Case Selection
Selection of participants for inclusion in the study is displayed in Fig. 1. Cases were excluded based on missing key data, lacking a diagnosis of AN, not being accepted for treatment or not attending treatment, not residing in the local are or moving during treatment to another service and having a physical health comorbidity that affected treatment. Remaining cases were assessed on physical risk, and those identified as being at high risk of deterioration and of developing refeeding syndrome were included. Two groups were created and included in final analysis: an inpatient and outpatient group.
Characteristics of Groups
Descriptive statistics, shown in Table 1, carried out on inpatient and outpatient groups revealed that baseline mean age, weight, BMI and percentage median BMI and intake were all lower amongst the inpatient group. Mean temperature was the same across both groups and mean weight loss was higher in the inpatient group. Mean QTc interval was shorter for the inpatient group, whilst heart rate was higher on average.
Descriptive statistics carried out on baseline blood results for both groups, shown in Table 1, showed that mean baseline blood results for all markers except neutrophils were lower in inpatients group compared to those of outpatients.
Out of all cases, only one inpatient (1.7%) had hypophosphatemia at baseline (0.11 mmol/L). This same case was the only one to have hypophosphatemia at time 1 (0.63 mmol/L). Despite having a low phosphate at baseline and time 1, phosphate did not drop further on refeeding and had increased to within the reference range by time 2 (1.46 mmol/L). No cases had hypophosphatemia at time 2, the end of the refeeding period.
Comparison of characteristics between groups before refeeding.
Baseline characteristics of inpatients and outpatients were compared to determine if any significant differences existed between groups on initial assessment (see Table 1).
Baseline blood results; magnesium, potassium and calcium in the inpatient group were found to be significantly lower those of the outpatient group (magnesium: t (56) = -3.39, p < 0.001, potassium: t (57) = -2.12, p = 0.04 and calcium: t (56) = -2.31, p = 0.02), with a difference of 0.06, 0.2 and 0.04 mmol/L. However, none of these markers were below reference ranges in either group (see Table 1 and Table 2).
Mean age, weight loss, intake, phosphate and GGT also differed significantly between groups. Mean age, intake, phosphate and GGT were lower in the inpatient group, whilst weight loss was higher when compared with outpatients, shown in Table 1 and Table 2.
Comparison of characteristics between groups during refeeding.
Mean characteristics of the two groups were again compared at time 1, after initiation of feeding, to determine if any significant differences existed between inpatient and outpatient groups, that may be related to the refeeding protocol used in either treatment setting. Results are displayed in Table 1 and Table 2.
Significant differences were found between various mean blood markers (potassium, phosphate, magnesium and white cell count) and mean daily intakes between groups, with all variables being significantly lower amongst the inpatient group when compared with outpatients, (potassium: t (52) = -4.59, p < 0.001, phosphate: t (53) = -2.52, p = 0.015, magnesium: t (52) = -3.32, p = 0.002, white cell count: U = 169.5, p = 0.044, daily intake: U = 120, p < 0.001).
Comparison of characteristics between groups at the end of refeeding.
Mean characteristics were, once again, compared between the two groups at time 2, to identify if any significant differences existed by the end of the refeeding period in either treatment setting, results are shown in Table 1 and Table 2.
Mean heart rate was significantly lower amongst the outpatient group compared to the inpatient group, (t (24) = 2.22, p = 0.036). Mean potassium and magnesium were shown to be significantly lower in inpatients compared with outpatients, (potassium: t (39) = -3.29, p = 0.002 and magnesium: t (37) = -3.75, p = 0.001).
Table 1
Comparison between inpatient and outpatient groups for cardiovascular, anthropometric and nutrition variables at baseline, time 1 and time 2 of refeeding.
