Canada and the prevalence and incidence rates of autism (again)

"During the period from 2004 to 2015, both prevalence and incidence rates of diagnosed ASD [autism spectrum disorder] in preschoolers and toddlers residing in Manitoba increased significantly."

That was the conclusion reached in the paper by Amani Hamad and colleagues [1] who undertook analysis of the Manitoba Population Research Data Repository to examine "the annual prevalence and incidence rate of ASD between 2004 and 2015 in children aged 1 to 5 years residing in Manitoba." Such research follows quite a longstanding theme, where Canada is quietly producing some important information about the growth of autism across its population (see here and see here).

I mentioned two words in the title of this post - prevalence and incidence - which perhaps need further explanation. Prevalence refers to the number of existing cases of a condition / disorder / disease, typically expressed as a proportion of a population. Incidence is more about the number of new cases of a condition / disorder / disease during a specific period of time. Hamad et al reported data on both measures, where "1685 ASD cases were diagnosed between 2004 and 2015."

So: "The crude ASD prevalence increased from 0.46% in 2004 to 0.97% in 2015" and "The crude incidence rate increased from 0.16% in 2004 to 0.39% in 2015." These combined findings illustrate that the number of cases of diagnosed autism in young children in Manitoba over the period of 2004 and 2015 was not static; more and more people were being diagnosed, and with an increasing rate of diagnosis.

What's more to say? Well this data puts another nail in the coffin to the old 'autism isn't increasing' argument that has slowly fizzled out over the past decade or so. Autism diagnoses are on the increase; and as per the Hamad focus - preschoolers and toddlers - at least some of the increase is in the young and not just older children and adults who might have 'slipped through the diagnostic net'. Next questions: why and what? Why is autism still on the increase? What factors are driving the increase? And please, enough with the 'increasing awareness' dogma on this question...

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[1] Hamad AF. et al. Annual trends in prevalence and incidence of autism spectrum disorders in Manitoba preschoolers and toddlers: 2004-2015. Can J Public Health. 2019 Feb 11.

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"a gradual decline in recorded diagnoses of CFS/ME since 2001"?

The quote forming the title of today's post comes from the paper by Simon Collin and colleagues [1] (open-access available here) who, based on analysis of the UK "Clinical Practice Research Datalink (CPRD), formerly known as the General Practice Research Database (GPRD)" set out to look at the "Incidence of CFS/ME [chronic fatigue syndrome/ myalgic encephalomyelitis], FM [fibromyalgia], post-viral fatigue syndrome (PVFS), and asthenia/debility." I say incidence but that last sentence should really read as  'recorded incidence'.

Searching the research database between January 2001 and December 2013, researchers looked at the [recorded] incidence (that's incidence not prevalence) of the various fatigue-related conditions/labels recorded by participating GP (general practice) surgeries.

Recorded diagnoses of CFS/ME showed a soft but noticeable decline over the period of study: "Annual incidence of CFS/ME decreased from 17.5 [per 100,000 people] in 2001 to 12.6 in 2013." A similar decline was also noted in respect of PVFS and asthenia/debility. When however it came to FM, there was an overall increase in cases between 2001 and 2013 (albeit characterised by peaks and troughs in recorded diagnoses across specific years).

Some other important data were also reported on. So: "All diagnoses showed strong evidence of variation by age and sex" and estimated socio-economic status (SES). Further: "Incidence rates of CFS/ME were 2.4-fold higher among women... with peak incidence in the 40–49 years age group." Women were also more likely to be over-represented in relation to a diagnosis of FM too.

This is potentially important data. It suggests that at least among participating GP practices in the CPRD, recorded diagnoses of CFS/ME seem to be going down. The caveats however mentioned by the researchers do need to be highlighted, not least that they "examined recorded data rather than actual incidence, i.e. we are describing incidence rates of GPs’ recording of diagnostic codes" and "diagnoses were not independently validated." In other words, this is data based on "GPs enter[ing] medical diagnoses and symptoms as Read codes." I might also add in another quote from the authors too: "In 2005, 48% of GPs in one English region did not feel confident about making a diagnosis of CFS/ME, and 28% did not recognise CFS/ME as a legitimate illness." A bit of an issue by all accounts if one would like to get accurate data on incidence or prevalence.

I also have a to raise a point in relation to this latest data and how it compares with other data produced by the same research group (see here). Keeping in mind that incidence is not the same as prevalence, I bring back to your attention the findings reported by Collin and colleagues [2] on another occasion suggesting that nearly 2% of 16-year olds in the ALSPAC cohort were affected by CFS. More work needs to be done when it comes to official monitoring of the numbers of cases of CFS/ME (and FM) outside of just reliance on GP practice recordings in order to get a true picture of numbers of cases. Of course, there is another possible explanation for the fall in recorded diagnoses: GPs are increasingly understanding that some of the symptoms included under the banner of CFS/ME overlap with various other conditions/labels too...

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[1] Collin SM. et al. Trends in the incidence of chronic fatigue syndrome and fibromyalgia in the UK, 2001-2013: a Clinical Practice Research Datalink study. J R Soc Med. 2017 Jan 1:141076817702530.

[2] Collin SM. et al. Chronic Fatigue Syndrome at Age 16 Years. Pediatrics. 2016 Feb;137(2):e20153434.

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Collin SM, Bakken IJ, Nazareth I, Crawley E, & White PD (2017). Trends in the incidence of chronic fatigue syndrome and fibromyalgia in the UK, 2001-2013: a Clinical Practice Research Datalink study. Journal of the Royal Society of Medicine PMID: 28358988

ADHD in the UK

I don't want to keep you too long today but thought it worthwhile to bring the paper by Adrian Hire and colleagues [1] to your attention and the suggestion that "socioeconomic deprivation" may play a role when it comes to ADHD (attention-deficit hyperactivity disorder).

Based on data derived from the "Clinical Practice Research Datalink (CPRD)" - a UK based resource "providing anonymised primary care records for public health research since 1987" - researchers set about looking at those children/young adults diagnosed with ADHD between 2004 and 2013. This information was stratified according to the region where the general practice (GP) surgery was based added to which a measure of deprivation status was calculated ("Practice Index of Multiple Deprivation (IMD) score").

The results: well, aside from something of quite a stable incidence (that's incidence not prevalence) of ADHD apart from the last 2 years studied (interestingly), Hire et al also reported that: "In almost every year studied, incidence rates were highest among the most deprived patients and lowest among the least deprived patients." They concluded that there may be quite a bit more to see when it comes to socioeconomic deprivation (i.e. poverty etc.) and the label ADHD.

