Use of Japanese Herbal Kampo Medicine in Patients With Acute Cardiovascular Disease　- A 12-Year Nationwide Cohort Analysis.

BACKGROUND: Kampo, a Japanese herbal medicine, is approved for the treatment of various symptoms/conditions under national medical insurance coverage in Japan. However, the contemporary nationwide status of Kampo use among patients with acute cardiovascular diseases remains unknown. METHODS AND RESULTS: Using the Japanese Diagnosis Procedure Combination database, we retrospectively identified 2,547,559 patients hospitalized for acute cardiovascular disease (acute myocardial infarction, heart failure, pulmonary embolism, or aortic dissection) at 1,798 hospitals during the fiscal years 2010-2021. Kampo medicines were used in 227,008 (8.9%) patients, with a 3-fold increase from 2010 (4.3%) to 2021 (12.4%), regardless of age, sex, disease severity, and primary diagnosis. The top 5 medicines used were Daikenchuto (29.4%), Yokukansan (26.1%), Shakuyakukanzoto (15.8%), Rikkunshito (7.3%), and Goreisan (5.5%). From 2010 to 2021, Kampo medicines were initiated earlier during hospitalization (from a median of Day 7 to Day 3), and were used on a greater proportion of hospital days (median 16.7% vs. 21.4%). However, the percentage of patients continuing Kampo medicines after discharge declined from 57.9% in 2010 to 39.4% in 2021, indicating their temporary use. The frequency of Kampo use varied across hospitals, with the median percentage of patients prescribed Kampo medications increasing from 7.7% in 2010 to 11.5% in 2021. CONCLUSIONS: This nationwide study demonstrates increasing Kampo use in the management of acute cardiovascular diseases, warranting further pharmacoepidemiological studies on its effectiveness.

Antiemetic Effect of Rikkunshito, a Japanese Kampo Herbal Medicine, on Cisplatin-induced Nausea and Vomiting: A Nationwide Database Study in Japan.

Objective The effect of Rikkunshito, a Japanese herbal Kampo medicine, on chemotherapy-induced nausea and vomiting (CINV) has been evaluated in several small prospective studies, with mixed results. We retrospectively evaluated the antiemetic effects of Rikkunshito in patients undergoing cisplatin-based chemotherapy using a large-scale database in Japan. Methods The Diagnosis Procedure Combination inpatient database from July 2010 to March 2019 was used to compare adult patients with malignant tumors who had received Rikkunshito on or before the day of cisplatin administration (Rikkunshito group) and those who had not (control group). Antiemetics on days 2 and 3 and days 4 and beyond following cisplatin administration were used as surrogate outcomes for CINV. Patient backgrounds were adjusted using the stabilized inverse probability of treatment weighting, and outcomes were compared using univariable regression models. Results We identified 669 and 123,378 patients in the Rikkunshito and control groups, respectively. There were significantly fewer patients using intravenous 5-HT3-receptor antagonists in the Rikkunshito group (odds ratio, 0.38; 95% confidence interval, 0.16-0.87; p=0.023) on days 2 and 3 of cisplatin-based chemotherapy. Conclusion The reduced use of antiemetics on day 2 and beyond of cisplatin administration suggested a beneficial effect of Rikkunshito in palliating the symptoms of CINV.

Machine Learning-based Models for Outpatient Prescription of Kampo Formulations: An Analysis of a Health Insurance Claims Database.

BACKGROUND: Despite the widespread practice of Japanese traditional Kampo medicine, the characteristics of patients receiving various Kampo formulations have not been documented in detail. We applied a machine learning model to a health insurance claims database to identify the factors associated with the use of Kampo formulations. METHODS: A 10% sample of enrollees of the JMDC Claims Database in 2018 and 2019 was used to create the training and testing sets, respectively. Logistic regression analyses with lasso regularization were performed in the training set to construct models with prescriptions of 10 commonly used Kampo formulations in 1 year as the dependent variable and data of the preceding year as independent variables. Models were applied to the testing set to calculate the C-statistics. Additionally, the performance of simplified scores using 10 or 5 variables were evaluated. RESULTS: There were 338,924 and 399,174 enrollees in the training and testing sets, respectively. The commonly prescribed Kampo formulations included kakkonto, bakumondoto, and shoseityuto. Based on the lasso models, the C-statistics ranged from 0.643 (maoto) to 0.888 (tokishakuyakusan). The models identified both the common determinants of different Kampo formulations and the specific characteristics associated with particular Kampo formulations. The simplified scores were slightly inferior to full models. CONCLUSION: Lasso regression models showed good performance for explaining various Kampo prescriptions from claims data. The models identified the characteristics associated with Kampo formulation use.

