Expert Answer:Sampling and Generalizability

Answer & Explanation:Sampling and GeneralizabilityFor this discussion, refer to the article you found in the Capella library. The article should be a research report on a quantitative research study in a topic area of interest to you. Use the Article Analysis Worksheet to prepare for this discussion. Briefly summarize the article (1–2 paragraphs). Identify the following aspects of the study:
Target population.
Sampling procedure.
Sample characteristics.
Note: Be sure to describe and identify the size of the population from which the sample will be drawn. If you are addressing representativeness and generalizability, make sure the sample is equitable in proportion to the population. For instance, if you are sampling fifth and sixth graders for level or moral development, how many boys and how many girls are there in both grades? And, then, how many are there in the sample (boys and girls)? In this case, the population is all students in grades 5 and 6. If you are sampling boys and girls in the fifth and sixth grades with ADD, describe how many in each grade, how many with ADD, and how many in your sample. In this case, the population from which the sample is drawn is not the total in both grades but the total with ADD.


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Susan E Levy, David S Mandell, Robert T Schultz
Autism spectrum disorders are characterised by severe deficits in socialisation, communication, and repetitive or
unusual behaviours. Increases over time in the frequency of these disorders (to present rates of
about 60 cases per 10 000 children) might be attributable to factors such as new administrative classifications, policy
and practice changes, and increased awareness. Surveillance and screening strategies for early identification could
enable early treatment and improved outcomes. Autism spectrum disorders are highly genetic and multifactorial,
with many risk factors acting together. Genes that affect synaptic maturation are implicated, resulting in neurobiological
theories focusing on connectivity and neural effects of gene expression. Several treatments might address core and
comorbid symptoms. However, not all treatments have been adequately studied. Improved strategies for early
identification with phenotypic characteristics and biological markers (eg, electrophysiological changes) might
hopefully improve effectiveness of treatment. Further knowledge about early identification, neurobiology of autism,
effective treatments, and the effect of this disorder on families is needed.
Lancet 2009; 374: 1627–38
Autism is a neurodevelopmental disorder in the category
of pervasive developmental disorders, and is characterised
by severe and pervasive impairment in reciprocal
socialisation, qualitative impairment in communication,
and repetitive or unusual behaviour. The Diagnostic and
Statistical Manual of Mental Disorders, 4th edition
(DSM-IV)1 and the International Classification of
Diseases, 10th edition (ICD-10),2 include autistic disorder,
Asperger’s syndrome, pervasive developmental disordernot otherwise specified (PDD-NOS), Rett’s syndrome,
and childhood disintegrative disorder as pervasive
developmental disorders. Clinicians and researchers use
autism spectrum disorders to include autism, Asperger’s
syndrome, and PDD-NOS, which we discuss in this
Seminar. For children with Rett’s disorder or childhood
disintegrative disorder, their clinical course, pathophysiology, and the diagnostic strategies used are
different and are not addressed in this Seminar.
We focus on prevalence of autism spectrum disorders
and possible causes of changes in prevalence. Although
estimates vary, prevalence seems to have increased greatly
since the 1960s, when rates included only autistic disorder.
In the 20 years since, in the USA and Europe prevalence
rates ranged from five to 72 cases per 10 000 children.3,4
These estimates were affected by screening, case-confirmation strategies, and sample size, with small sample
sizes resulting in high estimates. Prevalence of autistic
disorder is between ten and 20 per 10 000 children.5
Estimates of autism spectrum disorders have been more
consistent than have those for autistic disorder—perhaps
because they are less sensitive to small differences in case
definitions. These estimates are close to 60 per
10 000 children.6 However, in a prevalence study7
researchers reported a rate of 116 per 10 000 children for
all autism spectrum disorders. They used a small sample
of children in South Thames, UK, and relied on screening
and case-confirmation methods, with a broad definition
of these disorders. When the definition of autism was
narrowed, they reported a prevalence of 25 per 10 000.
A rise in the number of children identified with autism
spectrum disorders in educational systems has resulted
in public health concern.8 Some of the reported increase
is attributable to new administrative classifications in
special-education settings and the subsequent reclassification of children from a different category to
autism.8 Symptoms of these disorders might resemble
or arise with intellectual disability, attention deficithyperactivity disorder, or obsessive-compulsive disorder.9
Policy and practice changes rather than true changes in
community prevalence might be responsible for recorded
increases. Substantial small-area variation in prevalence
could be related to local health-care and education
resources,10 and pressure to obtain intensive services
might result in over-diagnosis.
