Table 2 Study and population characteristics: case-control studies

Henriksen 2015b [43] Denmark

Study setting: medical ED, ICU, community-based

Case definition: sepsis (non-severe), severe sepsis, or septic shock according to the ACCP/SCCM criteria.

Data electronically extracted from the patient’s records and validated by trained data. All admissions were manually reviewed. Predefined risk factors retrieved from several population-based registers

Control definition: all adults (≥15 years) with residence in the hospital catchment-area (N = 235,598) during the study period who had not been hospitalized up to 7 days before the index date.

Geographic scope: city/municipal

Recruitment years: September 1, 2010 to August 31, 2011

Criteria for COS: Patient had an infection at arrival within the first 48 hours after admission

Inclusion criteria (cases): All adults (≥15 years) admitted to the medical ICU or ED.

Inclusion criteria (controls): see controls definition and criteria

Exclusion criteria: cases with a prior hospitalization up to 7 days before the current admission. Patients transferred from other hospitals, patients residing outside the hospitals catchment-area at the time of admission and patients who were unidentified throughout the entire course of admission

N cases: 1,713 sepsis of any severity (n=621 non-severe sepsis, n=1,071 severe sepsis, and n=21 septic shock)

N controls: 227,054

Jovanovich 2014 [44] The USA

Study setting: tertiary-level care centres and small clinics and hospitals

Case definition: adults hospitalized for sepsis or severe sepsis; ICD-9 codes (995.91, 995.92)

Electronic health and administrative data

Control definition: randomly selected adult patients without sepsis diagnosis admitted within the same time period and matched 1:1 with cases by age, sex, race, and season of 25(OH)D measurement

Geographic scope: Inter-State (Utah and Idaho)

Criteria for COS: community-living adults

Inclusion criteria (cases): NR

Inclusion criteria (controls): NR

Recruitment years: 1 January 2008 and 31 December 2010

Exclusion criteria: NR

N cases: 211

N controls: 211

Legras 2009 [45] France

Study setting: ICU, hospital ward

Case definition: the ACCP/SCCM criteria was used (severe sepsis or septic shock)

Medical histories and data on previous prescriptions obtained from relatives and general practitioner. NSAID use was quantified by listing all the drugs taken during the observation period, and standard interviews were conducted by physicians

Geographic scope: regional

Control definition: Participants admitted to hospital for mild bacterial infection (without severe sepsis or septic shock)

Recruitment years: February 2004 to November 2005

Criteria for COS: Community-acquired (NR)

Inclusion criteria (cases): Participants >15 years admitted to an ICU with community-onset severe sepsis or septic shock

Inclusion criteria (controls): Participants admitted to hospital for mild bacterial community-acquired (non-sepsis) infection

Exclusion criteria: chronic kidney failure (creatinine clearance <30 ml/min), pregnancy, nosocomial infection, or congenital/acquired immunosuppression (defined as the presence of metastatic neoplasia, haemopathy, aplasia before the onset of sepsis), AIDS (independently of CD4+ T-cell count) and chronic administration of immunosuppressive treatments

N cases: n=152 (n=34 sever sepsis; n=118 septic shock)

N controls: 152

Wang 2013c [39] REGARDS-sepsis case-control study The USA

Study setting: community-based, hospital, ED

Case definition: laboratory confirmed infection plus ≥ 2 SIRS criteria

Structured interviews, in-home visits, lab results, monitoring every 6 months, medical and hospital admission records (clinical and lab data); blood samples collected from fasting subjects at their homes

Control definition: hospitalized for a serious infection (but did not meet sepsis criteria)

Criteria for COS: cohort of community-dwelling individuals. Presentation to the hospital consisted of the time of Emergency Department triage or admission to inpatient unit (for participants admitted directly to the hospital). To allow for acute changes in the participant's condition during early hospitalization, we used vital signs and laboratory test results for the initial 28 h of hospitalization. Our study focused on individuals presenting to the hospital or ED with community-acquired sepsis. We did not include “hospital-acquired” sepsis developing at later points of hospitalization

Geographic scope: Nationwide

Recruitment years: January 2003- October 2007

Inclusion criteria (cases): Patients hospitalized for sepsis during the observation period were eligible.

Inclusion criteria (controls): Individuals with serious infection who did not experience a hospitalization for sepsis, matching for age (±5 years), sex, and time epoch

Exclusion criteria: individuals hospitalized for conditions unrelated to infections

N cases: 162

N controls: 162