Safety of Japanese herbal Kampo medicines for the treatment of depression during pregnancy.

OBJECTIVE: To clarify the fetal safety of herbal Kampo medicines, including Hange-koboku-to, Koso-san, Nyoshin-san, Yokukansan, Yokukansan-kachinpi-hange, Saiko-keishikankyo-to, Keishi-karyukotu-borei-to, and Kanbaku-taisou-to, when administered to pregnant women with depression using a large healthcare administrative database. METHODS: We extracted data from the JMDC Claims Database (2005-2018) for this retrospective cohort study of pregnant women aged 19 years or older admitted to obstetric clinics or hospitals for delivery. Participants were classified into four groups: those without depression, those diagnosed with depression without medication, those given Kampo medicines for depression, and those given western medicines for depression. Neonatal outcomes (congenital anomalies, low birth weight, and preterm birth) were considered as the safety outcome measures. RESULTS: We identified 179 707 eligible mothers. The adverse outcomes did not differ significantly between participants receiving Kampo medicine and those not diagnosed with depression during pregnancy. The proportion of low-birth-weight neonates did not differ significantly between the Kampo medicine and non-depression groups (adjusted odds ratio [aOR] 1.28; 95% confidence interval [CI] 0.86-1.91), but was significantly higher in the unmedicated depression group (aOR 1.31; 95% CI 1.07-1.61) and western medicine group (aOR 1.47; 95% CI 1.18-1.83). CONCLUSION: Kampo medicines are safe for treating depression during pregnancy without increasing the incidence of congenital anomalies, low birth weight, or preterm birth.

Incidence of Sympathetic Ophthalmia after Inciting Events: A National Database Study in Japan.

PURPOSE: To analyze the incidence of sympathetic ophthalmia (SO) after inciting events (eye trauma or intraocular surgery). DESIGN: Retrospective cohort study. PARTICIPANTS: Patients experiencing inciting events between 2012 and 2019. Onset of SO was defined as the first date of SO diagnosis. METHODS: Using a nationwide administrative claims database in Japan, we calculated the cumulative incidence of SO after inciting events stratified by sex, 10-year age groups, and a categorical variable of primary or repeated, reflecting the history of inciting events in the past year (no inciting events, inciting events without trauma, or inciting events with trauma) using the Kaplan-Meier approach. We also estimated the adjusted hazard ratio (aHR) by Cox regression. We then restricted the population to those with only 1 inciting event during the observation period to investigate the pure effect of each inciting event. MAIN OUTCOME MEASURES: Cumulative incidence of SO over 60 months. RESULTS: A total of 888 041 inciting events (704 717 patients) were eligible. The total number of SO cases was 263, and the cumulative incidence of SO was 0.044% over 60 months. Female sex was not associated with onset of SO (aHR, 1.01; 95% confidence interval [CI], 0.79-1.29; P = 0.95). The group 40 to 49 years of age showed the highest incidence of 0.104% among the age groups (aHR vs. ≥80 years of age group [0.041%], 2.44 [95% CI, 1.56-3.80]; P < 0.001). Repeated inciting events with and without trauma showed higher incidences of SO (0.469% and 0.072%, respectively) than primary inciting events (0.036%) (aHR 11.68 [7.74-17.64] and 2.21 [95% CI, 1.59-3.07], respectively); P < 0.001 and P < 0.001, respectively). The incidence of SO after vitrectomy was much lower than after trauma (0.016% vs. 0.073%), and the incidence after scleral buckling was even lower. CONCLUSIONS: The cumulative incidence of SO over 60 months was estimated to be 0.044% at minimum. Repeated inciting events, especially those with trauma, increased the risk of SO developing. Trauma was 4 to 5 times as likely to induce SO than vitrectomy. The present findings will be valuable for counseling patients about the risks of SO after trauma and before performing intraocular surgeries.

Maoto plus neuraminidase inhibitor versus neuraminidase inhibitor alone for reducing hospitalization in older adults with seasonal influenza.

