Bawa Garba case

Clinical governance, Ethics, Generic

High Court ruling regarding Dr Hadiza Bawa-Garba following the tragic death of a 6-year-old boy in 2011. Subsequently convicted of manslaughter. Removed from the GMC register, although Medical Practitioners Tribunal Service (MPTS) decision was to suspend for a year.  GMC appealed, saying it had not taken into account the manslaughter conviction.

High Court then overturned erasure, saying that tribunal did not commit any errors in its procedures, and therefore its conclusions were valid.

The trust acknowledged systemic failures, so why the vindictiveness? Its report into the death (“no single error responsible for death”) was not brought before jury, as being beyond scope of the trial! Not lazy or under influence, rather, took on extra duties in overstretched hospital with very little supervision.

And since when was gross negligence manslaughter law the right way to deal with errors made by doctors in training?

Why not corporate manslaughter case against trust?

Concern about reflective notes being used in court – despite being confidential? Used in support of Dr Bawa-Garba to show remediation efforts.

Twitter response from consultants was to emphasise “WE are responsible – so long as you tell us what’s going on”.

Subsequently 2 reviews –

  • Marx review by GMC
  • Williams review by government into medical gross negligence.
    • Suggested that GMC lose right to appeal Tribunal decisions.  Most of these appeals have been regarding sexual misconduct cases.  Professional standards Authority would still be able to appeal.
    • Suggested that GMC not be allowed to access reflective notes eg portfolio.  Could still be used as evidence in prosecution, however, not clear whether would help defence or prosecution more
    • Touched on high rate of cases involving black or minority ethnic doctors, but did nothing other than suggest BAME representation in investigations
    • Recommends explanatory note for gross negligence law, to improve consistency.  Law remains the same, however

Insurance and genetic testing

Ethics, Generic

You have to answer truthfully any question you are asked when applying for insurance.  You do not need to volunteer information not asked for!

The Government and the ABI have a policy framework (‘Concordat’) for cooperation that includes a voluntary Moratorium on insurers’ use of predictive genetic test results (NOT diagnostic tests) until 1 November 2019, (to be reviewed in 2016).  So for most tests, companies cannot force test before providing cover, customers do not need to disclose result while insurance in place, and do not need to disclose results of blood relatives.

Only one exception currently, for cover above £500 000 and Huntingdons.  Certainly no need for time limited policies eg travel, private medical care; really just for life insurance, critical illness and income protection. Recognition that increased risks of a small minority can be mitigated by larger population of policies [2014]  Evidence from US is that significant proportion conceal their diagnosis.

Asymmetry of information—when the customer knows more than the insurer—is the industry’s nightmare.  Testing positive for ApoE4, a mutation of a gene related to increased risk of Alzheimer’s, would be a good reason to get life insurance before symptoms develop.

See also ethics.

Prevention of allergy and autoimmune disease

Allergy, General paediatrics, Immunology

See also asthma prevention.

Immune system starts development in the first trimester, in the womb. Some parts (eg IFN gamma) are constrained, probably to protect the placenta. Immunoglobulin (particular A) still developing through early years – airway mucosal dendritic cells still expanding up until puberty.

The major driving force behind postnatal immune development in all mammalian species is microflora of the gastrointestinal tract – “healthy” development requires not just the right balance of microflora, but also at a crucial window in time.

The hygiene hypothesis (David Strachan) has now been modified to include “old friends” (Graham Rook, talking about microbes that have co-evolved with humans) and finally the biodiversity hypothesis.

So lifestyle becomes important – time spent outdoors, time spent in contact with natural habitats, having diverse, unprocessed diets. Fresh fruit and vegetables have their own microbiome, for instance. And these things are heavily linked to socioeconomic status, particularly housing and green space. Role of artificial sweeteners, emulsifiers, plasticisers and other waste organic compounds?

Mode of birth/delivery affects neonatal colonisation (elective vs emergency section or vaginal) – although so far maternal-infant microbial seeding studies have failed to demonstrate health benefits.

More than 20 studies of probiotics and prevention of allergy.  No safety concerns.  15 found supplementation during pregnancy and lactation may reduce eczema, but no effect in asthma, food allergy, rhinitis.

Fish oil (omega-3) supplementation during pregnancy may reduce risk of allergic sensitisation to egg.

Cochrane 2013 review of prebiotics concluded “promising results in high risk populations”, WAO find in favour (probiotics too), but others institutions have not!

