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Kathleen R Merikangas

Publications and source records attributed to Kathleen R Merikangas.

At least 19 recordsLinked to original sources
PubMed2007

Spousal concordance for substance use and anxiety disorders.

Assortative mating -- the tendency for mate selection to occur on the basis of similar traits -- plays an essential role in understanding the genetic contribution to psychiatric illness. It also carries significant impact on clinical prognosis and is an important mechanism explaining spousal concordance. This study uses a family study design ascertaining 225 probands with substance abuse/dependence, anxiety disorders, and controls to address: (1) Is there spousal concordance or cross-concordance for substance use and/or anxiety disorders? (2) Is the spousal concordance or cross-concordance associated with worse clinical outcomes? (3) What is the mechanism of the concordance or cross-concordance? Results show a high magnitude of spousal concordance for substance use disorders with a third of the substance probands' spouses also substance dependent. In contrast, there was no spousal concordance for anxiety disorders. Couples were also concordant for having "no disorders." Both substance use and anxiety disorder concordance were associated with poorer global functioning and persistent illness. Assortative mating is a likely mechanism for spousal concordance given the elevated rate of substance use disorders among the relatives of spouses' of substance probands. Implications for family/genetic studies and the transmission of substance use disorders and "no disorders" include: (1) at the individual level, spousal concordance influences probands' course of illness, couples' marital functioning, and offspring's genetic and environmental context; and (2) at the population level, it shifts the general distribution of substance use disorders and "no disorders" by reducing the "average" couple concordance and increasing the number concordant and discordant couples at extremes of the distribution.

Adult↗
PubMed2006

Validity of the assessment of bipolar spectrum disorders in the WHO CIDI 3.0.

OBJECTIVE: Although growing interest exists in the bipolar spectrum, fully structured diagnostic interviews might not accurately assess bipolar spectrum disorders. A validity study was carried out for diagnoses of threshold and sub-threshold bipolar disorders (BPD) based on the WHO Composite International Diagnostic Interview (CIDI) in the National Comorbidity Survey Replication (NCS-R). CIDI BPD screening scales were also evaluated. METHOD: The NCS-R is a nationally representative US household population survey (n=9282 using CIDI to assess DSM-IV disorders. CIDI diagnoses were evaluated in blinded clinical reappraisal interviews using the non-patient version of the Structured Clinical Interview for DSM-IV (SCID). RESULTS: Excellent CIDI-SCID concordance was found for lifetime BP-I (AUC=.99 kappa=.88, PPV=.79, NPV=1.0), either BP-II or sub-threshold BPD (AUC=.96, kappa=.88, PPV=.85, NPV=.99), and overall bipolar spectrum disorders (i.e., BP-I/II or sub-threshold BPD; AUC=.99, kappa=.94, PPV=.88, NPV=1.0). Concordance was lower for BP-II (AUC=.83, kappa=.50, PPV=.41, NPV=.99) and sub-threshold BPD (AUC=.73, kappa=.51, PPV=.58, NPV=.99). The CIDI was unbiased compared to the SCID, yielding a lifetime bipolar spectrum disorders prevalence estimate of 4.4%. Brief CIDI-based screening scales detected 67-96% of true cases with positive predictive value of 31-52%. LIMITATION: CIDI prevalence estimates are still probably conservative, though, but might be improved with future CIDI revisions based on new methodological studies with a clinical assessment more sensitive than the SCID to sub-threshold BPD. CONCLUSIONS: Bipolar spectrum disorders are much more prevalent than previously realized. The CIDI is capable of generating conservative diagnoses of both threshold and sub-threshold BPD. Short CIDI-based scales are useful screens for BPD.

Bipolar Disorder↗
PubMed2006

First psychiatric hospitalizations in the US military: the National Collaborative Study of Early Psychosis and Suicide (NCSEPS).

