Psych and toxidromes

Question 1

Development of Language in Children

Answer 1

From birth until around 6 months, babies make a great deal of noise. They squeal, squeak, growl, yell, and give us raspberries. And they coo. Cooing is basically the production of what will later become vowels (a, e, i, o, and u).

From 6 months to about 10 months, they produce somewhat more complicated sounds called babbling. First, they practice their vowels more precisely, starting with the round, back vowels (oo, oh, ah…) and working their way to the unrounded front vowels (ee, eh, ay…). Then they add consonants

at this point they can perceive far more than they can pronounce – something called the fis phenomenon. They will not be able to say certain words, but can hear the difference

Mothers typically adjust their speech to fit the child’s level. This is called motherese. It is found in practically every culture on the planet, and it has certain common characteristics: The “sentences” are very short, there is a lot of repetition and redundancy, there is a sing-song quality to it, and it contains many special “baby words.”

often involves a subtle shaping called a protoconversation - asking questions and rewarding any response with happiness

From 12 to 18 months (or thereabouts) is called the one word (or holophrastic) stage. Each word constitutes a sentence all by itself. By 12 months, most kids can produce 3 or 4 words, and understand 30 to 40.

Two characteristics of this stage are overextension and underextension. For example, the word hat can mean just about anything that can be put on your head, a “goggie” applies to just about any animal, and “dada” (much to the embarrassment of moms everywhere) pretty much means any man whatsoever. On the other hand, sometimes kids engage in underextension, meaning that they use a general word to mean one very specific thing. For example, “baba” may mean MY bottle and my bottle only, and “soozies” may mean MY shoes and no one else’s.

may use unique words, sometimes actually invented by the child, called idiolects

Between 18 to 24 months (approximately), we see the beginnings of two word sentences, and telegraphic speech

After 24 months, children begin to use grammatical constructions of various sorts.

Three year olds are notorious for something called over-regularization. Most languages have irregularities, but 3 year olds love rules and will override some of the irregulars they learned when they were 2, e.g. “I go-ed” instead of I went and “foots” instead of feet. Three year olds can speak in four word sentences and may have 1000 words at their command.

Four year olds are great askers of questions, and start using a lot of wh- words such as where, what, who, why, when (learned in that order). They can handle five word sentences, and may have 1500 word vocabularies.

Five year olds make six word sentences (with clauses, no less), and use as many as 2000 words.

for questions:
21-24 months “What’s that?” (Or simply, “Dat?”)
26-32 months Asks where questions
36-40 months Asks who questions
37-42 months Asks “Is…?” and “Do…?” questions
42-49 months Asks when, why, and how questions

Question 2

cognitive development including piaget stages

Answer 2

first stage, Sensorimotor (ages 0 to 2 years of age), is the time when children master two phenomena: causality and object permanence. Infants and toddlers use their sense and motor abilities to manipulate their surroundings and learn about the environment. They understand a cause-and-effect relationship, like shaking a rattle may produce sound and may repeat it or how crying can make the parent(s) rush to give them attention. As the frontal lobe matures and memory develops, children in this age group can imagine what may happen without physically causing an effect; this is the emergence of thought and allows for the planning of actions. Object permanence emerges around six months of age. A six-month-old will look for partially hidden objects, while a nine-month-old will look for wholly hidden objects and uncover them; this includes engaging in peek-a-boo-type games. Separation and stranger anxiety emerge as the toddler understands that out of sight is not out of mind

Second is the “Pre-operational” stage (ages 2 to 7 years), when a child can use mental representations such as symbolic thought and language. Children in this age group learn to imitate and pretend to play. This stage is characterized by egocentrism, i.e., being unable to perceive that others can think differently than themselves, and everything (good or bad) somehow links to the self. In preschool years, magical and wishful thinking emerges; for example, the sun went home because it was tired. This ability may also give rise to apprehensions with fear of monsters, and having logical solutions may not be enough for reassurance. Perception will dominate over logic, and giving them an imaginary tool, like a monster spray, to help relieve that anxiety may be more helpful

Third is the “Concrete Operational stage” (ages 7 to 11 years), when the child uses logical operations when solving problems, including mastery of conservation and inductive reasoning.

Finally, the Formal Operational stage (age 12 years and older) suggests an adolescent can use logical operations with the ability to use abstractions. Adolescents can understand theories, hypothesize, and comprehend abstract ideas like love and justice.

these are sort of right but poorly generalisable and have flaws, eg current understanding is that a child masters the “Theory of Mind” by 4 to 5 years, much earlier than when Piaget suggested that egocentrism resolves

Question 3

common childhood fears and how they change over time

Answer 3

Infants feel stranger anxiety. When babies are about 8–9 months old, they can recognize the faces of people they know. That’s why new faces can seem scary to them — even a new babysitter or relative. They may cry or cling to a parent to feel safe.

Toddlers feel separation anxiety. When they’re 10 months–2 years old, many toddlers start to fear being apart from a parent. They don’t want a parent to leave them at daycare, or at bedtime. They may cry, cling, and try to stay near their parent.

Young kids fear “pretend” things. Kids 4–6 years old can imagine and pretend. But they can’t always tell what’s real and what’s not. To them, the scary monsters they imagine seem real. They fear what might be under their bed or in the closet. Many are afraid of the dark and at bedtime. Some are afraid of scary dreams. Young kids may also be afraid of loud noises, like thunder or fireworks.

Older kids may worry about getting hurt, weather, or danger. When kids are 7 or older, they know real from pretend. At this age, they may begin to fear things that could happen in real life. For example, some may fear being harmed by ‘bad’ people. Some may feel afraid about natural disasters, stormy weather, violence, or things they hear about in the media. Some may worry about family separations or losing a loved one.

Preteens and teens may have social fears. School and friendships have become a bigger part of their lives. They might feel anxious about homework, grades, and doing well in school. They may focus on how they look or worry about whether they will fit in, be judged, or be bullied. Social fears may cause them to feel anxious or afraid before they give a report in class, start a new school, take a big exam, play in a big game, or walk across the lunchroom. At this age, their worries and concerns may also focus on bigger issues — like the climate, injustice, and fairness.

Question 4

IQ testing

Answer 4

an IQ score can provide meaningful data
about a child’s cognitive abilities if put within a conceptual framework that does not overstate its meaning or implications for the child; it reflects a child’s performance on an intelligence test relative to that of children of the same age

for a child who is being tested to confirm a diagnosis of attention-deficit/hyperactivity disorder (ADHD), an intelligence test can confirm that the child’s academic difficulties do not indicate a specific cognitive weakness

IQ tests are composed of subtests that measure specific areas of functioning. Scoreson these subtests are combined to yield measures of verbal and nonverbal problem-solving abilities, as well as a full-scale IQ score. IQ scores are assumed to be normally distributed in the population; The
average IQ score on most IQ tests is 100, with a standard deviation of 15. Most IQ scores (about 68%) fall within 1 standard deviation on either side of the mean (eg, between 85 and 115)

IQ definitely correlates with some of the things you’d expect intelligence to correlate with: positively with performance in school/work/income, and negatively with crime. Still, that’s not the same as proving it measures intelligence. The only thing you can be pretty sure about is that IQ tests do a good job at measuring IQ

however large-scale correlation between IQ and socioeconomic status could also be said to represent the unaccounted-for influence of income and wealth upon one’s testing conditions, for example. twin studies may not account for various confounders. and studies are designed with a particular cultural and linguistic context and values particular skills and types of intelligence, which is why caucasian people tend to score higher on average

for intellectual disability:
mild ID (IQ 50–69) are capable of learning reading and mathematics skills to approximately the level of a typical child aged nine to twelve. They can learn self-care and practical skills, such as cooking or using the local mass transit system. As individuals with intellectual disabilities reach adulthood, many learn to live independently and maintain gainful employment
moderate ID (IQ 35–49) may have early speech delays and as adults at best live semi-independently with significant supportive services to help them, for example, manage their finances
severe ID (IQ 20–34) and profound ID (IQ 19 or below) will need more intense support all their lives

Question 5

attachment styles

Answer 5

Secure Attachment Style: Secure relation to others, adults are considered reliable,
helpful and trustworthy. The person has a sense that “I am OK, you’re OK, the world is
OK!” About 55-65% of the population have a secure attachment style.

Children who have an avoidant attachment pattern have learnt that their emotions are not responded to empathically. Such children have learnt to anticipate that expressions of their emotions will anger or irritate their carer. In order to cope with such parenting, children who have an avoidant attachment have learnt that in order to avoid distance and have the best chance of proximity to their carer they should deny and/or repress their emotional needs i.e. they minimise their attachment behaviour and become insular.

