Background
Methods
Study design and participants
Data collection and study variables
Identification of clinical warning signs predictive for mortality
Development and evaluation of predictive models
Results
Admission characteristics
Total SAM patients | Discharged | Died | P | |
---|---|---|---|---|
(n=780) | (n=653) | (n=127) | ||
Study related characteristics | ||||
Hospital stay (days), median (IQR) | 8.0 (6.0, 11.0) | 8 (6.0, 12.0) | 5 (3.0, 9.0) | <0.001 |
Study site, n (%) | ||||
Coast Provincial General Hospital | 290 (37.2) | 250 (38.3) | 40 (31.5) | |
Kilifi County Hospital | 179 (22.9) | 156 (23.9) | 23 (18.1) | |
Queen Elizabeth Central Hospital | 311 (39.9) | 247 (37.8) | 64 (50.4) | 0.03 |
Treatment arm of trial, n (%) | 390 (50.0) | 322 (49.3) | 68 (53.5) | 0.38 |
Demographic and anthropometric characteristics | ||||
Age in months, median (IQR) | 16.9 (10.8, 26.5) | 17.1 (11.0, 26.3) | 15.7 (10.1, 26.8) | 0.45 |
Age 6-59 months, n (%) | 738 (94.6) | 615 (94.2) | 123 (96.9) | 0.22 |
Male, n (%) | 420 (53.8) | 357 (54.7) | 63 (49.6) | 0.3 |
MUAC in cm (non-edematous), median (IQR) | n=534; 11.0 (10.4, 11.5) | n=454; 11.0 (10.5, 11.6) | n=80; 10.5 (9.5, 11.0) | <0.001 |
MUAC in cm, median (IQR) | 11.2 (10.5, 12.0) | 11.2 (10.5, 12.0) | 10.8 (9.8, 11.4) | <0.001 |
MUAC<10.5cm, n (%) | 192 (24.6) | 141 (21.6) | 51 (40.2) | <0.001 |
HAZ, median (IQR) | n=776; -3.0 (-4.3, -1.9) | n=124; -3.4 (-4.6, -2.0) | n=652; -2.9 (-4.2, -1.8) | 0.067 |
WAZ, median (IQR) | n=778; -3.9 (-4.9, -3.1) | n=651; -3.9 (-4.8, -3.0) | -4.5 (-5.4, -3.6) | <0.001 |
WHZ, median (IQR) | n=737; -3.5 (-4.2, -2.7) | n=617; -3.4 (-4.1, -2.6) | n=120; -3.9 (-4.7, -3.0) | <0.001 |
Comorbidities (observed upon admission only) | ||||
HIV status, n (%) | ||||
HIV- | 571 (73.2) | 507 (77.6) | 64 (50.4) | |
HIV+/exposed | 169 (21.7) | 122 (18.7) | 47 (37.0) | |
Refused testing/died before testing | 40 (5.1) | 24 (3.7) | 16 (12.6) | <0.001 |
Cerebral palsy, n (%) | 116 (14.9) | 99 (15.2) | 17 (13.4) | 0.61 |
Severe pneumonia, n (%) | 193 (24.7) | 153 (23.4) | 40 (31.5) | 0.054 |
Severe anemia, n (%) | 26 (3.3) | 22 (3.4) | 4 (3.1) | 0.9 |
Malaria, n (%) | 63 (8.1) | 57 (8.7) | 6 (4.7) | 0.13 |
Prevalence at admission of clinical signs observed daily | ||||
Chest indrawing, n (%) | 144 (18.5) | 105 (16.1) | 39 (30.7) | <0.001 |
Convulsions, n (%) | 37 (4.7) | 30 (4.6) | 7 (5.5) | 0.66 |
Diarrhea, n (%) | 328 (42.1) | 267 (40.9) | 61 (48.0) | 0.14 |
Fever, n (%) | 216 (27.7) | 180 (27.6) | 36 (28.3) | 0.86 |
Symptomatic hypoglycemia, n (%) | 13 (1.7) | 6 (0.9) | 7 (5.5) | <0.001 |
Hypothermia, n (%) | 43 (5.5) | 35 (5.4) | 8 (6.3) | 0.67 |
Nutritional edema, n/total non-missing (%) | 246/777 (31.6) | 47 (37.0) | 199/650 (30.6) | 0.13 |
Not able to complete feeds, n/total non-missing (%) | 450/773 (58.2) | 74/126 (58.7) | 376/647 (58.1) | 0.9 |