Obviously one has to be a little guarded in making too many sweeping generalisations from this data (including the use of "a surrogate measure" for deprivation status) but there is quite a bit more work to do in this area. Other statistics for example, have come to similar conclusions about socioeconomic disparities and ADHD diagnosis [2] crossing different geographies as well. That and the suggestion that ADHD + other diagnoses might show important effects as a function of societal variables such as poverty (see here) and one has some intriguing hypotheses to test with some potentially important conclusions reflective of lots of variables including social policy.

Music: Coldplay - Adventure Of A Lifetime (and a great video).

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[1] Hire AJ. et al. ADHD in the United Kingdom: Regional and Socioeconomic Variations in Incidence Rates Amongst Children and Adolescents (2004-2013). J Atten Disord. 2015 Nov 23. pii: 1087054715613441.

[2] QuickStats: Percentage of Children Aged 5-17 Years with Diagnosed Attention Deficit/Hyperactivity Disorder (ADHD),by Poverty Status and Sex - National Health Interview Survey, 2011-2014. MMWR Morb Mortal Wkly Rep. 2015 Oct 16;64(40):1156.

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Hire AJ, Ashcroft DM, Springate DA, & Steinke DT (2015). ADHD in the United Kingdom: Regional and Socioeconomic Variations in Incidence Rates Amongst Children and Adolescents (2004-2013). Journal of attention disorders PMID: 26604267

CFS/ME associated with pandemic influenza infection

"Pandemic influenza A (H1N1) infection was associated with a more than two-fold increased risk of CFS/ME [Chronic fatigue syndrome/myalgic encephalomyelitis]."

That was the headline finding from the study by Per Magnus and colleagues [1] looking at whether large population data might provide some clues about 'associated' variables when it comes to the various debilitating conditions headed under the terms CFS/ME.

I'm blogging at a slight disadvantage with regards to the Magnus study because I don't yet have the full-text paper. Looking at the source data - "Using the unique personal identification number assigned to everybody who is registered as resident in Norway" - and observing some notable names on the authorship list, I'm inclined to suspect that this study might have some MoBa undertones (see here) bearing in mind the focus on the "complete Norwegian population" not just pregnant women and their offspring. Indeed, other research from this authorship group provides some further clues about data derivation [2].

Focusing on those specifically diagnosed with CFS/ME - "diagnostic code G93.3 in the International Classification of Diseases, Version 10" researchers calculated hazard ratios (HRs) for CFS/ME "after influenza infection and/or vaccination." A few details emerged including:

• "The incidence rate of CFS/ME was 2.08 per 100,000 person-months at risk." At this point I might direct you towards some details on the difference between incidence and prevalence.
• Influenza infection seemed to confer something of an enhanced risk for CFS/ME as per the finding of an adjusted HR of 2.04 (95% CI: 1.78-2.33). 
• That being said, the authors report "no indication of increased risk of CFS/ME after [pandemic] vaccination." This has potentially important public health implications (see here).
• They conclude by suggesting that such natural infection = increased risk of CFS/ME vs. antigenic stimulation (vaccination) = no increased risk of CFS/ME might indicate "a model whereby symptomatic infection, rather than antigenic stimulation may trigger CFS/ME."

The first thing that struck me about these findings was the 'overlap' noted with a familiar concept to this blog: maternal immune stimulation and offspring outcomes. This is the idea that immune 'stimulation' during critical periods of pregnancy might have the propensity to affect offspring developmental outcomes in a behavioural fashion (see here for example). Two of the big names in this area (Alan Brown and the late Paul Patterson) wrote rather a good review of this area focused on how some of the tools of public health such as vaccination might already be affecting the risk of development/onset of schizophrenia in relation to the maternal immune activation (MIA) model [3] with viruses such as influenza in mind. More detailed work is of course indicated.

Without trying to equate CFS/ME with schizophrenia or any other related label, I do find it interesting that infection and the associated biological response associated with it, might show some 'connection' to CFS/ME in the same/similar way that such biology might also be involved in priming a person for later-life schizophrenia. If we've learned anything about CFS/ME this year aside from it being 'a real illness' (see here if you really needed telling) it is that in amongst the multitude of findings on the condition, there is some really interesting 'immune-related' features coming through (see here). I know the term 'immune-related features' covers a lot of ground but alongside the already tantalising idea that infection is linked to CFS/ME onset (see here) (why else would it be also referred to as post-viral fatigue syndrome), I'm talking about how infection and response to infection might so severely impact on a person and what could be done to potentially prevent it.

Further work is indicated on the basis of the Magnus findings including a focus not just on influenza and CFS/ME but other biological agents such as the really, really interesting prospect of a connection between cases of CFS/ME and acute enterovirus infection [4] for example. Assuming that genetic make-up probably plays an important role in the handling of such viruses in relation to labels like CFS/ME, I'd like to think that research is heading in the right direction to offer viable prevention / treatment options for such devastating disorders bearing in mind the heterogeneity present [5]...

Music: Therapy? - Nowhere.

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[1] Magnus P. et al. Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is associated with pandemic influenza infection, but not with an adjuvanted pandemic influenza vaccine. Vaccine. 2015 Oct 13. pii: S0264-410X(15)01433-4.

[2] Bakken IJ. et al. Two age peaks in the incidence of chronic fatigue syndrome/myalgic encephalomyelitis: a population-based registry study from Norway 2008-2012. BMC Med. 2014 Oct 1;12:167.

[3] Brown AS. & Patterson PH. Maternal Infection and Schizophrenia: Implications for Prevention. Schizophrenia Bulletin. 2011;37(2):284-290.

[4] Chia J. et al. Acute enterovirus infection followed by myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and viral persistence. J Clin Pathol. 2010 Feb;63(2):165-8.

[5] Zdunek M. et al. A Cross Cultural Comparison of Disability and Symptomatology Associated with CFS. Int J Psychol Behav Sci. 2015;5(2):98-107.

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Magnus P, Gunnes N, Tveito K, Bakken IJ, Ghaderi S, Stoltenberg C, Hornig M, Lipkin WI, Trogstad L, & Håberg SE (2015). Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is associated with pandemic influenza infection, but not with an adjuvanted pandemic influenza vaccine. Vaccine PMID: 26475444

Canada and the autism prevalence rate (yet again)

"At the end of 2013, the prevalence among children born in 2006 was 1 case of autism spectrum disorder per 46 children or 215.77 per 10 000."

