Existing Data Sources in Clinical Epidemiology: Database of Community Acquired Infections Requiring Hospital Referral in Eastern Denmark (DCAIED) 2018–2021

Figures & data

Table 1 Definitions of Sepsis

Sepsis 1 (1991)^Citation10

Systemic inflammatory response syndrome (SIRS): systemic inflammatory response to a variety of severe clinical insults:

Temperature >38°C or <36°C; heart rate >90 beats per min; respiratory rate >20 breaths per min or PaCO2 <32 mmHg; and white blood cell count >12,000/cu mm, <4000/cu mm, or >10% immature (band) forms

Sepsis is a systemic response to infection, manifested by two or more of the SIRS criteria as a result of infection.

Severe sepsis: Sepsis associated with organ dysfunction, hypoperfusion, or hypotension; hypoperfusion and perfusion abnormalities may include, but not limited to, lactic acidosis, oliguria, or an acute alteration in mental status or hypotension.

Septic shock: Sepsis-induced, with hypotension despite adequate fluid resuscitation along with the presence of perfusion abnormalities that may include, but not limited to, lactic acidosis, oliguria, or an acute alteration in mental status; patients who are receiving inotropic or vasopressor agents may not be hypotensive at the time that perfusion abnormalities are measured.

Sepsis 2 (2001)^Citation11

Infection: Documented or suspected and some of the following:

General parameters:

Fever (core temperature >38.3°C); hypothermia (core temperature <36°C); heart rate >90 beats per min or >2 SD above the normal value for age; tachypnea: respiratory rate >30 breaths per min; altered mental status; significant edema or positive fluid balance (>20 mL/kg−1 over 24 h). Hyperglycemia (plasma glucose >110 mg/dL−1 or 7.7 mML^−1) in the absence of diabetes

Inflammatory parameters:

Leukocytosis (white blood cell count >12,000/μL); leukopenia (white blood cell count <4000/μL); normal white blood cell count with >10% immature forms; plasma C-reactive protein >2 SD above the normal value; and plasma procalcitonin >2 SD above the normal value

Hemodynamic parameters:

Arterial hypotension (systolic blood pressure <90 mmHg, MAP <70 mmHg, or a systolic blood pressure decrease >40 mmHg in adults or <2 SD below normal for age, mixed venous oxygen saturation >70%, cardiac index >3.5 L min^−1 m^−2) Organ dysfunction parameters: Arterial hypoxemia (PaO2/FIO2 <300); acute oliguria (urine output <0.5 mL/kg^−1 h^−1 or 45 mM L^−1 for at least 2 h); creatinine increase ⩾0.5 mg/dL^−1; coagulation abnormalities (international normalized ratio >1.5 or activated partial thromboplastin time >60 s); ileus (absent bowel sounds); thrombocytopenia (platelet count <100,000 μL^−1) Hyperbilirubinemia (plasma total bilirubin >4 mg/dL^−1 or 70 mmol L^−1)

Tissue perfusion parameters:

Hyperlactatemia (>3 mmol/L^−1); decreased capillary refill or mottling

Sepsis 3 (2016)^Citation12

Sepsis is a life-threatening organ dysfunction caused by dysregulated host response to infection.

Clinical criteria for sepsis:

Suspected or documented infection and an acute increase of ≧2 SOFA points

The task force considered that positive qSOFA (quick SOFA) criteria should also prompt consideration of possible infection in patients not previously recognized as infected.

qSOFA criteria:

Altered mental status (GCS score <15)

Systolic blood pressure <100 mmHg

Respiratory rate >22 breaths per min

Septic shock is defined as a subset of sepsis in which underlying circulatory and cellular metabolism abnormalities are profound enough to substantially increase mortality.

Septic shock can be identified with a clinical construct of sepsis with persisting hypotension, requiring vasopressor therapy to elevate MAP ≥65 mmHg and lactate >2 mmol/L^−1 (18 mg/dL^−1) despite adequate fluid resuscitation

