Multicentre Studies into treatment of Steroid sensitive nephrotic syndrome, on going.
PREDNOS1
Extended steroid course 16 vs 8 weeks. Randomised at 4/52. 60 to 40/m2 alternate days vs 60 alternate days tapering by 10 fortnightly. No significant difference in time to relapse (139 vs 87 days), frequent relapsers, or need for alternative immunosuppressive treatment.
PREDNOS2
50% of relapses provoked by URTI, and about 50% URTI result in relapse. Indian study 2011 gave daily pred for 7 days, reduced relapses by 0.7/yr.
So for relapsing steroid sensitive (2+ relapses in previous 12/12). Can be on immunosuppressants except cyclophosphamide or rituximab in previous 3/12. Must be on less than 15/m2. To get 6/7 daily pred 15/m2, to start within 24hrs of onset, or not. Randomised ahead of time at clinic, not at time of URTI. Def as 2 of fever, sore throat etc for 24hrs. Discuss with renal team or study hotline to check indications met.
Depending on geographic location, different viruses cause viral meningitis. In some areas, arthropod borne viruses are important.
With new diagnostic methods, more of these cases are being given a specific aetiology.
Complications
Very unusual. Some small studies have suggested that early enterovirus meningitis linked to later language problems. Deafness is debatable – some large studies have not found any cases, yet antenatal infections and subclinical viral infections are felt to be causes for deafness in other clinical situations!
FeverPAIN scoring system – possibly better than Centor at avoiding antibiotics. For primary care settings, children over 3 and adults.
Fever in past 24hrs
Purulent tonsils
Attends rapidly (ie symptoms <=3 days)
Severe tonsil Inflammation
No cough/coryza
3 points gives 40-50% risk of strep, so treat at 4 points, consider delayed antibiotics for 3 points. Not for under 3s, and beware worsening after 3 days which might indicate more severe infection. [PRISM study 2014]
Centor and McIsaac scores to predict group A streptococcal pharyngitis. One point for each of the following:
Centor score is sum (0-4). The McIsaac score (1998) is an adjustment of +1 to account for the increased incidence of GAS in children <15yr and -1 for decreased incidence in those 45+ years. CDC advises treat empirically at score 3+ or at score 2 if rapid testing positive.
Original studies used small samples, but national US study confirmed validity in 65 000 patients aged 3-14yrs presenting to primary care. For children, GAS positive rates were:
the WHO rule (purulent oropharyngeal exudate and tender enlarged anterior cervical lymph nodes = bacterial pharyngitis);
the Abu Reesh rule (purulent oropharyngeal exudate or tender enlarged anterior cervical lymph nodes = bacterial pharyngitis); v low specificity of course
the Steinhoff rule (absence of rash, absence of moderate or severe rhinitis, presence of tender enlarged anterior cervical lymph nodes).
Rapid antigen test performs better, 85% sensitivity (similar to Abu Reesh rule) but much better PPV (48%).
Obesity is more than a number. As defined by the Obesity Medicine Association, it is a “chronic, relapsing, multi-factorial, neurobehavioral disease, wherein an increase in body fat promotes adipose tissue dysfunction and abnormal fat mass physical forces, resulting in adverse metabolic, biomechanical, and psychosocial health consequences”. It is therefore not “cured” simply by the numbers getting better.
Obesity is associated with a range of problems, including slipped upper femoral epiphysis and sleep apnoea that are clearly related to being overweight, plus psychological issues related to self image. But there are also unexpected complications such as higher rates of admission and longer hospital stays after road traffic accidents, and higher mortality with asthma (not necessarily due to worse asthma), and SARS-CoV2 (2.1x – but not an increased risk of getting it).
It does appear that adipose tissue produces inflammatory cytokines. The insulin resistance that can be associated with obesity also increases endothelial and platelet dysfunction, which increases the risk of vascular and thrombotic conditions.
It’s also true that BMI is only one factor in health – if you have one or more healthy lifestyle factors, you could well have better life expectancy than someone with normal BMI but high waist circumference and no healthy lifestyle factors. [BMJ 2016] Evidence that moderate/high levels of cardiorespiratory fitness appear to attenuate or even eliminate the risks.
