Clinical trial NCT03847753: Exploring the Comorbidity Between Mental Disorders and General Medical Conditions
Official title: Exploring the Comorbidity Between Mental Disorders and General Medical Conditions Among a Danish National Population
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Organic, Including Symptomatic, Mental Disorders
Substance Use
Schizophrenia
Mood [Affective] Disorders
Neurotic, Stress-related and Somatoform Disorders
Eating Disorder
Disorders of Adult Personality and Behavior
Mental Retardation
Disorder of Psychological Development
Behavioural Disorder
Hypertension
Dyslipidemias
Ischemic Heart Disease
Atrial Fibrillation
Heart Failure
Peripheral Occlusive Disease
Stroke
Diabetes Mellitus
Thyroid Disorder
Gout
Chronic Pulmonary Disease
Allergy
Chronic Gastritis
Chronic Liver Disease
Inflammatory Bowel Diseases
Diverticular Disease of Large Intestine
Chronic Kidney Diseases
Prostate Disorders
Connective Tissue Disorder
Osteoporosis
Pain
HIV/AIDS
Anemia
Cancer
Vision Disorders
Hearing Disorders
Migraine
Epilepsy
Parkinson Disease
Multiple Sclerosis
Neuropathy
Keywords: Comorbidity
Lead sponsor: University of Aarhus
Sponsor class: OTHER
First posted: 2019-02-20
Enrollment: 5940299
Sex: ALL
Minimum age (years): 1
Standard ages: CHILD
ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All individuals born in Denmark between 1900-2015 and who resided there between 2000-2016

Brief summary: Mental disorders have been shown to be associated with a number of general medical conditions (also referred to as somatic or physical conditions). The investigators aim to undertake a comprehensive study of comorbidity among those with treated mental disorders, by using high-quality Danish registers to provide age- and sex-specific pairwise estimates between the ten groups of mental disorders and nine groups of general medical conditions.

The investigators will examine the association between all 90 possible pairs of prior mental disorders and later GMC categories using the Danish national registers. Depending on whether individuals are diagnosed with a specific mental disorder, the investigators will estimate the risk of receiving a later diagnosis within a specific GMC category, between the start of follow-up (January 1, 2000) or at the earliest age at which a person might develop the mental disorder, whichever comes later. Follow-up will be terminated at onset of the GMC, death, emigration from Denmark, or December 31, 2016, whichever came first. Additionally for dyslipidemia, follow-up will be ended if a diagnosis of ischemic heart disease was received. A "wash-out" period will be employed in the five years before follow-up started (1995-1999), to identify and exclude prevalent cases from the analysis. Individuals with the GMC of interest before the observation period will be considered prevalent cases and excluded from the analyses (i.e. prevalent cases were "washed-out"). When estimating the risk of a specific GMC, the investigators will consider all individuals to be exposed or unexposed to the each mental disorder depending on whether a diagnosis is received before the end of follow-up. Persons will be considered unexposed to a mental disorder until the date of the first diagnosis, and exposed thereafter.

Detailed description: The investigators will analyse data from all individuals born in Denmark between 1900-2015 and who resided there between 2000-2016; giving a study size of over 5.5 million people. The National Patient Register, Cause of Death Register and National Prescription Registry of Denmark will all be used as sources of information about the mental disorders and general medical conditions (GMC) of interest. These are considered to be of high quality and validity.

The rate of diagnosis with a specific GMC group between those exposed and unexposed to each of ten mental disorders will be examined using hazard ratios (HRs) and 95% confidence intervals (CI), using Cox proportional hazards models with age as the underlying time scale. The following models will be run to provide all persons and sex-specific estimates, considering exposure to each mental disorder and whether the association differs depending on the time since onset of the mental disorder (lagged HRs):

Model A: adjusted for sex and birth date which, in combination with underlying age in the models, adjusts also for calendar time

Model B: additionally adjust for mental disorder comorbidity with onset before, but not after, the mental disorder of interest

Finally, cumulative incidence proportions of diagnosis with a GMC after being diagnosed with a mental disorder will be estimated. This will provide absolute risks of developing a GMC after a specific time, given a previous diagnosis of a mental disorder. To compare cumulative incidence proportions among people diagnosed with a mental disorder to those among people without a diagnosis, a matched reference group will be generated for each mental disorder. For every index person with the mental disorder, up to five age- and sex-matched individuals (who had not received a diagnosis of the relevant mental disorder by the age the index person was diagnosed) will be randomly selected. Cumulative incidence proportions will be generated for each reference group. All analyses will be performed on the secured platform of Statistics Denmark STATA/MP version 15.1 (Stata Corporation, College Station, Texas, USA).

An interactive webpage will be developed to visualize all results from this study. The Danish Data Protection Agency and the Danish Health Data Authority approved this study.

Eligibility criteria: Inclusion Criteria:

* Born in Denmark between 1900-2015
* Resided in Denmark during the study period (2000-2016)

Exclusion Criteria:

* Excluded from analyses for each specific GMC, if considered a prevalent case of that GMC (i.e. ascertained to have a diagnosis for the GMC during the washout period of 1995-1999)

Primary outcomes:
measure: Risk of circulatory system general medical conditions
timeFrame: Diagnosed during the study period (2000-2016), after at least 1 year of age
measure: Risk of Endocrine System general medical conditions
timeFrame: Diagnosed during the study period (2000-2016), after at least 1 year of age
measure: Risk of Pulmonary System general medical conditions
timeFrame: Diagnosed during the study period (2000-2016), after at least 1 year of age
measure: Risk of Gastrointestinal System general medical conditions
timeFrame: Diagnosed during the study period (2000-2016), after at least 1 year of age
measure: Risk of Urogenital System general medical conditions
timeFrame: Diagnosed during the study period (2000-2016), after at least 1 year of age
measure: Musculoskeletal System general medical conditions
timeFrame: Diagnosed during the study period (2000-2016), after at least 1 year of age
measure: Risk of Neurological System general medical conditions
timeFrame: Diagnosed during the study period (2000-2016), after at least 1 year of age
measure: Risk of Hematological System general medical conditions
timeFrame: Diagnosed during the study period (2000-2016), after at least 1 year of age
measure: Risk of Cancers
timeFrame: Diagnosed during the study period (2000-2016), after at least 1 year of age
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: National Centre for Register-Based Research, Aarhus University
name: John J McGrath, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Momen NC, Plana-Ripoll O, Agerbo E, Benros ME, Borglum AD, Christensen MK, Dalsgaard S, Degenhardt L, de Jonge P, Debost JPG, Fenger-Gron M, Gunn JM, Iburg KM, Kessing LV, Kessler RC, Laursen TM, Lim CCW, Mors O, Mortensen PB, Musliner KL, Nordentoft M, Pedersen CB, Petersen LV, Ribe AR, Roest AM, Saha S, Schork AJ, Scott KM, Sievert C, Sorensen HJ, Stedman TJ, Vestergaard M, Vilhjalmsson B, Werge T, Weye N, Whiteford HA, Prior A, McGrath JJ. Association between Mental Disorders and Subsequent Medical Conditions. N Engl J Med. 2020 Apr 30;382(18):1721-1731. doi: 10.1056/NEJMoa1915784.