Table 2 Sequential Organ Failure Assessment (SOFA) score¹²

SOFA SCORE	Central Nervous System	Cardiovascular System	Respiratory System	Coagulation	Liver	Renal Function
Score	Glasgow Coma Scale	Mean Arterial Pressure OR Administration of Vasopressors Required	PaO2/FiO2 [mmHg (kPa)]	Platelets×10^3/μL	Bilirubin (mg/dl) [μmol/L]	Creatinine (mg/dl) [μmol/L] (or Urine Output)
0	15	MAP ≥70 mmHg	≥400 (53.3)	≥150	< 1.2 [<20]	<1.2 [<110]
1	13–14	MAP <70 mmHg	<400 (53.3)	<150	1.2–1.9 [20–32]	1.2–1.9 [110–170]
2	10–12	Dopamine ≤5 μg/kg/min or dobutamine (any dose)	<300 (40)	<100	2.0–5.9 [33–101]	2.0–3.4 [171–299]
3	6–9	Dopamine >5 μg/kg/min OR epinephrine ≤ 0.1 μg/kg/min OR norepinephrine ≤0.1 μg/kg/min	<200 (26.7) and mechanically ventilated including CPAP	<50	6.0–11.9 [102–204]	3.5–4.9 [300–440] (or <500 mL/day)
4	< 6	Dopamine > μg/kg/min OR epinephrine >0.1 μg/kg/min OR norepinephrine >0.1 μg/kg/min	<100 (13.3) and mechanically ventilated including CPAP	<20	> 12.0 [>204]	>5.0 [>440] (or <200 mL/day)