BACKGROUND: Military samples provide an excellent context to systematically ascertain hospitalization for severe psychiatric disorders. The National Collaborative Study of Early Psychosis and Suicide (NCSEPS), a collaborative study of psychiatric disorders in the US Armed Forces, estimated rates of first hospitalization in the military for three psychiatric disorders: bipolar disorder (BD), major depressive disorder (MDD) and schizophrenia. METHOD: First hospitalizations for BD, MDD and schizophrenia were ascertained from military records for active duty personnel between 1992 and 1996. Rates were estimated as dynamic incidence (using all military personnel on active duty at the midpoint of each year as the denominator) and cohort incidence (using all military personnel aged 18-25 entering active duty between 1992 and 1996 to estimate person-years at risk). RESULTS: For all three disorders, 8723 hospitalizations were observed in 8,120,136 person-years for a rate of 10.7/10,000 [95% confidence interval (CI) 10.5-11.0]. The rate for BD was 2.0 (95% CI 1.9-2.1), for MDD, 7.2 (95% CI 7.0-7.3), and for schizophrenia, 1.6 (95% CI 1.5-1.7). Rates for BD and MDD were greater in females than in males [for BD, rate ratio (RR) 2.0, 95% CI 1.7-2.2; for MDD, RR 2.9, 95% CI 2.7-3.1], but no sex difference was found for schizophrenia. Blacks had lower rates than whites of BD (RR 0.8, 95% CI 0.7-0.9) and MDD (RR 0.8, 95% CI 0.8-0.9), but a higher rate of schizophrenia (RR 1.5, 95% CI 1.3-1.7). CONCLUSIONS: This study underscores the human and financial burden that psychiatric disorders place on the US Armed Forces.

Adolescent↗
PubMed2006

Association between parental and individual psychiatric/substance use disorders and smoking stages among Puerto Rican adolescents.

OBJECTIVE: To examine the associations between parental and individual psychiatric disorders and smoking stages among Puerto Rican youth from migrant and non-migrant families. METHOD: Analyses were conducted drawing on data collected as part of a migrant family study examining youth at high and low risk for substance use disorders based on the presence or absence of a parental history of substance abuse or dependence. Parents and their offspring were recruited in San Juan, Puerto Rico (n=450) and New Haven, CT, USA (n=350). RESULTS: Experimental smoking among adolescent offspring was associated with parent proband disorders. In contrast, regular smoking behavior, defined as at least weekly smoking for a month or more, and DSM-IV nicotine dependence were more strongly associated with the adolescents' own psychiatric disorders. With the exception of anxiety disorders, significant bivariate associations were shown between each psychiatric/substance use disorder and nicotine dependence. Once comorbidity was statistically controlled, only attention deficit hyperactivity disorder (ADHD), and alcohol and drug use disorders were significantly associated with nicotine dependence. After controlling for adolescents' psychiatric comorbidity, there was an association between parental disorders and both experimental and regular smoking in their adolescent offspring. CONCLUSIONS: By combining family and migrant research strategies within a single study, the present investigation was able to simultaneously examine familial, individual and sociocultural factors that may play a role in development and/or persistence of smoking behavior among Puerto Rican adolescents.

Adolescent↗
PubMed2006

Prevalence and effects of mood disorders on work performance in a nationally representative sample of U.S. workers.

OBJECTIVE: Research on the workplace costs of mood disorders has focused largely on major depressive episodes. Bipolar disorder has been overlooked both because of the failure to distinguish between major depressive disorder and bipolar disorder and by the failure to evaluate the workplace costs of mania/hypomania. METHOD: The National Comorbidity Survey Replication assessed major depressive disorder and bipolar disorder with the World Health Organization (WHO) Composite International Diagnostic Interview (CIDI) and work impairment with the WHO Health and Work Performance Questionnaire. A regression analysis of major depressive disorder and bipolar disorder predicting Health and Work Performance Questionnaire scores among 3,378 workers was used to estimate the workplace costs of mood disorders. RESULTS: A total of 1.1% of the workers met CIDI criteria for 12-month bipolar disorder (I or II), and 6.4% meet criteria for 12-month major depressive disorder. Bipolar disorder was associated with 65.5 and major depressive disorder with 27.2 lost workdays per ill worker per year. Subgroup analysis showed that the higher work loss associated with bipolar disorder than with major depressive disorder was due to more severe and persistent depressive episodes in those with bipolar disorder than in those with major depressive disorder rather than to stronger effects of mania/hypomania than depression. CONCLUSIONS: Employer interest in workplace costs of mood disorders should be broadened beyond major depressive disorder to include bipolar disorder. Effectiveness trials are needed to study the return on employer investment of coordinated programs for workplace screening and treatment of bipolar disorder and major depressive disorder.