Other dietary exposures, including maternal allergenic food avoidance, vitamin, mineral, fruit and vegetable intake did not appear to influence risk of allergic or autoimmune disease.

There is limited evidence to suggest that supporting mothers to breastfeed for longer reduces risk of eczema in the first year. Longer exclusive breastfeeding duration reduces risk of type 1 diabetes.

EAACI have recommended hypoallergenic formula (“one with documented preventive effect”) for 4/12  (Grade I, evidence A-B).  2024 Chinese systematic review found low quality evidence for extremely hydrolysed formula (EHF) reducing risk of cow’s milk allergy [relative risk (RR): 0.62]. Moderate quality evidence for partially hydrolysed (PHF) and EHF reducing risk of eczema in children (even after 2 y – RR: 0.71-0.79). Moderate quality evidence that PHF only reduced risk of wheeze at age 0-2 y compared with CMF (RR: 0.50), but cf with breast milk, both PHF and EHF increased the risk (RR: 1.61 and 64).

[PLoS Med metanalysis 2018]

Sun exposure around time of birth protects against allergy/atopy, according to French study – for one change in interquartile range, sun exposure prenatally had adjusted odds ratio of 0.47 for sensitisation at age 8-9yrs, and 0.32 for asthma. Postnatal effects less strong. Maternal vitamin D supplementation seemed to increase the risk. All the children were from Paris – sun exposure was calculated from meterological data around time of birth, not time spent outdoors. Ethnicity was not reported.  The suggestion is that the mechanism is vitamin D mediated. Previous studies have had mixed results.

Skin

Since eczema commonly precedes food allergy, it is assumed that disruption of the epithelial barrier is the first step in sensitisation (even when a baby is not eating any food) – the “dual allergen exposure” hypothesis. Peanut protein levels in household correlate with peanut sensitisation in high risk babies.

A couple of different skin “endotypes” – protein/ceramide expression, staph aureus abundance – that seem to predict food allergy. Filaggrin mutations are the strongest genetic risk factor for eczema, and the associated disruption in keratinocytes allows for allergens and irritants to penetrate the skin and trigger inflammation. Detergents/pollutants can further disrupt the skin barrier. Low humidity/temperature also affects (autumn/winter births more at risk).

S aureus colonisation is more likely with eczema, and is associated with severity and persistence – it is also associated with reduced tolerance to egg/peanut, and higher IgE milk/egg/peanut.

Cochrane review of emollients as preventive strategy found no evidence of benefit and possibly more infection. Frequent bathing and oil based bath additives increased the risk of eczema. STOP-AD study (ceramide based emollient, first 2 months of life) found reduced eczema incidence at 1yr in high risk infants. Other studies are looking at trilipid rather than petrolatum based emollients.

Japanese study of “proactive topical steroids” at 7-13 weeks of age (including non-affected skin) found 25% reduction in egg allergy but also reduced weight/length! Calcineurin inhibitors may get around the issue of steroid side effects, if safety data in infants becomes available (so far, so good). [Review, 2024]

Angelman syndrome

General paediatrics, Genetics, Neurology

Caused (mostly) by absence of maternal contribution to a region of the 15q chromosome.  Paternal uniparental disomy is one way this can happen, although mostly there is de novo maternal deletion.  The same region is also responsible for Beckwith-Wiedemann syndrome, but this syndrome is the result of a paternal deletion.

Characteristically “happy puppet” –

  • severe speech and language delay
  • learning disability and epilepsy
  • Movement disorder esp ataxia, also tremor, hyperreflexia
  • open mouthed expression, large mandible
  • Excitability, paroxysmal laughter

[https://www.omim.org/clinicalSynopsis/105830]

Hereditary spherocytosis

General paediatrics, Genetics, Haem/Oncology

One of the genetic red blood cell abnormalities that protects against malaria (cf sickle cell), as haemolysis shortens life span and potential for parasite reproduction.

Phenotype (severity) consistent within family, but very different between families. FH may be vague eg splenectomy, jaundice rather than awareness of underlying diagnosis…

Presentation

Anaemia, jaundice and splenomegaly classically. Splenomegaly is usually mild and there is no increased risk of rupture. Neonatal jaundice can be severe but does not predict severe disease! Severe cases (assessed when well, not during crises, only about 5%) can be transfusion dependent in first years of life (erythropoietin helpful) but not usually afterwards.

May present with parvovirus aplastic crisis (not just red cells; white cells and platelets often drop too) – only happens once.

