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. 2020 Jul 22;15(7):e0236339. doi: 10.1371/journal.pone.0236339

The applicability of commonly used predictive scoring systems in Indigenous Australians with sepsis: An observational study

Josh Hanson 1,2,*, Simon Smith 1, James Brooks 3,4, Taissa Groch 5, Sayonne Sivalingam 3, Venessa Curnow 6, Angus Carter 3, Satyen Hargovan 3
Editor: Biswadev Mitra7
PMCID: PMC7375531  PMID: 32697796

Abstract

Background

Indigenous Australians suffer a disproportionate burden of sepsis, however, the performance of scoring systems that predict mortality in Indigenous patients with critical illness is incompletely defined.

Materials and methods

The study was performed at an Australian tertiary-referral hospital between January 2014 and June 2017, and enrolled consecutive Indigenous and non-Indigenous adults admitted to ICU with sepsis. The ability of the ANZROD, APACHE-II, APACHE-III, SAPS-II, SOFA and qSOFA scores to predict death before ICU discharge in the two populations was compared.

Results

There were 442 individuals enrolled in the study, 145 (33%) identified as Indigenous. Indigenous patients were younger than non-Indigenous patients (median (interquartile range (IQR) 53 (43–60) versus 65 (52–73) years, p = 0.0001) and comorbidity was more common (118/145 (81%) versus 204/297 (69%), p = 0.005). Comorbidities that were more common in the Indigenous patients included diabetes mellitus (84/145 (58%) versus 67/297 (23%), p<0.0001), renal disease (56/145 (39%) versus 29/297 (10%), p<0.0001) and cardiovascular disease (58/145 (40%) versus 83/297 (28%), p = 0.01). The use of supportive care (including vasopressors, mechanical ventilation and renal replacement therapy) was similar in Indigenous and non-Indigenous patients, and the two populations had an overall case-fatality rate that was comparable (17/145 (12%) and 38/297 (13%) (p = 0.75)), although Indigenous patients died at a younger age (median (IQR): 54 (50–60) versus 70 (61–76) years, p = 0.0001). There was no significant difference in the ability of any the scores to predict mortality in the two populations.

Conclusions

Although the crude case-fatality rates of Indigenous and non-Indigenous Australians admitted to ICU with sepsis is comparable, Indigenous patients die at a much younger age. Despite this, the ability of commonly used scoring systems to predict outcome in Indigenous Australians is similar to that of non-Indigenous Australians, supporting their use in ICUs with a significant Indigenous patient population and in clinical trials that enrol Indigenous Australians.

Introduction

Globally, sepsis is estimated to kill 11 million people every year, predominantly in low- and middle income countries [1]. Even in the well-resourced Australian health system, sepsis kills over 5000 people annually [2]. However, the case-fatality rate is not uniform across Australia [3]. This can be partly explained by differences in the complexity of patient care at different sites, but other factors also contribute and include patient age and demographics, the geographical location of the Intensive Care Unit (ICU), and the local prevalence of different pathogens [3].

In an effort to ensure that all Australians admitted to ICU are receiving high-quality care, predictive scoring systems are used to measure patients’ disease severity and determine their expected outcomes [4–8]. While these scores have limited utility in the management of individual patients, they can be used by institutions to benchmark ICU performance. They are also important in clinical trials where they can be used to help evaluate interventions by providing a measure of study patients’ disease severity. However, these scoring systems are most frequently derived and validated in metropolitan referral centres in high-income settings, their predictive ability may differ in other patient populations [9, 10].

Aboriginal and Torres Strait Islander people (hereafter respectfully referred to as Indigenous Australians) are disproportionately represented in Australian ICUs and sepsis is one of the most common indications for admission [11]. Several studies have examined the characteristics of undifferentiated cohorts of Indigenous Australians admitted to ICU, and have identified that they are younger, have greater comorbidity and live more frequently in remote locations [11–14]. While, the overall case-fatality rate of Indigenous Australians is similar to that of non-Indigenous Australians in these series, there has been limited examination of the comparative performance of predictive scoring systems in Indigenous patients [11–14]. This is important, because in some parts of the country, Indigenous Australians represent a significant proportion of ICU admissions [12, 13].

This study was performed to determine the applicability of commonly used predictive scoring systems in Indigenous Australians admitted to ICU with sepsis. It was hoped that the study might validate the use of these scoring systems in both Aboriginal and Torres Strait Islander Australians, which would support their use in future clinical sepsis trials enrolling Indigenous patients. It would also provide justification for their use in benchmarking the performance of ICUs with a greater proportion of Indigenous patients [15].

Materials and methods

This retrospective study used data collected in the ICU of Cairns Hospital, the only ICU in the Far North Queensland (FNQ) region. FNQ’s population of 279,354—approximately 17% of whom identify as Indigenous Australians—is dispersed across an area of 204,255 km2 [16].