Absenteeism↗
PubMed2005

Genomewide significant linkage to migrainous headache on chromosome 5q21.

Familial typical migraine is a common, complex disorder that shows strong familial aggregation. Using latent-class analysis (LCA), we identified subgroups of people with migraine/severe headache in a community sample of 12,245 Australian twins (60% female), drawn from two cohorts of individuals aged 23-90 years who completed an interview based on International Headache Society criteria. We report results from genomewide linkage analyses involving 756 twin families containing a total of 790 independent sib pairs (130 affected concordant, 324 discordant, and 336 unaffected concordant for LCA-derived migraine). Quantitative-trait linkage analysis produced evidence of significant linkage on chromosome 5q21 and suggestive linkage on chromosomes 8, 10, and 13. In addition, we replicated previously reported typical-migraine susceptibility loci on chromosomes 6p12.2-p21.1 and 1q21-q23, the latter being within 3 cM of the rare autosomal dominant familial hemiplegic migraine gene (ATP1A2), a finding which potentially implicates ATP1A2 in familial typical migraine for the first time. Linkage analyses of individual migraine symptoms for our six most interesting chromosomes provide tantalizing hints of the phenotypic and genetic complexity of migraine. Specifically, the chromosome 1 locus is most associated with phonophobia; the chromosome 5 peak is predominantly associated with pulsating headache; the chromosome 6 locus is associated with activity-prohibiting headache and photophobia; the chromosome 8 locus is associated with nausea/vomiting and moderate/severe headache; the chromosome 10 peak is most associated with phonophobia and photophobia; and the chromosome 13 peak is completely due to association with photophobia. These results will prove to be invaluable in the design and analysis of future linkage and linkage disequilibrium studies of migraine.

Adult↗
PubMed2005

Nosology and treatment of primary headache in a Swiss headache clinic.

We assessed demographics, diagnoses, course, severity, impact and treatment of primary headache outpatients from records in the Headache and Pain Clinic, Neurological Department, Zürich University Hospital. All outpatients seen from 1996 to 1998 for migraine, tension-type headache, and both, were included. Diagnoses, drug, physical and alternative treatments before and after referral were listed. Descriptive statistics were used for differences between the general population and this sample, the diagnoses, and treatments. The coexistence of migraine and tension-type headache, and the high frequencies of headache days would have excluded most migraine patients from typical drug trials: at best, only one third were eligible. The socioeconomic impact of combined and difficult syndromes calls for comprehensive management beyond simple treatment with instant relief drugs. The diagnostic and therapeutic practices of referring physicians exposed a deficit of information on headache, and a need for relevant education.

Adolescent↗
PubMed2005

Families at high and low risk for depression: a three-generation startle study.

BACKGROUND: Anxiety symptoms might be a vulnerability factor for the development of major depressive disorder (MDD). Because elevated startle magnitude in threatening contexts is a marker for anxiety disorder, the present study investigated the hypothesis that enhanced startle reactivity would also be found in children and grandchildren of individuals with MDD. METHODS: The magnitude of startle was investigated in two tests (anticipation of an unpleasant blast of air and during darkness) in children (second generation) and grandchildren (third generation) of probands with (high risk) or without (low risk) MDD (first generation). RESULTS: Startle discriminated between the low- and high-risk groups. In the probands' children, the high-risk group showed increased startle magnitude throughout the fear-potentiated startle test. In the probands' grandchildren, a gender-specific abnormality was found in the high-risk group with high-risk girls, but not boys, exhibiting elevated startle magnitude throughout the procedure. CONCLUSIONS: Increased startle reactivity in threatening contexts, previously found in patients with anxiety disorder and in children of parents with an anxiety disorder, might also constitute a vulnerability marker for MDD. These findings suggest that there might be common biologic diatheses underlying depression and anxiety.

Acoustic Stimulation↗
PubMed2005

Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication.