That was the conclusions reached in the study by Lorine Pelly and colleagues [1] looking at "the incidence and 1-year cohort prevalence for autism spectrum disorders in children less than 15 years of age and living in the Avalon Peninsula at the time of diagnosis." The Avalon Peninsula by the way, is located in Canada.

Looking at data derived from the "Janeway Children’s Health and Rehabilitation Centre (St. John’s)" and specifically information pertinent to those with autism (this facility is apparently "the only child development centre in the region and is the only centre giving comprehensive autism spectrum disorder diagnoses to patients in this region") researchers set about looking at the numbers for autism diagnosis in the area. Autism spectrum disorder (ASD) diagnoses were based on DSM-IV criteria, confirmed through "multiple observations" and in most instances, involved data derived from the gold-standard assessment instrument that is ADOS (Autism Diagnostic Observation Schedule). Incidence and prevalence analyses were both undertaken.

So: "Between 2006 and 2010, 272 new cases of autism spectrum disorder were diagnosed within the study population." Most of these cases were male, and, get this, the median age of diagnosis was... 3.84 years. The lion's share of cases were autistic disorder (~47%) followed by autism spectrum disorder (27%) and then Asperger syndrome (20%). Complementing those diagnostic divisions and age at diagnosis was the fact that a module 1 ADOS was used for over 40% of assessments. The calculated incidence for 2006 was 10.1 per 10,000. This increased to 16.7 per 10,000 in 2010. The difference was statistically significant. Prevalence, as I've already said, was 1 in 46 in this cohort with males shouldering the largest risk.

Then, another important point emerges: "Our review found that many patients had at least one of the co-morbidities often associated with autism; the most prevalent were behavioural issues (n = 28), attention-deficit/hyperactivity disorder (n = 27) and anxiety disorder (n = 25)." It all sounds very ESSENCE-like if you ask me.

These are interesting data and add to previous studies looking at the autism numbers game in Canada (see here and see here). In that instance as in this, the numbers were increasing for whatever reason(s) and starting to look similar to the top-end CDC estimates from last year (2014). Pelly et al don't go into the specific hows and whys potentially linked to the increase in cases so I can't comment too much on that angle in their paper. Other recent publications talking about diagnostic substitution as one possible factor [2] in the increasing rate of autism makes a valid point but I dare say that things aren't so simple when it comes to the reasons behind the increase in different parts of the world [4]. Whether also such a increased rate of autism merits the term 'epidemic' is another issue covered recently in another paper [3] although I'm not getting too involved in that debate.

Music: Gossip - Standing In The Way Of Control.

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[1] Pelly L. et al. Incidence and cohort prevalence for autism spectrum disorders in the Avalon Peninsula, Newfoundland and Labrador. CMAJ Open. 2015. July 29.

[2] Polyak A. et al. Comorbidity of intellectual disability confounds ascertainment of autism: Implications for genetic diagnosis. Am J Med Genet B Neuropsychiatr Genet. 2015 Jul 22.

[3] Lilenfeld SO. et al. Fifty psychological and psychiatric terms to avoid: a list of inaccurate, misleading, misused, ambiguous, and logically confused words and phrases. Front. Psychol. 2015. August 3.

[4] Randall M. et al. Autism spectrum disorder: Presentation and prevalence in a nationally representative Australian sample. Aust N Z J Psychiatry. 2015 Aug 17. pii: 0004867415595287.

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Pelly, L., Vardy, C., Fernandez, B., Newhook, L., & Chafe, R. (2015). Incidence and cohort prevalence for autism spectrum disorders in the Avalon Peninsula, Newfoundland and Labrador CMAJ Open, 3 (3) DOI: 10.9778/cmajo.20140056

Trends in the diagnosis of autism in Australia

"The frequency of ASD [autism spectrum disorder] diagnoses in Australia has increased substantially from previously published estimates."

That was one of the conclusions reached in the study by Catherine Bent and colleagues [1] (open-access here) who aimed to "investigate the frequency and age at diagnosis of autism spectrum disorder (ASD) in children aged under 7 years living in Australia."

Drawing on "de-identified data" extracted from Helping Children with Autism Package (HCWAP) - an Australian Government initiative - covering the period 1 July 2010 and 30 June 2012, researchers examined various variables including: age at diagnosis, frequency of an ASD diagnosis and how particular child characteristics might have influenced both age and frequency of diagnosis.

Some 15,000 children under 7 years of age were reported to be in receipt of an ASD diagnosis over the study period. The blanket ASD description included the labels of classical autism (autistic disorder), Asperger syndrome and Pervasive Developmental Disorder - Not Otherwise Specified (PDD-NOS). Autistic disorder took the lion's share of diagnoses, with over two-thirds of the cohort in receipt of this label.

"The average age at diagnosis of ASD in children registered with the HCWAP is currently 49 months, with the most frequently reported age being 71 months." There were however some interesting differences noted in terms of age at diagnosis as a function of label under the ASD umbrella. Those diagnosed with autistic disorder showing a pretty clear advantage in mean age at diagnosis (46.5 months) compared with those with Asperger syndrome (mean age: 59.5 months) and PDD-NOS (mean age: 51.1 months). Taken as a whole, the cohort tended to be diagnosed between 25-72 months of age with the peak age for diagnosis falling between 37-48 months of age. Compared with previous prevalence/incidence estimates for ASD in Australia, the data from Bent et al also "suggests that the incidence of ASD in Australia has increased substantially from previous estimates" with 0.74% of under-7 year olds diagnosed with ASD between 2010 and 2012.

These are interesting findings. I've briefly touched upon some of the research behind the epidemiology of autism (autism spectrum disorder) in Australia before on this blog (see here) and how parts of Oz seemed to be lagging behind other estimated population rates of autism [2]. Accepting that there may be various factors affecting the estimates of autism prevalence across different countries and even different regions of countries, the figures from Bent (0.74%) start to become more comparable with the Danish estimates reported some 4 years ago.