Consecutive adults (≥ 18 years) admitted between 1 January 2014 and 30 June 2017 to the ICU with a primary admission diagnosis of sepsis (Acute Physiology and Chronic Health Evaluation (APACHE) III-J diagnostic codes 501–504: non-urinary sepsis, urinary sepsis, non-urinary sepsis with shock, and urinary sepsis with shock respectively) were eligible for the study. Demographic, clinical and laboratory data were collected and correlated with the patients’ clinical course. Comorbidities were said to be present if they were pre-existing and documented in the medical record (MetaVision®) These included a history of cardiovascular disease, respiratory disease, renal disease, haematological disease or malignancy, liver disease immunocompromise or diabetes mellitus. Hazardous alcohol consumption was defined as regular consumption of greater than 4 standard drinks/day [17]. The data were collected by 4 members of the research team (SH SS TG JB) who met regularly to confirm uniformity of documentation. If patients were admitted to ICU more than once during the study period, only their first admission was included in the analysis.

All individuals receiving care in Queensland’s public health system, are asked whether they identify as an Aboriginal Australian, a Torres Strait Islander Australian, both or neither. Commonly used disease severity prediction scores including the Australia and New Zealand Risk Of Death (ANZROD) score [4], the APACHE-II and APACHE-III scores [18], the Simplified Acute Physiology Score (SAPS) II score [19] and the quick Sequential Organ Failure Assessment (qSOFA) score [20] were calculated using variables collected at the time of ICU admission. The Sequential Organ Failure Assessment (SOFA) score was calculated using the worst values recorded in the first 24 hours of the ICU admission [8]. The scores’ ability to predict both death prior to ICU discharge and at 90 days was determined using the patient’s medical record and the Hospital Based Corporate Information System (HBCIS).

Statistical analysis

Data were de-identified, entered in an electronic database (S1 Dataset) and analysed using statistical software (Stata version 14.2). Groups were compared using the Kruskal-Wallis, Chi-square test or Fisher’s exact test where appropriate. Multivariate analysis was performed using backwards stepwise logistic regression. The Indigenous population was further examined by dividing the Indigenous population into those who identified as Aboriginal Australians and those who identified as Torres Strait Islander Australians. Those who identified as both, were not included in analyses comparing the two Indigenous populations.

The ability of the scores to predict death were determined by measuring the area under receiver operator characteristic (AUROC) curve [21]; the optimal cut-off for the tests for the different populations were determined using Liu’s method [22].

Ethics approval

Ethics approval was obtained from the Far North Queensland Human Research Ethics Committee (HREC/17/QCH/93/AMO2). As the data were retrospective and de-identified, the Committee waived the requirement for informed consent.

Results

There were 442 individuals admitted to ICU for sepsis, on 500 occasions, during the study period. Their median (interquartile range (IQR)) age at their first presentation was 59 (48–70) years, 238 (54%) were male. Of the 442 patients, 145 (33%) identified as Indigenous Australians, 94 (65%) identified as Aboriginal, 36 (25%) identified as Torres Strait Islanders, while 15 (10%) identified as both. Among the 442 patients, 416 (94%) were FNQ residents; Indigenous patients were more likely to reside in a rural or remote location than non-Indigenous patients (88/144 (61%) versus 128/272 (47%), p = 0.006).

Patient characteristics

Indigenous patients were younger than non-Indigenous patients (median (IQR): 53 (43–60) versus 65 (52–73) years, p = 0.0001) and were more likely to have a significant comorbidity (118/145 (81%) versus 204/297 (69%), p = 0.005).

Indigenous patients were more likely to have diabetes mellitus than non-Indigenous patients (odds ratio (OR): 4.7, 95% confidence interval (CI): 3.1–7.2), which contributed to a significantly greater burden of cardiovascular disease and renal disease (Table 1). Diabetes was more common in Torres Strait Islanders than Aboriginal Australians (27/36 (75%) versus 48/94 (51%), p = 0.01). No fewer than 32/145 (22%) Indigenous patients had a history of sepsis (hospitalisation with APACHE III-J diagnostic codes 501–504 prior to January 2014).

Table 1. Demographic characteristics and comorbidities of the cohort, stratified by Indigenous status.

Variable Indigenous n = 145 Non-Indigenous n = 297 p
Age 53 (43–60) 65 (52–73) 0.0001
Male gender 68 (47%) 170 (57%) 0.04
Residence in a remote location a 88/144 (61%) 128/272 (47%) 0.006
Inter-hospital transfer 56 (39%) 115 (39%) 0.98
Admitted from Emergency Department 44 (30%) 95 (32%) 0.73
Admitted from a nursing home 0 0 -
Planned admission after surgery 3 (2%) 2 (1%) 0.34
Admitted from hospital ward 42 (29%) 83 (28%) 0.82
Admission at night 94 (65%) 182 (61%) 0.47
Hazardous alcohol consumption 58 (40%) 53 (18%) <0.0001
Cigarette smoker 88 (61%) 134 (45%) 0.002
History of sepsis prior to the study period 32 (22%) 30 (10%) 0.001
History of cardiovascular disease 58 (40%) 83 (28%) 0.01
History of respiratory disease 31 (21%) 49 (17%) 0.21
History of renal disease 56 (39%) 29 (10%) <0.0001
History of haematological disease or malignancy 7 (5%) 29 (10%) 0.10
History of liver disease 18 (12%) 22 (7%) 0.09
History of diabetes mellitus 84 (58%) 67 (23%) <0.0001
History of metastatic cancer 6 (4%) 29 (10%) 0.04
Immunocompromised 9 (6%) 52 (18%) 0.001
Significant comorbidity 118 (81%) 204 (69%) 0.005
Body mass index 27 (22–33) 28 (24–33) 0.07
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Absolute numbers (%) or median (interquartile range) are presented.

a Only includes the 416 Far North Queensland residents.