CONTEXT: Little is known about lifetime prevalence or age of onset of DSM-IV disorders. OBJECTIVE: To estimate lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the recently completed National Comorbidity Survey Replication. DESIGN AND SETTING: Nationally representative face-to-face household survey conducted between February 2001 and April 2003 using the fully structured World Health Organization World Mental Health Survey version of the Composite International Diagnostic Interview. PARTICIPANTS: Nine thousand two hundred eighty-two English-speaking respondents aged 18 years and older. MAIN OUTCOME MEASURES: Lifetime DSM-IV anxiety, mood, impulse-control, and substance use disorders. RESULTS: Lifetime prevalence estimates are as follows: anxiety disorders, 28.8%; mood disorders, 20.8%; impulse-control disorders, 24.8%; substance use disorders, 14.6%; any disorder, 46.4%. Median age of onset is much earlier for anxiety (11 years) and impulse-control (11 years) disorders than for substance use (20 years) and mood (30 years) disorders. Half of all lifetime cases start by age 14 years and three fourths by age 24 years. Later onsets are mostly of comorbid conditions, with estimated lifetime risk of any disorder at age 75 years (50.8%) only slightly higher than observed lifetime prevalence (46.4%). Lifetime prevalence estimates are higher in recent cohorts than in earlier cohorts and have fairly stable intercohort differences across the life course that vary in substantively plausible ways among sociodemographic subgroups. CONCLUSIONS: About half of Americans will meet the criteria for a DSM-IV disorder sometime in their life, with first onset usually in childhood or adolescence. Interventions aimed at prevention or early treatment need to focus on youth.

Adolescent↗
PubMed2005

Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication.

BACKGROUND: Little is known about the general population prevalence or severity of DSM-IV mental disorders. OBJECTIVE: To estimate 12-month prevalence, severity, and comorbidity of DSM-IV anxiety, mood, impulse control, and substance disorders in the recently completed US National Comorbidity Survey Replication. DESIGN AND SETTING: Nationally representative face-to-face household survey conducted between February 2001 and April 2003 using a fully structured diagnostic interview, the World Health Organization World Mental Health Survey Initiative version of the Composite International Diagnostic Interview. PARTICIPANTS: Nine thousand two hundred eighty-two English-speaking respondents 18 years and older. MAIN OUTCOME MEASURES: Twelve-month DSM-IV disorders. RESULTS: Twelve-month prevalence estimates were anxiety, 18.1%; mood, 9.5%; impulse control, 8.9%; substance, 3.8%; and any disorder, 26.2%. Of 12-month cases, 22.3% were classified as serious; 37.3%, moderate; and 40.4%, mild. Fifty-five percent carried only a single diagnosis; 22%, 2 diagnoses; and 23%, 3 or more diagnoses. Latent class analysis detected 7 multivariate disorder classes, including 3 highly comorbid classes representing 7% of the population. CONCLUSION: Although mental disorders are widespread, serious cases are concentrated among a relatively small proportion of cases with high comorbidity.

Adolescent↗
PubMed2004

Prevalence, severity, and unmet need for treatment of mental disorders in the World Health Organization World Mental Health Surveys.

CONTEXT: Little is known about the extent or severity of untreated mental disorders, especially in less-developed countries. OBJECTIVE: To estimate prevalence, severity, and treatment of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) mental disorders in 14 countries (6 less developed, 8 developed) in the World Health Organization (WHO) World Mental Health (WMH) Survey Initiative. DESIGN, SETTING, AND PARTICIPANTS: Face-to-face household surveys of 60 463 community adults conducted from 2001-2003 in 14 countries in the Americas, Europe, the Middle East, Africa, and Asia. MAIN OUTCOME MEASURES: The DSM-IV disorders, severity, and treatment were assessed with the WMH version of the WHO Composite International Diagnostic Interview (WMH-CIDI), a fully structured, lay-administered psychiatric diagnostic interview. RESULTS: The prevalence of having any WMH-CIDI/DSM-IV disorder in the prior year varied widely, from 4.3% in Shanghai to 26.4% in the United States, with an interquartile range (IQR) of 9.1%-16.9%. Between 33.1% (Colombia) and 80.9% (Nigeria) of 12-month cases were mild (IQR, 40.2%-53.3%). Serious disorders were associated with substantial role disability. Although disorder severity was correlated with probability of treatment in almost all countries, 35.5% to 50.3% of serious cases in developed countries and 76.3% to 85.4% in less-developed countries received no treatment in the 12 months before the interview. Due to the high prevalence of mild and subthreshold cases, the number of those who received treatment far exceeds the number of untreated serious cases in every country. CONCLUSIONS: Reallocation of treatment resources could substantially decrease the problem of unmet need for treatment of mental disorders among serious cases. Structural barriers exist to this reallocation. Careful consideration needs to be given to the value of treating some mild cases, especially those at risk for progressing to more serious disorders.