The idea that individual diagnoses covered under the umbrella term ASD might also translate into differences in age at diagnosis is also interesting if not new news. I recently covered some of the issues around the diagnosis of autism (see here) and in particular, some of the factors that seem to have some bearing on age at diagnosis (see here). Thinking back to some of my own research in this area [3] I remember detecting some differences in age of symptom onset/diagnosis according to diagnostic grouping albeit not significant in that particular cohort. The larger numbers from Bent and colleagues add to that sentiment and how, outside of sex differences in presentation, the differences between the various labels might affect the diagnostic journey.

"Given that research suggests a reliable and accurate diagnosis is possible for many children with ASD at 24 months... finding[s] represents a possible average delay of 2 years (and common delays of up to 4 years)." Accepting that in amongst the various 'autisms' there may be cases where onset is not normally present before 2 years of age, even potentially confounded by other behaviours/comorbidity, the onus seems to be very much on improved screening and detection of autism and quite a few more resources put into investigating "barriers that delay the diagnosis of ASD." Said barriers might also focus on healthcare providers as well as other factors [4] (see here for my take on this paper).

Music: Portishead - Sour Times.

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[1] Bent CA. et al. Mapping the diagnosis of autism spectrum disorders in children aged under 7 years in Australia, 2010-2012. Med J Aust. 2015 Apr 6;202(6):317-20.

[2] Parner ET. et al. A comparison of autism prevalence trends in Denmark and Western Australia. J Autism Dev Disord. 2011 Dec;41(12):1601-8.

[3] Whiteley P. Developmental, behavioural and somatic factors in pervasive developmental disorders: preliminary analysis. Child Care Health Dev. 2004 Jan;30(1):5-11.

[4] Zuckerman KE. et al. Parental Concerns, Provider Response, and Timeliness of Autism Spectrum Disorder Diagnosis. Journal of Pediatrics. 2015. 14 April.

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Bent CA, Dissanayake C, & Barbaro J (2015). Mapping the diagnosis of autism spectrum disorders in children aged under 7 years in Australia, 2010-2012. The Medical journal of Australia, 202 (6), 317-20 PMID: 25832158

Autism in the UK: levelling off?

A short post today based on the paper by Brent Taylor and colleagues* (open-access) adding to the considerable literature on the autism numbers game. The headlines generated from this study are no better encapsulated than that of the BBC: "UK autism cases have 'levelled off'".

Reaching the summit? @ Wikipedia

The crux of the paper is that based on an analysis of the UK General Practice Research Database (GPRD) which carries details of several million patient records following patient contact with what's known as a General Physician (GP) here in the UK, cases of autism spectrum disorder included in those records were counted and annual prevalence and incidence rates based on 8-year olds were generated.

The results: cases of autism recorded on the GPRD suggested that "the annual prevalence of autistic spectrum disorders was estimated at 3.8 per 1,000 boys and 0.8 per 1,000 for girls".

Importantly, from the BBC: "The study concluded there was "compelling evidence that a major rise in incidence rates of autism, recorded in general practice, occurred in the decade of the 1990s but reached a plateau shortly after 2000 and has remained steady through 2010"".

There are also a few interesting nuggets of information to take from the Taylor paper such as the reason(s) put forward for the dramatic increase in cases witnessed during the 1990s. Another quote I'm afraid on whether greater awareness or broadening diagnostic criteria or diagnostic substitution were the sole causes of the increase: "it seems unlikely that these factors materially explain the extraordinary increase in the number of children diagnosed in the 1990s; nor the steady state that followed thereafter in 2004 through 2010". This is in line with what other commentators have talked about (see here).

The Taylor paper is an interesting one and no doubt will generate some discussion about the numbers of cases of autism. I note that the figures reported by Taylor and colleagues are somewhat at odds with other studies using different data collection methods based in other parts of the world such as that 1 in 50 figure in the US discussed quite recently (see here) or other incidence data (see here). Whether this is down to how the data are collected and verified or truly representative of differing rates of autism in different geographical populations is yet more substance for discussion.

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* Taylor B. et al. Prevalence and incidence rates of autism in the UK: time trend from 2004–2010 in children aged 8-years. BMJ Open. 2013; 3: e003219

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Brent Taylor, Hershel Jick, Dean MacLaughlin (2013). Prevalence and incidence rates of autism in the UK: time trend from 2004–2010 in children aged 8-years BMJ Open DOI: 10.1136/bmjopen-2013-003219

Canada and the autism prevalence rate continued

So, in my last post this morning I was talking about the paper by Hélène Ouelette-Kuntz and colleagues* on the autism numbers game in various regions of Canada. Thanks to Natasa, I now have the full-text of the paper and just wanted to pass some further comments on the findings reported and potentially how important they might be.

• OK, three regions in Canada were scrutinised based on the NEDSAC initiative for cases of autism: Newfoundland and Labrador (2003-2008 period), Prince Edward Island (2003-2010) and Southeastern Ontario (2003-2010) and a total of 2377 cases of autism were identified across various age groups (2-5 years, 6-9 years, 10-14 years). Response rates - to get more detailed information about the children identified with an autism spectrum disorder (ASD) - per region were not exactly great but ranged between 32% and 45%.
• The prevalence of autism "increased significantly among all age groups" over the various surveillance periods. There were however some variations across the different regions such that for example, prevalence in the age group 2-5 years old in Southeastern Ontario did show something like a plateau in the later years of study. The authors however do not rule out "incomplete capture of preschool children with autism" as accounting for their results there. Indeed Southeastern Ontario was reported to also have contributed a "larger proportion of false positive" diagnoses based on some small-scale case validation investigation using ADOS or ADI as the standards which may also have accounted for some of the final figure they report.
• Age of diagnosis and the issue of diagnostic delay are covered in the data presented. Another quote: "in all three regions many children were not diagnosed until they were older". So much for the practical application of all those 'catch 'em early' sentiments.
• The authors pass comment on the issue of age at diagnosis as affecting any prevalence estimates using the Parner paper** as an example and the suggestion that a younger age at diagnosis would artificially inflate the prevalence rate for that age group. Allowing for potential bias in the reporting of age at diagnosis they concluded: "it does not appear that an earlier age at diagnosis contributed in any meaningful way to prevalence increases in the youngest age group".
• The sex ratio also came under scrutiny. Interestingly that Icelandic study*** also looking at autism prevalence rates which I mentioned in my last post seemed to take an interest in one of my studies on the topic (see here****). The Icelanders decided that their results did not accord with our own where we talked about an widening gap in the gender ratio towards boys over the years. The Canadian study reported that "the boy:girl prevalence ratio increased between the first and final years of the surveillance period". Indeed in one region Prince Edward Island the ratio went from 3.7:1 in 2003 to 6.7:1 in 2010 (peaking at 6.9:1 in 2009). I'm don't want to say too much about this for now bearing in mind all the possible confounders which could account for results, but certainly if I were an official based somewhere in Prince Edward Island I'd be minded to ask a few questions about the hows and whys of these findings. 
• The authors admit that the various explanations they've looked at as accounting for the increase in cases "appeared to account for only a small portion of the increases observed". In other words, the numbers are going up but to say that it is better awareness or just that kids are being diagnosed earlier or that it is diagnostic reclassification (which doesn't really cover the period of this study in terms of DSM or ICD changes for example) doesn't really cut the mustard when looking at the size of the increase they uncovered. I'll leave you to determine what else might be able to account for the increase they reported.