Children who show an ambivalent attachment style have typically experienced a primary carer who is inconsistent and unreliable in their ability to meet the child’s emotional needs. This may be due to the adult’s preoccupation with their own difficulties, for example depression, drug and/or alcohol use or more subtle difficulties in tuning into the meaning of the emotional expressions of their child (which can be due to the adult’s own attachment difficulties).

Children with an ambivalent approach will work very hard to get their needs met by their primary carer by any means necessary e.g. angry, exaggerated, threatening, clinging behaviours. This is borne of a learnt expectation that they are undeserving of automatic, unsolicited attention. When such children are successful in gaining the attention of their hard-to-reach carer they are typically angry and rejecting of that carer, thus resulting in a constant “push-pull” battle

The most extreme and disturbing style of attachment is the Disorganised pattern. This is typically displayed by children exposed to a parenting style which does not allow them to develop a “safe” response to their attachment needs i.e. their carer is typically the cause of their distress as well as being the child’s only figure for resolving distress. No matter what the child does in response to their own needs it does not bring proximity, safety and comfort from their primary carer.

Children who have a disorganised attachment will typically be somewhat bizarre in their way of relating to others because they have not learnt any clear way to relate and regulate their emotion through relating. They can show chaotic, confused, incoherent and angry ways of relating to others.

Of the four patterns of attachment (secure, avoidant, resistant and disorganized), disorganized attachment in infancy and early childhood is recognized as a powerful predictor for serious maladjustment in children

Question 6

separation anxiety disorder

Answer 6

SAD is an exaggeration of otherwise developmentally normal anxiety and manifests as excessive concerns, worry, and even dread of the actual or anticipated separation from an attachment figure or home

separation anxiety is a developmentally appropriate phenomenon, the disorder manifests with improper intensity at an inappropriate age or in an inappropriate context

Developmentally appropriate separation anxiety manifests between 6 to 12 months of age. This normative or physiological separation anxiety remains steadily observable until approximately age 3 and, under normal circumstances, diminishes afterward. Developmentally appropriate separation anxiety eventually extinguishes as a child develops a greater sense of autonomy, cognitive ability, and an understanding that a separated attachment figure will return

School functioning is generally significantly impaired by SAD, as many children may demonstrate disruptive behaviors until reunited with their caregiver or refuse to attend school altogether. Common manifestations at home include a child being afraid to be in a room alone, refusing to sleep alone, and shadowing or clinging to the caregiver’s side. When the child is separated from the caregiver, similar severe anxiety can occur, including crying and screaming. Another common SAD symptom is the pervasive worry that harm will come to the caregiver if separated, leading to severe distress and nightmares. Similarly, the child may worry about becoming lost, kidnapped, or having an accident if separated from their caregiver.

if persistent or impacting daily life then child will need referral to CAMHS for CBT

Question 7

oppositional defiant disorder and conduct disorder

Answer 7

ODD sx last at least 6mo and include:
Often and easily loses temper
 Is frequently touchy and easily annoyed by others
 Is often angry and resentful
 Often argues with adults or people in authority
 Often actively defies or refuses to comply with adults’ requests or rules
 Often deliberately annoys or upsets people
 Often blames others for his or her mistakes or misbehaviour
 Is often spiteful or vindictive

Conduct disorder is characterized by aggressive behavior, rule-breaking, and engaging in many defiant –– and often dangerous –– behaviors. The severity varies greatly from mild cases (where someone might break their parents’ rules about curfew) to severe cases (where someone might use a weapon to hurt someone). The average onset is around 10 to 12 years old in boys and 14 to 16 years old in girls.

problematic behavior in conduct disorder extends to far more areas and may be much more severe. For example, while someone with ODD may get angry, argumentative, and break an authority figure’s rules, they likely won’t engage in behaviors like hurting animals, sexually assaulting someone, or lighting someone’s property on fire. Behavior related to conduct disorder is more dangerous and law-breaking than behavior linked to ODD –– such as rape, theft, or arson.

Additionally, it is more common for conduct disorder to evolve into antisocial personality disorder later in life rather than ODD.

Undertake an initial assessment for a suspected conduct disorder if a child or young person’s parents or carers, health or social care professionals, school or college, or peer group raise concerns about persistent antisocial behaviour

consider using the Strengths and Difficulties Questionnaire (completed by a parent, carer or teacher) and assess for depression, PTSD, ADHD, ASD, learning disability, substance misuse

If any significant complicating factors are present refer the child or young person to a specialist CAMHS for a comprehensive assessment, otherwise direct referral for an intervention

group parent training if child 3-11yo and has ODD or conduct disorder
group social and cognitive problem-solving programmes to children and young people aged between 9 and 14 years
multimodal interventions, for example, multisystemic therapy, to children and young people aged between 11 and 17 years for the treatment of conduct disorder.

An expert in conduct disorders might consider risperidone for the short-term management of severely aggressive behaviour in young people with a conduct disorder who have problems with explosive anger and severe emotional dysregulation and who have not responded to psychosocial interventions.

Question 8

anaclitic and introjective depression

Answer 8

Anaclitic depression involves excessive interpersonal concerns, including feelings of loneliness, weakness, helplessness and abandonment fears. Introjective depression denotes achievement concerns, and is characterized by a tendency towards self-criticism and self-evaluation

in general if suspect depression, screen using PHQ9 or age appropriate things

if mild can refer for CBT, group therapies, IPT

Children and young people presenting with moderate to severe depression should be reviewed by a CAMHS team with CBT for at least 3 months; CAMHS may start fluoxetine in combination with this; sertraline and citalopram under specialist guidance only

Inpatient treatment should be considered for children and young people who present with a high risk of suicide, high risk of serious self‑harm or high risk of self‑neglect, and/or when the intensity of treatment (or supervision) needed is not available elsewhere, or when intensive assessment is indicated

Question 9

gratification disorder

Answer 9

Often there is just repeated crossing of legs or thighs (scissoring) rather than direct stimulation of the genitalia. What is often noted is that the child is staring, or has a faraway look, and can move or shake one or more limbs for several minutes at a time. Sometimes the child may adopt a odd posture, have rocking movements, and other features such as sweating, facial flushing and grunting may also be observed. The child may not immediately respond when called but if
interrupted he/she may get angry or show annoyance. The situations in which these episodes occur often tend to be similar e.g. in the high chair, car seat, the baby walker or when lying prone

reported in up to 94% of boys and 55% of girls at some point in their childhood

may go unrecognized initially and be mistaken for seizures, or a movement disorder or
abdominal pain. The right diagnosis is reached by a careful analysis of the history and video footage of the episode

it is a normal variant in development and child will outgrow

Scolding the child could result in reinforcing such behaviours and causing low self-esteem; rather they should be gently spoken to on the need to avoid such behaviours; try to identify the triggers using a chart of what was happening before, and then try to avoid triggers

Question 10

acute pyschosis

Answer 10

relatively uncommon and often presents itself in a complex manner. Psychosis is defined as a “disruption in thinking, accompanied by delusions or hallucinations.” Delusions are “false, fixed beliefs that cannot be resolved through logical argument, while hallucinations are false perceptions that have no basis in external stimuli.”

cute onset (within a period of less than 2 weeks) may underline a medical disease rather than a psychiatric illness. Anyone who presents with a likely psychiatric diagnosis will need to undergo a medical evaluation to exclude reversible causes of psychosis.

ddx:
hypoglycemia
cerebral hypoxia (T1RF/T2RF, anaemia, shock)
drug intoxication (hallucinogens, cannabis, anticholinergics, sympathomimetics, 5HT syndrome, benzo withdrawal)
neuro disease (tumour, wilsons, autoimmune encephalitis inc NMDAr, infectious encephalitis, stroke, post-ictal psychosis or strange seizures eg frontal lobe)

will need: FBC, U&Es, LFTs, TFTs, BM, urine tox screen, consider tests for wilsons, LP, CTH

verbal de-escalation where possible; if not then oral benzo; if not an option then IM; loraz (can rpt if not effective) or promethazine, if stable situation allow at least 1 hour before repeating; if need to repeat before this point move to IM admin instead of repeating oral

if extreme agitation/psychosis can add olanzapine to benzo

if doing IM or adding antipsych make sure consultant is aware; in severely agitated patients where chemical restraint is necessary because of immediate safety risks to the patient, other patients or staff, call 2222 and request the paediatric medical emergency team