Table 3 Major Epidemiological Studies Reporting Sepsis Outcomes and Trends

Study	Country	Study Period	Criteria Used for Diagnosis	Setting/Population	Data Source	Incidence	Mortality
CDC, JAMA, 1990^Citation17	USA	1979–1987	Septicemia based on hospital discharge diagnoses	Nationwide	Administrative data: NHDS	73.6 to 175.9 per 100,000 (139% relative increase)	NA
Angus et al, Crit Care Med, 2001^Citation18	USA	1995	ICD-9-CM discharge codes	Acute hospitalization/Estimated nationwide	Administrative data: HCFA	300.0 per 100,000 population	In-hospital mortality: 28.6%
Martin et al, NEJM 2003^Citation19	USA	1979–2000	ICD-9-CM discharge codes	Hospitalization/Estimated nationwide	Administrative data: NHDS	82.7 to 240.4 per 100,000 population (8.7%, Estimated increase per year)	27.8% to 17.9%
Flaatten, Crit Care Lond Engl. 2004^Citation20	Norway	1999	ICD-10 discharge codes	Hospitalized/Nationwide	Administrative data: NPR	Sepsis: 149 per 100,000 population, Severe sepsis: 56 per 100,000 population	In-hospital mortality: Sepsis: 13.9%, Severe sepsis: 27%
Finfer et al, Intensive Care Med 2004^Citation21	Australian and New Zealand	1999	SEPSIS-1/PROWESS	ICU	Clinical Database	Severe Sepsis: 77 per 100,000 population (Estimated)	28-day mortality: 32.4%
Brun-Buisson et al, Intensive Care Med. 2004^Citation22	France	2001	Sepsis-1	ICU/Estimated nationwide	Clinical Database	Severe Sepsis: 95 per 100,000 population (Estimated)	30-day mortality: 35%
Esper et al, Crit Care Med, 2006^Citation23	USA	1979–2003	ICD-9-CM discharge codes	Hospitalization/Estimated nationwide	Administrative data: NHDS	Sepsis: 82.7 to 275.4 per 100,000 population, Severe sepsis: NA	In-hospital mortality: 20.3%
Harrison et al, Crit. Care Lond. Engl. 2006^Citation24	England, Wales, and Northern Ireland	1996–2004	PROWESS	ICU/Estimated nationwide	Clinical Database: ICNARC	Severe Sepsis 46 to 66 per 100,000 population (Estimated)	In-hospital mortality: 48.3–44.7% (Estimated decrease)
Dombrovskiy et al, Crit Care Med 2007^Citation25	USA	1993–2003	ICD-9-CM	Acute hospitalization/Estimated nationwide	Administrative data: NIS	Severe sepsis: 65.0 to 135.0 per 100,000 population (Estimated increase)	In-hospital mortality: 45.8% to 37.8% (Estimated decrease)
Wang et al, Crit Care Med 2007^Citation26	USA	2001–2004	ICD-9-CM discharge codes	ED/Estimated nationwide	Administrative data: NHAMCS	Severe Sepsis: 194.0 per 100,000 population	NA
Karlsson et al, Intensive Care Med. 2007^Citation27	Finland	2004–2005	Sepsis-1	ICU/Nationwide	Clinical Database	Severe Sepsis: 69.0 per 100,000 population	ICU mortality: 15.5% In-hospital Mortality: 28.3%
Wilhelms et al, Crit Care Med 2010^Citation28	Sweden	1987–2005	ICD-9/10	Nationwide	Administrative data: SHDR	Severe Sepsis: 10.0–35.0 per 100,000 population, 3.0–13.0 per 100,000 population, and 26.0–43.0 per 100,000 population (depending on method used, Estimated)	Severe Sepsis: In-hospital mortality: 22.1%, 22.4%, and 29.2% (depending on method used)
Kumar et al, Chest 2011^Citation29	USA	2000–2007	ICD-9-CM	Acute hospitalization/Estimated nationwide	Administrative data: NIS	Severe Sepsis: 143 to 343 per 100,000 population (Estimated increase)	In-hospital mortality: 39% to 27% (Estimated decrease)
Lagu et al, Crit Care Med 2012^Citation30	USA	2003–2007	ICD-9-CM	Acute hospitalization/Estimated nationwide	Administrative data: NIS	Severe Sepsis: 303 to 1074 per 100,000 population (depending on method used, Estimated)	In-hospital mortality: 14.0%
Gaieski et al, Crit Care Med 2013^Citation31	USA	2004–2009	ICD-9-CM	Acute hospitalization/Estimated nationwide	Administrative data: NIS	Severe Sepsis: 300 to 1031 per 100,000 population (depending on method used, Estimated)	In-hospital mortality: 14.7% and 29.9% (depending on method used), overall estimated decrease
Kaukonen et al, JAMA 2014^Citation32	Australia and New Zealand	2000–2012	Sepsis-1	ICU	Clinical Database: ANZICS	NA	Severe sepsis with and without shock (In-hospital mortality): 35.0% to 18.4%, (estimated decrease: 1.3% per year)
Bouza et al, BMC Infect Dis 2014^Citation33	Spain	2006–2011	ICD-9-CM	Nationwide	Administrative data: NMBD	Severe sepsis: 63.9 to 105.5 per 100,000 population (increase).	In-hospital mortality rate: 32.1 to 45.3 cases per 100,000 (decrease)
Kadri et al, Chest 2017^Citation34	USA	2005–2014	Clinical surveillance definition (concurrent vasopressors, blood cultures, and antibiotics) vs ICD-9-CM discharge codes	Acute hospitalization/Estimated nationwide	Clinical Database/EHR	Septic shock (Clinical Data): 1280 to 1860 per 100,000 population (average, 4.9% increase per year) Septic shock (ICD-9-CM): 670 to 1930 per 100,000 (19.8% increase per year)	Septic shock (in-hospital mortality, Clinical Data): 54.9% to 50.7% (estimated decrease), 48% to 39.3 Septic shock (in-hospital mortality, ICD-9-CM): 48.0% to 39.3% (estimated decrease)
Lee et al, J Infect 2017^Citation35	Taiwan	2002–2012	ICD-9-CM	Acute hospitalization/Nationwide	Administrative data: NHICD	Sepsis (severe sepsis and septic shock): 637.8 to 772.1 per 100,000 (relative increase: 21.1%)	Sepsis (In-hospital mortality): 23.3% to 17.9% (decrease), Septic shock (In-hospital mortality): 40.5% to 33.2% (decrease)
Rhee et al, JAMA 2017^Citation4	USA	2009–2014	Sepsis-3 (Clinical Criteria) vs ICD-9-CM discharge codes	ED/Estimated nationwide	Clinical Database/EHR	Sepsis (Clinical criteria): 6% (+0.6% relative change per year, not significant), Sepsis/Severe Sepsis/Septic Shock (ICD-9-CM): (+7.3% per year to +10.3% per year).	Sepsis (In-hospital mortality, clinical criteria): 15.6% (3.3% decrease per year) Sepsis (In-hospital mortality, ICD-9-CM): (7.0% decrease per year)
Rubens et al, J Intensive Care Med 2018^Citation36	USA	2005–2014	ICD-9-CM	ED/Estimated nationwide	Administrative data: NIS	541,694 to 1,338,905 (124% relative increase)	31.9% to 17.1% (46% relative decrease)
Fleischmann-Struzek et al, Crit Care Med 2018^Citation37	Germany	2010–2015	ICD-10-GM	Nationwide	Administrative data:	Sepsis: 280 to 370 per 100,000 population (5.7% increase per year), Severe sepsis: 108 to 158 per 100,000 population (7.9% increase per year)	Severe Sepsis/Septic shock: In-hospital mortality: 47.8 to 41.7%, decrease.
Oh SY et al, Crit Care Med 2019^Citation38	Korea	2007–2016	ICD-10	Nationwide	Administrative data: NHIS	173.8 to 233.6 per 100,000 population (increase)	30.9 to 22.6% (decrease)
Rudd et al, Lancet 2020^Citation2	Global	1990–2017	ICD-9 and ICD-10	Global estimates	Administrative data: GBD	Sepsis: 1074.7 to 677.5 per 100,000 population (Estimated decrease of 37.0%)	Sepsis (overall mortality): 148.1 per 100,000 population, (relative decrease 29.7%)

Note: Epidemiological studies of sepsis, severe sepsis and septic shock.