While Indigenous patients, as a group, were more likely to have a history of hazardous alcohol or tobacco use, hazardous alcohol use was more common in the Aboriginal patients than in Torres Strait Islanders (49/94 (52%) versus 7/36 (9%) (p = 0.001). The difference in smoking rates between Aboriginal and Torres Strait Islanders failed to reach statistical significance (63/94 (67%) versus 18/36 (50%), p = 0.07). Other demographic characteristics of the cohort and their comorbidities—stratified by Indigenous status—are presented in Table 1.

Source of sepsis and microbiological characteristics

The commonest presumed source of sepsis was the respiratory tract, although skin and soft tissue infections (SSTI) were also common and occurred more frequently in Indigenous patients, particularly those with diabetes (31/41 (76%) Indigenous patients with a SSTI were diabetic, compared with 53/104 (51%) with another source, p = 0.007). Staphylococcus aureus was the most commonly isolated pathogen in the cohort and was responsible for 66 (15%) admissions; 13 (18%) of the isolates were methicillin resistant. In general, however, drug resistant pathogens and “tropical” pathogens were relatively uncommon (Table 2).

Table 2. Source and aetiology of the sepsis, stratified by Indigenous status.

Variable Indigenous n = 145 Non- Indigenous n = 297 p
Respiratory source 51 (35%) 97 (33%) 0.60
Genitourinary source 32 (22%) 64 (22%) 0.90
Bone/joint source 7 (5%) 6 (2%) 0.13
Central nervous system source 0 (0%) 6 (2%) 0.18
Skin/soft tissue source 41 (28%) 43 (14%) 0.0001
Abdominal source 13 (9%) 43 (14%) 0.10
Other source 10 (7%) 47 (16%) 0.01
Bacterial infection 103(71%) 194 (65%) 0.23
Gram negative bacteria 63 (43%) 131 (44%) 0.90
Gram positive bacteria 55 (38%) 84 (28%) 0.04
Fungal infection 7 (5%) 9 (3%) 0.42
Viral infection 10 (7%) 22 (7%) 0.85
Drug resistant organism 5 (3%) 11 (4%) 1.0
Bacteraemia 56 (39%) 128 (43%) 0.37
Polymicrobial infection 34 (23%) 46 (15%) 0.04
Escherichia coli 15 (10%) 44 (15%) 0.20
Staphylococcus aureus 26 (18%) 40 (13%) 0.22
Methicillin-resistant S. aureus 7 (5%) 6 (2%) 0.13
Pseudomonas aeruginosa 15 (10%) 28 (9%) 0.76
Klebsiella pneumoniae 9 (6%) 15 (5%) 0.66
Influenza A 5 (3%) 13 (4%) 0.80
Burkholderia pseudomallei 8 (6%) 8 (3%) 0.17
Streptococcus pyogenes 16 (11%) 9 (3%) 0.001
Leptospirosis 0 11 (4%) 0.02
Streptococcus pneumoniae 6 (4%) 10 (3%) 0.79
Pneumocystis jirovecii 2 (1%) 4 (1%) 1.0
Mycobacterium tuberculosis 0 1 (0.3%) 1
Plasmodium falciparum 0 1 (0.3%) 1
Rickettsia australis 1 (0.7%) 0 0.33
Vibrio vulnificus 1 (0.7%) 0 0.33
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Absolute numbers (%) presented.

Clinical and laboratory findings at presentation

Renal impairment and metabolic acidosis were more common among Indigenous patients, but other laboratory findings in the Indigenous and non-Indigenous patients were similar (Table 3).

Table 3. Clinical and laboratory findings at presentation, stratified by Indigenous status.