Some US states reporting declines in rates of childhood obesity. Australia has plateaued. The COVID pandemic was bad for obesity with figures from NHS England and Public Health Scotland showing a sharp increase – obesity prevalence at reception age (4-5yrs) is up from 9.9% in 2019/20 to 14.4% in 2020/21, and Year 6 (age 10-11), from 21.0% to 25.5%.
Ethnicity is a major risk factor – Black and Asian have higher rates than whites, Chinese lower. Boys outnumber girls slightly in both age groups. Risk at least twice as high in most deprived areas cf least deprived. In London, 30% of 10-11yr olds now obese.
Obesity and Child Protection
Growing evidence linking adolescent and adult obesity with childhood sexual abuse, violence and neglect. In US preschool children, obesity linked to neglect and physical punishment even after controlling for socioeconomic group.
Wouldn’t be surprising if food became a way of dealing with stress (or feeding a way of dealing with distress) but obvious confounding.
A study of obese children in care found only 1% of the obese children were obese when taken into care, and risk increased with time in care. So can hardly be argued that putting children in care likely to help severely obese children!
So probably not itself a child protection concern, but may be part of wider concerns. Development of obesity and then failure to tackle also 2 different things. Consistent failure to engage with lifestyle changes or outside support IS a sign of neglect. Parental capacity is important. Environment often very unhelpful.
If looked at from children’s rights perspective, health can be seen as shared responsibility of the state, parents, and child themselves – note right to health, play, safe spaces, clean air etc. [Health Hum Rights. 2016]
Obesity Detection
About half of parents of overweight/obese children fail to recognise it. Particularly true for young children. Doctors are not great at perceiving obesity visually either – in small study of 100 patients, 19% of obese were underestimated, and 25% of overweight [BJMP 2012;5(2):a520]. When presented with photos, GPs incorrectly assessed the majority of obese and about half the overweight patients presented in photographs. To be fair, this poor performance is probably true of the general population too.
BMI vs Fat
There are probably different obese phenotypes. BMI is only a moderately good predictor of adiposity in children, and poor in younger children. It is also true that there appear to be ethnic differences, for example Indian boys tend to have relatively higher percentage fat at all BMI levels.
Abdominal circumference in adults probably more important when it comes to metabolic (type 2 diabetes) and cardiovascular risk. Triceps skinfold thickness centiles available, over 14-15mm 95th centile for under 8 boys, 15-20mm for under 8 girls, 16-23mm for over 8 boys and 21-30 for over 8 girls.
When it comes to monitoring, changes in BMI have reasonable sensitivity but poor specificity when it comes to changes in adiposity – so beware over intepreting [BMC Ped 2018].
Weight (self) Perception
Weight (self) perception has a complicated relationship with actual weight, and whether young people engage in extreme weight management practices. People who were underweight or overweight were mostly aware of their weight (80%, 96%), but bizarrely over 80% of those of healthy weight and obese inaccurately assessed their weight. Overassessors with healthy weight more likely to have extreme weight management practices, and even more true if underweight and female (OR 12.6, 95% CI: 3.4–46.6). [n=14,722 US high-school students, J PedGN 2014]
40% of men don’t recognise that they are overweight/obese (cf 19% of women), esp lower social class and ethnic minorities (“visual normalisation”). And seems to be getting worse over time. [England, Obesity 2018]
Factors
Sleep deprivation
Associated with short duration of sleep in several cross sectional studies. Longitudinal study in NZ 3-5yrs old found longer sleep reduced BMI at age 7 by 0.48 per extra hour, with a 61% reduction in risk of being overweight. Controlled for physical activity, diet etc. BMJ 2011:342:d2712. Late bed times (after 9pm) an independent risk factor (for waist measurement) in age 2-6 [Sweden, Peds 2020].
Screen time
More TV time associated with increases in BMI from ages 14-18 in White middle class American kids with starting BMI average or above average. Obesity 2013 Mar; 21(3): 572–575. doi: 10.1002/oby.20157]
Having TV sets in bedrooms associated with excess weight gain.