Diagnosis by spherocytes on film, reduced MCV, high reticulocytes (but retics do not go up during aplastic crisis), unconj hyperbilirubinaemia, splenomegaly. There are other causes of spherocytes, and they can be seen in normal neonatal blood films.

Differential is autoimmune haemolytic anaemia, which is associated with acute viral infection (direct Coombs test usually positive). Osmotic fragility test does not distinguish, can be false negative in iron deficiency, and is unreliable in the first few months of life. New EMA dye binding test takes 2 hours and is 92% sensitive. Gene tests don’t add much.

Other problem is gallstones. High reticulocyte count predicts.

Folate probably only necessary for severe cases.

Splenectomy

Most children are asymptomatic, but severe cases can have growth failure, lethargy, heart failure and leg ulcers. Should be delayed until at least 5 yrs, potentially laparascopic and/or partial. Do cholecystectomy at same time if symptomatic. Platelets rise to abnormally high levels after splenectomy, but no apparent increase in thrombosis.

[Arch Dis Child PMID 15321852]

Haemolysis

General paediatrics, Haem/Oncology

ie red cell breakdown.

Intravascular (eg disseminated intravascular coagulation) or Extravascular (eg hypersplenism)?

Immune or non-immune? Do Indirect Coombs (anti-globulin) test.

Differential:

  • disseminated intravascular coagulation – eg sepsis.  Sick! Low platelets, low Hb, abnormal clotting, high inflammatory markers.
  • Hypersplenism eg G6PD deficiency, storage disorders
  • autoimmune haemolysis (see below)
  • Hereditary spherocytosis

Autoimmune

Type of AHA is usually revealed by antibody screen as part of Direct Antiglobulin Test (DAT) – pattern of anti IgG plus anti C3. 

Basically, warm, cold or paroxysmal cold haemoglobinuria.

Can be primary, or associated with autoimmune disease (eg SLE), lymphoproliferative disorder, infection (EBV, mycoplasma), drugs. Big spleen usually suggests secondary.

Warm means haemolysis at body temperature. Cold means triggered by cold exposure – acrocyanosis (even ischaemia) can be a feature.

Titre less important than threshold temperature for activation!

Paroxysmal cold haemoglobinuria – most common autoimmune haemolytic anaemia in under 3 yrs. Post viral. NB normal platelets, no fragments on film cf HUS. It is intravascular however, unlike warm/cold, so no liver/spleen. Donath-Landsteiner antibody. Can be with localised cold exposure eg hands in cold water, even just drinking cold water!  IgG vs P antigen on RBC.  Can be associated with syphilis. Renal failure. Plasma exchange helps.

Osteoporosis

General paediatrics, Medical, Orthopaedic

Various causes of secondary osteoporosis: coeliac disease,  hyperthyroidism, hypogonadism, IBD, chronic liver disease, JIA, chronic renal, immobility.

Consider calculating fracture risk if secondary osteoporosis or previous fragility fracture, frequent use of systemic steroids, FH hip fracture, low BMI, smoking/alcohol etc.

Use online tools FRAX or QFracture to estimate 10yr predicted fracture risk (FRAX includes previous bone mineral density value if DXA done, not necessary).  If risk is in the region of “intervention threshold” for proposed treatment, consider doing DXA and recalculate FRAX.  Tools may underestimate risk if history of multiple fractures, previous vertebral fracture, high dose steroids, other causes of secondary osteoporosis. These tools are meant for adults over 30-40yrs however.

“Intervention thresholds” are NOT covered in guideline, it says see local guidance!

For WOS, no Dexa for coeliac until in 20s.

[NICE osteoporosis guideline ]

MRSA

General paediatrics, Infectious disease, Microbiology

=methicillin resistant staphylococcus aureus.  Cf methicillin sensitive staph, MSSA.

Methicillin resistance equates with flucloxacillin resistance. mecA is the methicillin resistance gene, which codes for a low affinity PBP (penicillin binding protein) – ie penicillin can’t bind easily. The gene has probably crossed from coag neg staph on at least 5 occasions to create MRSA strains. As with MSSA, different strains exist, carrying a range of different pathogenic genes.