Variable Indigenous n = 145 Non- Indigenous n = 297 p
Heart rate (beats/min) 99 (89–118) 97 (81–114) 0.28
Systolic blood pressure (mmHg) 107 (94–118) 106 (94–122) 0.42
Mean arterial pressure (mmHg) 73 (66–82) 72 (65–83) 0.50
Temperature (°C) 36.8 (36.5–37.4) 36.9 (36.5–37.3) 0.53
Respiratory rate (breaths/min) 20 (17–26) 20 (16–25) 0.99
Glasgow Coma Score 15 (14–15) 15 (14–15) 0.98
Glucose (mmol/L) 6.9 (5.0–9.4) 6.6 (5.4–8.5) 0.96
Lactate (mmol/L) 1.8 (1.1–3.0) 1.7 (1.1–2.8) 0.29
pH 7.36 (7.24–7.42) 7.37 (7.30–7.43) 0.13
PaO2/FiO2 291 (194–398) 269 (158–375) 0.02
PaCO2 (mmHg) 34 (27–39) 34 (29–42) 0.0496
Bicarbonate (mmol/L) 18 (15–21) 20 (17–23) 0.001
Base excess (mmol/L) -6.2 (-10.9 to -2.8) -4.5 (-8.4 to -2.2) 0.004
Anion gap 9 (7–12) 9 (7–12) 0.44
Haemoglobin (g/dL) 100 (87–122) 111 (93–124) 0.007
White cell count (x109/L) 13.8 (9.3–21.9) 13.8 (7.9–22.2) 0.67
Neutrophils (x109/L) 10.7 (7.1–19.2) 11.6 (6.2–19.4) 0.80
Eosinophils (x109/L) 0 (0–0.1) 0(0–0) 0.001
Platelets (x109/L) 170 (111–257) 160 (101–236) 0.17
C-reactive protein (mg/L)) 165 (67–295) 172 (85–286) 0.57
Troponin I (ng/mL) 0.07 (0.04–0.39) 0.11 (0.04–0.43) 0.85
Prothrombin (seconds) 16 (14–21) 16 (14–18) 0.07
APTT (seconds) 39 (34–47) 36 (31–40) 0.0001
INR 1.5 (1.3–1.9) 1.4 (1.3–1.6) 0.03
Fibrinogen (g/L) 6.2 (4.6–8.3) 6.6 (4.9–8.2) 0.35
Total Bilirubin (μmol/L) 18 (12–31) 20 (13–31) 0.31
Conjugated bilirubin (μmol/L) 8 (4–19) 7 (4–15) 0.43
Albumin (g/L) 24 (20–27) 25 (22–29) 0.007
Protein (g/L) 58 (52–65) 52 (48–60) 0.0001
AST (IU/mL) 45 (21–104) 52 (27–106) 0.12
ALT (IU/mL) 25 (12–42) 35 (20–65) 0.0001
GGT (IU/mL) 41 (22–65) 51 (26–94) 0.01
ALP (IU/mL) 91 (69–134) 82 (57–119) 0.01
LDH (IU/mL) 333 (248–482) 329 (239–439) 0.43
Sodium (mmol/L) 133 (131–137) 135 (133–138) 0.0004
Potassium (mmol/L) 4.1 (3.6–4.8) 4.0 (3.7–4.5) 0.31
Chloride (mmol/L) 104 (99–109) 104 (100–108) 0.92
Creatinine (μmol/L) 162 (87–403) 118 (75–190) 0.0003
eGFR (ml/min/1.73m2) 29 (11–65) 49 (24–80) 0.0002
Calcium (mmol/L) 2.2 (2.1–2.3) 2.2 (2.1–2.3) 0.99
Magnesium (mmol/L) 0.73 (0.66–0.87) 0.75 (0.65–0.88) 0.48
Phosphate (mmol/L) 1.5 (1.0–2.0) 1.1 (0.9–1.5) 0.0001
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Median (Interquartile range) presented. PaO2/FiO2: ratio of arterial oxygen partial pressure (PaO2 in mmHg) to fractional inspired oxygen. PaCO2: arterial carbon dioxide partial pressure. APTT: activated partial thromboplastin time; INR: International normalised ratio; AST: aspartate aminotransferase; ALT: alanine aminotransferase; GGT: Gamma-glutamyl transferase; ALP: alkaline phosphatase; LDH: lactate dehydrogenase; eGFR: estimated glomerular filtration rate.

Intensive care support

The supportive care provided to the Indigenous and non-Indigenous patients in the ICU was similar (Table 4). While a greater proportion of Indigenous patients required renal replacement therapy (RRT), this did not reach statistical significance in this small sample (19/145 (13%) versus 27/297 (9%), p = 0.20).

Table 4. Intensive care support delivered to the cohort, stratified by Indigenous status.

Variable Indigenous n = 145 Non- Indigenous n = 297 p
Vasopressors on admission 102 (70%) 204 (69%) 0.72
Number of vasopressors required 1 (1–1) 1 (0–1) 0.89
Antibiotics administered on admission 142 (98%) 288 (97%) 0.56
Endotracheal intubation 28 (19%) 64 (22%) 0.59
Minute ventilation (Litres) 7.3 (5.8–8.8) 7.7 (6.6–9.0) 0.30
PICC line 40 (28%) 89 (30%) 0.61
Central venous line 61 (42%) 121 (41%) 0.79
Arterial line 122 (84%) 246 (83%) 0.73
Nasogastric feeding 28 (19%) 63 (21%) 0.64
Indwelling urinary catheter 117 (81%) 252 (85%) 0.27
Renal replacement therapy 19 (13%) 27 (9%) 0.20
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Absolute numbers (%) and median (interquartile range) presented. PICC: Peripherally inserted central catheter

Case-fatality rate

There were 55 deaths in the cohort prior to ICU discharge: 17/145 (12%) Indigenous patients compared with 38/297 (13%) non-Indigenous patients, p = 0.75. There were 14 (15%) deaths among the 94 Aboriginal Australians and 2 (6%) among the 36 Torres Strait Islander Australians (p = 0.23). There was one (7%) death among the 15 patients who identified as both Aboriginal and Torres Strait Islander Australians.

Patients that died before ICU discharge were older than those who survived (median (IQR): 62 (54–73) versus 59 (46–69 years), p = 0.01) and more likely to have a significant comorbidity (47/55 (85%) versus 275/387 (71%), p = 0.03). Among the 416 FNQ residents in the cohort, 29/50 (58%) living in a rural or remote location died compared with 187/366 (51%), with an urban address (p = 0.36). In a multivariate analysis model which included age, Indigenous status, significant comorbidity and remote or rural residence, only age had a statistically significant association with death (OR: 1.03 (95%CI): 1.01–1.05), p = 0.007).

After 90 days, 93/442 (21%) had died. Death at 90 days was linked to age (p = 0.0001), but not to Indigenous status (p = 0.26) or rural/remote residence (p = 0.29). Indigenous patients, however, died at a younger age than non-Indigenous patients (median (IQR): 56 (52–62) versus 68 (61–76) years, p = 0.0001).