In France, in boys only. Explained 26-42% of body adiposity, other leisure activities didn’t make much difference. [Obesity 2017]
In US, boys and girls. 30% higher risk of being >85%, even after controlling for TV time! [Peds 2002]
Interventions to reduce screen time have also reduced obesity (not because more physical activity – less snacking!) [2yr study of age 4-7. Success higher in lower social class] Epstein LH, Arch Pediatr Adolesc Med. 2008;162:239-45.]
These things all go together of course –
The cluster with the most screen time, shorter night-time sleep duration, average dinner timing and outside playtime had the highest overweight/obesity prevalence (15.1%)
This cluster also had the highest proportion of irregular mealtimes and the most screen time for both parents.
Cf cluster with the least screen time, the longest sleep duration, the earliest dinner timing and average outside playtime (4.0%).
Most people overestimate their own levels of activity, compared with accelerometer recordings. Fitness helps boost mood, which can positively influence diet adherence. Muscle mass will increase calories burned even at rest.
When it comes to losing weight, physical activity really needs to be at the high intensity level to be effective, especially if dietary changes are limited.
The concept of regular exercise or sport is both alien and inconvenient to the majority of the UK population. In recent years, rhetoric has
switched from sport to physical activity.
Stigma
People who identify themselves as overweight have worse mental health, for example greater risk of depression and reduced quality of life. Not sure if there is any evidence for this in children but this presents a major problem when it comes to trying to improve health outcomes. [ObesRev 2017]
Obesity among Health care professionals
In England at any rate, nurses are no more likely to be obese than people in non-health professions (25%) but more likely to be obese than other health care professionals. Unregistered care workers have the highest rate of obesity (31%) [BMJOpen 2017].
Health professionals of normal weight are more confident in their weight management practice, perceive fewer barriers to weight management and have more positive outcome expectations, and have a stronger role identity. But also have more negative attitudes towards obese individuals.
Being female and having knowledge and clinical experience of weight management appeared to predict positive attitudes towards obesity/obese patients and high self-efficacy in weight management. [ObesityReviews 2011]
Limited quality data to recommend one treatment program over another, but combined behavioural lifestyle interventions appear to be better than “standard care” or self-help. Mean benefit of 0.3 Z score in children under 6.
Poor evidence for “parent only” interventions. Poor evidence that interventions to change behaviour of health professionals or the organisation of care (dietician, doctor, combined etc) makes any difference!
In obese adolescents, orlistat, metformin, and sibutramine should be considered as an adjunct to lifestyle interventions, but balance against potential for adverse effects. Average BMI benefit of 1.3, high drop out rate (25%) although only 5% due to adverse effects. [Cochrane 2016]
Surgery produced mean loss of 34.6kg in adolescents in Australia. 28% required further revisional surgery. Only 1 RCT! At 2 years, only benefit in 2 of 8 QOL measures. [Cochrane 2015]
Research needed into psychosocial determinants for behaviour change, strategies to improve clinician-family interaction, and cost-effective programs for primary and community care.
Childhood obesity can be prevented – Cochrane updated evidence 2011!
Most effective interventions change social and physical environments and norms, not just individual behaviour. Policies for healthy eating and physical activity in schools and early childcare settings, support for teachers to do health promotion, parent support and home activities that encourage children to be more active, eat more nutritious foods and spend less time in screen based activities. Esp 6-12yrs but heterogeneous.
Fast food patronage is a frequent reality for many children and their parents. Although there are increasingly healthier alternatives for popular menu items (apple slices instead of French fries), they are infrequently selected.
Lifestyle factors cluster of course. Boys’ adherence to a healthy lifestyle pattern (combining a nutrient‐dense diet and limited screen time) at 5 years was positively associated with prosocial behaviours (β = 0.14; 95% confidence interval [CI] 0.01, 0.26) and inversely related to hyperactivity‐inattention symptoms (β = −0.12; 95% CI −0.23, −0.01) at 8 years. But in the EDEN cohort, there was no association with BMI, and for girls, a mixed lifestyle pattern (sugar or artificially sweetened beverages, high screen, physical activity and low sleep times) was still associated with prosocial behaviours (β = 0.12; 95% CI 0.01, 0.23). [DOI:10.1111/ppe.12926]
What would Batman eat? Priming
Study of 22 children presented with 12 photos of 6 admirable and 6 less admirable models incl Batmand and Superman. Asked, ‘Would this person order apple fries or French fries?’ In the health prime condition, the same children were shown 12 photos of 6 healthy foods and 6 less healthy foods and asked to indicate if each food was healthy or unhealthy.