Allow 30 minutes for lorazepam and promethazine to work before giving a second dose.
If some effect from lorazepam is seen, repeat at the same dose. If no effect or paradoxical agitation is seen, give promethazine instead of second dose of lorazepam.
If both lorazepam and promethazine fails to improve agitation, an anti-psychotic drug can
be considered after at least 45 minutes.
Lorazepam and olanzapine must be given at least 1 hour apart due to the risk of hypotension

Calm and alert patient:-
o 30 min observations for 2 hours after last sedative
 Patient with a reduced level of consciousness:-
o One to one nursing in resus
o Continuous SpO2 monitoring
o Vital signs and GCS assessed every 15 minute until stability is established
clinically

Question 11

s/e profile of different antipsychotics

Answer 11

First-generation antipsychotics (FGAs) are associated with significant extrapyramidal side effects. Anticholinergic adverse effects like dry mouth, constipation, urinary retention are common with low potency dopamine receptor antagonists like chlorpromazine, thioridazine. The action of H1 histamine blocking by first-generation antipsychotics causes sedation. Chlorpromazine is the most sedating, while fluphenazine, haloperidol, and pimozide are less sedating. First-generation antipsychotics can also lower the seizure threshold, and prolong the QT interval

Leukopenia, thrombocytopenia, and blood dyscrasia are rare side effects of treatment with FGAs. Increased serum prolactin concentrations along with galactorrhoea, breast enlargement, amenorrhea, impotence in men, and anorgasmia in women are known adverse effects due to the action of the dopamine receptor block in the tuberoinfundibular tract.

Neuroleptic malignant syndrome is a rare but fatal adverse effect that can occur at any time during treatment with FGAs. The onset of symptoms is over 24 to 72 hours with increased temperature, severe muscular rigidity, confusion, agitation, elevation in white blood cell count, elevated creatinine phosphokinase concentrations, elevated liver enzymes, myoglobinuria, and acute renal failure. The antipsychotic should be immediately discontinued, and dantrolene given along with hydration, and cooling; risk higher with FGAs bu SGAs can also cause

Second-generation antipsychotics (SGAs) have a decreased risk of extrapyramidal side effects as compared to first-generation antipsychotics. SGAs are associated with significant weight gain and the development of metabolic syndrome.

Risperidone is associated with dizziness, anxiety, sedation, and extrapyramidal side effects. Paliperidone can cause temperature sensitivity to hot or cold temperatures and QTc prolongation. Olanzapine has been associated most frequently with weight gain, increased appetite, and somnolence. Quetiapine is the least likely to cause extrapyramidal side effects. The most common side effects of quetiapine are somnolence, orthostatic hypotension, and dizziness. Aripiprazole is the most common side effect of agitation, headache, and akathisia-like restlessness. Clozapine can cause hypersalivation, tachycardia, hypotension, and anticholinergic side effects. Clozapine is unusual in that it suppresses dyskinesia. Clozapine can cause clinically important agranulocytosis, leukopenia, and therefore requires monitoring of white blood cells and absolute neutrophil count

Question 12

lithium monitoring and toxicity

Answer 12

prescribe by brand

After stabilization of new patients, blood lithium levels should be monitored typically 3 monthly:
* Sample should be taken at least 8 hours post dose

every 6mo check U&Es and T4 /TSH
every 12mo check weight, BP, urine dip

Common side effects of lithium include
* GI disturbances (e.g. nausea, diarrhoea, dry mouth)
* Weight gain
* Oedema
* Fine tremor
* Polyuria
* Polydipsia
* Hypothyroidism

Signs of lithium toxicity include:
Blurred vision, muscle weakness, nausea, vomiting, drowsiness, coarse tremor, dysarthria (slurred speech), ataxia (unsteady gait, problems with balance, falling over), confusion, convulsions, ECG changes.

if signs of toxicity then stop lithium immediately, check levels and U&Es, seek psych advice

Question 13

amphetamine toxicity

Answer 13

Sympathomimetic syndrome with potential for life-threatening vascular complications (ischemia, dissection and haemorrhage)

sweating
dry mouth
anxiety
dehydration
hyponatraemia
hypertonia
hyperreflexia
hallucinations or psychosis
hypertension
supraventricular arrhythmia
coma
convulsions
haemorrhagic CVA
rhabdomyolysis
metabolic acidosis

benzos for agitation and seizures, give GTN or sodium nitroprusside if hypertensive crisis (not labetalol, need to avoid unopposed alpha action giving vasoconstrictive crisis)

If T>39.5C external cooling is required

ECG, BM, U&Es, CK, trop, CTH/CTA if suspect complication

Patients who are asymptomatic or exhibit mild toxicity can often be monitored in a ward environment.
More severe toxicity requires ongoing care in an HDU/ ICU setting.

Question 14

MDMA overdose

Answer 14

MDMA is a monoamine releaser and uptake inhibitor affecting serotonin, potentially increasing the risk of serotonin syndrome

toxicity may be features of sympathomimetic or 5HT syndrome, described below:

drugs that can cause or interact to cause: MAOIs, SSRIs, SNRIs, TCAs, lithium, tramadol, pethidine, MDMA, LSD, amphetamines, cocaine, ondansetron

mild sx:
Inducible clonus
Tachycardia
Tremor
Anxiety
Lower limb hyper-reflexia

moderate:
Agitation
Sustained clonus
Ocular clonus
Hyperthermia <39oC

severe:
Hyperthermia >39oC
Seizures
Muscle rigidity
Severe agitation, confusion

12 lead ECG, blood glucose and paracetamol concentration in deliberate self-poisoning
Depending on severity further investigations may be necessary to exclude significant complications including urea, creatinine, electrolytes, creatinine kinase, troponin

discuss with toxicologist/consult toxbase, but in general benzos can treat sx and if refractory then +/- 5HT antag (chlorpromazine or cyproheptadine)

Question 15

cocaine toxicity

Answer 15

Cocaine hydrochloride powder or paste: processed from the alkaloid extracted from cocoa leaves, it cannot be smoked as it decomposes at high temperatures
Cocaine base (crack cocaine) or free-base: created by combining cocaine hydrochloride with an alkaline substance, it is heat stable.

small doses, particularly in non-tolerant patients, may result in significant intoxication

20-30 mg = usual recreational dose when a line of cocaine is snorted
>1 g = potentially lethal

Sympathomimetic, vasospastic and sodium channel blocking effects

rapid onset
duration of effect ~1 hour, but may persist for hours

Euphoria
Anxiety, dysphoria, agitation and aggression
Paranoid psychosis with visual and tactile hallucination
Hyperthermia, rigidity and myoclonic movements
Seizures

Tachycardia and hypertension may be severe
Arrhythmia and cardiac conduction abnormalities
Acute coronary syndromes: vasospastic and /or coronary thrombotic
QT prolongation
Acute pulmonary oedema

Hyperthermia
Muscle fasciculations
Mydriasis, sweating and tremor

watch for: Hyperthermia induced rhabdomyolysis, renal failure, and cerebral oedema
Aortic and carotid dissection
Subarachnoid and intracerebral haemorrhage
Ischaemic colitis

UEC – renal failure and hyponatraemia
ECG, CK and troponin — ACS, QT prolongation and rhabdomyolysis; Brugada type pattern
CXR — aortic dissection; aspiration
CT head — intracranial haemorrhage

mx:
hypertension, agitation, seizures get benzos, can give GTN or nitroprusside infusion but avoid beta blockers, chest pain gets aspirin + GTN + verapamil; if in VT will need bicarb or lignocaine infusion; rapid cooling if temp > 39.5

Question 16

mx of long acting opioid overdose

Answer 16

IV infusion is indicated when:
* previous bolus doses of naloxone have been given and symptoms of overdose have
recurred.
* the opioid taken has a long half life (eg methadone, patches, buprenorphine, or MR formulations like zomorph or MST etc)
* or it is suspected that a large quantity of opioid has been taken.

ideally infuse via central access but can use large peripheral vein if needed; infuse at 60% of bolus dose needed for response per hour

Monitoring to include blood pressure, pulse, respiratory rate, oxygen saturation and level of consciousness.
Patients should be observed for a minimum of six hours after the last dose of naloxone.