Correspondence to:
Prof Susan E Levy, Children’s
Hospital of Philadelphia,
University of Pennsylvania,
School of Medicine, Center for
Autism Research, 3535 Market
Street, Philadelphia, PA 19104,
Search strategy and selection criteria
We searched Medline, Psychinfo, and Cochrane Library
databases from January, 1998, to December, 2008, with the
search terms “autism”, “autistic disorder”, “pervasive
developmental disorder”, “autism spectrum disorder”, and
“Asperger syndrome” in combination with “evaluation”,
“diagnosis”, “treatment”, “therapy”, “medication”,
“pharmacotherapy”, “epidemiology”, “genetics”,
“neuroimaging”, “behavior therapy”, “early identification”,
“outcome”, and “complementary and alternative therapy.”
We largely selected reports published within the past 5 years,
but did not exclude commonly referenced and highly
regarded older publications. We also searched references
from recent reviews and other reports identified by this
search strategy, and selected those we judged relevant.
Review articles and book chapters are cited to provide more
details and references than are provided in this Seminar. Our
reference list was modified on the basis of comments from
peer reviewers. Vol 374 November 7, 2009
Published Online
October 12, 2009
Children’s Hospital of
Philadelphia (Prof S E Levy MD,
Prof R T Schultz PhD) and
Department of Psychiarty
(Prof S E Levy, Prof R T Schultz,
D S Mandell ScD), University of
Pennsylvania, School of
Medicine, Center for Autism
Research, Philadelphia, PA, USA
Clinical characteristics and screening
Core symptoms of autism spectrum disorders affect
domains of socialisation, communication, and behaviour
(panel 1). Clinical signs are usually present by age 3
years, but typical language development might delay
identification of symptoms. Results of prospective
studies11 of infants at risk (ie, younger siblings of affected
children) have shown that deficits in social
responsiveness, communication, and play can be present
in those as young as age 6–12 months. Diagnoses show
heterogeneity of clinical phenotype, severity, and type
and frequency of symptoms. Autism spectrum disorders
Panel 1: Core domains of autism1
• Impaired use of non-verbal behaviours to regulate
• Delayed peer interactions, few or no friendships, and little
• Absence of seeking to share enjoyment and interests
• Delayed initiation of interactions
• Little or no social reciprocity and absence of social judgment
• Delay in verbal language without non-verbal
compensation (eg, gestures)
• Impairment in expressive language and conversation, and
disturbance in pragmatic language use
• Stereotyped, repetitive, or idiosyncratic language
• Delayed imaginative and social imitative play
Restricted, stereotyped, and repetitive patterns of
• Preoccupation with stereotyped or restricted interests or
• Adherence to routines, rigidity, and perseverative behaviour
• Stereotyped, repetitive motor mannerisms, and
selfstimulatory behaviour
• Preoccupation or fascination with parts of items and
unusual visual exploration
have characteristic diagnostic criteria, ages of symptom
recognition, associated medical and developmental
features, standard effective treatments, and usual
courses of development (table 1).
Early detection enables referral to intervention services
and for family support, with the goal of an improved
outcome.13 Two methods of identification have emerged.
The strategy in the UK combines targeted or selective
screening with recognition of alerting signals by
clinicians and families.14 The practice endorsed in the
USA is routine general developmental surveillance with
disorder-specific screening for those who are identified
to be at risk during routine screening, or universal
autism-specific screening at high-risk ages (eg, 18 and
24 months or 30 months), or both.15 Few data are available
to compare the effectiveness of these approaches.