Results
When children were asked what various admirable people – such as Batman or Spiderman – would eat, 45% then chose apple slices over French fries (cf 9% in control group). Incidentally, knowing which foods were healthy or not made no sigificant difference to food choice. [Wansink et al, Pediatric Obesity, 7: 121–123. doi: 10.1111/j.2047-6310.2011.00003.x]
Weight talk in the home—parents talking to their children about their weight, shape or size— is associated with many negative health outcomes in children and adolescents, although the majority of research has been with adolescents. Most psychological (e.g., emotional problems) and social (e.g., peer problems) outcomes differed significantly by race/ethnicity!
no significant associations between weight talk and biopsychosocial outcomes were found for Hmong and Latino children;
negative association (e.g., less healthy functioning) was found for African American and Somali children;
a positive association (e.g., healthier functioning) was found for Native American children. [DOI:10.1007/s10826-022-02351-9]
Under-recognized, particularly when chronic blockage (without itch/sneezing) rather than sneeze/discharge. Late phase reactions involving Eosinphil induction by T cells tends to produce chronic swelling and non-specific irritability eg cold air. Nose problems impact with everything connected eg eyes, sinuses, middle ear, lungs. Differential is wide eg CF/PCD, deviated septum, polyps.
Considered trivial, and indeed work and school attendance not much affected but quality of work much more so – proven sleep problems, tiredness, impaired cognitive function. In a study of UK 15-17yr olds , students who dropped a grade between prelims and finals were significantly more likely to have had allergic rhinitis symptoms, to have taken antihistamines, and in particular, Piriton (OR=1.7). 43% increased odds of dropping an exam grade, goes up to 71% if using a sedating antihistamine [Samantha Walker, JACI 2007: 120; 381-387]
In asthma, prevalence of rhinitis increases over time to very high levels. If significant symptoms then OR=4 for poor asthma control (equivalent to poor inhaler technique!), plus combination of acute rhinitis and URTI gives OR=20 for asthma exacerbation.
Persistent defined as more than 4/7 per week, for more than 4/52. Mod/severe defined as any impairment of sleep or activity, else “troublesome symptoms” (BSACI includes seasonal or not, where you might be considering immunotherapy).
On examination (with auroscope), blue boggy wet mucosa, ?nasal crease.
SPT is pretty good at finding causes – depends how many you screen for, of course! In a US study, 65% of patients (mixed adults/children) had a positive: house dust mite (HDM) most commonly, else trees, weeds, moulds. Aspergillus and Penicillium are indoor moulds, Alternaria is outdoors. Cat allergens are commonly found in homes without cats! Nasal challenge can be done if neg SPT/IgE (Rondon, Curr Op Allerg Clin Imm 2010).
Children/adults same, just watch for doses/side effects.
Intranasal steroids most effective. Antihistamines, both intranasal and oral, are effective. Consider also leukotriene receptor antagonist (LRTA) eg montelukast (esp if co-existing asthma). Oral decongestants and steroids are also used short term sometimes.
For intermittent symptoms or mild persistent, no preferred treatment option – intranasal antihistamine, oral antihistamine, decongestant, LTRA, or combination. Nasal saline douches eg Sterimar have some evidence for efficacy, also nasal filters (not caught on yet!).
If co-existing conjunctivitis, prob best to go straight to nasal steroid, else add oral/topical antihistamine, or topical cromone, or saline.
Oral decongestant should only be used for max 10/7, can be useful diagnostically. Similarly oral steroids, if poor response or where diagnosis still unsure.
Cromoglycate (Rynacrom) has a role in young children but prob less effective than topical steroid or anthistamine, and at 4-6x a day, certainly less convenient.