BACKGROUND: Maoto is a Japanese Kampo formula used for treating febrile illnesses. However, researchers have not yet clarified its effect in preventing severe influenza among older adults. We evaluated the association between the addition of maoto to a neuraminidase inhibitor in older adults and reduced hospitalization following influenza. METHODS: Using a prefecture-wide health insurance claims database, we identified outpatients aged ≥60 years who were diagnosed with influenza between September 2012 and August 2017. We performed one-to-one propensity score matching between patients who received maoto in addition to a neuraminidase inhibitor and those who received a neuraminidase inhibitor alone. Hospitalization within 7 days of influenza diagnosis was compared using the McNemar's test. We performed subgroup analyses based on sex, age, and other characteristics. RESULTS: We identified 57,366 eligible patients with influenza. Maoto was used in 8.1% of these patients. In 4,630 matched pairs, the 7-day hospitalization rate was 1.77% (n = 82) and 1.62% (n = 75) for patients with and without maoto, respectively; the difference between the groups was insignificant (P = 0.569). Subgroup analysis showed a tendency toward more hospitalizations within 7 days among patients aged 90 years or older who were prescribed maoto than those who were not (9.7% vs. 6.6%, P = 0.257). CONCLUSIONS: Maoto use was not associated with decreased hospitalization rates in older adults with influenza. This warrants further research to evaluate the safety and effectiveness of maoto in different patient groups, particularly the oldest-old population.

Association between Maoto Use and Hospitalization for Seasonal Influenza in a Nonelderly Cohort in Japan.

Objective Maoto is a traditional Japanese Kampo formula used to treat influenza. However, clinical evidence for maoto has been limited to small-scale studies of its effect in alleviating symptoms. The present study evaluated whether or not the addition of maoto to a neuraminidase inhibitor was associated with a reduction in hospitalization following influenza. Methods Using the JMDC Claims Database, we identified outpatients <60 years old who were diagnosed with influenza by an antigen test from September 2013 to August 2018. One-to-five propensity score matching was conducted between patients who received maoto in addition to a neuraminidase inhibitor and those who received a neuraminidase inhibitor alone. Hospitalization within seven days of the influenza diagnosis was compared in the matched groups using the Mantel-Haenszel test. Results We identified 1.79 million cases of influenza from the database in the 5-year study period. Maoto was prescribed for 3.9% of the 1.67 million cases receiving a neuraminidase inhibitor. In the 64,613 propensity score-matched groups of patients, the 7-day hospitalization rate was 0.116% (n=75) for patients with maoto and 0.122% (n=394) for patients without maoto. The difference between these treatment groups was nonsignificant (common odds ratio, 0.95; 95% confidence interval, 0.74 to 1.22; p=0.695). Conclusion The addition of maoto to a neuraminidase inhibitor was not associated with a decrease in hospitalization among nonelderly patients with influenza. Further research is necessary to clarify the indication and efficacy of maoto.

Effect of Japanese herbal Kampo medicines on live birth rate in women with recurrent pregnancy loss.

OBJECTIVE: To determine the effectiveness of Japanese Kampo medicines on the overall live birth rate among patients with recurrent pregnancy loss (RPL) in a real-world setting. METHODS: In the current retrospective cohort study, we used the JMDC Claims Database to extract information on women diagnosed with RPL between January 1, 2005 and August 31, 2018. Eligible women were divided into two groups according to Kampo medicines administered as treatments for RPL. The primary outcome was the live birth rate during the study period. Propensity score matching, Kaplan-Meier cumulative incidence plots, log-rank test, and Cox proportional-hazards regression model were used to compare the primary outcome between patients with and without Japanese herbal Kampo medicines. RESULTS: Among 5517 eligible patients, 1652 used Kampo medicines and 3865 did not. After propensity score matching, the live birth rate at 2.0 years was 15.7% in the Kampo group and 11.2% in the non-Kampo group. At 4.0 years, the difference between the two groups had slightly increased. The overall live birth rate differed significantly between the two groups (hazard ratio 1.32, 95% confidence interval 1.13-1.53; P < 0.001). CONCLUSION: Japanese herbal Kampo medicines may improve the live birth rate in patients with RPL.

Outpatient Prescriptions of Kampo Formulations in Japan.