Universal whole-population screening with standardised
tests has not been supported in the UK16 because of poor
sensitivity and specificity of tests.14
Tebruegge and colleagues14 investigated the effect of
targeted checks—more than a third of children with
autism spectrum disorder were not identified at
age 2 years. These researchers supported routine child
health surveillance at age 2·0 years and 3·5 years by
health professionals with awareness of typical development. The joint working party on child-health surveillance and the American Academy of Pediatrics
(AAP)16 recommended education of clinicians and
families to recognise red flags or alerting signals. Other
countries have adopted similar strategies, combining
routine child-health surveillance with a standardised
method. In Japan, the young autism and other developmental disorders checkup tool (YACHT) is administered
by public health nurses to children aged 18 and
24 months.17 Wong and colleagues18 have modified the
checklist for autism in toddlers (CHAT) for use in
China, with a two-stage screening strategy in CHAT-23,
incorporating a questionnaire and a direct observation
Asperger’s syndrome
Pervasive developmental disordernot otherwise specified (PDD-NOS)
Age of recognition (diagnosis*)
0–3 years (3–5 years)
>3 years (6–8 years)
About 25% (social or communication)
Sex ratio (male:female)
Male>female (variable)
Poor; >2 DSM-IV criteria
Delayed, deviant; might be non-verbal
No early delay; qualitative and
pragmatic difficulties later
More impaired than in Asperger’s syndrome
or PDD-NOS (includes stereotypy)
Variable (circumscribed interests)
Intellectual disability
Mild to none
Mild to severe
More likely to establish genetic or other cause
than in Asperger’s syndrome or PDD-NOS
25% over lifespan
Roughly 10%
Roughly 10%
Poor to fair
Fair to good
Fair to good
DSM-IV=Diagnostic and Statistical Manual of Mental Disorders, 4th edition. *Average age at diagnosis. Data adapted from Volkmar and Pauls.12
Table 1: Differential diagnostic features of autism spectrum disorders
1628 Vol 374 November 7, 2009
stage that has more sensitivity and specificity than does
Children identified to be at risk should be referred for
comprehensive developmental and diagnostic assessment
for autism spectrum disorders. This assessment might
be done through community resources (eg, early
intervention staff, educators, psychologists, or speech
pathologists), educational agencies, or local developmental
clinicians. Reviews of early identification and screening
are available.15,17,19 If concerns that a child has autism
spectrum disorder are validated, comprehensive
diagnostic assessment is needed (figure 1). These
assessments should be multidisciplinary, addressing
core symptoms, cognition, language, and adaptive,
sensory, and motor skills. The multidisciplinary team
should include clinicians skilled in speech and language
therapy, occupational therapy, education, psychology, and
social work. Ozonoff and colleagues19 reviewed domains
of assessment, including neuropsychological, attention,
executive function, and academic functioning.
Diagnostic assessment of autism spectrum disorders
includes use of ICD or DSM diagnostic criteria,21 and
standardised methods to assess core (panel 1) and
comorbid symptoms (table 2). This multidisciplinary
assessment includes a review of caregiver concerns,
descriptions of behaviour, medical history, and
questionnaires.21 Input from families about their
observations and concerns are crucial. Although parents
are often aware of developmental problems in their child
from age 18 months, a diagnosis is often not made until
2 years after the initial expression of parental concern. In
some cases diagnosis has not been confirmed until close
to age 6 years,28 which is sometimes associated with
delays attributable to access to services and regional
variations in diagnosis.
Table 3 shows methods for diagnosis and categorisation of autism spectrum disorders.19 Standardised
questionnaires such as the social responsiveness scale
provide data about severity of core deficits of
socialisation, and the revised repetitive behaviour scale
provides information about stereotyped or repetitive
behaviours (figure 1). Use of two research quality, goldstandard assessment methods based on DSM criteria,
the autism diagnostic observation schedule (ADOS)58
and the revised autism diagnostic interview (ADI-R),59
have improved accuracy and reliability of diagnosis.19
The ADOS is a semistructured standardised assessment
for social behaviour, communication, and imaginative
play, and is used in research and clinical settings. To
diagnose individuals with intellectual disability is
difficult because behaviours might not be specific to
autism spectrum disorders; the ADOS diagnostic
algorithm was revised to address these issues. The time
needed for administration of the ADI-R (1–3 h)
precludes its use in many clinical settings. Vol 374 November 7, 2009
Concerns of parents, health visitor, or other care provider
Red flags, high-risk status
Refer if present
Stage 1: general developmental assessment early
intervention, special education, other community
based providers*
Record review, interviews, developmental assessment,
screening checklists or questionnaires
Consistent with possible ASD?
Stage 2: comprehensive diagnostic assessment
Interdisciplinary or multi-agency assessment (MAA)*
Trained team of clinicians
Include stage 1 data
Observations across settings
Cognitive, communication, and ASD-specific assessment
Medical assessment (causes, comorbidity)
Differential diagnosis
Monitor and continue early intervention or
developmental, educational services
ASD diagnosis confirmed?
