urticaria finding
generalized urticaria finding
UrticariaGen
hives finding
decreased level of consciousness finding
ConscDecr
Reduced alertness or awareness of the outside world.
tonic-clonic manifestation finding
A sequence consisting of a tonic followed by a clonic phase
sneezing finding
An involuntary (reflex), sudden, violent, and audible expulsion of air through the mouth and nose.
Sneeze
difficulty breathing finding
reported anaphylaxis
Level 3 of certainty of anaphylaxis - post ICPE
Following the ICPE meeting in Montreal 2013, MC clarified with JB that the guideline should be understood as "if there is a minor cardiovascular criteria, then we need 2 other systems involved, including respiratory, dermatologic, gastrointestinal and laboratory" and similarly if there is a respiratory criteria. The first iteration was interpreted as (1 minor cardiovascular OR respiratory criterion) AND 2 minors from systems that are neither respiratory nor cardiovascular (dermatologic, gastrointestinal , laboratory systems) to mimic behavior of the ABC tool.
minor respiratory criteria set for anaphylaxis according to Brighton - post ICPE
Following meeting at ICPE Montreal 2013, MC and JB clairfied that "difficulty breathing without wheeze or stridor" should be understood as "difficulty breathing"
minor dermatological criterion for anaphylaxis according to Brighton - post ICPE
Following meeting at ICPE Montreal 2013, MC and JB clairfied that "genralized pruritus withou rash" should be understood as "generalized pruritus"
Level 2 of certainty of anaphylaxis according to Brighton - post ICPE
Level 3 of certainty of anaphylaxis - PHAC form
20130912: In the paper http://dx.doi.org/10.1016/j.vaccine.2010.04.041 "Can the Brighton Collaboration case definitions be used to improve the quality of Adverse Event Following Immunization (AEFI) reporting? Anaphylaxis as a case study", the form used by PHAC and shown in Appendix E states as a footnote "for level III, a skin MAJOR can count as a minor criterion"
increased use of accessory respiratory muscles-token
recession-token
tachypnoea-token
tachycardia-token
capillary refill time above 3s-token
reduced central pulse volume-token
decreased level of consciousness or loss of consciousness-token
An acute hypersensitivity reaction with multi-organ-system involvement that can present as, or rapidly progress to, a severe life-threatening reaction.