Traditionally MRSA was found in institutions and the elderly, but now can be seen frequently in the young and healthy, causing the same infections that MSSA causes eg skin/soft tissue. It can also be responsible for rarer, more severe diseases eg necrotizing fasciitis. The US Center for Disease Control details criteria for distinguishing hospital acquired and community acquired MRSA infections – community acquired strains are typically SCCmec type IV (this is the cassette that contains mecA), which are sensitive to most non-beta lactam antibiotics, but on the other hand is associated with Panton Valentine Leucocidin (PVL, a cytotoxin associated with necrotizing disease). But again, this distinction is becoming less clear with strains associated with community acquired infection becoming more frequent in hospital acquired cases, and having variable levels of non-beta lactam antibiotic resistance.

In itself, antibiotic resistance may not translate to increased virulence and pathogenicity – it may just make it harder to treat. Studies have shown that after correcting for other factors eg age and co-morbidity, mortality is not significantly different. However, one important factor is use of inappropriate antibiotics, which of course is more likely with MRSA. Furthermore, in the US many MRSA outbreaks are caused by the USA300 clone, which carries a number of genes (in common with Methicillin sensitive staphylococcus aureus) eg PVL, ACME which are associated with enhanced pathogenicity.

PVL seen in 50% of symptomatic (skin) community MRSA in the US. Now also being reported in hospital acquired MRSA. Prevalence much lower in Europe, but risk of spread. Geographical areas tend to have their own clones (eg type 80 in Europe), with occasional pandemic.

Epidemiology

  • MRSA has been shown to survive on sterile packaging for at least 6 months.Journal of hospital infection 2001;49(4):255-61.
  • Basic simple infection control like hand washing works.
  • MRSA prevalence in hospitals is associated with macrolide and 3rd generation cephalosporin use.Clinical microbiology and infection 2007;13(3):269-76.
  • Alcohol hand rub reduces its transmission and hospitals which have introduced a policy of using this between patient contacts reduce their MRSA rate.
  • Isolation and screening work but may be impracticable in emergency admissions or in hospitals with near 100% occupancy.

In the UK, most MRSA are resistant to quinolones and macrolides. Even if sensitive to quinolones, treatment is not recommended as resistance evolves rapidly. Most MRSAs are sensitive to tetracyclines (but not for use under 12yrs), rifampicin, co-trimoxazole, and linezolid, all of which can be given orally. Clindamycin can be effective but beware inducible resistance – see below. No evidence for trimethoprim alone (cf septrin); use in combination with rifampicin? Probably best not to give rifampicin or fusidic acid monotherapy anyway as resistance frequently induced.  See antibiotic classes.

In MRSA skin infections (cellulitis/abscesses), most will get better anyway, esp after I&D, but using the wrong antibiotic increases risk of treatment failure by odds ratio of 2.80 (87% success cf 95% of patients who received an active antibiotic). Topical agents will induce resistance if used for high load infections eg wounds, catheter sites so should be combined with systemic therapy.  About 12% are resistant to topical mupirocin.

For intravenous therapy, gentamicin, vancomycin and teicoplanin are effective, although vancomycin resistance has been described since 2002. Teicoplanin levels can be unpredictable, and treatment failure associated with low levels has been seen; checking levels would make sense (aiming for trough of at least 10, 20 in endocarditis) but is rarely done. In line infections, vancomycin or linezolid should be used if the infection is severe; if milder, then removal of the line and oral therapy may be sufficient.

In bone infection, linezolid is good but should be given for a maximum of 28 days. Fusidic acid and Rifampicin are good adjuncts (rifampicin has in vitro activity against biofilms). Clindamycin and co-trimoxazole have also been used for bone infections. Early surgery (eg within 2/7 of onset of symptoms) is important esp where a prosthesis is present.

Necrotising pneumonia with MRSA post-influenza has mortality up to 75%.

For bacteraemia/endocarditis, vancomycin is the drug of choice, as treatment failures have been described with teicoplanin. Rifampicin or fusidic acid can be considered as adjuncts; there is no evidence for adding an aminoglycoside. A minimum of 14 days treatment is required (although oral treatment may be appropriate for maintenance) but should be extended if vegetations seen on trans-oesophageal echo. Infected pacemakers should be considered the same as orthopaedic prostheses.

Clindamycin resistance is sometimes only 1 mutation away from erythromycin resistance. If the bug is erythromycin sensitive, then there is no issue, and clindamycin is a good choice (and can be given orally). On the other hand, if erythromycin resistance is seen, then the D test should be done: if a D-shaped zone appears around the clindamycin disk when an erythromycin disk is placed nearby, then you have induced resistance and clindamycin should be avoided. The erm gene is responsible for erythromycin-inducible resistance; the mrsA gene also confers resistance to erythromycin but does not affect clindamycin.