Abbreviations: ANZICS, Australian and New Zealand Intensive Care Society adult ICU patient database; GBD, Global Burden of Diseases, Injuries, and Risk Factors Study; ED, Emergency Department; EHR, electronic health record; HCFA, health care financing administration (USA); ICD-9-CM, Clinical Modification of the International Statistical Classification of Diseases – Ninth Revision; ICD-10, International Statistical Classification of Diseases – Tenth Revision; ICD-10-GM, ICD-10 German Modification; ICU, intensive care unit; ICNARC, Intensive Care National Audit & Research Centre; NMBD, national minimum basic data set (Spain); NA, not available; NHAMCS, National Hospital Ambulatory Medical Care Survey (USA); NHICD, National Health Insurance claims database (Taiwan); NIS, nationwide inpatient sample (USA); NHDS, National Hospital Discharge Survey (USA); NHIS, National Health Insurance Service (Korea); NPR, Norwegian Patient Registry; PROWESS, Protein C Worldwide Evaluation in Severe Sepsis (study of drotrecogin alfa); SHDR, Swedish Hospital Discharge Database.

Table 4 Definitions Used in the Database of Community: Acquired Infections in Eastern Denmark 2018–2022

		Criteria
A	Suspected infection (Presence of criteria 1 and/or 2)	1: Clinician obtained any specimens for culture from any anatomic site (irrespective of the result) or microbiological analyses
		2: Administered any duration of antimicrobial therapy within 24 h after arrival
B	Suspected Sepsis (Presence of both criteria 1 and 2)	1: Clinician obtained blood culture (irrespective of the result)
		2: Administered antimicrobial therapy within 24 h after arrival
C	Sepsis (Presence of both criteria 1 and 2)	1: Suspected Sepsis (Definition B)
		2: SOFA score of ≥2 points within 24 h of admission (Table 2).
D	Septic Shock (Presence of both criteria 1 and 2)	1: Sepsis (Definition C)
		2: Vasopressor to maintain MAP ≥65 mmHg and Serum lactate ≥18 mg/L, in the absence of hypovolemia

Abbreviations: MAP, mean arterial pressure; SOFA, Sequential Organ Failure Assessment.

Table 5 Variables Included in Database of Community Acquired Infections and Sepsis in Eastern Denmark (DCAISED)