| Baseline | Time 1 | Time 2 |
Characteristic | Inpatients (n = 19) | Outpatients (n = 40) | P Value | Inpatients (n = 19) | Outpatients (n = 40) | P Value | Inpatients (n = 19) | Outpatients (n = 40) | P Value |
Age, years | 13.6 ± 1.5 | 14.7 ± 1.8 | 0.033 | - | - | - | - | - | - |
Weight, kg | 39.4 ± 7.8 | 42.5 ± 7.9 | 0.170 | 39.4 ± 7.8 | 42.7 ± 7.9 | 0.152 | 41.5 ± 8.3 | 43.7 ± 7.7 | 0.322 |
Height, cm | 161.2 ± 9.6 | 162.9 ± 8.4 | 0.489 | - | - | - | - | - | - |
BMI, kg/m2 | 15.1 ± 1.8 | 15.9 ± 2.2 | 0.180 | 15.1 ± 1.8 | 15.9 ± 2.2 | 0.176 | 15.9 ± 1.6 | 16.5 ± 2.1 | 0.368 |
mBMI, % | 78.1 ± 9.1 | 79.9 ± 10.3 | 0.533 | 78 ± 9.1 | 81 ± 11 | 0.303 | 81.6 ± 8.5 | 82.3 ± 9.7 | 0.622 |
Weight loss, kg | 0.86 ± 0.7 | 0.38 ± 0.7 | 0.003 | - | - | - | - | - | - |
Intake, kcal/d | 374 ± 205 | 621 ± 348 | 0.001 | 1331 ± 309 | 1500 ± 0 | < 0.001 | 2321 ± 322 | 2437 ± 202 | 0.094 |
Temperature, ˚C | 36.5 ± 0.7 | 36.5 ± 0.5 | 0.559 | 36.4 ± 0.2 | 36.5 ± 0.2 | 0.936 | 36.5 ± 0.1 | 36.4 ± 0.4 | 0.231 |
QTc, ms | 396 ± 25 | 397 ± 20 | 0.198 | 407 ± 9 | 405 ± 30 | 0.885 | 400 ± 0 | 389 ± 3 | 0.333 |
Heart rate, bpm | 66 ± 24 | 60 ± 18 | 0.172 | 57 ± 12 | 59 ± 12 | 0.628 | 66 ± 14 | 55 ± 12 | 0.036 |
Glucose, mmol/L | 4.4 ± 1.1 | 4.6 ± 1.2 | 0.573 | 4.6 ± 1.2 | 3.3 ± 0.7 | 0.054 | 4.2 ± 0.4 | 3.2 ± 1.7 | 0.271 |
Phosphate, mmol/L | 1.1 ± 0.3 | 1.2 ± 0.2 | 0.011 | 1.2 ± 0.2 | 1.3 ± 0.1 | 0.015 | 1.4 ± 0.2 | 1.3 ± 0.2 | 0.140 |
Magnesium, mmol/L | 0.87 ± 0.1 | 0.93 ± 0.1 | 0.001 | 0.82 -± 0.1 | 0.89 ± 0.1 | 0.002 | 0.82 ± 0.1 | 0.9 ± 0.1 | 0.001 |
Potassium, mmol/L | 3.9 ± 0.4 | 4.2 ± 0.3 | 0.035 | 3.8 ± 0.5 | 4.3 ± 0.4 | < 0.001 | 4.1 ± 0.4 | 4.4 ± 0.4 | 0.002 |
Calcium, mmol/l | 2.2 ± 0.1 | 2.2 ± 0.1 | 0.024 | 2.2 ± 0.1 | 2.2 ± 0.1 | 0.264 | 2.2 ± 0.1 | 2.2 ± 0.1 | 0.521 |
WCC, 109/L | 4.9 ± 1.5 | 5 ± 1.1 | 0.816 | 4.3 ± 1.6 | 5.2 ± 1.4 | 0.022 | 4.7 ± 1.3 | 5.2 ± 1.4 | 0.344 |
Neutrophils, 109/L | 2.7 ± 1.4 | 2.7 ± 0.9 | 0.328 | 2.1 ± 1 | 2.5 ± 1 | 0.086 | 2.4 ± 0.8 | 2.6 ± 1.1 | 0.496 |
AST, units/L | 22 ± 4 | 27 ± 8 | 0.035 | 26 ± 18 | 25 ± 9 | 0.300 | 23 ± 12 | 26 ± 7 | 0.421 |
GGT, units/L | 9 ± 4 | 14 ± 7 | 0.004 | 9 ± 3 | 13 ± 7 | 0.056 | 9 ± 5 | 13 ± 7 | 0.060 |
Data are mean ± SD. P values represent comparisons between inpatient and outpatient groups obtained from independent-sample t test and Mann-Whitney u test. Time 1 represents data from days 2–5 of refeeding and Time 2 represents data from days 7–10 of refeeding. BMI, body mass index; mBMI, median BMI for height and gender; WCC, white cell count; AST, aspartate aminotransferase; GGT, gamma-glutamyl transpeptidase. P < 0.05 indicates significance. |
Table 2
Comparison between inpatient and outpatient groups for cardiovascular, anthropometric and nutrition variables at baseline, time 1 and time 2 of refeeding; test statistics, confidence intervals and significance values.