Nasal ipratroprium recommended for rhinorrhoea.
Azelastine spray (Rhinolast) has been discontinued, so only nasal antihistamine is now the combination product Dymista (with flutic, from age 12). Not as good as steroid, doesn’t seem to have much effect on congestion (prob non-type 1 mechanism). Bad taste, irritation.
Montelukast licensed for rhinitis in asthmatics where resistant to other treatments, from age 15! ARIA recommend for over 6.
Intranasal steroids superior to top/systemic antihistamine, LRTA (even combinations). They also help eye symptoms, whereas nasal antihistamines don’t. Beclometasone (from age 6yr) and budesonide have relatively high bioavailability so better to use fluticasone (from age 4, furoate or propionate) or mometasone (from age 6), esp if other steroid use eg for asthma/eczema.Technique is often an issue – most gets sprayed or sniffed into back of throat!
Nasal spray Technique – (see video) Shake, head slightly forward, aim at ceiling (better to use opposite hand?), don’t sniff. Gargle and spit if taste unpleasant. Keep with toothbrush or other marker of habitual routine.
See also immunotherapy – some evidence that immunotherapy for rhinitis reduces risk of asthma!
Difficult to determine the psychosocial harms and benefits of testing in childhood. A systematic review (Genetics in Medicine, 2015, doi:10.1038/gim.2015.181) found that serious adverse psychological outcomes were uncommon, and most studies reported no significant increase in mean anxiety, depression, and distress scores. However, some children experienced intrafamilial distress, discrimination, and guilt/regret. Some children were more concerned about their own health or their family members’ health. It wasn’t very easy to anticipate adverse impact.
Objections-
No direct or medical benefit? Duty to protect the future autonomy of the child, i.e. preserving the right for the child to make her/his own decision to be tested or not.
Possible psychosocial harm from knowing diagnosis? Existing guidelines are often based on assumptions rather than empirical evidence of such harm, viz possible lessened self esteem, distortion of the family’s perception of the child, altered upbringing, discrimination and increased anxiety both of parent and child.
On the other hand, it has been argued that parents have the right to make decisions on behalf of their children because they have primary responsibility for their child and they know their child best.
Similarly, not testing may mean that the child loses the opportunity to grow up with and adapt to genetic knowledge during his/her formative years. Plus, parental anxiety, difficulty of living with uncertainty.
The authors of the systematic review highlighted the lack of data regarding genetic testing for conditions that may not be treatable/modifiable, and the dearth of longitudinal studies. So they conclude that caution remains essential for the ethical integration of genetic testing in children.
Non–IgE-mediated severe gastrointestinal food hypersensitivity, typically presents in early infancy with repeated vomiting, dehydration, lethargy, metabolic acidosis (even mimicking sepsis). Watery diarrhoea (sometimes with blood and/or mucus) can develop in some cases. The severity is really what makes it worthy of a distinct name, debatable if it is actually distinct from other non-IgE mediated food allergy.
Probably underdiagnosed.
A few unusual features cf type 1 allergy.
The most common offending foods are cow’s milk and soy in young infants; in older infants, there are a range of food triggers including some foods usually not considered allergenic eg rice, oat, chicken, sweet potato! Egg an unusual cause in some countries! Cases in breastfed infants have been reported, even severe hypotension requiring intensive care.
Acute symptoms occur 1 to 5 hours after ingesting the offending food. Lasts up to 24 hours. Not always consistent, which might suggest co-factors important.
In Europe, rare to get multiple food FPIES but in UK/US/Australia about 25% (English speaking!?).
Diagnosis
Diagnosis is based, predictably for a non-IgE condition, on clinical history and food challenges. Leucocytosis and methaemoglobinaemia are associated but low specificity/sensitivity.
2017 Consensus out of date but diagnostic criteria still used –
Major – vomiting at 1-4 hours in absence of type 1 skin/resp symptoms.
Minor – at least 3 minor criteria eg second episode of repetitive vomiting after same food; extreme lethargy; hypotension; need for hospital care or IV fluids; etc
Probably mild, mod and severe! Proposed BIO-FPIES criteria includes abdominal pain, nausea, increase in neutrophil count (but 3 points for second episode of repetitive vomiting after same food).
