History of Medical Failures

Where to start!? Leaches, blood letting, pretty much everything doctors did in the pre-modern period…

Thalidomide and birth defects, of course. But unforeseen.

X-rays for pregnancy monitoring. Took years before people paid attention to the alarms. X-rays were also used for tinea capitis – not just brain tumours, strokes and ischaemic heart disease about 30% higher too.

Ribavirin (via SPAG machines) for RSV. Not harmful, just useless and expensive.

Iron supplements for preterm babies – increased sepsis.

Allergy and mental health

Evidence that having a peanut allergy has worse quality of life for a family than having diabetes… Mostly due to fear of unexpected severe reaction, and restrictions on social activities particularly eating out, parties and holidays.

Allergic patients can feel embarrassed or even ridiculed for declaring their allergy. Allergy is often mocked in the media (Cobra Kai, the Box Trolls, Peter Rabbit).

School and nursery are a particular area of concern, whether the right foods will be served, whether teachers or other children might bring allergens into school (food is sometimes used in classes, for example making bird seed balls), whether reactions will be managed appropriately, school trips. Children have died in school (Nasar Ahmed, Mohammed Ismaeel Ashraf).

Mums tend to be more concerned by limitations in the child’s own social life, dads seem to care more about limitations in the whole family’s social life. [Stensgaard, Clin Exp Allergy 2017]. Mums are the ones most studied. There probably are significant differences between mums and dads. In some studies, parents overrate their child’s quality of life, but in others (particularly with teenagers) parents can be seen as over anxious. Teenagers tend to take on the perspective of the parent of the same sex.

How bad previous reactions have been, interestingly, does not in itself contribute significantly to quality of life – in some cases, not having ever had a reaction can make families more anxious, because they don’t know what to expect! In one study, having multiple allergies and having an adrenaline pen was associated with worse quality of life. [Protudger, Clin Transl Allergy 2016]

Parents can feel guilty if their child has a reaction, a failure of their duty to protect. Mums can feel guilty about having “caused” their child’s allergy, either through their own medical history or what they ate or didn’t eat in pregnancy (even there is no good evidence for this being a factor).

Better quality of life is seen in allergic families with greater self efficacy for food allergy management, and lower perceived likelihood of a severe reaction [Knibb, Pediatric Allergy & Immunology. 27(5):459-464, August 2016].

APPEAL-1 study

8 European countries, questionnaire study of adults and children with peanut allergy

Only a minority remembered getting any training in future emergencies or use of medication, after their initial reaction. There was a low rate of satisfaction with AAI training! 

43% reported bullying, and a third of these described it as severe. 

65% confident in ability to recognize a reaction, but only 45% confident about knowing when to use an AAI and 59% how.  62% say the carry AAI all the time.

25-30% said it was not easy (or rarely easy) to talk to friends or family about their allergy, although most felt confident talking to new people about their allergy. Friends and family were generally seen as “believing there is too much concern over allergy” even though overall they were seen as having a good awareness and understanding of allergy (cf other people, where this was seen as the opposite).

Dutch respondents had lowest rates of uncertainty and stress around activities, and for feeling anxious.  At same time, they had the highest rates of confidence around knowing when and how to use AAI.  France had highest rate of being made to feel different in a negative way, and feelings of isolation.

NB – likely to be the most affected families who participated.

[Dunngalvin, Allergy 2020]

Expert patients

Idea came from Prof Kate Lorig, rheumatologist in US. Trained lay educators had better outcomes than conventional clinic appointments. In 2001, became an NHS programme, aimed at cutting costs of chronic disease.

Technology has aided this massively – see “E-patients“. But of course variations in access to technology and tech literacy.

Patient centred networks not well understood. Can have links to health professionals, but can also be tied to industry/commercial interests, may even be driven by industry.  Online resources scored higher with e-patients for convenience, emotional support, empathy, death and dying, in depth medical information, practical help.  Specialist physicians rated highest for diagnosis, technical knowledge (just), managing condition after diagnosis.  So online resources score highest where medics poorest and vice versa.  So combination of both ideal!  Also, medics come and go.  Some patient groups have published their own research eg GIST group.

But behaviour change, specifically when talking about self-efficacy, is very individual and psychology focussed. Less exploration of social influences, other than focus on peer modelling.

Foucault, of course, was fascinated by how people can become obedient, self governing, and how this is produced by the efforts of “pastoral power”, in a similar way to the Christian church and the process of confession.

Trisha Greenhalgh would say that although collaboration between patient and doctor is important, it’s still just one aspect of a whole system that includes community, material conditions, law/policy, social deprivation, cultural norms etc.

Guillain Barre Syndrome

An acute inflammatory demyelinating polyradiculopathy, almost certainly autoimmune since antibodies to ganglioside are often found (GQ1b in particular is highly sensitive and specific for Miller-Fisher syndrome = ophthalmoplegia with ataxia & absent reflexes). Some cases are purely motor, others are mixed. About a quarter follow Campylobacter infection, and there is clear homology between epitopes and gangliosides. Strongly associated with HIV in the tropics.