Adult↗
PubMed2004

Correlates of sleep-wake patterns among children and young adolescents in Taiwan.

STUDY OBJECTIVE: To determine correlates of morning and evening sleep-wake patterns in a community sample of children. DESIGN: A school-based cross-sectional survey. PARTICIPANTS: Sample included 1572 students, grades 4 to 8 (response rate, 98.4%), using a multistage sampling method. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Student participants completed a Sleep Habits Questionnaire, which included sleep schedules, a mood scale, substance use, the morningness/eveningness (M/E) scale, pubertal development scale, sleep disturbance scale, and parental monitoring scale. The morning (n = 367) and evening (n = 364) groups were operationally defined as participants who scored in the top or bottom 25% of the M/E scale, respectively. Linear mixed and tree-based classification models were used to explore correlates of sleep-wake patterns. Our results showed the evening type was associated with older school grade level, increased coffee drinking, moodiness, decreased parental monitoring, daytime sleepiness, and several sleep disturbances, including early insomnia, fear of sleeping in darkness, bedwetting, and going to bed later than 3 am. The 2 most potent discriminators between evening and morning subtypes were higher grade level, an index of age, and moodiness. The association of moodiness with the evening type was greater in boys than girls. CONCLUSIONS: These findings suggest that further research should address explanations for the association between evening type and mood and anxiety symptoms, including order of the effects, developmental factors, environmental determinants of sleep time such as school start time and parental bedtime monitoring, and circadian maturation.

Adolescent↗
PubMed2004

Similarities and differences in sleep-wake patterns among adults and their children.

STUDY OBJECTIVE: To determine associations and differences in sleep-wake patterns among children and their parents and to explore the correlates for sleep-wake patterns among adults. DESIGN: A school-based cross-sectional survey. PARTICIPANTS: Sample included 1479 fourth to eighth graders and their parents, using a multistage sampling method. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Students and their parents completed a Sleep Habit Questionnaire, which included sleep schedules, a mood scale, and the morningness/eveningness scale. Statistical methods included Pearson and Spearman correlations and analysis of variance using a mixed model. Results showed low correlations in sleep schedules and sleep-wake patterns between children and those parents who did not work shifts or have an evening or night job. Compared to their children, parents tended to go to bed and rise later, have shorter nighttime sleep duration, have less weekend compensation of sleep, and have the morning-type sleep profile. In addition, junior-high students (seventh and eight graders) demonstrated different sleep-wake patterns compared to elementary-school students (fourth to sixth graders). Young age, moodiness, and shift work were associated with tendencies to be the evening type among parent participants. CONCLUSIONS: Our findings indicate that age, social demands (school work for children and adolescents and employment type for adults), and mood status are associated with sleep-wake patterns. Future study examining the association between evening-sleep type and neurotic traits and psychopathology in the adult population will be our next step.

Adult↗
PubMed2004

Latent class and genetic analysis does not support migraine with aura and migraine without aura as separate entities.