Disease severity scores and their ability to predict death

The severity scores of the Indigenous and non-Indigenous patients were similar (Table 5). There was no statistically significant difference in the ability of the various severity scores to predict death in Indigenous and non-Indigenous patients (Tables 6 and 7). Among Indigenous patients, the ANZROD and APACHE-III scores had the highest AUROC curve (0.85 (95% CI: 0.77–0.92 and 0.84 (95% CI: 0.76–0.92), although these values were only statistically superior to that of the qSOFA scores (Tables 6 and 7). The very low case-fatality rate in the Torres Strait Islanders and relatively small sample size precluded meaningful comparison of the relative performance of the prediction scores in Aboriginal and Torres Strait Islanders.

Table 5. Severity score values on admission to ICU, stratified by Indigenous status.

Variable number Indigenous n = 145 Non- Indigenous n = 297 p
qSOFA 348 1 (1–2) 1 (1–2) 0.83
SOFA 378 9 (6–11) 8 (6–11) 0.20
ANZROD 430 0.24 (0.10–0.44) 0.23 (0.10–0.46) 0.86
APACHE-II 430 21 (15–26) 20 (15–26) 0.65
APACHE-III 430 70 (52–87) 69 (53–87) 0.87
SAPS-II 413 35 (25–51) 38 (28–58) 0.12
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Median (interquartile range) presented. qSOFA: quick SOFA score; SOFA: Sequential Organ Failure Assessment score; ANZROD: Australia and New Zealand Risk Of Death score; APACHE-II: Acute Physiology, Age, Chronic Health Evaluation-II score; and APACHE-III: Acute Physiology, Age, Chronic Health Evaluation-III score; SAPS-II: Simplified Acute Physiology Score.

Table 6. Performance of the severity scores in predicting death before ICU discharge, stratified by Indigenous status.

Severity score Number of Indigenous patients in whom the score could be calculated AUROC (95% CI) Optimal cut-off in Indigenous patients Number of Non- Indigenous patients in whom the score could be calculated AUROC (95% CI) Optimal cut-off in Non-Indigenous patients p
qSOFA 116 (80%) 0.71 (0.57–0.84) 2 232 (78%) 0.58 (0.46–0.70) 2 0.17
SOFA 120 (83%) 0.75 (0.64–0.87) 10 258 (87%) 0.72 (0.63–0.80) 10 0.62
ANZROD 138 (95%) 0.85 (0.77–0.92) 0.33 292 (98%) 0.79 (0.71–0.87) 0.35 0.32
APACHE-II 138 (95%) 0.78 (0.64–0.91) 30 292 (98%) 0.76 (0.67–0.84) 27 0.61
APACHE-III 138 (95%) 0.84 (0.76–0.92) 82 292 (98%) 0.79 (0.71–0.87) 88 0.37
SAPS-II 136 (94%) 0.80 (0.70–0.90) 46 277 (93%) 0.85 (0.78–0.92) 66 0.40
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qSOFA: quick SOFA score; SOFA: Sequential Organ Failure Assessment score; ANZROD: Australia and New Zealand Risk Of Death score; APACHE-II: Acute Physiology, Age, Chronic Health Evaluation-II score; and APACHE-III: Acute Physiology, Age, Chronic Health Evaluation-III score; SAPS-II: Simplified Acute Physiology Score.

Table 7. Performance of the severity scores in predicting 90-day mortality, stratified by Indigenous status.

Severity score Number of Indigenous patients in whom the score could be calculated AUROC (95% CI) Optimal cut-off in Indigenous patients Number of Non- Indigenous patients in whom the score could be calculated Non-Indigenous n = 297 Optimal cut-off in Non-Indigenous patients p
qSOFA 116 (80%) 0.66 (0.53–0.79) 2 232 (78%) 0.59 (0.50–0.68) 2 0.42
SOFA 120 (83%) 0.75 (0.64–0.85) 11 258 (87%) 0.66 (0.58–0.74) 9 0.22
ANZROD 138 (95%) 0.85 (0.79–0.92) 0.33 292 (98%) 0.78 (0.71–0.84) 0.29 0.09
APACHE-II 138 (95%) 0.74 (0.62–0.85) 30 292 (98%) 0.72 (0.65–0.79) 21 0.78
APACHE-III 138 (95%) 0.85 (0.78–0.92) 73 292 (98%) 0.77 (0.71–0.84) 75 0.13
SAPS-II 136 (94%) 0.78 (0.68–0.88) 36 277 (93%) 0.75 (0.69–0.82) 39 0.66
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qSOFA: quick SOFA score; SOFA: Sequential Organ Failure Assessment score; ANZROD: Australia and New Zealand Risk Of Death score; APACHE-II: Acute Physiology, Age, Chronic Health Evaluation-II score; and APACHE-III: Acute Physiology, Age, Chronic Health Evaluation-III score; SAPS-II: Simplified Acute Physiology Score.

Discussion

In this cohort of ICU patients with sepsis there were significant differences in the age, burden of comorbidities and source of infection between Indigenous and non-Indigenous individuals. However, the ability of commonly used disease severity scoring systems to predict mortality in the two populations was similar.