Question 17

methanol toxicity

Answer 17

windshield fluid, antifreeze, paint, paint removers, gasoline, adhesives, glass cleaner, a solvent/cleaner.

in itself if is not very toxic, however metabolised to formaldehyde -> formic acid

symptoms develop 12-24 hours post ingestion (although may have temporary intoxicated appearance for a few hours after ingestion)
neurology: cerebral oedema, seizures, meningeal irritation, cerebral infarction, blurred vision -> blindness, scotomata, papilloedema, loss of light reflexes
respiratory failure
circulatory shock

raised osmolar gap
severe metabolic acidosis (raised anion gap)
send bloods for paracetamol, salicylate, alcohol, methanol, ethylene glycol, bone profile, U&Es, get a VBG

decreased production of toxic metabolites:
-> ethanol (competitive inhibitor to alcohol dehydrogenase)
-> fomepizole (same as ethanol but preferred as easier to titrate and no sedative effects)
-> sodium bicarbonate (undissociated formic acid more toxic than the dissociated product – give if pH < 7.3)
-> folinic acid: 50mg Q4hrly (decreases formate levels and decreases toxicity)

increase elimination:
-> haemodialysis

Question 18

ethylene glycol toxicity

Answer 18

automotive antifreeze, solvent, polish, paints, cosmetics, brake fluid, car wash fluid

> 1 mL/kg or a mouthful in a child is potentially lethal
ethylene glycol itself is relatively non-toxic -> metabolites extremely toxic (glycolate is neurotoxin and oxalate which forms Ca oxalate deposition in kidneys, damaging them, and causes hypocalc sometimes)
rate limiting step = alcohol dehydrogenase activity

30 minutes -> 12 hours post ingestion: excitement, confusion, disorientation -> ataxia, lethargy, stupor, coma, nausea/vomiting, myoclonus, seizures, cranial nerve deficits: nystagmus, ophthalmoplegia, facial palsy, dysarthria, dysphagia
12 – 24 hours: progressive cardiorespiratory failure with possible ARDS or shock
24 – 72 hours: renal failure from ATN

severe metabolic acidosis (high anion gap) from glycolic acid accumulation; send bloods for paracetamol, salicylate, alcohol, methanol, ethylene glycol, bone profile, U&Es, get a VBG

competitive antag at ADH with ethanol or ideally fomepizole, haemodialysis to remove

Question 19

salicylate poisoning

Answer 19

General:
Tachypnea.
Tachycardia.
Diaphoresis.
Hyperthermia.
Hypoglycemia
Neurologic:
Tinnitus, vertigo, ataxia, deafness.
Delirium, agitation, lethargy.
Seizure, coma.
GI:
Nausea/vomiting.
Diarrhea.
Can cause gastritis with hematemesis.
Pulmonary:
ARDS

(1) First finding is respiratory alkalosis.
Salicylate affects the medulla directly, increasing respiratory drive.
(2) Second, an anion-gap metabolic acidosis develops as well, creating a mixed picture.
Metabolic acidosis reflects increases in ketoacid, salicylic acid, and lactic acid.
Most of the elevated anion gap is not due to salicylate itself (<5 mM contribution)
(3) Respiratory acidosis may rarely occur.
This is often a pre-terminal event (reflecting respiratory exhaustion, ARDS, or severe CNS dysfunction). cidemia promotes entry of salicylate into the brain, worsening the intoxication. This creates the possibility of a death spiral involving hypercapnia, acidosis, and CNS dysfunction

check salicylate levels but note limitations - ionised form causes damage but like with Ca you need to account for pH to as well as raw conc to tell this; levels usually peak around six hours after ingestion. However, the peak may be delayed for >12 hours in patients who have ingested enteric coated tablets

Glucose should be given to patients with altered mental status, even if their serum glucose levels are normal as CNS levels often lower
Seizures: IV benzodiazepines
ARDS will require PEEP

activated charcoal dose is 1g/kg in kids and l may be given to the alert and cooperative patient up to 8 hours following an overdose >150 mg/kg. needs intubation first if >300 mg/kg
Any patient who is symptomatic require urinary alkalisation with sodium bicarb (catheter needed to monitor urine pH), if not feasible or levels rising despite this then haemodialysis, likewise if altered GCS, acidaemia

Therapy is ceased when salicylate levels fall to within normal range and the clinical features and acid-base abnormalities have resolved

patients with significant toxicity will need ICU

Question 20

TCA overdose

Answer 20

In overdose, the tricyclics produce rapid onset (within 1-2 hours) of:

Sedation and coma
Seizures, agitation, clonus
Hypotension
Tachycardia
Broad complex dysrhythmias
Anticholinergic syndrome (tachycardia, mydriasis, dry mouth, urinary retention, flushed skin)

Tricyclics mediate their cardiotoxic effects via blockade of myocardial fast sodium channels (QRS prolongation, tall R wave in aVR), inhibition of potassium channels (QTc prolongation) and direct myocardial depression. Other toxic effects are produced by blockade at muscarinic (M1), histamine (H1) and α1-adenergic receptors

> 10mg/kg potentially life threatening

ECG changes:
Intraventricular conduction delay: QRS > 100 ms in lead II
Terminal R wave > 3 mm in aVR or R/S ratio > 0.7 in aVR
Patients with tricyclic overdose will also usually demonstrate sinus tachycardia secondary to muscarinic (M1) receptor blockade

QRS > 100 ms is predictive of seizures
QRS > 160 ms is predictive of ventricular arrhythmias

if any ECG changes then needs monitored bed, IV bicarb, intubate + hyperventilate for pH >7.5, 1g/kg activated charcoal if presents within 1 hr; benzos for seizures, barbiturates then propofol if not working; bolus for hypotension and if fails then vasopressors; more bicarb then lidocaine for arrhythmias, avoid amiodarone

increasing the serum pH with bicarbonate -> increases the proportion of non-ionised drug which -> increase in drug distribution throughout rest of body and away from heart

Question 21

beta blocker overdose

Answer 21

CVS: hypotension, bradycardia, AV block, heart failure
RESP: bronchospasm
METABOLIC: hypoglycaemia, hyperkalaemia
NEURO: stupor, coma, seizures

two beta-blockers require special consideration:
— propanolol -> causes sodium channel blockade -> QRS widening -> treat with NaHCO3
— sotalol -> causes potassium efflux blockade -> long QT -> monitor for Torsades

fluids, atropine, glucagon, pacing

glucagon activates adenyl cyclase and exerts an inotropic and chronotropic effect by a pathway that bypasses the b receptors - however, this is controversial and toxicology advice should be sought

Question 22

solvent abuse

Answer 22

contain volatile hydrocarbons which cause euphoria and disinhibition via NMDA antagonism and GABA stimulation.

in solvents, glues, paints, lighter fluid, aerosol propellants

Symptoms of acute intoxication may initially include:
Euphoria, Excitability, Disinhibition, Impulsive behavior
Later, symptoms of CNS depression develop and include:
Slurred speech, Confusion, Hallucinations, Diplopia, Tremors, Ataxia, Visual Changes, Weakness
Eventually, persistent exposure can lead to:
Marked drowsiness, obtundation, coma, seizures, and death.

Hydrocarbons disrupt surfactant.
Hydrocarbons also cause inflammation, edema, and necrosis.

associated with various tachydysrhythmias, including ventricular fibrillation due to sensitisation to catecholamines

can see NAGMA and hypokalemia

Hydrocarbons can dissolve lipids in the skin.
May lead to mild inflammation or more serious chemical burns.
Huffers may develop perioral rash – “glue sniffer’s rash“

benzos for seizures, cardiac monitor and consider beta blockers and amiodarone, replete electrolytes, and may need intubation, exogenous surfactant

Question 23

nitrous oxide toxicity

Answer 23

N2O is a short-acting anaesthetic agent, with a history of recreational use

When someone inhales nitrous oxide, the gas rapidly dissolves into the bloodstream, and
reaches the brain within seconds. A rush of dizziness and euphoria is commonly reported,
and people often burst into laughter. Sound distortion also occurs.
Hallucinations are possible, from simple moving bright dots to complete detailed
dreamscapes, although most users do not experience complex hallucinations. Due to the
anaesthetic properties of the gas, coordination and awareness are strongly affected, and
users may fall over if they are not sitting or lying down. The effects are short lasting,
wearing off within two minutes. Nitrous oxide also reduces anxiety and pain.
Additionally, when purely nitrous oxide is inhaled recreationally, the gas displaces air in the
lungs, temporarily preventing much or any oxygen from reaching the blood. This may
cause the heart to beat faster, and limbs to feel tingly or heavy.