| | | Baseline | Time 1 | Time 2 |
Characteristic | t/Z* value | 95% CI | P Value | t/Z* value | 95% CI | P Value | t/Z* value | 95% CI | P Value |
Age, years | -2.124* | - | 0.033 | - | - | - | - | - | - |
Weight, kg | -1.139 | -7.46, 1.34 | 0.170 | -1.456 | -7.86, 1.26 | 0.152 | -1.000 | -6.69, 2.24 | 0.322 |
Height, cm | -0.696 | -6.61, 3.2 | 0.489 | - | - | - | - | - | - |
BMI, kg/m2 | -1.357 | -1.92, 0.37 | 0.180 | -1.373 | -2.03, 0.38 | 0.176 | -0.900* | - | 0.368 |
mBMI, % | -0.626 | -7.25, 3.79 | 0.533 | -1.041 | -9.1, 2.89 | 0.303 | -0.502* | - | 0.622 |
Weight loss, kg | -2.921* | - | 0.003 | - | - | - | - | - | - |
Intake, kcal/d | -2.921* | - | 0.001 | -5.577* | - | < 0.001 | -1.674* | - | 0.094 |
Temperature, ˚C | -0.595* | - | 0.559 | -0.068* | - | 0.936 | -1.522* | - | 0.231 |
QTc, ms | -0.858* | - | 0.198 | 0.149 | -27.7, 31.5 | 0.885 | -1.633* | - | 0.333 |
Heart rate, bpm | -0.958* | - | 0.172 | -0.489 | -9.64, 5.89 | 0.628 | 2.224 | 0.83, 22.2 | 0.036 |
Glucose, mmol/L | -0.568 | -1.09, 0.61 | 0.573 | -4.887* | - | 0.054 | 1.140 | -0.83, 2.78 | 0.271 |
Phosphate, mmol/L | -2.262* | - | 0.011 | -2.524 | -0.23,-0.03 | 0.015 | 1.507 | -0.03, 0.20 | 0.140 |
Magnesium, mmol/L | -3.387 | -0.09,-0.03 | 0.001 | -3.326 | -0.1, -0.03 | 0.002 | -3.754 | -0.12, -0.04 | 0.001 |
Potassium, mmol/L | -2.166 | -0.39, -0.02 | 0.035 | -4.589 | -0.75,-0.29 | < 0.001 | -3.285 | -0.60, -0.14 | 0.002 |
Calcium, mmol/l | -2.312 | -0.08, -0.01 | 0.024 | -1.129 | -0.05, 0.01 | 0.264 | 0.648 | -0.03, 0.05 | 0.521 |
WCC, 109/L | -0.234 | -0.78, 0.62 | 0.816 | -2.015* | - | 0.022 | -0.960 | -1.36, 0.49 | 0.344 |
Neutrophils, 109/L | -0.455* | - | 0.328 | -1.375* | - | 0.086 | -0.689 | -0.86, 0.43 | 0.496 |
AST, units/L | -1.818* | - | 0.035 | -0.534* | - | 0.300 | -0.815 | -8.52, 3.64 | 0.421 |
GGT, units/L | -2.637* | - | 0.004 | -1.595* | - | 0.056 | -1.899* | - | 0.060 |
*P values represent significance of comparisons between inpatient and outpatient groups obtained from independent-sample t test and Mann-Whitney u test. Time 1 represents data from days 2–5 of refeeding and Time 2 represents data from days 7–10 of refeeding. CI, confidence interval. BMI, body mass index; mBMI, median BMI for height and gender; WCC, white cell count; AST, aspartate aminotransferase; GGT, gamma-glutamyl transpeptidase. P < 0.05 indicates significance
Exploration of Treatment Outcomes of Inpatients and Outpatients
Weight change over treatment.
Descriptive statistics were used to explore mean discharge weight and discharge percentage median BMI (%mBMI) for each group. All inpatients and all but one outpatient had both measures reported at discharge. Mean discharge weight was higher for the outpatient group compared to the inpatient group. Mean percentage median BMI was similar in the outpatient group compared to the inpatient group.