I'll finish by reiterating that the autism numbers game is a complicated area. One has to be careful not to make too many sweeping generalisations on how figures, and the potential reasons for those figures, in one area are necessarily representative of autism prevalence in all other areas. 

That being said, the Ouelette-Kuntz paper does perhaps indicate that we should perhaps be widened the debate about why autism is on the rise above and beyond the notion that we're just better at finding it. Yes, there are factors like socio-economic status (SES) to consider but dare I even mention that we might also start to take seriously how environment (however you wish to define this) might also be impacting on the numbers of cases being diagnosed and indeed the concept of gene - environment interactions***** (open-access)?

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* Ouellette-Kuntz H. et al. The changing prevalence of autism in three regions of Canada. J Autism Dev Disord. 2013 Jun 16.

** Parner ET. et al. A comparison of autism prevalence trends in Denmark and Western Australia. J Autism Dev Disord. 2011 Dec;41(12):1601-8. doi: 10.1007/s10803-011-1186-0.

*** Saemundsen E. et al. Prevalence of autism spectrum disorders in an Icelandic birth cohort. BMJ Open. 2013 Jun 20;3(6). pii: e002748. doi: 10.1136/bmjopen-2013-002748.

**** Whiteley P. et al. Gender Ratios in Autism, Asperger Syndrome and Autism Spectrum Disorder. Autism Insights. 2010:2 17-24.

***** Chaste P. & Leboyer M. Autism risk factors: genes, environment, and gene-environment interactions. Dialogues Clin Neurosci. 2012 September; 14(3): 281–292.

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Ouellette-Kuntz H, Coo H, Lam M, Breitenbach MM, Hennessey PE, Jackman PD, Lewis ME, Dewey D, Bernier FP, & Chung AM (2013). The changing prevalence of autism in three regions of Canada. Journal of autism and developmental disorders PMID: 23771514

Canada and the autism prevalence rate

[Update: 01/07/13: Further discussion on this topic can be found here].

The autism numbers game has been a long running discussion in many quarters. Even with estimates now suggesting that anywhere between 1 in 88 children or 1 in 50 children (or 1 in 57 if you prefer) in the United States (depending on who and how you count) might present with an autism spectrum condition, arguments still rage about the hows and whys, often over and above the question: 'what are we going to do about it'.

Waterloo Bridge @ Wikipedia 

I'm sitting on the fence a bit about why the numbers are increasing as they are. I appreciate that we are better at detecting autism than we were 30 or 40 years ago and all the related opinions about changes in diagnostic schedules (see here) and reclassification from other conditions in favour of the autism spectrum. There is little doubt that these factors exert an effect and are probably going to be significant ones.

Having said that though I'm not yet ready to give up on the idea that some of the increase in cases is due to other factors including being representative of a true and real increase in cases. My reasoning for this opinion is multi-faceted but includes the fact that we have, at least in the Western world, more than adequate provisions for the detection of [pediatric] autism and to say that its all about reclassification or awareness really brands our autism diagnosticians as being pretty incompetent over the years. They're not by the way; indeed they do a sterling job often in very, very difficult circumstances. What I should also point out is that the reasons for the increase might not necessarily be the same for every part of the world.

Just before also you tell me there is no evidence that the incidence - not prevalence - of autism is increasing, I beg to differ as per some of my previous posts which can be seen here and here. Indeed this leads into an interesting paper that has recently appeared by Hélène Ouelette-Kuntz and colleagues* on the prevalence rate of autism in several regions in Canada which forms the topic of this post.

I'll admit to not having the full-text of the Oueltte-Kuntz paper so you might need to do some further fact-checking on any conclusions that I reach. Actually, the chances are that I'm probably not going to reach any conclusions on the paper so maybe this is a moot point.

The first thing that we do get from the abstract to the paper is that based on an analysis of data from the National Epidemiologic Database for the Study of Autism (NEDSAC) (yes same author) autism prevalence is increasing in this study. That increase in annual prevalence ranges from 9.7% up to 14.6% I assume because of the differing prevalence rates among the different regions of Canada the study authors looked at.

The next thing to glean from the abstract are some of the reasons put forward to account for the increase: previously unidentified cases being identified and the issue of "in-migration" which concerns movement between regions of the same country/territory.

Finally, a quote: "we cannot rule out the possibility of a true increase in incidence, particularly given the lack of a leveling-off of prevalence among the 6- to 9-year olds". In other words, the door is still open to a 'real' increase in cases being contributory to the numbers.

I'm sure the arguments will continue about the hows and whys of the autism numbers game. One thing is abundantly clear from most of the emerging data: autism is fast becoming a 'common condition' as per another recent report on the autism numbers game from Evald Saemundsenand and colleagues** (open-access) and a particularly interesting table. As we stand at the moment, we don't really know all the reasons why and what to do about it.

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* Ouellette-Kuntz H. et al. The changing prevalence of autism in three regions of Canada. J Autism Dev Disord. 2013 Jun 16.

** Saemundsen E. et al. Prevalence of autism spectrum disorders in an Icelandic birth cohort. BMJ Open. 2013 Jun 20;3(6). pii: e002748. doi: 10.1136/bmjopen-2013-002748.

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Ouellette-Kuntz H, Coo H, Lam M, Breitenbach MM, Hennessey PE, Jackman PD, Lewis ME, Dewey D, Bernier FP, & Chung AM (2013). The changing prevalence of autism in three regions of Canada. Journal of autism and developmental disorders PMID: 23771514

1 in 50 children with parent-reported autism in the US

An estimated 1 in 50 US children aged between 6 - 17 years old present with an autism spectrum disorder (ASD). Attention-grabbing isn't it?