Usually gradual onset over a few days but rarely can be over a few hours. Presents with pain, numbness, paraesthesiae, weakness. Weakness may initially be proximal or distal (distal alone suggests a withering axonopathy eg toxin). Facial nerves often affected. Reflexes usually lost early but sometimes persist (ie axonopathy rather than radiculopathy). Autonomic features may occur eg urinary retention, sinus tachycardia, ileus. The degree of paralysis can be extreme – up to 20% require ventilation. Monitor respiratory ability serial peak flows. Gradually worsens, peaks at around 2 weeks (by definition, within 4 weeks). Then there is a variable plateau phase. 20% will have persisting disability; fatigue is common.

The diagnosis is often pretty obvious but investigations should be done to rule out other causes. If purely motor, differential includes hypokalaemia, polio, myasthenia gravis, botulism, acute myopathy.

  • MRI brain and spinal cord � low threshold! consider if acute or rapidly progressive, predominantly sensory symptoms (including back pain), predominant sphincter disturbance at presentation, clear sensory or marked motor level. MRI will exclude:
    1. a spinal lesion (eg prolapsed disc, haemorrhage or tumour)
    2. para-sagital cerebral lesion, which can present as acute painful flaccid paraparesis
    3. Acute Transverse Myelitis
    4. ADEM
  • Lumbar puncture – Elevated CSF protein has high PPV but not specific (and may be normal within seven days of onset). Pleocytosis eg >50 cells/mm3 suggests another diagnosis. In children, lumbar puncture is not always necessary to make a definite diagnosis, and should be reserved for cases where the diagnosis is in doubt.
  • Nerve conduction studies – may be normal in the first week! Demyelinating pattern. May be useful in children who present with atypical features, normal CSF protein after the first week following presentation or in categorising the subtype of GBS – for example, AMAN
  • U&E (hypokalaemia)
  • Creatine kinase (myositis)
  • Acute and convalescent serum for viral and mycoplasma antibody titres (Mycoplasma pneumoniae, EBV, CMV, Borrelia burgdorferi).
  • Throat swab; stool microscopy, culture and sensitivities (Campylobacter jejuni)
  • Antiganglioside antibodies (for example, anti-GQ1b antibodies in Miller-Fisher syndrome)

Consider also:

  • Heavy metals and toxins (lead, mercury, arsenic, organophosphates)
  • Urinary porphyrins
  • Botulinum toxin identification (stool, serum) (but eyes usually involved)
  • Diphtheria (but eyes usually involved)
  • Drug toxicology screen
  • trial of intravenous edrophonium (Tensilon) and/or oral pyridostigmine (minimum of five days) for a myasthenia syndrome if investigations have been normal or negative
  • Enteroviruses incl Poliomyelitis – fever, asymmetry of weakness, lack of sensory involvement, CSF findings and PCR from throat/stool
  • In endemic regions, tick bite paralysis closely resembles AIDP. Seasonal, affects young children predominantly. CSF protein is usually normal and the electrophysiological studies are consistent with a pre-synaptic defect at the neuromuscular junction rather than a peripheral neuropathy. The patient usually recovers rapidly after removal of the tick but full return of strength may take several weeks. Failure to detect the tick may result in the death of the patient.

The initial progressive phase lasts 10-30 days. If deterioration continues beyond four weeks, the diagnosis of GBS is pretty much excluded – suggests chronic inflammatory polyneuropathy (CIDP). In rapid, aggressive disease complete quadriplegia can develop in 2�5 days; usually severe respiratory involvement with ventilatory failure, and autonomic involvement placing them at risk of life-threatening arrhythmias and hypertension. Aspiration pneumonia is another major risk.

Children should be admitted to PICU if they have:

  • flaccid tetraparesis
  • severe rapidly progressive course
  • reduced vital capacity at or below 20 ml/kg
  • bulbar palsy with symptoms
  • autonomic cardiovascular instability viz persistent hypertension or labile blood pressure, or arrhythmias.

Plasma exchange is gold standard. Surprisingly, steroids do not appear to have any benefit (cf CIDP), as they can sometimes make things worse or slow the recovery. Perhaps nerve damage at presentation is already programmed/complete? Or do they impair healing? IVIG 0.4g/kg for 5 days (started as soon as possible and ideally within first 2 weeks, although benefit may extend up to 4 weeks) is as effective as plasma exchange (in adults, Cochrane) and probably quicker as well as safer. In kids, 250 ml/kg volume exchange or roughly a triple-volume exchange probably best. The conventional dose of immunoglobulin is a total of 2 g/kg, over 3-5 days, whatever protocol that avoids waste best!

For pain which is resistant to conventional analgesia, gabapentin and carbamazepine may be useful.

Mortality in childhood GBS is less than 5%. Deaths may be caused by ventilatory failure (rare now), cardiac arrhythmias, dysautonomia and pulmonary embolism. Full recovery within 3�12 months is experienced by 90�95% of children with GBS; that leaves 5-10% with permanent neuro deficits, but most of those tend to have only minor disability.