Results relating to outcomes of both groups are displayed in Table 5 and Table 6. Differences between discharge weight and percentage median BMI were not statistically significant between groups, (weight: t (56) = -0.86, p = 0.39, %mBMI: t (56) = 0.109, p = 0.914).
Changes in BMI and weight between baseline and discharge were explored. Mean change in weight was marginally higher in the inpatient group compared to the outpatient group. Mean change in percentage median BMI was also higher for inpatients compared to outpatients, although, neither if these differences were statistically significant (see Table 6).
Table 5
Comparison of weight and percentage median BMI change after 7–10 days of refeeding and upon discharge between inpatients and outpatients.
| Time 2 | Discharge |
Marker | Inpatients (n = 19) | Outpatients (n = 37) | P Value | Inpatients (n = 19) | Outpatients (n = 39) | P Value |
Weight change, kg | 11.6 ± 8.2 | 10.4 ± 7.5 | 0.598 | 51.1 ± 9.7 | 53 ± 7.2 | 0.392 |
mBMI change, % | 16.5 ± 13.5 | 15 ± 10 | 0.590 | 94.8 ± 10.5 | 94.5 ± 10 | 0.914 |
Data are mean ± SD. P value represent comparisons made between groups obtained from independent t test and Mann-Whitney u test. mBMI, median body mass index for height and age. Time 2 represents the end of the refeeding period, day 7–10. Discharge represents the end of eating disorder treatment for both groups. P < 0.05 indicated significance.
Table 6
Comparison of weight and percentage median BMI change after 7–10 days of refeeding and upon discharge between inpatients and outpatients; test statistics and significance values.
| Time 2 | Discharge |
Marker | t/Z* | 95% CI | P Value | t/Z* | 95% CI | P Value |
Weight change, kg | 0.530 | -3.19, 5.49 | 0.598 | -0.862 | -6.49, 2.58 | 0.392 |
mBMI change, % | -0.547* | - | 0.590 | 0.109 | -5.40, 6.02 | 0.914 |
P value represent comparisons made between groups obtained from t, independent t test and Z*, Mann-Whitney u test. mBMI, median body mass index for height and age. Time 2 represents the end of the refeeding period, day 7–10. Discharge represents the end of eating disorder treatment for both groups. P < 0.05 indicated significance.
Weight change over the refeeding period.
Mean weight and percentage median BMI increased from initial assessment to the end of the refeeding period in both inpatient and outpatient groups, see Table 7 and Table 8. Increase in both weight and percentage median BMI over the refeeding period was statistically significant for both groups (inpatients: Z = -3.507, p < 0.001 and Z = -3.201, p = 0.001), (outpatients: Z = -3.85, p = 0.000 and Z = -3.598, p < 0.001).
Mean weight gain and increase in percentage median BMI were both higher amongst the inpatient group when compared with the outpatient group, however these differences were not statistically significant (U = 303.5, p = 0.411 and U = 314, p = 0.520).
Table 7
Comparison of weight and percentage median BMI between baseline and time 2 in inpatients and outpatients.
| Inpatients | Outpatients |
| Baseline (n = 19) | Time 2 (n = 19) | P Value | Baseline (n = 40) | Time 2 (n = 37) | P Value |
Weight, kg | 39.4 ± 7.8 | 41.5 ± 8.3 | < 0.001 | 42.5 ± 7.9 | 43.7 ± 7.7 | < 0.001 |
mBMI, % | 78.1 ± 9 | 81.6 ± 8.5 | 0.001 | 79.9 ± 10.3 | 82.3 ± 9.7 | < 0.001 |
Data are mean ± SD. P value represent comparisons made between groups obtained from independent t test and Mann-Whitney u test. mBMI, median body mass index for height and age. Time 2 represents the end of the refeeding period, day 7–10. P < 0.05 indicated significance.
Table 8
Comparison of weight and percentage median BMI between baseline and time 2 in inpatients and outpatients; test statistics and significance values.
| Inpatients | Outpatients |
| t/Z** | 95%CI | P Value | t/Z** | 95%CI | P Value |
Weight, kg | -3.507** | - | < 0.001 | -3.850** | - | < 0.001 |
mBMI, % | -3.201** | - | 0.001 | -3.598** | - | < 0.001 |
P value represent comparisons made between groups obtained from t, independent t test and Z**, Wilcoxon signed rank test. mBMI, median body mass index for height and age. Time 2 represents the end of the refeeding period, day 7–10. P < 0.05 indicated significance.