Today's post is based on the source of that soundbite, the publication by Stephen Blumberg and colleagues* (open-access) describing results from data mining of the 2007 and 2011-2012 US National Survey of Children's Health (NSCH) relevant to the numbers of cases of ASD.

Testing 1, 2, 3 @ Wikipedia  

The autism-numbers game is something that has been discussed previously on this blog; most recently with the CDC 1 in 88 estimate in mind (see here) and the even more recent data from New Jersey (see here). The direction of the figures seems only one way - up - but the reason(s) for the increase still remain the source of discussion.

The Blumberg report is open-access, but a few pointers might be useful:

• Based on 91,642 telephone interviews in 2007 and 95,677 interviews between 2011-2012, parental reports of receipt of an ASD diagnosis (autism, Asperger syndrome, PDD) in offspring were noted, alongside other variables such as age of the child, severity of presentation (mild, moderate, severe) and aged when first diagnosed.
• Actually in the age range 6-17 years old, data were collected from 63,967 interviews (2007) and 65,556 (2011-2012).
• Results: "based on parental reports, the prevalence of diagnosed ASD in 2011-2012 was estimated to be 2.00% for children aged 6-17". This compared with 1.16% or 1 in 86 for 6-17 year olds in 2007.
• The increase in prevalence was noted across the age ranges when they were sub-categorised and perhaps not surprisingly, there was a greater increase in prevalence in boys (2007: 1.8% vs. 2011-2012: 3.23%) than girls (2007: 0.49% vs. 2011-2012: 0.70%). Reported severity also shifted between the various data points (and age ranges) indicating that there was a trend towards less severe presentation (milder ASD) post 2008 diagnosis.
• The authors were able to some degree, rule out "survey-based measurement error" as being a major contributor to the prevalence increase and there is some discussion about the data not necessarily reflecting "factors that exist prior to or occur just after birth". Indeed the authors very firmly suggest that the changes are a consequence of either "recognition of ASD by health professionals or survey-based measurement changes over time". They also conclude that increases in the prevalence of parent-reported ASD especially for children aged 6-13 "was the result of diagnoses of children with previously unrecognized ASD".
• As per the report on this story in USA Today "15% to 20% of children who were once diagnosed with autism no longer have the condition". Which raises similar questions as to that of the Fein study on 'outgrowing autism' and 'optimal outcomes' which created so many column inches recently (see here and here).

Bearing in mind that this was a prevalence study not an incidence study (see here for the difference) and issues with regards to response rates (2007: 46.7% vs. 2011-2012: 23.0%), and the sole reliance on parental judgement of variables like severity, the data being presented are indeed stark.

That the rates of autism have seen an inordinate shift from what was once considered a rare condition to something which theoretically should [almost] appear in every school classroom at least once is an eye-opener. As mentioned, the debates rumble on about factors such as better awareness of autism, better case ascertainment, diagnostic switching and broadening, etc. as being the source of the increase. A real increase in cases? Hardly a mention in this latest data. The implication that for example our screening methods and skilled professionals have been able to miss or mis-diagnoses a staggering number of children presenting with an ASD is truly mind-boggling and worthy of an inquiry or two in the US and beyond. Indeed better be quick with that investigation with the DSM-V revision deadline fast approaching and the potential impact that might have on the autism numbers game (including adult numbers**).

So 1 in 50 children with an ASD. What happens next? Sure, many children were described as falling into the mild and moderate ability ranges but as I've said before, terms like 'high-functioning' don't necessarily mean 'can function' with regards to daily living skills, quality of life and onwards translating into positive outcomes in adulthood. Certainly society has to play its role in helping people with autism reach their potential (I have a post scheduled on job interviews and autism coming up soon) and changes are indeed on-going (e.g. the implementation of the Autism Act here in the UK). But let's not be too proud of the achievements done in this area, as still many people on the autism spectrum, their families and concerned others have to fight daily for appropriate recognition, provisions and services.

Another important issue also springs to my mind on the basis of the new prevalence figure. Comorbidity, of which autism is by no means immune from, are not mentioned. The realisation that autism is often very much more than the sum of its triad - soon to be dyad - in terms of comorbidity must surely factor into the potential impact of the latest figures. Not least because of the quite startling health inequalities which seem to be present when an ASD is diagnosed and how as was very recently detailed in the CIPOLD report, such inequality can in some cases, have the most profound and far-reaching effects. I'm not trying to scare anyone; just sayin' that we need to be mindful of the whole person not just their autism.

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* Blumberg SJ. et al. Changes in prevalence of parent-reported autism spectrum disorder in school-aged U.S. children: 2007 to 2011–2012. National Health Statistics Reports. 2013: 65.

** Wilson CE. et al. Comparison of ICD-10R, DSM-IV-TR and DSM-5 in an adult autism spectrum disorder diagnostic clinic. J Autism Dev Disord. March 2013.

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Wilson, C., Gillan, N., Spain, D., Robertson, D., Roberts, G., Murphy, C., Maltezos, S., Zinkstok, J., Johnston, K., Dardani, C., Ohlsen, C., Deeley, P., Craig, M., Mendez, M., Happé, F., & Murphy, D. (2013). Comparison of ICD-10R, DSM-IV-TR and DSM-5 in an Adult Autism Spectrum Disorder Diagnostic Clinic Journal of Autism and Developmental Disorders DOI: 10.1007/s10803-013-1799-6

Autism prevalence increasing in New Jersey

A quote to begin with from the paper by Walter Zahorodny and colleagues* with special thanks to Natasa for the full-text of the paper on the prevalence of autism spectrum disorders (ASDs) in New Jersey: "Regardless of whether one acknowledges an increased ASD prevalence, all the epidemiological and administrative studies confirm that ASD is now among the most common, severe, developmental disorders".

Edison in his NJ workshop @ Wikipedia  

For me this quote encapsulates everything about the various autism prevalence (and incidence) debates which have been, and continue to be, rife particularly in cyberspace.

It kinda says, yep we don't know all the details behind the quite enormous rise in cases of autism - which lets face it, basically boils down to whether or not you believe environment in whatever form contributes to autism aetiology - but whatever the reason(s), autism is not an uncommon condition and has a huge range of implications stretching from the diagnosed individual, their families, their schools, their doctors through to society as a whole.