Objective Kampo is a traditional Japanese medicine using formulae of natural agents. Although Kampo is widely practiced, information regarding the current prescriptions of Kampo formulations is lacking. The aim of the study was to describe the outpatient use of Kampo formulations in the current Japanese health insurance system. Methods From the JMDC Claims Database, we identified subscribers with outpatient prescriptions of Kampo extract formulations between April 2017 and March 2018. Prescription records were summarized at the individual level to describe the pattern of each formula's use, such as the frequency of prescription and the number of days within a year that were covered by the prescriptions. We also examined whether or not Kampo formulations were prescribed in combination with other drugs. Results Of the 4.5 million subscribers, 13.5% received prescriptions of Kampo extracts within 1 year, and 54% of Kampo users were women. The most commonly prescribed Kampo formulae included kakkonto, shoseiryuto, and maoto, which were used for the short term covering a median of 5 to 7 days. There were also several formulae that were prescribed for longer periods. The median numbers of days covered by kamishoyosan and keishibukuryogan were 60 and 56, respectively. Kampo formulations were used in combination with Western drugs in 85% of prescriptions. Conclusion Kampo formulations are commonly prescribed under the Japanese insurance system and are frequently used in combination with Western drugs. The pattern of prescriptions varied across different formulae.

Periprocedural hypotension after conscious sedation versus local anesthesia during defibrillator implantation for left ventricular dysfunction: analysis of a national inpatient database in Japan.

The association between periprocedural hypotension and conscious sedation (CS) during defibrillator implantation remains to be elucidated. The aim of the present study was to compare the occurrence of periprocedural hypotension after CS or local anesthesia (LA) during defibrillator implantation in a retrospective cohort study using a national inpatient database. Using the Japanese Diagnosis Procedure Combination database, we retrospectively collected data for adult inpatients who underwent implantation of a cardioverter defibrillator or cardiac resynchronization therapy device from July 2010 to March 2016. Multivariable logistic regression analyses were performed to compare the occurrence of periprocedural hypotension between the CS and LA groups with adjustment for patient background characteristics and hospital factors. Additional analysis was performed after dividing the CS group into each specific anesthetic use. We identified 4842 patients, comprising 1533 patients with CS and 3309 with LA. The CS group had a significantly higher proportion of periprocedural hypotension than the LA group (13.4% versus 9.7%; adjusted odds ratio, 1.56; 95% confidence interval, 1.19-2.04; p = 0.001). Body mass index < 18.5 kg/m2, New York Heart Association Class IV, and use of cardiac resynchronization therapy device were independently associated with occurrence of periprocedural hypotension. Additionally, ketamine and dexmedetomidine were significantly associated with higher incidence of hypotension than the LA group (adjusted odds ratio, 2.64; 95% confidence interval, 1.32-5.26; p = 0.006; adjusted odds ratio, 1.86; 95% confidence interval, 1.11-3.12; p = 0.019, respectively). Periprocedural hypotension was significantly more likely to occur in the CS group than the LA group, and was associated with CS.

Safety and effectiveness of Japanese herbal Kampo medicines for treatment of hyperemesis gravidarum.

OBJECTIVES: To investigate whether Japanese Kampo medicines, including Sho-hange-kabukuryou-to, Touki-syakuyaku-san, and Hange-kouboku-to, are safe for fetuses, and whether these medicines reduce hospitalizations and medical costs in pregnant women with hyperemesis gravidarum. METHODS: We used the Japan Medical Data Center database to extract data for pregnant women (aged ≥19 years) admitted to obstetric clinics or hospitals for delivery between January 1, 2005, and December 31, 2016. Eligible patients were classified into three groups: Kampo medicines for hyperemesis gravidarum, other medicines for hyperemesis gravidarum, and without hyperemesis gravidarum. Safety outcome measures were neonatal outcomes (congenital anomalies, low birthweight, and preterm birth), and effectiveness measures were mother's unplanned hospitalization for hyperemesis gravidarum and total medical costs within 20 weeks of gestation. RESULTS: We identified 121 287 eligible mothers. No significant differences in the safety measures were observed among the groups. The Kampo medication group had a significantly lower proportion of mothers with unplanned hospital admission (odds ratio 0.80, 95% confidence interval [CI] 0.69-0.92) and lower total costs (coefficient [US$] 12.8, 95% CI -23.2 to -2.4) than the other medication group. CONCLUSION: Kampo medicines may reduce unplanned admissions and medical costs among pregnant women with hyperemesis gravidarum. UMIN Clinical Trials Registry: R000037298 UMIN000032706.