Reduced consciousness, n (%) | 24 (3.1) | 13 (2.0) | 11 (8.7) | <0.001 |
Shock, n (%) | 25 (3.2) | 16 (2.5) | 9 (7.1) | 0.007 |
Vomiting, n (%) | 215 (27.6) | 183 (28.0) | 32 (25.2) | 0.52 |
Survival outcome
Prevalence of clinical signs
Daily CWS predictive for mortality
Main analysis | Sensitivity analysis | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Full Mortality Model | Reduced Mortality Model | Reduced Discharge Model | Reduced Mortality Model: scenario 1 | Reduced Mortality Model: scenario 2 | ||||||
Extended Cox PH with daily clinical signsEvent=death; Censored=discharge | Extended Cox PH with indentified daily CWSEvent=death; Censored=discharge | Extended Cox PH with identified daily CWSEvent=discharge; Censored=death | Extended Cox PH with identified daily CWSSigns set to “not present” after dischargeEvent=death; Censored=discharge | Extended Cox PH with selected daily CWSSigns set to discharge value (not present/present) after dischargeEvent=death; Censored=discharge | ||||||
HR (95% CI) | P | HR (95% CI) | P | HR (95% CI) | P | HR (95% CI) | P | HR (95% CI) | P | |
A priori predictors (measured only at admission): | ||||||||||
MUAC | 0.79 (0.68–0.93) | 0.01 | 0.80 (0.68-0.93) | 0.004 | 1.16 (1.09–1.22) | <0.001 | 0.77 (0.65–0.92) | 0.003 | 0.78 (0.66–0.92) | 0.00 |
HIV status: | ||||||||||
HIV- | 1.00 (ref) | 1.00 (ref) | 1.00 (ref) | 1.00 (ref) | 1.00 (ref) | |||||
HIV+/exposed | 1.36 (0.86–2.16) | 0.19 | 1.29 (0.83–2.01) | 0.26 | 0.85 (0.69–1.04) | 0.11 | 1.53 (0.99–2.37) | 0.06 | 1.55 (1–2.41) | 0.05 |
Refused testing/died before testing | 7.74 (4.17–14.38) | <0.001 | 7.58 (4.18–13.74) | <0.001 | 1.24 (0.82–1.89) | 0.31 | 5.84 (3.64–9.35) | <0.001 | 5.83 (3.63–9.36) | <0.001 |
Potential predictors (measured only at admission): | ||||||||||
Study site: | ||||||||||
Coast Provincial General Hospital | 1.00 (ref) | 1.00 (ref) | 1.00 (ref) | 1.00 (ref) | 1.00 (ref) | |||||
Kilifi County Hospital | 1.22 (0.68–2.20) | 0.50 | 1.09 (0.60–1.97) | 0.77 | 0.94 (0.76–1.17) | 0.59 | 1.21 (0.71–2.06) | 0.48 | 1.14 (0.67–1.95) | 0.63 |
Queen Elizabeth Central Hospital | 3.09 (1.87–5.10) | <0.001 | 2.90 (1.81–4.63) | <0.001 | 2.59 (2.14–3.13) | <0.001 | 2.38 (1.53–3.71) | <0.001 | 2.39 (1.52–3.74) | <0.001 |
Trial arm | 1.07 (0.73–1.58) | 0.72 | ||||||||
Age | 1.01 (0.99–1.02) | 0.40 | ||||||||
Male | 1.19 (0.81–1.73) | 0.37 | ||||||||
Severe anemia | 0.92 (0.28–3.02) | 0.89 | ||||||||
Cerebral palsy | 1.07 (0.60–1.88) | 0.83 | ||||||||
Malaria | 0.92 (0.39–2.19) | 0.85 | ||||||||
Severe pneumonia | 1.14 (0.73–1.79) | 0.55 | ||||||||
Daily clinical signs | ||||||||||
Chest indrawing | 2.89 (1.81–4.60) | <0.001 | 2.94 (1.91–4.52) | <0.001 | 0.15 (0.06–0.36) | <0.001 | 3.26 (2.02–5.25) | <0.001 | 3.44 (2.14–5.53) | <0.001 |
Convulsions | 1.68 (0.71–3.98) | 0.24 | ||||||||
Diarrhea | 1.54 (1.03–2.32) | 0.04 | 1.54 (1.04–2.27) | 0.03 | 0.10 (0.05–0.17) | <0.001 | 1.83 (1.21–2.76) | 0.00 | 1.82 (1.21–2.72) | 0.00 |