Phenotype switching
Egg and nut FPIES often go on to develop IgE sensitisation (about 20%), less for others. Of those, about 30% of milk FPIES will switch to type 1 phenotype, 15% for egg, less for other foods. But overall, unlikely to make much of a difference to care (and doesn’t help predict resolution).
For introducing weaning foods, when known FPIES to one food, start with low risk foods, supervise common triggers eg rice/egg.
Challenge
Challenge is necessary to decide whether things are getting better or not. Consensus is that 12-18 months after last reaction is a good balance between chances of things being better, and risk of causing severe reaction.
50% milk/soya resolve by age 3-4, more like 4-5 years for other foods.
Traditional protocol is 0.3g/kg protein, divided into 3 doses over 30 mins. But unrealistic for low protein foods eg fruit. And doesn’t really make sense to split dose when you don’t expect a reaction for hours (but risk of switch to type 1 allergy for egg/nuts).
2 day protocol (25% portion then whole portion next day) had less severe reactions.
25-30% of age appropriate portion triggers reaction in most children. [Baked???] Over 50% react after at least 2 hours.
Public health surveillance use 85th centile as definition for overweight, and 95th centile for obesity (UK says “at risk of obesity”…). Clinical definitions (SACN/RCPCH 2012, NICE) however are different: (UK 1990, use special BMI chart)
Obesity = BMI >98th centile for age (2 standard deviations, one tail)
Overweight = >91st centile (1.3 SD)
Growth charts then label:
Severe obesity = 99.6th centile (2.67 SD)
Morbid obesity = 3.33 SD. High probability of co-morbidity, unlikely to improve by age 16.
(some guidelines use Extreme = 4 SD)
Cut off for overweight/obesity high in babies, starts at 18/20 age 2, nadir of 17/19 at age 5, rising to 20/24 at 10 then usual 25/30 at age 18. Girls same as boys, slightly fatter after 10 yrs. [International data, BMJ 320:1242.] Charts are available at the RCPCH.
Centile charts show centile spaces that are equivalent to 2/3 of a standard deviation. When you get to high centiles, you need something better than “above the 99.8th centile” so you use Z score, which is the number of standard deviations above the mean
Low dose dexamethasone test (more sensitive than above but needs overnight admission) – cortisol should suppress below 100, else suggests Cushings
CT head (if suspicion of raised intracranial hypertension
Homa-IR >4.5 for insulin resistance [Score = (Fasting insulin)*(Fasting glucose) / 405, measuring in mg/dl]. Transient increase in insulin resistance seen in puberty, independent of BMI.
Total choles:HDL 3.6 95th, 4.3 99th but no great paed data.
ALT>70 twice should proceed to USS to look for fatty liver, >100 urgent (for differential more than anything, although non alcoholic fatty liver disease can be progressive).
Communication
Delicate! Moral issue too – for example:
uncertain benefits on physical health
negative psychosocial consequences including uncertainty, fear, stigmatization
aggravating inequalities
disregarding the social and cultural value of eating
infringement upon personal freedom regarding lifestyle choices and raising children
Addressing these issues may avoid resistance [Erasmus medical centre, Obes Rev. 2011 Sep;12(9):669-79. doi: 10.1111/j.1467-789X.2011.00880.x. Epub 2011 May 4]
Terms such as ‘obese’ are not generally well accepted by parents/carers
Opportunistic is good, but probably sensible to check that this is a good time, or at least create an invitation to start this conversation. And then, do more questioning and listening than advising.
What works?
The above section may already have brought up issues of low self-esteem and poor motivation. Building a therapeutic relationship, using motivational interviewing skills, is key then, especially where parents/children may have sensed discrimination and bias in the past.
General advice should include: (SIGN)
Healthier eating, and decreased calorie intake
At least 60 mins of moderately vigorous activity per day, pref habitual eg brisk walking! Given that evidence that moderate/high levels of cardiorespiratory fitness appear to attenuate or even eliminate the risks, just as important to emphasize fitness as weight loss?