PMID 18032711

Brutalist medicine

“Architecture of medicine” a better metaphor than “art of medicine”, as it has a clear purpose? 

So Brutalist medicine: where so intentionally functional that it erects its own barriers. Eg protocols, scoring systems, electronic records that become monuments to themselves. But you can perhaps defend Brutalism’s desire to avoid unnecessary adornments.

[Benjamin Mazer, Yale-New Haven school of medicine]

Acute pancreatitis

Incidence increasing, approaching that of adults!? INSPPIRE international study. 

Diagnosis

Amylase 3x upper limit, radiology positive. 

Cullen’s and Grey Turner signs (umbilical and flank bruising respectively).

Amylase level not prognostic. False positive liver/renal impairment, GI inflammation.  False negative in 10%, esp drug induced!

Lipase more specific, only done in Huddersfield?! Stays high for longer.

Low calcium, high glucose seen.

Diagnosis mostly clinical. USS usually sensitive, else CT – more for complications (focal or diffuse enlargement, heterogeneous enhancement, irregular or shaggy outline, oedema of surrounding fat).

AXR may show sentinel loop, free gas (loss of psoas shadow). CXR for effusion.

Causes

I GET SMASHED

  • idiopathic (25% in children)
  • gall stones
  • ethanol
  • trauma
  • steroids – and other drugs, esp anti-epileptics, immunosuppressants eg azathioprine, cancer drugs.
  • mumps (even without parotitis), malignancy
  • autoimmune
  • scorpion sting!

But misses IBD, sepsis, Mycoplasma (early or late), genetic causes! 

Management

Prognosis good in children. Scoring systems in adults eg Modified Glasgow-Imrie not applicable, various paediatric versions, of debatable value. 

Fluid resuscitation then 1.5-2x maintenance requirements (not much evidence – don’t be afraid of positive balance! Keep urine output at 1ml/kg/hr), analgesia, early enteral nutrition if possible (to avoid bacterial translocation) else parenteral.

Antibiotics only for suspected sepsis.

Surgery eg necrosectomy. 

1/3 acute recurrent (defined as recurrence after full recovery). Often anatomical problems. Chronic associated with genetic disorders, metabolic, autoimmune.

ERCP for anatomical causes. Pancreatic enzymes. Non opiate pain management eg tricyclics. 

[NASPGHAN 2018 Guidelines]

Ophthalmia neonatorum

Sticky eyes pretty common in babies, especially if tear duct blocked (usually sorts itself out eventually, but can take months).

Otherwise typical bacteria and viruses eg Haemophilus, HSV, adenovirus.

Concern however, especially if severe, that sexually transmitted infection responsible, and risk to eye.

Neisseria gonococcus

Gonococcus onset 0-5 days after birth. Gram neg diplococci on microscopy is a big clue because nothing else looks like it. Risk of haematogenous spread, especially joint.

Single dose cefotaxime effective!

Chlamydia trachomatis

Chlamydia does not gram stain in conventional way, it is an intracellular pathogen and will not grow on standard culture swabs.

Typically lower respiratory tract signs/symptoms as well.

Blood stained discharge has 100% PPV and specificity for chlamydia in Hong Kong study (n=90)!

Treat with oral erythromycin.



Systemic onset JIA

Features

  • Prolonged pyrexia (see below)
  • Intermittent characteristic rash (see below)
  • Raised CRP, ESR, ferritin (esp over 1000 – also haemophagocytic syndromes, haemochromatosis, liver disorders, malignancy)
  • Poor response to IVIG (cf Kawasakis)
  • Leucocytosis (neutrophilia, can be leukaemoid)
  • Thrombocytosis
  • Arthritis
  • Hepatosplenomegaly
  • Generalised lymphadenopathy
  • Pericarditis

Can be systemically very unwell and potentially life threatening complications may occur early in the disease course (eg pericarditis, macrophage activation syndrome or HLH, sepsis). See the Big Sick film from Netflix. Start high dose corticosteroids after careful exclusion of other diagnoses, especially infection, Kawasaki disease, and malignancy – difficult when arthritis is absent! But maybe you have to look harder…

Systemic features may predate the arthritis by several weeks and occasionally longer. Typically involves small joints of the hands and wrists, ankles, hips, knees, and cervical spine – about 30% ultimately develop severe polyarthritis.

There are no pathognomic tests or agreed diagnostic criteria for SOJIA! Classic features:

  • quotidian (=daily) evening spiking temperature, that returns to or falls below baseline by the morning.
  • Rash is faint, salmon pink maculopapular, most obvious during pyrexia. Usually not on the face so easily missed – typically on the trunk, inner thigh and axillae, especially on areas of trauma or pressure (Koebner phenomenon).

Treat with IV methylprednisolone pulses (30mg/kg over 4 hours, max 1g, once daily for 3 days) and ibuprofen (seems better than piroxicam for SOJIA!). Oral prednisolone may then be used while methotrexate is introduced.