Acutely, the following have been reported:
1. injuries secondary to intoxication or syncope
2. hypoxia and asphyxiation (leading to arrhythmias, seizures, hypoxic brain injury, or
death)
3. barotrauma (pneumothorax, pneumomediastinum, tympanic membrane rupture)
4. confusion, hallucinations
5. vomiting with aspiration
6. cold injuries to the lips or mucosa
Typically, there is no specific toxicological management

Consequences of chronic N2O toxicity are classically either neurological (sensory, motor,
or co-ordination deficits) or haematological (megaloblastic anaemia).
The toxicity from chronic N2O use relates to oxidation of the cobalt ion within cobalamin
(vitamin B12), which renders it functionally inactive. This inactivation leads to a reduction
in methionine synthase activity which:
1. prevents the conversion of homocysteine to methionine by methionine synthase
(MS), reducing myelin production.
2. prevents the conversion of 5-methyl-tetrahydrofolate to tetrahydrofolate impacting
on DNA synthesis.
Additionally, inactivation of cobalamin reduces the activity of the mitochondrial enzyme,
methylmalonyl-CoA mutase (MMCoAM), leading to increased methylmalonic acid (MMA)
concentrations, which can lead to demyelination

Question 24

garcia effect

Answer 24

Conditioned taste aversion occurs when an animal acquires an aversion to the taste of a food that was paired with aversive stimuli. The Garcia effect explains that the aversion develops more strongly for stimuli that cause nausea than other stimuli. This is considered an adaptive trait or survival mechanism that enables the organism to avoid poisonous substances (e.g., poisonous berries) before they cause harm

This is the mechanism of disulfram, a drug used to treat alcohol dependence by inhibiting aldehyde dehydrogenase which causes a rapid buildup of the hangover-causing compound acetaldehyde when consuming alcoholic beverages, thereby pairing a negative stimulus with consumption of alcohol

Question 25

interventions for ASD

Answer 25

for diagnostics see other flashcard

assessment, management and coordination of care for autistic children and young people should be provided through local specialist community-based multidisciplinary teams;
Local autism teams should ensure that every child or young person diagnosed with autism has a case manager or key worker to manage and coordinate treatment, care, support and transition to adult care

Assess factors that may increase the risk of behaviour that challenges in routine assessment and care planning in autistic children such as co-existing mental health, environmental factors, developmental change, changes to routine and develop a care plan to address these

ffer the following to address factors that may trigger or maintain behaviour that challenges:
treatment for physical disorders, or coexisting mental health and behavioural problems

interventions aimed at changing the environment, such as:
providing advice to families and carers
making adjustments or adaptations to the physical surroundings

If behaviour remains challenging despite attempts to address the underlying possible causes, consult senior colleagues and undertake a multidisciplinary review

If no coexisting mental health or behavioural problem, physical disorder or environmental problem has been identified as triggering or maintaining the behaviour that challenges, offer the child or young person a psychosocial intervention (informed by a functional assessment of behaviour) as a first-line treatment

Consider antipsychotic medication (aripiprazole) for managing behaviour that challenges in autistic children and young people when psychosocial or other interventions are insufficient or could not be delivered because of the severity of the behaviour, in the short term for eg 8 weeks

Offer autistic children and young people support in developing coping strategies and accessing community services, including developing skills to access public transport, employment and leisure facilities

Be aware that feeding problems, including restricted diets can result in nutritional deficiencies that may have serious consequences. Advice on diet and food intake should be sought from a dietician for children and young people with ASD who display significant food selectivity and dysfunctional feeding behaviour

In children with ASD who have sleep difficulties which have not resolved following behavioural interventions, a trial of melatonin to improve sleep onset should be considered

Question 26

ADHD - diagnosis

Answer 26

A diagnosis of ADHD should only be made by a specialist psychiatrist, paediatrician or other appropriately qualified healthcare professional with training and expertise in the diagnosis of ADHD, on the basis of:

a full clinical and psychosocial assessment of the person; this should include discussion about behaviour and symptoms in the different domains and settings of the person’s everyday life and

a full developmental and psychiatric history and

observer reports and assessment of the person’s mental state

A diagnosis of ADHD should not be made solely on the basis of rating scale or observational data. However, rating scales such as the Conners’ rating scales and the Strengths and Difficulties Questionnaire are valuable adjuncts

symptoms of hyperactivity/impulsivity and/or inattention should:

meet the diagnostic criteria in DSM‑5 or ICD‑11 (hyperkinetic disorder; but exclusion based on a pervasive developmental disorder or an uncertain time of onset is not recommended) and

cause at least moderate psychological, social and/or educational or occupational impairment based on interview and/or direct observation in multiple settings and

be pervasive, occurring in 2 or more important settings including social, familial, educational and/or occupational settings.

The main signs of inattentiveness are:

having a short attention span and being easily distracted
making careless mistakes – for example, in schoolwork
appearing forgetful or losing things
being unable to stick to tasks that are tedious or time-consuming
appearing to be unable to listen to or carry out instructions
constantly changing activity or task
having difficulty organising tasks

The main signs of hyperactivity and impulsiveness are:

being unable to sit still, especially in calm or quiet surroundings
constantly fidgeting
being unable to concentrate on tasks
excessive physical movement
excessive talking
being unable to wait their turn
acting without thinking
interrupting conversations
little or no sense of danger

Question 27

ADHD management

Answer 27

Offer an ADHD-focused group parent-training programme to parents or carers of children under 5 years with ADHD as first-line treatment; Do not offer medication for ADHD for any child under 5 years without a second specialist opinion from an ADHD service with expertise in managing ADHD in young children (ideally a tertiary service)

Give information about ADHD and offer additional support to parents and carers of all children aged 5 years and over and young people with ADHD; inform school with consent

If a child aged 5 years or over or young person has ADHD and symptoms of oppositional defiant disorder or conduct disorder, offer parents and carers a parent-training programme

Offer medication for children aged 5 years and over and young people only if their ADHD symptoms are still causing a persistent significant impairment in at least one domain after environmental modifications have been implemented and reviewed

Consider a course of cognitive behavioural therapy (CBT) for young people with ADHD who have benefited from medication but whose symptoms are still causing a significant impairment in at least one domain, addressing the following areas:

social skills with peers
problem-solving
self-control
active listening skills
dealing with and expressing feelings

Offer methylphenidate (either short or long acting) as the first line pharmacological treatment for children aged 5 years and over and young people with ADHD
Consider switching to lisdexamfetamine for children aged 5 years and over and young people who have had a 6‑week trial of methylphenidate at an adequate dose and not derived enough benefit in terms of reduced ADHD symptoms and associated impairment
Consider dexamfetamine for children aged 5 years and over and young people whose ADHD symptoms are responding to lisdexamfetamine but who cannot tolerate the longer effect profile

Offer atomoxetine (SNRI) or guanfacine to children aged 5 years and over and young people if:

they cannot tolerate methylphenidate or lisdexamfetamine or their symptoms have not responded to separate 6‑week trials of lisdexamfetamine and methylphenidate, having considered alternative preparations and adequate doses

For people taking medication for ADHD:

measure height every 6 months in children and young people, measure weight every 3 months in children 10 years and under, measure weight at 3 and 6 months after starting treatment in children over 10 years and young people, and every 6 months thereafter, or more often if concerns arise

Monitor heart rate and blood pressure and compare with the normal range for age before and after each dose change and every 6 months.

Question 28

Dyspraxia

Answer 28

Developmental Coordination Disorder (DCD), also known, in the UK, as dyspraxia, is a
common but serious disorder affecting movement and coordination in children, young
people and adults, with symptoms present since childhood

there are likely to be substantial difficulties with:
Fine and / or gross motor coordination skills i.e. difficulties achieving developmental milestones in postural control and balance (e.g. jumping, hopping), hand-eye coordination (e.g. ball skills) and / or actions requiring sequencing such as running or riding a bike. This will impact on participation in activities at home and school, such as physical education lessons, games and sports. There may also be difficulties in fine motor skills such as object manipulation and tool use. This includes difficulties with pen / pencil skills such as drawing and handwriting, typing and using scissors.

hild will usually need to meet all of the following criteria:

their motor skills are significantly below the level expected for their age and opportunities they have had to learn and use these skills
their lack of motor skill significantly and persistently affects their day-to-day activities and achievements at school
their symptoms first developed during an early stage of their development
their lack of motor skills isn’t better explained by long-term delay in all areas (general learning disability) or rare medical conditions, such as cerebral palsy or muscular dystrophy
DCD should only be diagnosed in children with a general learning disability if their physical co-ordination is more impaired than would be expected for their mental (cognitive) ability.