Fever | 1.59 (0.97–2.59) | 0.06 | 1.52 (0.95–2.44) | 0.08 | 0.09 (0.04–0.19) | <0.001 | 1.95 (1.21–3.14) | 0.01 | 1.91 (1.19–3.09) | 0.01 |
Hypothermia | 1.11 (0.52–2.39) | 0.79 | ||||||||
Not able to complete feeds | 2.37 (1.54–3.65) | <0.001 | 2.50 (1.63–3.84) | <0.001 | 0.42 (0.32–0.55) | <0.001 | 3.58 (2.14–6.01) | <0.001 | 3.25 (2.01–5.27) | <0.001 |
Nutritional edema | 1.73 (1.03–2.88) | 0.04 | 1.66 (1.01–2.74) | 0.04 | 0.22 (0.15–0.33) | <0.001 | 2.12 (1.31–3.43) | 0.00 | 1.92 (1.21–3.06) | 0.01 |
Reduced conciousness | 6.89 (3.84–12.36) | <0.001 | 3.92 (1.88–8.15) | <0.001 | 0.39 (0.05–2.82) | 0.35 | 5.46 (3.54–8.42) | <0.001 | 5.65 (3.66–8.73) | <0.001 |
Shock | 1.35 (0.67–2.70) | 0.40 | ||||||||
Symptomatic hypoglycemia | 3.70 (1.73–7.88) | <0.001 | 4.18 (2.06–8.48) | <0.001 | 0.00 (0–Inf) | 0.99 | 2.90 (1.3–6.47) | 0.01 | 2.99 (1.32–6.75) | 0.01 |
Vomitting | 1.05 (0.65–1.70) | 0.85 | ||||||||
Reduced consciousness: timea | 1.15 (1.03–1.28) | 0.01 | ||||||||
Observations (n) | 6806 | 6852 | 6852 | 14381 | 14349 | |||||
Events (n) | 124 | 124 | 637 | 124 | 124 | |||||
P of PH-testb for mortality models | 0.84 | 0.45 | Not applicable | Not applicable | Not applicable |
Using CWS for daily mortality risk assessment
Predictive Model 1: Admission Score | Predictive Model 2: Daily Score | Predictive Model 3: Daily Count (among all 8 identified CWS) | Predictive Model 4: Daily Count among Top 5 CWS | |||||
---|---|---|---|---|---|---|---|---|
HR (95% CI) | P | HR (95% CI) | P | HR (95% CI) | P | HR (95% CI) | P | |
CWS (in order of importance, as determined by decreasing HR in Predictive Model 2) | ||||||||
1 Reduced conciousness | 3.6 (1.87–6.95) | <0.001 | 7.04 (4.25–11.67) | <0.001 | ||||
2 Symptomatic hypoglycemia | 3.65 (1.66–8.06) | 0.001 | 4.74 (2.47–9.11) | <0.001 | ||||
3 Chest indrawing | 1.93 (1.26–2.96) | 0.002 | 3.33 (2.18–5.09) | <0.001 | ||||
4 Not able to complete feeds | 0.71 (0.49–1.05) | 0.09 | 2.42 (1.58–3.7) | <0.001 | ||||
5 MUAC <10.5cma | 1.7 (1.18–2.45) | 0.005 | 1.82 (1.25–2.66) | 0.002 | ||||
6 Diarrhea | 1.46 (1.03–2.08) | 0.04 | 1.8 (1.23–2.62) | 0.002 | ||||
7 Nutritional edema | 1.59 (1.06–2.38) | 0.02 | 1.62 (1.01–2.59) | 0.047 | ||||
8 Fever | 0.89 (0.57–1.4) | 0.62 | 1.37 (0.88–2.15) | 0.16 | ||||
Counted number of CWSb | ||||||||
0 | 1.00 (ref) | 1.00 (ref) | ||||||
1 | 4.67 (1.8–12.15) | 0.002 | 3.44 (1.92–6.18) | <0.001 | ||||
2 | 7.06 (2.67–18.68) | <0.001 | 10.68 (5.83–19.56) | <0.001 | ||||
3 | 28.02 (10.84–72.46) | <0.001 | 46.51 (24.83–87.13) | <0.001 | ||||
>3 | 100.38 (39.13–257.51) | <0.001 | 177.29 (81.27–386.79) | <0.001 | ||||
Observations (n) | 770 | 6852 | 6852 | 6852 | ||||
Events (n) | 126 | 124 | 124 | 124 | ||||
C-index (95% CI)c | 0.69 (0.63–0.74 ) | 0.81 (0.77–0.86) | 0.79 (0.75–0.84) | 0.79 (0.74–0.84) |