Reduction in exacerbation of COPD in patients of advanced age using the Japanese Kampo medicine Dai-kenchu-to: a retrospective cohort study.

PURPOSE: Patients with symptomatic COPD are recommended to use inhaled bronchodilators containing long-acting muscarinic receptor antagonists (LAMAs). However, bronchodilators may cause gastrointestinal adverse effects due to anticholinergic reactions, especially in advanced-age patients with COPD. Dai-kenchu-to (TU-100, Da Jian Zhong Tang in Chinese) is the most frequently prescribed Japanese herbal Kampo medicine and is often prescribed to control abdominal bloating and constipation. The purpose of this study was to evaluate the role of Dai-kenchu-to as a supportive therapy in advanced-age patients with COPD. PATIENTS AND METHODS: We used the Japanese Diagnosis Procedure Combination inpatient database and identified patients aged ≥75 years who were hospitalized for COPD exacerbation. We then compared the risk of re-hospitalization for COPD exacerbation or death between patients with and without Dai-kenchu-to using 1-to-4 propensity score matching. A Cox proportional hazards model was used to compare the two groups. We performed subgroup analyses for patients with and without LAMA therapy. RESULTS: Patients treated with Dai-kenchu-to had a significantly lower risk of re-hospitalization or death after discharge; the HR was 0.82 (95% CI, 0.67-0.99) in 1-to-4 propensity score matching. Subgroup analysis of LAMA users showed a significant difference in re-hospitalization or death, while subgroup analysis of LAMA non-users showed no significant difference. CONCLUSION: Our findings indicate that Dai-kenchu-to may have improved the tolerability of LAMA in advanced-age patients with COPD and, therefore, reduced the risk of re-hospitalization or death from COPD exacerbation. Dai-kenchu-to may be recommended as a useful supportive therapy for advanced-age patients with COPD.

Effect of Hangeshashin-To (Japanese Herbal Medicine Tj-14) on Tolerability of Irinotecan: Propensity Score and Instrumental Variable Analyses.

Irinotecan hydrochloride (CPT-11) is used to treat a wide spectrum of malignant tumors. Hangeshashin-to (Japanese herbal medicine TJ-14) is reportedly effective in preventing and controlling diarrhea associated with CPT-11. However, the effect of TJ-14 on tolerability of chemotherapy with CPT-11 has not been fully investigated. We used the Japanese Diagnosis Procedure Combination inpatient database to retrospectively identify patients who had received CPT-11 on their first admission with and without TJ-14. Patients who did receive TJ-14 (N = 7092) received CPT-11 more often and in larger doses than those who did not receive TJ-14 (N = 82,019). The incidence rate ratio of CPT-11 administration was 1.34 for frequency (95% confidence interval [CI], 1.31⁻1.38; p < 0.001), and 1.16 for total dose (95% CI, 1.14⁻1.19; p < 0.001) according to stabilized inverse probability treatment weighting using propensity scores. Instrumental variable analysis showed similar trends. In-hospital mortality was significantly lower in patients who received TJ-14 than in those who did not. Odds ratios of in-hospital death in patients receiving TJ-14 was 0.81 (95% CI, 0.71⁻0.93; p = 0.002) according to stabilized inverse probability treatment weighting using propensity scores and 0.42 (95% CI, 0.22⁻0.81; p = 0.009) according to instrumental variable analysis. Our findings indicate that TJ-14 improve the tolerability of CPT-11.

Oral fluorouracil vs vinorelbine plus cisplatin as adjuvant chemotherapy for stage II-IIIA non-small cell lung cancer: Propensity score-matched and instrumental variable analyses.