Children with DCD may also have other conditions, such as:
attention deficit hyperactivity disorder (ADHD)
dyslexia
autism

treatment plan, combined with extra help at school, can help your child manage many of their physical difficulties, improve their general confidence and self-esteem, and help them to become a well-adjusted adult; this will be developed with paeds OT

Question 29

dyslexia

Answer 29

person with dyslexia may:

read and write very slowly
confuse the order of letters in words
be confused by letters that look similar and write letters the wrong way round (such as “b” and “d”)
have poor or inconsistent spelling
understand information when told verbally, but have difficulty with information that’s written down
find it hard to carry out a sequence of directions
struggle with planning and organisation

dyslexia assessment normally requested by parents through school and carried out by an educational psychologist or an appropriately qualified specialist dyslexia teacher

educational and lifestyle interventions then made

Question 30

carbon monoxide poisoning

Answer 30

Carbon monoxide diffuses rapidly through the alveolar membrane and binds with an affinity that is 230–300 times that of oxygen, preferably to the iron ion in heme. Conformation changes lead to a leftward shift in the position of the oxyhemoglobin dissociation curve, to reduced oxygen transport capacity, and to reduced oxygen release into the peripheral tissue

At the cellular level, carbon monoxide leads—among others—to an activation of neutrophils, to a proliferation of lymphocytes, to mitochondrial dysfunction, and to lipid peroxidation as well as evelopment of oxygen radicals, oxidative stress, inflammation, and apoptosis

clinical symptoms of acute carbon monoxide intoxication range from headache and dizziness to loss of orientation, symptoms of cardiac angina, loss of consciousness, and death; in the long term, neurological injuries will manifest—for example, ataxias, dementia, concentration deficits, or abnormal behaviour

as presentation is non-specific, in patients with unclear neurological symptoms and possible exposure, carbon monoxide should be urgently considered as a differential diagnosis

For the purposes of verification, carboxyhemoglobin (COHb) should be measured in a blood gas analysis

Administration of 100% oxygen as early as possible is recommended for all patients with a relevant suspected diagnosis (in alert patients, for example, by means of non-invasive continuous airway pressure (CPAP), or respiration using a mask with a demand valve, or administration of 15 L/min O2 through a reservoir mask) - continue aiming for SpO2 100% until asymptomatic and carboxyhaemoglobin normalises - half life should be about 80mins in 100% O2

Question 31

lead poisoning

Answer 31

Lead toxicity occurs after occupational or home exposure to lead. There is no threshold level for toxicity.

Older buildings in particular are common sources of lead poisoning in children due to the presence of lead-based paint and lead-contaminated dust. The old paint will peel off and crumble into dust, which eventually sits on the surfaces inside the home and in the soil surrounding the outside of the home

mainstay of treatment is removal of the source. Chelation therapy is given for blood levels ≥2.2 micromoles/L (≥45 micrograms/dL) in a child or >3.4 micromoles/L (>70 micrograms/dL) in an adult, or if the patient is symptomatic.

Acute lead encephalopathy is a medical emergency requiring aggressive chelation therapy in an intensive care setting.

Acute symptoms resolve with treatment, but neurological impairments and cardiovascular toxicities are irreversible

lead is involved in the dysregulation of various organ systems, including the hematologic system, renal system, and nervous system. This is largely due to its similarity with divalent cations, namely calcium, zinc, and magnesium; linked to microcytic anemia primarily due to inhibition of delta-aminolevulinic acid dehydratase (d-ALA) and ferrochelatase enzymes, which are essential in the biosynthesis of heme; disrupts synaptic pruning leading to neurodev effects; impairs proximal tubule function

In children, the signs and symptoms of lead poisoning typically present in a non-specific manner, manifesting as headaches, irritability, anorexia, constipation, and abdominal pain. If the dose and duration of lead exposure persist, paediatric patients are at an increased risk of CNS involvement, whether it be in the acute setting or in the chronic, subclinical setting. Acutely, lead encephalopathy presents as clumsiness, agitation, ataxia, seizures, vomiting, and, in severe cases, coma and death. Symptomatic lead poisoning must be treated emergently. Lead encephalopathy occurs in response to lead-induced cerebral microvascular changes, which result in subsequent cerebral oedema and increased intracranial pressure. Comparatively, subclinical CNS findings such as cognitive impairment are more common in the paediatric population

reduced haemoglobin and haematocrit levels, along with either normochromic, normocytic anaemia or hypochromic, microcytic anaemia, as well as venous blood smears with basophilic stippling (representing ribosomal precipitates) are key features of chronic exposure

Question 32

iron toxicity

Answer 32

Ingested iron can cause direct caustic injury to the gastrointestinal mucosa, resulting in nausea, vomiting, abdominal pain, and diarrhoea. Significant fluid and blood loss can lead to hypovolemia. Haemorrhagic necrosis of gastrointestinal mucosa can lead to hematemesis, perforation, and peritonitis

During the first stage (0.5 to 6 hours), the patient mainly exhibits gastrointestinal (GI) symptoms including abdominal pain, vomiting, diarrhea, hematemesis, and hematochezia.
The second stage (6 to 24 hours) represents an apparent recovery phase, as the patient’s GI symptoms may resolve despite toxic amounts of iron absorption.
The third stage (6 to 72 hours) is characterized by the recurrence of GI symptoms, shock, and metabolic acidosis. Iron-induced coagulopathy, hepatic dysfunction, cardiomyopathy, and renal failure are also observed in this stage.
The fourth stage (12 to 96 hours) is characterized by an elevation of aminotransferase levels and possible progression to hepatic failure.
The fifth stage (2 to 8 weeks) represents the consequences of the healing of the injured GI mucosa including pyloric or proximal bowel scarring and obstruction.
A patient may present in or skip any of the five stages

Patients who remain asymptomatic 4 to 6 hours after ingestion or those who have not ingested a potentially toxic amount do not require any treatment for iron toxicity.

Patients who have GI symptoms that resolve after a short period of time and have normal vital signs require supportive care and an observation period, as it may represent the second stage of iron toxicity.

Patients who are symptomatic or demonstrate signs of hemodynamic instability require aggressive management and admission to an intensive care unit. The following is used for the treatment of iron toxicity:

IV crystalloid infusion is administered to correct hypovolemia and hypoperfusion.
Deferoxamine, a chelating agent that can remove iron from tissues and free iron from plasma, is indicated in patients with systemic toxicity, metabolic acidosis, worsening symptoms, or a serum iron level predictive of moderate or severe toxicity

Coagulopathy can be corrected with vitamin K (5 to 10 mg subcutaneously) and fresh frozen plasma

Gastric lavage with a large-bore orogastric tube is only indicated if abdominal x-ray demonstrates a large number of visible pills in the stomach

Patients with GI symptoms or evidence of dehydration should be admitted. Patients receiving deferoxamine treatment should be admitted as well. Intensive care unit admission is indicated for patients presenting with coma, shock, metabolic acidosis, or iron levels over 1000 mg/dL. Psychiatric referral is indicated for patients with an intentional overdose. Patients can be safely discharged if they are asymptomatic after a 6 to 12-hour observation period and have a negative radiograph, or if they have mild GI symptoms that resolve without metabolic acidosis and serum iron level under 350 mg/dL after a 6 to 12 hour observation period

Question 33

how many half lives to clear a drug and types of adverse drug reaction

Answer 33

94 to 97% of a drug will have been eliminated after 4 to 5 half-lives. Thus, it follows that after 4 to 5 half-lives, the plasma concentrations of a given drug will be below a clinically relevant concentration and thus will be considered eliminated

Type A reactions result from an exaggeration of a drug’s normal pharmacological actions when given at the usual therapeutic dose and are normally dose-dependent. Examples include respiratory depression with opioids or bleeding with warfarin.

Type B Reactions Type B (bizarre) reactions are novel responses that are not expected from the known pharmacological actions of the drug. These are less common, and so may only be discovered for the first time after a drug has already been made available for general use. Examples include anaphylaxis with penicillin or skin rashes with antibiotics

Type C Reactions Type C, or ‘continuing’ reactions, persist for a relatively long time. An
example is osteonecrosis of the jaw with bisphosphonates.

Type D Reactions Type D, or ‘delayed’ reactions, become apparent some time after the use of a medicine. The timing of these may make them more difficult to detect. An example is leucopoenia, which can occur up to six weeks after a dose of lomustine.

Type E Reactions Type E, or ‘end-of-use’ reactions, are associated with the withdrawal of a medicine. An example is insomnia, anxiety and perceptual disturbances following the withdrawal of benzodiazepines

Question 34

section 47

Answer 34

section 47 - A Section 47 Enquiry is initiated to decide whether, and what type of, action is required to safeguard and promote the welfare of a child who is suspected of, or likely to be, suffering significant harm

might also be referred to as a Child Protection enquiry

initiated when a childrens service, or the police, receive info that a child might have suffered significant harm; they will have a strategy meeting to make a recommendation, such as that a child protection conference should take place

Question 35

mental health act

Answer 35

Section 131 of the Mental Health Act is a section of the legislation which covers the informal/voluntary admission of patients.