FNQ, in tropical Australia, shares a border with Papua New Guinea and has a unique blend of infectious diseases; it has the country’s highest incidence of leptospirosis and an increasing incidence of melioidosis and rickettsial disease [23–25]. The rates of methicillin-resistance in S. aureus isolates are among the highest reported in the country, while antibiotic resistance in other common pathogens is also increasing [26, 27]. The population is widely dispersed across a large geographical area and there are very limited specialist services outside the administrative hub of Cairns. It is a region which contains 3 of the 10 most socio-economically disadvantaged local government areas in the country, all 3 are communities with a predominantly Indigenous population [28]. It is the only part of Australia which has the homelands of both Aboriginal and Torres Strait Islander Australians, peoples that are frequently conflated but who are ethnologically quite distinct. All these factors might be expected to have implications for local patterns of sepsis, its presentation and its outcomes [15, 29–31]. However, while Indigenous patients were younger, more likely to live in a rural/remote location and more likely to have a significant comorbidity than non-Indigenous patients, the severity of their sepsis–as determined by commonly used predictive scoring systems was similar to that of non-Indigenous patients.

Although Indigenous Australians bear a greater burden of sepsis, there are surprisingly few studies that examine sepsis in the Indigenous population systematically. The demography and comorbidities in our series are very similar to that of a prospective study of sepsis in the Northern Territory, which also included patients that were not admitted to the ICU [15]. That study identified that Indigenous Australians were over-represented in the cohort, suffered disproportionately from diabetes and renal disease, and reported higher rates of smoking and hazardous alcohol use. Although APACHE-II and SOFA scores were collected in the study, the comparability of their performance in Indigenous and non-Indigenous populations was not presented.

While there are relatively few published data examining the ICU care of Australian Indigenous patients with sepsis specifically, there are several studies that have examined the clinical characteristics and outcomes of Indigenous patients admitted to ICU [11–14]. These studies are strikingly similar and show that, as in our cohort, Indigenous patients with critical illness are younger, have greater comorbidity and are more frequently admitted from remote locations than non-Indigenous patients. These studies also universally show that there is no difference in the proportion of Indigenous and non-Indigenous patients who die in the ICU. Whilst some authors have suggested that Indigenous deaths in ICU are therefore “healthcare preventable” [13], this represents a narrow view of healthcare, de-emphasising the primary holistic care that should prevent the hospitalisation in the first place. Whilst other authors have noted that there is “no mortality gap” between Indigenous and non-Indigenous Australians admitted to ICU [11], this overlooks the fact the Indigenous patients who are admitted to ICU are younger and are dying at a younger age. In an ICU series from the Northern Territory, 7% of both Indigenous and non-Indigenous patients admitted to the ICU died, but the Indigenous patients who died were much younger than their non-Indigenous counterparts (mean age of 45 versus 56) [12]. This pattern was seen in our series: although the proportion of Indigenous patients and non-Indigenous patients dying before ICU discharge was similar, the median age of death of Indigenous patients (56 years) was 12 years lower than that of the non-Indigenous patients. To close this gap, we need evidence-based strategies to address the unique challenges faced by Indigenous Australians in the country’s health system. Our study shows that predictive scoring systems are a valid way of measuring disease severity among Indigenous Australians with sepsis and can therefore be used to compare the efficacy of interventions with confidence.

Our study has many limitations. As a single centre study, it reflects only the experience of a unique part of Australia; the applicability of the results to the broader Indigenous patient population requires validation, although the similarity between the Indigenous population seen in this study and those in other locations is, as previously noted, striking [11–15]. The study was retrospective and examined only patients admitted to ICU and will therefore underestimate the true sepsis burden [32]. The sample size was relatively small, increasing the risk of a type II error.

Clearly there is still much to do to address the disparity in health outcomes between Indigenous and non-Indigenous Australians [31]. Once Indigenous Australians with sepsis enter ICU, they receive high quality care, but they are still dying at a much younger age than their non-Indigenous counterparts. Interventions at a community level including efforts to facilitate access to care, reduce crowding, enhance health literacy, improve sanitation and ensure appropriate nutrition are likely to be most helpful [33, 34]. At a primary health level optimising management of conditions like diabetes that predispose to sepsis and ensuring comprehensive vaccination, particularly for those at high risk are also likely to assist. Expanded programmes to assist with smoking cessation and encourage alcohol moderation are also essential [35, 36]. Community controlled health services which have a focus on prevention, early intervention and comprehensive care, may be the best suited to deliver this care [37, 38]. These services are frequently provided by members of the local community who have a greater understanding of the personal, community, and environmental factors influencing the health of the people and are therefore may be more likely to provide effective care [39].

However, even with optimal preventative interventions, patients will still require ICU care for sepsis. This study suggests that standard predictive scores predict outcomes in Indigenous patients as well as they do in non-Indigenous patients and therefore may be used in future studies to examine strategies to enhance the care of all Australians.

Supporting information

S1 Dataset

(XLSX)

Click here for additional data file. (381.4KB, xlsx)

Acknowledgments

The authors would like to acknowledge all the health workers who were involved in the care of the patients.

Data Availability

All relevant data are within the manuscript and its Supporting Information files.

Funding Statement

The authors received no specific funding for this work.