Eradication

Once colonized, about 40% of patients develop persistence – commoner where skin breaks present. Vancomycin does not clear nose, throat or gut.

Eradication of S. aureus nasal colonization eg with 72 hour mupirocin has been successful. However, recolonization usually occurs within a relatively short time, and the Cochrane review did not find much evidence in favour. Use of mupirocin to prevent infection in endemic settings eg dialysis centers have shown conflicting results although metanalysis suggests benefit (but fear of mupirocin resistance). Neomycin is even less effective, but is an alternative where mupirocin resistance is seen.

Combined treatment seems sensible, and recent RCT of 2% chlorhexidine gluconate washes, 2% mupirocin ointment intranasally, oral rifampin and doxycycline for 7 days vs no treatment confirms. At 3 months of follow-up, 74% cf 32% had cleared. Still significant benefit at 8 months (54% of those treated culture negative). On multivariable analysis, having a mupirocin-resistant isolate increased the risk of treatment failure nearly 10 fold. Mupirocin resistance emerged in only 5% of follow-up isolates. Clin Infect Dis. 2007 Jan 15;44(2):178-85.

Other control measures include a combination of active surveillance cultures of high risk patients, improved health care worker hand hygiene, consistent use of contact precautions for colonized/infected patients, and directed treatment of health care workers implicated in transmission. PIDJ January 2005 pp 79-80

Screening patients seems to reduce hospital acquired infection in the Netherlands, but not in Switzerland. UK guidelines say do for high risk only eg previous carriers, transfers, ICU. Standard infection control procedures alone seem to have worked in UK although what do you compare with? Rapid test (PCR) did not help (in crossover trial) except in reducing inappropriate isolation. 3-4x as expensive.

[UK guidelines, J antimicro chemo 2006 PMID 16507559]

 

 

Benign transient hyperphosphatasaemia

Common, General paediatrics

Common, typically young children with minor infections.

Due to decreased clearance, probably, carbohydrate side chains changed, affecting recognition – characteristic iso enzyme pattern on electrophoresis (ie not usual bone/liver forms).

Can be as high as 50x normal upper limit viz 10 000+!  Can last up to 6 months.

Just show that other liver function tests normal, normal calcium/phosphate and no suspicion of myositis, rickets.

Asthma

Common, General paediatrics, OPD, Respiratory

See BTS/SIGN/NICE 2025 guidance on asthma,  asthma prevention, asthma and obesity

FeNO is expensive and available in only a minority of GP practices and hospital services.  Requiring it means GPs can no longer make diagnosis themselves.

Spirometry results in most primary care patients with asthma are normal!

Spacer best for everyone! Orange aerochamber is small mask, up to 18 months, yellow is 1-5yrs. Green is 5+, blue is adult. You can get blue with mask, not green.

200 doses in an MDI.   2 puffs BD exhausts an MDI in 50 days. Multidosing 5 puffs 4hrly will exhaust it in 6 days.

Growth Restriction

Children who use inhaled steroids for asthma grow slower than their peers in the first year of taking the medication, by about half a centimetre per year. Metanalysis of 25 trials, various types of steroid.  Seems to be most obvious in initial year of treatment.  Only 1 study followed children into adulthood – budesonide, used for average of 4 years – reduction in final height of  1.2cm (Kelly, PMID 22938716).

Should therefore be prescribed at the lowest effective dose. Cochrane 2014 found significant difference between low dosing (50-100 Clenil equivalent) and medium dosing  of 0.2cm per year but noted that the  majority of trials did not report height data.

However, the small effect on growth needs to be weighed against the proven benefits of these drugs in controlling asthma, and ensuring children’s lungs grow to their full capacity.   Undertreated asthma is much more likely to have a harmful effect on a child’s development than a small reduction in growth.

Newer Therapies

Xolair=Omalizumab, monoclonal vs IgE. Subcut, 2-4 weekly, for age 6+ where conventional therapy not working.  Other criteria are total igE >30, positive tests for aeroallergens, FEV1<80%.

Airsonett is evidence based, temperature controlled laminar flow system for bedroom. Noisy!

Management

See National review of asthma deaths.  Recommendations include:

  • Refer specialist if >=2 courses oral steroids within 12 month period
  • Follow up after every ED/OOH attendance
  • Hospital follow up after every hospital attendance
  • Annual inhaler technique check
  • Personal asthma plan for everyone

See MyLungsMyLife.org website for self management.