Category	Description	Data Variable/Source^b
Demographic variables	Civil registration number	DCRS
	Age
	Gender
	Date of Birth
	Municipality of Residence
	Migration status
	Vital status
ED contact	Place of Admission (Department, Hospital, Region)	DNPR
	Date and time of hospitalization
	Date and time of first triage
	Reason for admission
	Referral type (referred by GP, ambulance, self-referral)^a
Diagnoses	Inpatient and outpatient diagnosis	DNPR
	Main diagnosis from the index hospital contact
	Discharge diagnoses.
Vital parameters	Systolic blood pressure (mmHg)	Triage/EWS
	Diastolic blood pressure (mmHg)
	Heart rate (beats/min)
	Saturation (%)
	Altered mental status (GCS/AVPU)
	Temperature (C)
Laboratory variables	Hemoglobin (g/L)	NPU system
	Leukocytes (× 10^9/L)
	Neutrophils (× 10^9/L)
	Lymphocytes (× 10^9/L)
	Thrombocytes/Platelets (× 10^9/L)
	CRP (mg/L)
	Creatinine (μmol/L)
	Bilirubin (μmol/L)
	INR
	Lactate (mmol/L)
Microbiological variables	Blood cultures	Microbiological laboratory information system (Site; Herlev)
	Sampling time
	Number of positive blood culture bottles
	Number of blood culture bottles inoculated
	Bacterial/fungal species and results from antimicrobial
	Susceptibility testing
	Respiratory samples:
	Gram stain and culture results, including species and antimicrobial susceptibility testing
	PCR results for atypical bacterial pathogens (Legionella spp., Mycoplasma pneumoniae, Chlamydia pneumoniae and Chlamydia psittaci)
	PCR results for respiratory viruses (SARS-CoV-2, influenza virus A and B, adenovirus, parainfluenza virus, respiratory syncytial virus, human metapneumovirus, and rhinovirus)
	Urine:
	Culture results, including species and antimicrobial susceptibility testing
	Urine antigen testing (Legionella pneumophila, Streptococcus pneumoniae)
	CSF
	Gram stain and culture results, including species and antimicrobial susceptibility testing
	PCR results from syndromic panels
	Other fluids and tissues
	Culture results, including species and antimicrobial susceptibility testing
	Swabs
	Anatomic localization
	Culture results, including species and antimicrobial susceptibility testing
Medication	Known medication upon ED arrival	ATC codes
	Medication administered during admission/hospitalization
	Time of prescription
	Medication dispensed
	Indication, strengths, volume, frequency	Unique code/unifier
Computational covariates	Comorbidity	ICD-10
	Cerebrovascular disease (ICD-10: I60–I69; G45; G46)
	Dementia (ICD-10: F00–F03; F05.1; G30)
	Chronic pulmonary disease (ICD-10: J40–J47; J60–J67; J68.4; J70.1; J70.3; J84.1; J92.0; J96.1; J98.2; J98.3)
	Connective tissue disease (ICD-10: M05; M06; M08; M09; M30; M31; M32; M33; M34; M35; M36; D86)
	Ulcer disease (ICD-10: K22.1; K25–K28)
	Mild liver disease (ICD-10: B18; K70.0–K70.3; K70.9; K71; K73; K74; K76.0)
	Diabetes I and II (ICD-10: E10.0, E10.1; E10.9, E11.0; E11.1; E11.9)
	Hemiplegia (ICD-10: G81; G82)
	Moderate-to-severe renal disease (ICD-10: I12; I13; N00–N05; N07; N11; N14; N17–N19; Q61)
	Diabetes with end organ (ICD-10: E10.2–E10.8; E11.2–E11.8)
	Any tumor (ICD-10: C00–C75)
	Leukemia (ICD-10: C91–C95)
	Lymphoma (ICD-10: C81–C85; C88; C90; C96)
	Moderate-to-severe liver disease (ICD-10: B15.0; B16.0; B16.2; B19.0; K70.4; K72; K76.6; I85)
	Metastatic solid tumor (ICD-10: C76–C80)
	Acquired immune deficiency syndrome (ICD-10: B21–B24)
	CCI (ICD-10 coded hospital discharge diagnoses from the previous 10 years)
	Low level of comorbidity (0)
	Moderate level of comorbidity (1–2)
	High (>2) level of comorbidity
	SOFA score	NPU/EWS/ATC
	Computed from six variables (each representing an organ system).
	Each organ system is assigned a point value from 0 (normal) up to 4 (severe degree of dysfunction/failure)
	Ranges from 0 to 24
	Site of organ failures	NPU/EWS/ATC
	Cardiovascular
	Renal
	Coagulation
	Hepatic
	CNS
	Respiratory
Outcome	30-day mortality	DCRS/DNPR
	90-day mortality
	365-day mortality
	Length of entire hospital contact (course)
	ICU length of stay
	ICU 30-day mortality
	Prevalence (presence of and type of infection, sepsis, septic shock)	ATC/ICD-10/microbiological laboratory information system

Notes: ^aSelf-referral: Patients attending the ED on their own initiative (without a referral from a GP or brought in by ambulance/prehospital service. ^bInformation from registries DCRS and DNPR are integrated in the electronic medical journal (EMS) provided by EPIC.

Abbreviations: ATC system, the Anatomical Therapeutic Chemical Classification System; AVPU scale, “alert, verbal, pain, unresponsive”; CCI, Charlson Comorbidity Index Score; DCRS, Danish Civil Registration System; DNPR, Danish National Patient Registry; ED, emergency department; EWS, early warning score; GCS score, Glasgow Coma Scale; GP, general practitioner; ICU, intensive care unit; ICD-10 codes, International Classification of Diseases, 10th revision; CNS, central nervous system; NPU system, International System of Nomenclature; INR, (international normalized ratio), Properties, and Units; SOFA score, Sequential Organ Failure Assessment score; SBT, systolic blood pressure.

Figure 1 (A) Overview of the five regions of Denmark (Total population ~ 5.8 million). (1) North Denmark Region (population ~0.6 million), (2) Central Denmark Region (population ~1.3 million), (3) Region of Southern (population ~1.2 million) Denmark, (4) Zealand Region (population ~0.8 million) and (5) Capital Region of Denmark (population ~1.8 million). The DCAIED database comprise all adult ED visits of patients (age ≥18 years) in whom an infection is suspected, and the background population are inhabitants living in Regions 4 and 5 (eastern part of Denmark). The EDs provide all together 24-h acute emergency care for 2.6 million inhabitants. Red dots represent EDs in the Zealand region. (B) Overview of the Capital Region of Denmark. EDs are represented by red (24-h acute emergency care) and blue dots (day-time acute emergency care). The municipalities highlighted by green color, and the EDs situated within, are served by the Department of Clinical Microbiology, Herlev.

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