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Decision Letter 0

Biswadev Mitra

9 Jun 2020

PONE-D-20-14432

The applicability of commonly used predictive scoring systems in Indigenous Australians with sepsis: an observational study

PLOS ONE

Dear Dr. Hanson,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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Biswadev Mitra, MBBS, MHSM, PhD, FACEM

Academic Editor

PLOS ONE

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: I Don't Know

Reviewer #2: I Don't Know

Reviewer #3: I Don't Know

**********

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

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Reviewer #3: Yes

**********

5. Review Comments to the Author

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Reviewer #1: Thank you for the opportunity to review this important piece of work. The single centre retrospective study presents original research, not elsewhere reported, comparing the ability of several mortality predicting scoring tools to predict mortality in ICU and at 90 days in Aboriginal and Torres Strait Islander peoples and non-Indigenous Australians, with sepsis. The authors report a similar predictive ability of the ANZROD, APACHE II, APACHE III, SAPS 2, qSOFA and SOFA scores in predicting death in Indigenous and non-Indigenous patients with sepsis over a 3-4 year period.

I have made several comments for the authors to consider in the attached PDF manuscript file and it may be easier for the authors to review this as opposed to me listing all of the notations here, but I outline major concerns below, in addition to minor concerns (highlighted with comments in the attached PDF).

1. Taking into account the NHMRC guideline on ethical conduct in research with Aboriginal and Torres Strait Islander peoples and communities I am curious as to whether the authors are familiar with this document and/or whether any Aboriginal and/or Torres Strait Islander peoples or communities were involved in any aspect of the study or in drafting of the manuscript?

The six core guiding principles of this guideline are key to any research undertaken with Aboriginal and Torres Strait Islander people and communities, however it was not clear from the manuscript whether the authors have considered these principles:

• respects the shared values of Aboriginal and Torres Strait Islander Peoples

• is relevant for Aboriginal and Torres Strait Islander priorities, needs and aspirations

• develops long-term ethical relationships among researchers, institutions and sponsors

• develops best practice ethical standards of research.

I recommend the authors consider these guidelines and incorporate a reflection of how they have considered these guidelines into the manuscript; methods, results and discussion. If there has not been any consultation with Indigenous persons regarding the research, this is a major limitation (and justification for rejection of the manuscript) and should be added to the limitations within the discussion. I suggest, if the journal has not already done so, that they consider enlisting an Aboriginal and/or Torres Strait Islander researcher to review this article and provide comment from an Aboriginal and/or Torres Strait Islander perspective. I am happy to make recommendations of appropriate reviewers, if needed.

2. The authors state that the primary objective of the study was to compare mortality predicting scoring systems in Indigenous and non-indigenous Australians. However, I feel the methods and results also emphasize understanding important characteristics of the populations and comparisons of these populations and that this should be considered.

I would be happy to review an edited version of the manuscript should the journal be able to seek peer review from an Aboriginal and/or Torres Strait Islander researcher.

Reviewer #2: Although Aboriginal and Torres Strait Islander is longer to write it is the preferred terminology for Aboriginal and Torres Strait Islander people in Australia. Please change throughout the paper. Another preferred terminology that you might like to use is Australia's First Nation people.

Line 186 page 8

Please indicate what supportive care means

Line 221 page 10

Different font colour

Line 231 page 10

“It is the only part of Australia which has the homelands of both Aboriginal and Torres Strait Islander Australians, peoples that are frequently conflated but who are ethnologically quite distinct”

Has “conflated” been recognised and confirmed by the community members? This can’t be just assumed. If this has not had input from community members, please remove word from this sentence.

“ethnologically” This word is a derogative term please remove it.

This sentence needs rewording to capture Aboriginal and Torres Strait Islander people’s distinct cultural groups.

Reviewer #3: The information provided with this article is not new to anyone familiar with the health determinants of the Australian Indigenous population in North Australia.

However, I think it is important to publish this research as it will stress/reiterate the need for more research and also the feasibility of using scoring systems for comparison of patient for multicentre research as well as country wide and internationally.

**********

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: Yes: Ulrich Orda, NWHHS, James Cook University, Australia

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Decision Letter 1

Biswadev Mitra

2 Jul 2020

PONE-D-20-14432R1

The applicability of commonly used predictive scoring systems in Indigenous Australians with sepsis: an observational study

PLOS ONE

Dear Dr. Hanson,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Aug 16 2020 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

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  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Biswadev Mitra, MBBS, MHSM, PhD, FACEM

Academic Editor

PLOS ONE

[Note: HTML markup is below. Please do not edit.]

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Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: (No Response)

Reviewer #3: (No Response)

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Yes

Reviewer #3: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

Reviewer #3: I Don't Know

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

Reviewer #3: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

Reviewer #3: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: This is a very important subject for Aboriginal and Torres Strait Islander people and this manuscript has covered the subject well. The manuscript is well written and should be published.

Reviewer #3: I think there is a typo in line 278.

shouldn't it read: "... and have a significantLY HIGHER comorbidity ...

Two other comments with the second read of the revised subscription (not necessarily for correction but if a revision is requested to consider:

1) The title of the manuscript focusses on predictive scoring systems.

The conclusion however discusses in its first sentence the case fatality and that the Indigenous patients die at a younger age. Whilst this is a very important fact / statement (and not new), this was not the question of this study. The conclusion in regard to the question of the study is mentioned (like a dependend variable) in the second sentence / statement. Would it be worth to swab them?