BACKGROUND: Adjuvant chemotherapy with vinorelbine plus cisplatin (VNR/CDDP) is a standard regimen for treatment of postoperative stage II-IIIA non-small cell lung cancer (NSCLC). However, oral fluorouracil offers a feasible alternative adjuvant chemotherapeutic regimen. We compared the prognoses of patients with NSCLC treated with adjuvant chemotherapy with either VNR/CDDP or oral fluorouracil. METHODS: We identified patients with stage II-IIIA NSCLC who underwent lung surgery followed by adjuvant chemotherapy with VNR/CDDP (n = 384) or oral fluorouracil (n = 268) between July 2010 and March 2015, using the national Japanese inpatient and outpatient Diagnosis Procedure Combination database. We compared recurrence-free survival between the groups by multivariable Cox regression analysis for one-to-one propensity score-matched patients and by instrumental variable analysis. RESULTS: Younger patients and patients with positive N2 nodes were more likely to receive VNR/CDDP, while older patients and those with T3N0 classification were more likely to receive oral fluorouracil. Among 172 pairs of propensity-matched patients, time to adjuvant chemotherapy was shorter for oral fluorouracil compared with VNR/CDDP. Oral fluorouracil was also significantly associated with improved recurrence-free survival compared with VNR/CDDP, according to multivariable Cox regression analysis (hazard ratio, 0.41; 95% confidence interval, 0.26-0.64). Instrumental variable analysis showed a similar relationship (hazard ratio, 0.19; 95% confidence interval, 0.038-0.92). CONCLUSIONS: On a large nationwide cohort, adjuvant chemotherapy with oral fluorouracil prolonged recurrence-free survival in patients with postoperative stage II-IIIA NSCLC, compared with VNR/CDDP. Oral fluorouracil may thus be a useful alternative to VNR/CDDP for the adjuvant treatment of these patients.

Japanese Herbal Kampo Hochu-Ekki-To or Juzen-Taiho-To after Surgery for Hip Fracture Does Not Reduce Infectious Complications.

BACKGROUND: Infectious complications after hip fracture surgery are common in the elderly. Although experimental studies have suggested that kampo medicine, Hochu-ekki-to and Juzen-taiho-to, can prevent infectious complications, only a few small clinical studies have been published to date. PRIMARY STUDY OBJECTIVE: The aim of the present study is to investigate the impact of Hochu-ekki-to or Juzen-taiho-to on postoperative infectious complications in patients undergoing surgery for hip fracture. METHODS AND DESIGN: In this retrospective cohort study using a nationwide inpatient database in Japan, we performed propensity score matching to compare patients who did or did not receive kampo medicine after surgery for hip fracture. SETTINGS: A nationwide inpatient database. PARTICIPANTS: Patients who did or did not receive kampo medicine after surgery for hip fracture. INTERVENTION: Kampo medicine after surgery for hip fracture. PRIMARY OUTCOME MEASURES: Infectious complications. RESULTS: The proportions of postoperative infectious complications were not significantly different between the 424 propensity-matched pairs with and without kampo medicine (11 versus 8, P = 0.644). CONCLUSION: The present study suggests that Hochu-ekki-to or Juzen-taiho-to postoperatively is not associated with decreased occurrence of infectious complications in patients who underwent surgery for hip fracture.

Higher calorie diets increase rate of weight gain and shorten hospital stay in hospitalized adolescents with anorexia nervosa.

PURPOSE: Current recommendations for refeeding in anorexia nervosa (AN) are conservative, beginning around 1,200 calories to avoid refeeding syndrome. We previously showed poor weight gain and long hospital stay using this approach and hypothesized that a higher calorie approach would improve outcomes. METHODS: Adolescents hospitalized for malnutrition due to AN were included in this quasi-experimental study comparing lower and higher calories during refeeding. Participants enrolled between 2002 and 2012; higher calories were prescribed starting around 2008. Daily prospective measures included weight, heart rate, temperature, hydration markers and serum phosphorus. Participants received formula only to replace refused food. Percent Median Body Mass Index (%MBMI) was calculated using 50th percentile body mass index for age and sex. Unpaired t-tests compared two groups split at 1,200 calories. RESULTS: Fifty-six adolescents with mean (±SEM) age 16.2 (±.3) years and admit %MBMI 79.2% (±1.5%) were hospitalized for 14.9 (±.9) days. The only significant difference between groups (N = 28 each) at baseline was starting calories (1,764 [±60] vs. 1,093 [±28], p < .001). Participants on higher calories had faster weight gain (.46 [±.04] vs. .26 [±.03] %MBMI/day, p < .001), greater daily calorie advances (122 [±8] vs. 98 [±6], p = .024), shorter hospital stay (11.9 [±1.0] vs. 17.6 [±1.2] days, p < .001), and a greater tendency to receive phosphate supplementation (12 vs. 8 participants, p = .273). CONCLUSIONS: Higher calorie diets produced faster weight gain in hospitalized adolescents with AN as compared with the currently recommended lower calorie diets. No cases of the refeeding syndrome were seen using phosphate supplementation. These findings lend further support to the move toward more aggressive refeeding in AN.