Indeed, the paper from Zahorodny has lots of other soundbites worthy of quoting, but just before I head out that way, a few snippets of information about the paper are in order:

• This was a study all about comparing the estimated prevalence of ASD in the New Jersey Metropolitan Area (NJMA) in 2002 with some newer data from 2006.
• The focus was on using "identical methods and procedures" between the two time points drawing on the ADDM method which included active-screening and subsequent independent case determination. 
• Children born in 1998 and residing in the study area in 2006, classified as being educated under any special education classification (equivalent to receiving a SEN) were the starting point, filtered down to those with a documented or suspected ASD diagnosis, whose data were subsequently subjected to clinician review and analysis. "Agreement between previous ASD diagnosis and ASD case status by the surveillance method was 99%".
• Results: In 2006, out of a population of 30,570 8-year olds, 3,332 child records were reviewed, 923 of which met criteria for further review, which identified 533 with study-determined ASD, equal to a prevalence of 17.4 per 1000 (1.7%). This compared with 2002 data (8-year olds born in 1994) suggestive of a prevalence rate of ASD of 10.6 per 1000 (1.1%). The data is a little confusing because two different estimates are given based on the use of curtailed and non-curtailed populations; one used a sort of comparator to assess any changes in population affecting the estimates. 
• Allowing for the slight differences, the authors determined that 1 in 57 8-year olds in NJMA in 2006 had an ASD and a "startling" 1 in 35 boys.
• Between the sexes, ASD prevalence in boys grew from 17 to 28.7 per 1000 between 2002 and 2006 and 4.1 to 5.9 per 1000 in girls. 
• Regression, that most interesting of phenomenon with autism in mind, was relatively unchanged; the rate hovering around the 20% of cases mark.
• Quite a few factors potentially influencing the numbers were also taken into account including migration. That on top of the fact that DSM-IV TR was the main assessment criteria across the time periods.

This is an interesting study for lots of reasons. Not least because using identical protocols and identical criteria, a change in the prevalence of ASD was noted over 4 years. One therefore, to quite a strong degree, also rules out changes in DSM diagnostic revisions as a cause of the changes and to some extent those arguments about widening criteria as was evidenced between DSM-III and DSM-IV. That being said, the issue of increased awareness and its impact cannot be ascertained from this data; indeed also diagnostic substitution to some extent also remains a possibility (i.e. from learning disability to autism) as does under-diagnosis of ASD in non-white groups. This last point however needs to be tempered by the authors demonstrating a 90% increase in cases of ASD among Black, non-Hispanic children but also indicating "a broadly based escalation of ASD, rather than an increase reflecting improved case-finding in specific populations".

I get the impression that the authors were hinting that the change they reported might be more administrative over real. So they say: "It is too soon to know at what point ASD prevalence will plateau", which implies to me that they are looking to the autism rate increase to somehow eventually 'bottom out' when the message finally gets through about autism awareness and what it is. I hope I don't seem too rude when I say that we've all been waiting for that plateau for quite a few years now so as to save those 'it must be better case ascertainment' arguments, but so far there is no end it sight at least according to the latest CDC estimates. I'm sure even the staunchest supporters of the better awareness et al camp would quite logically admit that at least part of the increase might not necessarily reflect just 'better awareness' and 'more diagnostic substitution' but rather some other factor or factors also being involved? Or maybe not....

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* Zahorodny W. et al. Increasing autism prevalence in metropolitan New Jersey. Autism. November 2012.

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Zahorodny, W., Shenouda, J., Howell, S., Scotto Rosato, N., Peng, B., & Mehta, U. (2012). Increasing autism prevalence in metropolitan New Jersey Autism DOI: 10.1177/1362361312463977

Nature on autism part two

Yesterday I posted a link to the Nature special series on autism spectrum conditions. There was quite a bit of information to take on-board from the various articles and discussion pieces included, but after a little time reading, I feel there are a few issues worthy of some discussion in this separate post.

This was quite a wide-ranging series covering most of the main talking points about autism and where we think we are in terms of things like definition, research and the various aspects on possible aetiology, intervention and politics. With multiple authors and commentators, opinions abound; some to be agreed with, others to be debated depending on your point of view.

So:

The numbers game
For any undergraduate student faced with a question on a term paper like: are cases of autism increasing? the paper by Karen Weintruab gives about as good and up-to-date a picture on prevalence (and incidence) as you might need. The short answer is yes, the numbers of diagnoses have increased over the years, although the reasons for the increase are complex. Covering old favourites like better awareness, diagnostic substitution (changing criteria), parental age [I have a new post on this topic scheduled for the weekend], etc as reasons for the increase, the various commentators included in this article suggest that just over half of the increase in cases of autism might already be explicable. Given my reading of the various research down the years, this estimate might not be too far of the mark. Fine you might say, but what about the remaining 46% of the increase? What about the fact that different weighting to different factors at different time periods might pertain? 'Describe and discuss..' (making sure you use evidence-based critical thinking).

Systemisers, empathisers and assortative mating theory
Historically, the discipline of psychology is replete with generalised theories of people and explanations of their behaviour. I remember my first psychology textbook, Richard Gross 'Psychology: the science of mind and behaviour'. To read it you would assume that humans are perfectly predictable creatures and like the laws of physics (pre-CERN), put us in a specific situation and nod knowingly as we behave as expected. Psychology is however changing. Individual differences, people not living in a vacuum (or a psychology lab), and importantly the old gestalt phrase 'the whole is greater than the sum of its parts' are coming and pushing aside many of those generalised theories. The realisation that just because a person has one condition/issue/diagnosis does not mean that they can't have others which might exert some effect also seems to be in the pipeline.

So many of these concepts appear to align with our current understanding of autism. I think most people have by now figured out that there is probably no global, over-arching theory of autism which covers the entire spectrum of ability and disability. We have seen theories come and go; probably the most widely covered, again from a psychological perspective, has been the suggestion of a lack of theory of mind and the subsequent evolution of such ideas into systemisers and empathisers and to quote Francesca Happé the concept of 'geek chic'. The paper by Lizzie Buchen takes on the various suggestions proposed and comes to about the same conclusions: interesting, and not to say relevant for some on (and off) the autism spectrum, but please don't generalise and bear in mind that the spectrum of autism extends to quite a few people where life is not just about engineering or mathematical prowess.