2) I still think that from 2014 - 2017 Cairns Hospital was NOT addressed as a Tertiary Hospital but as a retrieval "base" hospital. This is reflected by the CSCF (and also the ACEM accreditation for their Emergency Department) I know that there is a recent push / move towards addressing Cairns Hospital as a Tertiary facility (despite the lack of especially neurosurgery and cardiothoracic surgery)- but this was definitely not applicable at the time where the study data were collected,

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

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Reviewer #2: No

Reviewer #3: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PLoS One. 2020 Jul 22;15(7):e0236339. doi: 10.1371/journal.pone.0236339.r004

Author response to Decision Letter 1

2 Jul 2020

The response to the reviewers is also provided as colour coded word document in the submission

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: (No Response)

Reviewer #3: (No Response)

________________________________________

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Yes

Reviewer #3: Yes

Response: We are happy that the reviewers believe that the manuscript is technically sound.

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

Reviewer #3: I Don't Know

Response: We are happy that the reviewers have not raised any concerns about the statistical analysis.

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4. Have the authors made all data underlying the findings in their manuscript fully available?

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Reviewer #2: Yes

Reviewer #3: Yes

Response: We are happy that the reviewers have had the opportunity to review all the data supporting our study.

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

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Reviewer #2: Yes

Reviewer #3: Yes

Response: We are happy that the reviewers have found our manuscript intelligible.

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6. Review Comments to the Author

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Reviewer #2: This is a very important subject for Aboriginal and Torres Strait Islander people and this manuscript has covered the subject well. The manuscript is well written and should be published.

Response: We are happy that reviewer #2 has recommended publication of our manuscript.

Reviewer #3: I think there is a typo in line 278.

shouldn't it read: "... and have a significantLY HIGHER comorbidity ...

Response: We agree with the reviewer that the sentence was poorly constructed and contained an additional typographic error. We have amended it in the revised manuscript (lines 277-278).

Two other comments with the second read of the revised subscription (not necessarily for correction but if a revision is requested to consider:

1) The title of the manuscript focusses on predictive scoring systems.

The conclusion however discusses in its first sentence the case fatality and that the Indigenous patients die at a younger age. Whilst this is a very important fact / statement (and not new), this was not the question of this study. The conclusion in regard to the question of the study is mentioned (like a dependend variable) in the second sentence / statement. Would it be worth to swab them?

Response: We understand the point that the reviewer is making here. The focus of the study was severity scores, so the reviewer is suggesting that severity scores be mentioned in the first line of the conclusion.

This is largely a question of style, however we would also argue that

1. As death is the dependent variable for prediction scores, it makes sense to describe the variable in more detail, to address the possibility of confounding factors.

2. As the reviewer notes this is an important fact and while sadly not a new observation for Australian readers, it will help the International reader - who may not be familiar with this information – in their interpretation of our findings.

2) I still think that from 2014 - 2017 Cairns Hospital was NOT addressed as a Tertiary Hospital but as a retrieval "base" hospital. This is reflected by the CSCF (and also the ACEM accreditation for their Emergency Department) I know that there is a recent push / move towards addressing Cairns Hospital as a Tertiary facility (despite the lack of especially neurosurgery and cardiothoracic surgery)- but this was definitely not applicable at the time where the study data were collected

Response: We understand the point that the reviewer is making here. However we would argue that a hospital with advanced diagnostics (MRI, PET scanning, molecular laboratory) and which has over 500 beds (including adult and neonatal ICU) and which provides specialist medical, surgical, psychiatric, obstetric, paediatric and cancer care (including radiotherapy) is a tertiary referral hospital.

It would appear to satisfy most definitions of the term.

https://en.wikipedia.org/wiki/Tertiary_referral_hospital

It is true that there is no neurosurgery or cardiothoracic surgery but many of the authors have trained in metropolitan tertiary centres in Australia which have no paediatric, obstetric or neonatal facilities and yet they would still be recognised as tertiary centres.

We think that most practicing clinicians would understand what a tertiary centre is and would agree with our assessment. We feel that this is more than a semantic argument; it is is important that the reader can understand the context of the patient’s care and the impact that this might have had on the mix of patients in the ICU and their case-fatality rates (the dependent variable for the severity scores).

We will leave it to the Editor to adjudicate. If the Editor were unpersuaded by our arguments, we would be happy for the abstract which currently reads as

The study was performed at an Australian tertiary-referral hospital between January 2014 and June 2017, and enrolled consecutive Indigenous and non-Indigenous adults admitted to ICU with sepsis.

To be replaced with

The study was performed at Cairns Hospital, in tropical Australia, between January 2014 and June 2017, and enrolled consecutive Indigenous and non-Indigenous adults admitted to ICU with sepsis.

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Decision Letter 2

Biswadev Mitra

7 Jul 2020

The applicability of commonly used predictive scoring systems in Indigenous Australians with sepsis: an observational study

PONE-D-20-14432R2

Dear Dr. Hanson,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Biswadev Mitra, MBBS, MHSM, PhD, FACEM

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Acceptance letter

Biswadev Mitra

9 Jul 2020

PONE-D-20-14432R2

The applicability of commonly used predictive scoring systems in Indigenous Australians with sepsis: an observational study

Dear Dr. Hanson:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

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Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Prof. Biswadev Mitra

Academic Editor

PLOS ONE

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