Latent class and genetic analyses were used to identify subgroups of migraine sufferers in a community sample of 6,265 Australian twins (55% female) aged 25-36 who had completed an interview based on International Headache Society (IHS) criteria. Consistent with prevalence rates from other population-based studies, 703 (20%) female and 250 (9%) male twins satisfied the IHS criteria for migraine without aura (MO), and of these, 432 (13%) female and 166 (6%) male twins satisfied the criteria for migraine with aura (MA) as indicated by visual symptoms. Latent class analysis (LCA) of IHS symptoms identified three major symptomatic classes, representing 1) a mild form of recurrent nonmigrainous headache, 2) a moderately severe form of migraine, typically without visual aura symptoms (although 40% of individuals in this class were positive for aura), and 3) a severe form of migraine typically with visual aura symptoms (although 24% of individuals were negative for aura). Using the LCA classification, many more individuals were considered affected to some degree than when using IHS criteria (35% vs. 13%). Furthermore, genetic model fitting indicated a greater genetic contribution to migraine using the LCA classification (heritability, h(2)=0.40; 95% CI, 0.29-0.46) compared with the IHS classification (h(2)=0.36; 95% CI, 0.22-0.42). Exploratory latent class modeling, fitting up to 10 classes, did not identify classes corresponding to either the IHS MO or MA classification. Our data indicate the existence of a continuum of severity, with MA more severe but not etiologically distinct from MO. In searching for predisposing genes, we should therefore expect to find some genes that may underlie all major recurrent headache subtypes, with modifying genetic or environmental factors that may lead to differential expression of the liability for migraine.

Adult↗
PubMed2004

The National Comorbidity Survey Replication (NCS-R): background and aims.

The National Comorbidity Survey Replication (NCS-R) is a new nationally representative community household survey of the prevalence and correlates of mental disorders in the US. The NCS-R was carried out a decade after the original NCS. The NCS-R repeats many of the questions from the NCS and also expands the NCS questioning to include assessments based on the more recent Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) diagnostics system (American Psychiatric Association, 1994). The NCS-R was designed to (1) investigate time trends and their correlates over the decade of the 1990s and (2) expand the assessment of the prevalence and correlates of mental disorders beyond the assessment in the baseline NCS in order to address a number of important substantive and methodological issues that were raised by the NCS. This paper presents a brief review of these aims.

Comorbidity↗
PubMed2003

The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R).

CONTEXT: Uncertainties exist about prevalence and correlates of major depressive disorder (MDD). OBJECTIVE: To present nationally representative data on prevalence and correlates of MDD by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria, and on study patterns and correlates of treatment and treatment adequacy from the recently completed National Comorbidity Survey Replication (NCS-R). DESIGN: Face-to-face household survey conducted from February 2001 to December 2002. SETTING: The 48 contiguous United States. PARTICIPANTS: Household residents ages 18 years or older (N = 9090) who responded to the NCS-R survey. MAIN OUTCOME MEASURES: Prevalence and correlates of MDD using the World Health Organization's (WHO) Composite International Diagnostic Interview (CIDI), 12-month severity with the Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR), the Sheehan Disability Scale (SDS), and the WHO disability assessment scale (WHO-DAS). Clinical reinterviews used the Structured Clinical Interview for DSM-IV. RESULTS: The prevalence of CIDI MDD for lifetime was 16.2% (95% confidence interval [CI], 15.1-17.3) (32.6-35.1 million US adults) and for 12-month was 6.6% (95% CI, 5.9-7.3) (13.1-14.2 million US adults). Virtually all CIDI 12-month cases were independently classified as clinically significant using the QIDS-SR, with 10.4% mild, 38.6% moderate, 38.0% severe, and 12.9% very severe. Mean episode duration was 16 weeks (95% CI, 15.1-17.3). Role impairment as measured by SDS was substantial as indicated by 59.3% of 12-month cases with severe or very severe role impairment. Most lifetime (72.1%) and 12-month (78.5%) cases had comorbid CIDI/DSM-IV disorders, with MDD only rarely primary. Although 51.6% (95% CI, 46.1-57.2) of 12-month cases received health care treatment for MDD, treatment was adequate in only 41.9% (95% CI, 35.9-47.9) of these cases, resulting in 21.7% (95% CI, 18.1-25.2) of 12-month MDD being adequately treated. Sociodemographic correlates of treatment were far less numerous than those of prevalence. CONCLUSIONS: Major depressive disorder is a common disorder, widely distributed in the population, and usually associated with substantial symptom severity and role impairment. While the recent increase in treatment is encouraging, inadequate treatment is a serious concern. Emphasis on screening and expansion of treatment needs to be accompanied by a parallel emphasis on treatment quality improvement.

Adult↗