Autism in the Middle East
Regular readers of this blog probably know that I am more than impressed with the autism research efforts coming out of the Gulf region. If you need to be reminded, have a look at this post and this one, both of which head into some pretty novel areas for further study originating from the Kingdom of Saudi Arabia. Mo Costandi (one of the first to tweet about the Nature special on autism) talks about autism in the Gulf states and also the genetic research goldmine that is consanguineous marriages and very large families. The impression is that autism, research and practice, is starting to take centre stage in Middle Eastern climes and parents and professionals are embracing education and other behavioural interventions for autism alongside social and cultural shifts in the region about autism.

From the limited contact I have had with people involved with autism in places like Saudi Arabia, Kuwait and the UAE, there are lots of good things happening. And unlike the jagged history of autism in more Western nations, the Middle East benefits from what we have learned down the years and also the mistakes we have made (without having to make them all over again).

Other papers discussing the ins and outs of biomarkers for autism for example, included as part of the series have already been covered on this blog.

Asking myself what more could have been said in the Nature series, I perhaps would have a few suggestions which hopefully won't come across as a rant. First, what about comorbidity? The various comorbidities, somatic and psychiatric, and what relationship they might have to autism, indeed to what degree some comorbidities in some cases can be more 'disabling' than the core autistic features. Yes, some of those comorbidities might be a little uncomfortable to discuss but science is science (apparently) and Nature is never one for shying away from uncomfortable issues. Second, talking about education and behavioural intervention is all well and good, but why stop there? How about recognising some of the other data available on the biology / biochemistry of autism as is being done in other conditions, or even things closer to my heart like that on diet and nutrition? No unanimous, universal effect for strategies like the gluten- and casein-free diet but that goes for just about every intervention for autism doesn't it? Finally, genes, SNPs and CNVs. Interesting and dare I say one of the primary ways forward in research bearing in mind recent lessons from other conditions. But how about the bigger picture, genes interacting with environment, as per Tom Insel's oft-quoted piece on the 'Autism Spring'? Environment covers a lot and a lot has changed environmentally over the period of the growth in cases of autism. Maybe a special edition all of its own.

With all things nature and the natural world in mind, I end with a song (it means 'no worries' apparently).

Nature on autism

A very, very quick post to direct readers to a special edition on autism spectrum conditions carried by Nature. I am still reading through the various articles which cover topics such as the numbers game, the assortative mating theory, biomarkers and much, much more.

Stay tuned for a Nature on autism part two post (as soon as I manage to read through the interesting bits).

Schizophrenia and epilepsy

Whilst few universal commonalities outside of overt clinical presentation are seemingly present in autism spectrum conditions, there are various co-morbidities which appear to be more strongly associated with a diagnosis. Learning or intellectual disability is perhaps the most frequently cited; but in terms of overall health (and risk of early mortality), the presence of epilepsy or seizure-type disorders is one of the most worrisome.

I have talked about epilepsy and autism on this blog previously. In this post however I turn my attention to a new piece of research which suggests that schizophrenia might also be a risk factor for epilepsy and likewise epilepsy might be a risk factor for schizophrenia. The study is this one by Yu-Tzu Chang and colleagues* published in the journal Epilepsia.

The details of this two-part study include:

• Based on Taiwanese health data, analysis 1 looked at over 5,000 people with an incidence of schizophrenia during the period 1999-2008 compared with over 20,000 asymptomatic controls. They reported that the incidence (note incidence not prevalence) of epilepsy in the schizophrenia group was some six times higher than the control group (6.99 vs. 1.19 per 1,000 person-years).
• Analysis 2 looked at over 11,000 patients newly diagnosed with epilepsy compared with over 46,000 age- and sex-matched controls. The incidence of schizophrenia was again much higher in the epilepsy group compared with controls (3.53 vs. 0.46 per 1,000 person-years).
• Gender seemed also to exert an effect: women with schizophrenia were more likely to present with epilepsy but men with epilepsy were at greater risk of presenting with schizophrenia.

Cumulatively what this data suggests is that the links, the bi-directional relationship, between schizophrenia and epilepsy might be quite strong. Given the information presented in my previous post on the use of EEGs and epilepsy (and autism) and the link between epilepsy and the electrical circuits of the brain, one can perhaps see how such a relationship might make sense. What we know about schizophrenia, the neurology, the neurochemistry, the biochemistry, the genetics is however the same as what we know about autism; that is, it is very, very complicated.

As the BBC report on this paper adds, psychosis has been previously linked to epilepsy exemplified by studies like this one. Whether there are shared genes, shared environmental factors between the conditions is at this moment unknown but I wouldn't be surprised if there were. I do wonder about the possible influence of things like diet in relation to this work. Dohan's hypothesis on schizophrenia and gluten and casein, the link between some cases of epilepsy and the use of a keotgenic / modified Atkins diet (low carbohydrate diet), what happens to epilepsy in some cases of autism where a gluten-free diet is implemented; all factors circling this important study and its important relationships.

* Yu-Tzu Chang et al. Bidirectional relation between schizophrenia and epilepsy: A population-based retrospective cohort study. Epilepsia. September 2011.

More prevalence and incidence data on autism

Only a quick post this one, I promise. I, like many people, have been following the various studies looking at the prevalence of autism spectrum conditions quite closely over the years. There are literally hundreds of research papers on prevalence out there to choose from; nearly all pretty much saying the same thing - the prevalence of autism spectrum conditions is increasing. We can add a few more papers to the roll call following on from my mammoth post(s) covering the South Korean study, the UK adult study, the Utah data and the others that I have discussed during my short time on (in?) the blogosphere.

First, there was this paper describing the prevalence of autism in Israel between 1986 and 2005 from registry information. I say 2005, but these dates covered the children born. The actual data presented suggested an increase in the prevalence rate from those born in 1986 (1.2 per 1,000 children) to 3.6 per 1,000 for those born in 2003.

Second, there was this paper describing the incidence (note the word incidence) of autism spectrum conditions in Massachusetts, USA. The authors reported that incidence increased from 56 per 10,000 for those born in 2001, to 93 per 10,000 for those born in 2005 - again based on administrative records.

Both these studies are interesting. The Massachusetts (I always seem to think about the Bee Gees song when I say this place) study is particularly interesting because they have used the word 'incidence' over 'prevalence' which implies that the risk of being diagnosed with an autism spectrum condition increased between 2001 and 2005, at least in Massachusetts, USA. 

I am not convinced that from the abstract the Israeli study may also have been determining incidence (being based on birth cohort data); but without yet seeing the full-text of the paper, I can offer no more information at this time.