Toxic shock syndrome in children

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					Vitamin D Deficiency in Children:
        a call for a network approach


                       Colin Michie
                      No commercial interests
                       No conflicts of interest




                     Ealing Hospital ICO
                     Outline

• Why children?

• Perspectives

   • What initiated my interest in vitamin D?
   • Patters of variation
   • Implications for presentation, diagnosis, treatment
     (including a brief look at vitamin D toxicity)
   • Problems identified relating to vitamin D in west London
   • Gap analysis: precautions, monitoring: a networked
     approach
    Some biology and paediatrics

• Biological view of infant mortality

•   Nutrition in pregnancy, infancy, breast-feeding
•   Adolescents and the next generation
•   Social evolution
•   Imprinting or late effects

The infant is the crucible of our species (we must
  strive to get infancy right!)
A series of hypocalcemic seizures

• January 2007 three hypocalcemic seizures
  presented over a weekend in Ealing Hospital

•   Case series: 18 cases (M 8, age 2.5-6 weeks)
•   Corrected calcium levels at presentation (1.19-1.46 mmol/l normal
    2.15-1.55)
•   Vitamin D levels at presentation (2.3-15 nmol/l)
•   Alkaline phosphatase (350-2300 IU/l, normal up to 300)
•   Ethnicity (15 Asian or Afro-Caribbean, 7 Somalian)



The biology of vitamin D deficiency is variable
                   4 years later

•   13 well and asymptomatic, normal growth patterns (others lost to
    follow-up)
•   4/13 achieved 1,25 OHD > 80 nmol/l, 3/13 never > 50 nmol/l
•   4/13 showed gross motor delays
•   2/13 have damage to tooth enamel
•   Follow-up continues


The outcome of severe deficiency varies; moderate
  to mild deficiency is common
                                                                                                         Serum Vitamin D
                                                                                                   October 2009 to December 2009

                                                       1400

                                                                   1231
                                                       1200
                                                                          1105


                                                       1000


                                                                                 790
                                                       800
                                           Frequency




                                                       600



                                                       400
                                                                                       312   292
                                                                                                   240    226        205
                                                       200                                                                   159
                                                                                                                                     127      109
                                                              65                                                                                    85        81
                                                                                                                                                         59         49          37
                                                                                                                                                                          22
                                                         0
                                                              10    20     30    40    45    50    55      60        65       70         75   80    85   90   100   110   120   >120
                                                                                                                Serum Vitamin D nmol/L
           Homo sapiens




• We are the same species!
Variation…
                   Variation
• ‘Hapmap 3’:
  http://hapmap.ncbi.nlm.nih.gov/publications.html.en

• Binding to sites on genome
• Binding to sites with known disease associations
• Clinical associations

Just how wide is the variation in our species in the
  responses/biology of vitamin D?
The complex system
                 Variations

•   Rates at which system functions
•   Metabolic activity of components (vitamers)
•   Binding proteins for individual metabolites
•   Role of other metabolites e.g. calcium,
    phosphate, magnesium, vitamin A
A helpful cloud?
             Return to biology

  • The complex system has at least two rate
    limiting points:

     • Skin (homeostatic system)
     • Renal hydroxylation (Type 1)
     • ? Intranuclear (Type 2)

What is the outcome of
abnormalities at these points?
Studies of rare disorders have
value
The complex system
 Some unpopular points

• Normal curves – what about the top 5%?
• Crucial to define in order to proceed with clear risk
  definitions
• The vitamin OTC market has proved recession resistant:
  how can we find out about self-medication?
• Prescriptions for vitamin D are soaring
A problem at the zoo…
Vitamin D Toxicity

• What biological system should one test?
• What are the variations within populations?
• What level of vitamin D is dangerous, what level is
  ‘toxic’?
• Hypercalcemia and hypercalcuria, with fatigue, muscle
  pain or weakness, polyuria and polydipsia, high blood
  pressure [blood tests… 24 hour urine tests…!]
• BPSU study planned
 Returning to Ealing…

• In 2011/2012: known 4 cases of hypercalcemia, one
  symptomatic, related to vitamin D overdose. All caused
  by over-supplementation by parents.
   • Corrected serum calcium: 2.7-3.0, urinary calcium > 350 mg/day
     in all cases
• Others have observed unexpected levels of
  hypercalcemia
• No good epidemiology relating to this problem: what is
  the system whereby overdose is managed and
  preferably avoided?
 Problems identified

• Lack of knowledge relating to vitamin D in antenatal
  clinics, both among mothers and staff. No concept of
  requirement or risk Identified in adolescents in ward
  school
• Lack of compliance with national recommendation for
  vitamin supplements and antenatal care; Healthy Start
  vitamins not available, licence debates
• Lack of appreciation of the importance of obesity
• Maps…
Geography of hypocalcemic seizure
Geography: blood tests for vitamin D
  Geography: Top 10 prescribing
practices for vitamin D supplements
          Mapping observations

• There is variation in clinical symptoms and care provision at
  the level of the street
• The distribution of cases corresponds with socioeconomic
  factors
• There is no more/very little new funding to change this
• (High levels of vitamin D were in W5 and W13)
                         Gaps

• Deficiency in this nutrient, related to geography and lifestyle,
  particularly for lower socioeconomic groups
• Distances between scientific knowledge and clinicians are
  growing
• Sources of messages or information relating to vitamin D are
  diversifying and multiplying
• UK studies show varied understanding, poor compliance
  with existing guidelines, incomplete guidelines and problems
  with reasonably priced, licensed medications
• There will be no more funding

Systems analysis: educate the public and professionals,
  develop a network, manage that network
    Stratgies for the future


• Introduce yourself to your neighbours: network
• Clinical networks (www.rcpch.ac.uk/networks)
   • Create, participate, identify goals, publish
   • Guidelines needed: concordance and publication
• Maps (www.rightcare.nhs.uk)
   • Standards
   • Peer review
                Conclusions

• Vitamin D deficiency is a public health problem,
  treatment of which will require a robust approach
  including careful monitoring
• Accurate and informed education of the public
  and professionals is required
• Meetings of this nature are critical in establishing
  a network to promote responsible management



                            RCPCH Nutrition Committee
                            Colin.Michie@eht.nhs.uk
                            Colinmichie@nhs.net
    Acknowledgements and Thanks

•   The organisers of this meeting
•   Patients and colleagues who have helped
    collect details and perform audits (school
    teachers and junior mayor)

•   Patients and colleagues who have, and I
    hope will continue to point out my
    significant areas of ignorance

				
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