This means that patients can be admitted for care and treatment without formal restrictions, and they are free to leave at any time.

To be admitted under section 131, patients must meet the following criteria:

The patient must have capacity
The patient must consent to the admission
The patient must not resist the admission

Section 2 of the Mental Health Act is used for compulsory detention for assessment.

A person can be detained under section 2 only if both of the following apply:

The person suffers from a mental disorder that warrants detention in hospital for assessment for at least a limited period.
The person ought to be detained in the interests of their own health or safety or the protection of others.
The maximum period a person can be detained for assessment is 28 days, which cannot be renewed.

The application for admission can be made by an approved mental health professional (AMHP) or the nearest relative. This application must be supported by two doctors, one of which must be an approved section 12 doctor.

Section 3 of the Mental Health Act is used for compulsory detention for treatment
The maximum period a person can be detained under this section is 6 months, which can be renewed.

The application for admission can be made by an AMHP or the nearest relative. The nearest relative can oppose this and/or request it is rescinded (unlike section 2).

This application must be supported by two doctors, one of which must be an approved section 12 doctor

Section 5(2) is an emergency order where an inpatient who is a voluntary patient in hospital can be detained for up to 72 hours for a mental health act assessment.

Only one doctor (usually the one in charge of the patient’s care) is required to make an application for this section

Section 5(4) is similar but a patient can be detained by a nurse for up to 6 hours to allow further assessment by medical staff

Section 135 is a court order that allows police officers to enter private property, by force, to remove a person suffering from a mental health disorder and place them in a place of safety (usually an Emergency Department or police station)

Section 136 allows police officers to detain someone suspected of suffering from a mental health disorder, from a public place to a place of safety without a warrant, for up to 24 hours

Question 36

data visualisation and graph types

Answer 36

Continuous variables can take on any numeric value, and it can be meaningfully divided into smaller increments, including fractional and decimal values. There are an infinite number of possible values between any two values. Typically, you measure continuous variables on a scale. For example, when you measure height, weight, and temperature

With continuous variables, you can assess measures of central tendency and variability, such as the mean, median, distribution, range, and standard deviation

Histograms are a standard way to graph continuous variables; When you have two continuous variables, you can graph them using a scatterplot; Use correlation to assess the strength of this relationship or regression analysis to derive the equation for the line that provides the best fit for these data; Line charts show changes in value across continuous measurements, such as those made over time

When you have continuous variables that are divided into groups, you can use a boxplot to display the central tendency and spread of each group

Discrete quantitative data are a count of the presence of a characteristic, result, item, or activity. These measures cannot be meaningfully divided into smaller increments. For example, a single household can have 1 or 2 cars, but it cannot have 1.6.

With discrete variables, you can calculate and assess a rate of occurrence or a summary of the count, such as the mean, sum, and standard deviation

Bar charts are a standard way to graph discrete variables. Each bar represents a distinct value, and the height represents its proportion in the entire sample; ie values are indicated by the length of bars, each of which corresponds with a measured group.

There are three types of qualitative variables—categorical, binary, and ordinal; With these data types, you’re often interested in the proportions of each category. Consequently, bar charts and pie charts are conventional methods for graphing qualitative variables

Categorical data have values that you can put into a countable number of distinct groups based on a characteristic. For a categorical variable, you can assign categories, but the categories have no natural order eg car colour; if only two options (yes and no eg obese or not) then this is binary

Ordinal data have at least three categories, and the categories have a natural order. Examples of ordinal variables include overall status (poor to excellent), agreement (strongly disagree to strongly agree), and rank (such as sporting teams)

Question 37

basic stats

Answer 37

normal distribution:
Mean, mode and median are all equal, and lie at the peak of the curve.
68% of the area under the curve is within 1 standard deviation either side of the mean.
Normal distributions can be entirely defined in terms of the mean and standard deviation in the data set
Although truly normal distributions are symmetrical about the mean, there may be some distortion in this. One type of distortion is skew
Another distortion that may be present in the data is kurtosis. This can be thought of as the ‘pointiness’ of the peak in the distribution - Positive kurtosis refers to a distribution that is more pointy; When a small number of big deviations from the mean are recorded in the data, positive kurtosis is observed

we want to draw conclusions about a population based on a smaller sample; if we were to take lots of samples, it is not likely that the sample statistics for each sample would be the same (this is due to sampling variation); however, there should be a tendency towards the true value for the population; if we do this lots of times we would generate lots of means – plotting the distribution of these means would give us the sampling distribution of the mean. If the sample size is large, the sampling distribution of the mean will have a normal distribution regardless of the actual distribution in the population. If the sample size is smaller, the sampling distribution of the mean will only be normal if the actual distribution in the population is normal

standard deviation among the means of all these samples can be calculated and is called the standard error of the mean - deviation is used to express variation in the data of our sample; standard error should be used to describe the precision in the sample mean; standard error of the mean can be estimated as standard deviation / srt (sample N)

A normal distribution with a mean of 0 and a standard deviation of 1 is called the standard normal distribution (SND); As the standard deviation of this graph is 1, any value on the x-axis is equal to the number of standard deviations away from the mean; Any value on the x-axis of any normal distribution can be converted to a corresponding x-axis value on the standard normal distribution (a z-value); this is helpful to find out what percentage of the data lay beyond a certain point or within a particular range on the curve of your normal data set

Question 38

confidence intervals and statistical significance

Answer 38

useful to find a range within which we think the value is going to lie (an interval estimate). With a 95% confidence interval (CI) we are saying that ‘we are 95% certain that the true value for the population lies within this range’. therefore larger CI = larger range where we’re that level of confident the number is = more imprecise estimate; a wide CI suggests an imprecise result and indicates that the results should be interpreted with caution regardless of statistical significance, ie P value tells us statistical significance, CI tells us how precise our data is

upper and lower bounds of this range given by mean +/- (z score x (standard deviation/sqrt(N)); note this is z score times standard error; z-score is a number that corresponds to the percentage of confidence interval you want to calculate (e.g. the z-score for an 80% CI = 1.282

Hypothesis tests allow us to establish the likelihood that the association we are observing is genuine, or simply due to chance. They start with the statement of a null hypothesis – there will not be a significant difference in outcome between the groups. The p-value is effectively the probability that the null hypothesis is true. Therefore, the smaller the p-value becomes, the more likely that the null hypothesis is disproven

We have two groups (an exposure and a control) and two mean outcome values (one for each group). Calculating the difference between the means and dividing this by the standard error gives a z-score. The z-score is the number of standard deviations away from the mean that the mean difference lies (or the value on the x-axis on the graph of the standard normal distribution

Let’s say our z-score was 1.96. This corresponds to an area under the SND curve of 0.025. This means that beyond 1.96 on the x-axis of the SND lies 2.5% of the data on one side of the curve. Typically, two-sided p-values are used in analyses – this means that the assessment is of the size of the difference to the null hypothesis, not the direction in which that difference is (above or below the mean). It also means we have to double the area we have found as we need to look at points outside of -1.96 as well as 1.96. Based on this we find that 5% of the data lies outside of our interval between -1.96 and 1.96. As 5% is equal to 0.05 as a decimal, our p-value is 0.05 (which by conventional standards is the threshold for statistical significance).