Yes, but additional questions or concerns
Stage 3: tertiary, ASD assessment, consultation with
specialist(s) at MAA or academic centre
Qualified/highly trained clinician(s)
Include stages 1–2 data
Might include some or all:
Specialised assessment methods
Natural environment observation
Subspecialty referral for evaluation of causes,
• Counsel about resources and develop
family-care plan
• Educational or early intervention plan
• Monitor
Figure 1: Stages of identification and diagnosis of autism spectrum disorder
ASD=autism spectrum disorder. Adapted from the National Austictic Society and 15 and the Pennsylvania
Department of Public Welfare.20
Comorbid disorders are common in children60 and
families of children with autism spectrum disorders,
and might have a greater effect on function and outcome
than do core symptoms (table 2). Parents of affected
children have increased rates of stress and mental
health comorbidity (eg, anxiety and depression), which
might be associated with their child’s behavioural
problems.61 Comorbid behavioural or developmental
disorders include intellectual delays, inattention or
other symptoms of attention deficit-hyperactivity
disorder, externalising behaviours (such as aggression
and disruption), affective difficulties (such as depression
or anxiety), sleep disruption, and sensory differences.22
Medical comorbidities, such as gastrooesophageal
reflux, food selectivity, and neurological disorders (eg,
tics and seizures) also have a substantial effect on
management and on the family. Some behavioural
or affective comorbidities might be targets for
A comprehensive diagnostic assessment should
include medical investigation for causes and associated
diagnoses.62 Results will inform families about related
Frequency Treatments
Cognitive; intellectual disability
Language deficits
Communication training, speech and language therapy
Attentional problems, impulsivity,
or hyperactivity
Behavioural intervention, psychopharmacotherapy (eg,
stimulants, atomoxetine, or alpha blockers)
Motor delay
Physical therapy
Physical therapy
Behavioural treatment such as relaxation, cognitive
behavioural treatment, psychopharmacotherapy
(eg, SSRIs or alpha-2 agonists)
Obsessive compulsive disorder or
interfering repetitive behaviour
Psychotherapy, antidepressants
Behavioural treatment, SSRIs and other drugs such as
atypical antipsychotics
Oppositional defiant disorder
Behavioural treatment
Behavioural problems
Behavioural treatment
Behavioural intervention, atypical antipsychotics (eg,
risperidone or arapiprazole)
Disruptive, irritable, or aggressive
Self-injurious behaviour
Behavioural intervention; drugs (eg, risperidone,
naltrexone, and others)
Occupational therapy, behavioural treatment, and
Auditory sensitivity
Occupational therapy
Seizures and epilepsy
Alpha-2 agonists (clonidine and guanfacine) and others
such as atomoxetine
Behavioural treatment, investigation as appropriate for
gastrointestinal difficulties
Gastrointestinal investigations as appropriate (eg,
barium swallow or milk scan for gastrooesophageal
reflux; flat plate, clean out, stool softener, or cathartic for
constipation as clinically indicated)
Sleep diary, sleep hygiene, behavioural supports,
investigation of possible medical comorbidities as cause,
drugs (eg, melatonin and clonidine)
Food selectivity
Gastro-oesophageal reflux,
Sleep disruption
SSRI=selective serotonin reuptake inhibitor.
Table 2: Comorbid symptoms or disorders
genetic, neurological, or medical problems, and risk of
recurrence in future siblings. An appropriate medical
investigation for causes includes a detailed history and
physical examination (with careful examination for
dysmorphology). Clinical genetic assessment might
include laboratory studies ordered by the primary care
practitioner or referral to a clinical geneticist. Genetic
laboratory studies can include routine karyotype and
molecular DNA testing for fragile X, or comparative
genomic hybridisation, or both.63 Associated medical
problems such as seizures show a need for
electroencephalogram (EEG), substantial regression a
need for metabolic investigation, and abnormal head size
a need for neuroimaging in some. Routine brain imaging
or EEG is not recommended unless specific clinical
features are indicative of an active neurological process
needing clinical diagnosis.
Attempts to identify unified theories explaining core and
comorbid deficits have been unsuccessful, which is not
surprising in view of the heterogeneous expression of
autism spectrum disorders. In studies64 of this disorder
as a neurodevelopmental disorder of prenatal and
postnatal brain development, researchers have attempted
to elucidate these theories by examination of brain
growth, functional neural networks, neuropathology,
electrophysiology, and neurochemistry. Neurocognitive
theories include pragmatic language impairment and
difficulties in intersubjectivity (theory of mind), executive
function and problem-s …
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