What a p-value cannot tell us, is the clinical relevance or importance of the observed treatment effects. Specifically, a p-value does not provide details about the magnitude of effect. Despite a significant p-value, it is quite possible for the difference between the groups to be small. This phenomenon is especially common with larger sample sizes in which comparisons may result in statistically significant differences that are actually not clinically meaningful. For example, a study may find a statistically significant difference (p < 0.05) between the visual acuity outcomes between two groups, while the difference between the groups may only amount to a 1 or less letter difference - thus we need to know the magnitude of effect

magnitude of effect is most often represented as the mean difference between groups for continuous outcomes, such as visual acuity on the logMAR scale, and the risk or odds ratio for dichotomous/binary outcomes, such as occurrence of adverse events; these data can also be present as NNT/NNH

Null value refers to the value of the test statistic when the null hypothesis is true. In an example on difference in mean reduction in blood sugar between a standard hypoglycemic and a new drug, the null hypothesis is that there is no difference in the mean reduction in blood sugar by the two drugs or that the difference in the means between the two groups being compared is zero. The null value here is zero and any confidence interval computed for the difference in the means which includes zero is not significant; or e.g. alcohol intake and an outcome such as liver disease are being related. The appropriate measure of association between these variables is the odds ratio and the null value- that is when there is no relationship between alcohol intake and liver disease- is 1. Hence a confidence interval including 1 will not be a significant interval.

note then that he p value and confidence interval are two equivalent methods of interpreting results of a statistical analysis. Whether or not we have a significant result can be determined from the p value based on whether it is less than 5% or not; or the confidence interval based on whether the null value lies within the interval

Question 39

statistical tests

Answer 39

Although the normal distribution is very common in medical statistics, it is not the only way in which data can be distributed. Data distributed in a pattern that is not normal is described as nonparametric

Assess the difference between two groups: parametric uses two sample t test, non parametric uses wilcoxon rank sum test or mann whitney U

Assess the difference between more than two groups: ANOVA for parametric, otherwise Kruskal-Wallis test

Measure strength of association between variables: parametric is correlation coefficient, non parametric is Spearman’s rank correlation

assess the difference between paired observations: parametric is paired t test, non parametric is Wilcoxon signed rank test; note re using a paired test: it compares the means of the same group or item under two different scenarios. The values in each group are related, usually before and after values measured on the same subject. For example, you might use a paired t-test to measure a plant’s growth before and after using a new fertilizer

chi squared tests are applied to establish whether there is a significant difference between two groups of categorical data. It works by comparing the observed data with the data that could be expected if the null hypothesis was true; the chi-squared test returns a statistic – the corresponding p-value for this statistic can then be found on a table and if greater than the critical value for our desired P value we can reject the null hypothesis; When looking for critical values in a table, you will often have to find the row with the appropriate number of degrees of freedom. This is simply the number of other categorical outcomes there could have been eg if binary data then degrees of freedom is one

Question 40

risk and odds ratios

Answer 40

risk ratio is risk in exposed group/risk in unexposed - risk ratio of 1 implies that there is no difference, and a ratio of less than 1 would imply that the exposure had a protective influence over the outcome

odds is probability that X happens/probability that X does not happen, and OR is odds in exposed group/odds in unexposed group; if OR = 1 there is no difference in odds, if >1 then odds increased in exposed group and if <1 odds decreased in exposed group

Question 41

NNT and NNH

Answer 41

A distinction should be made, however, between statistical significance and clinical significance. In general, a larger sample size will reduce the probability of a Type I error and therefore decrease the P-value. This raises the possibility that a clinically insignificant difference may be found to be statistically significant. The actual magnitude of the treatment effect should always be considered separately from considerations of statistical significance. The NNT is one tool that addresses the magnitude of the clinical effect. In particular, NNT places study results in a context that allows discussion of broader issues such as the cost of treatment to society and the exposure of patients to potential adverse reactions

NNT is defined as the number of patients that would have to receive the intervention in question in order to prevent one adverse event

can be calculated by finding the reciprocal of the difference in risk between the two groups

Imagine there is a drug that reduces the risk of death following stroke by 20% (this is equivalent to a risk ratio of 0.80). In order to know how significant this is, we must first identify what the risk of death following stroke is without the drug - lets say that risk before is 0.5 and risk after is 0.4, risk difference thus 0.1 and NNT 1/0.1 or 10

NNH similar but for interventions that are harmful to health

Question 42

sensitivity, specificity, likelihood ratio, and PPV/NPV

Answer 42

true positive, false positive, true negative, false negative

Sensitivity is defined as the proportion of those with the disease who are correctly identified by the test. In contrast, specificity is the proportion of those without the disease that are correctly identified by the test

calculated as:
sens = TP/(TP+FN)
spec = TN/(TN+FP)

Likelihood ratio (LR) is linked to sensitivity and specificity. The LR for a positive result is the chance of a true positive versus that of a false positive. An LR of 3 indicates that if the result is positive, the subject is three times more likely to truly have the disease than not

LR = sens/(1-spec)

Sensitivity and specificity tell us about the diagnostic capacity of the test. However, the predictive values demonstrate how likely it is that an individual does or does not have the disease based on their test result

PPV = TP/(TP+FP)
NPV = TN(TN+FN)

the predictive values are influenced by the prevalence of the disease amongst those in the study. Likelihood ratios give similar information to predictive values, however, they are not influenced by the prevalence of the disease

Question 43

sample size and power

Answer 43

prior to starting study, must select the alpha (α) level at which the hypothesis will be declared “supported”. The α represents how much risk the researcher is willing to take that the study will conclude H1 is correct when (in the full population) it is not correct (and thus, the null hypothesis is really true). In other words, alpha represents the probability of rejecting H0 when it actually is true; the most commonly chosen level is 0.05 but studies where it is especially important to avoid concluding a treatment is effective when it actually is not, the alpha may be set at a much lower value; it might be set at 0.001 or even lower

The P value is simply the obtained statistical probability of incorrectly accepting the alternate hypothesis. The P value is compared to the alpha value to determine if the result is “statistically significant”

the error of accepting H1 when it is not true in the population; this is called a Type I error; and is a false positive. The alpha defines the probability of a Type I error.

It is also possible to make an erroneous decision in the opposite direction; by incorrectly rejecting H1 and thus wrongly accepting H0. This is called a Type II error (or a false negative). The β defines the probability of a Type II error. The most common reason for this type of error is small sample size, especially when combined with moderately low or low effect sizes. Both small sample sizes and low effect sizes reduce the power in the study.

Power, which is the probability of rejecting a false null hypothesis, is calculated as 1-β (also expressed as “1 - Type II error probability”). For a Type II error of 0.15, the power is 0.85. Since reduction in the probability of committing a Type II error increases the risk of committing a Type I error (and vice versa), a delicate balance should be established between the minimum allowed levels for Type I and Type II errors. The ideal power of a study is considered to be 0.8 - sufficient sample size should be maintained to obtain a Type I error as low as 0.05 or 0.01 and a power as high as 0.8 or 0.9

Although increasing the sample size is suggested to decrease the Type II errors, it will increase the cost of the project and delay the completion of the research activities in a foreseen period of time. In addition, it should not be forgotten that redundant samples may cause ethical problem - thus we want to calculate a desired sample size before the study commences (rarely seen in clinical papers); there are various ways to do this including manual calculations as well as nomograms, or using computers as power calculation gets very complicated

Question 44

different study designs

Answer 44

A non-analytic or descriptive study does not try to quantify the relationship but tries to give us a picture of what is happening in a population, e.g., the prevalence, incidence, or experience of a group. Descriptive studies include case reports, case-series, qualitative studies and surveys (cross-sectional) studies, which measure the frequency of several factors, and hence the size of the problem.

An analytic study attempts to quantify the relationship between two factors, that is, the effect of an intervention (I) or exposure (E) on an outcome (O). To quantify the effect we will need to know the rate of outcomes in a comparison (C) group as well as the intervention or exposed group
In experimental studies, the researcher manipulates the exposure - RCTs
In analytic observational studies, the researcher simply measures the exposure or treatments of the groups. Analytical observational studies include case-control studies, cohort studies and some population (cross-sectional) studies; case control studies give an odds ratio, cohort studies give a relative risk (Relative risk cannot be calculated in case-control studies because incidence cannot be measured. In a case-control study, the groups are defined based on the end conditions, which makes it difficult to determine the risk of something occurring)

The type of study can generally be worked at by looking at three issues

Q1. What was the aim of the study?

To simply describe a population (PO questions) descriptive
To quantify the relationship between factors (PICO questions) analytic.
Q2. If analytic, was the intervention randomly allocated?

Yes? RCT
No? Observational study
For observational study the main types will then depend on the timing of the measurement of outcome, so our third question is:

Q3. When were the outcomes determined?

Some time after the exposure or intervention? cohort study (‘prospective study’)
At the same time as the exposure or intervention? cross sectional study or survey
Before the exposure was determined? case-control study (‘retrospective study’ based on recall of the exposure)

crossover study - A controlled trial where each study participant has both therapies, e.g, is randomised to treatment A first, at the crossover point they then start treatment B. Only relevant if the outcome is reversible with time, e.g, symptoms.

Advantages:

all subjects serve as own controls and error variance is reduced thus reducing sample size needed;
all subjects receive treatment (at least some of the time);
statistical tests assuming randomisation can be used;
blinding can be maintained.
Disadvantages:

all subjects receive placebo or alternative treatment at some point;
washout period lengthy or unknown;
cannot be used for treatments with permanent effects