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.

Effect of rice bran extract on in vitro rumen fermentation and methane production.

This study was done to investigate which components of rice bran (RB) are involved in the inhibition of methanogenesis by fractionating the rice bran and adding it to a rumen in vitro culture system. The RB extract obtained using ethanol and water was screened in an in vitro fermentation system. The experimental treatment conditions were as follows: a control group containing a substrate without supplements; substrates with 0.06 g of RB; 0.6 mL of ethanol; 0.6 mL of distilled water (DW); 0.6 mL of ethanol-soluble fraction (ESF); 0.06 g of ethanol-insoluble rice bran (EIRB); 0.6 mL of water-soluble fraction (WSF); and 0.06 g of water-insoluble rice bran (WIRB). Based on the result of the analysis, the addition of ESF significantly decreased CH4 and CH4 /g dry matter digested, methanogen population (p < 0.05), while gas and dry matter digestibility (DMD) were comparable with the control group. Total short-chain fatty acid (SCFA), and proportion of propionate were reduced, and the proportion of butyrate was increased by the addition of ethanol and ESF (p < 0.05). This result suggests that the supplementation of 10% ESF can substantially reduce methane production in vitro without a negative effect on substrate digestibility.

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.

Effectiveness and safety of the co-administration of Yokukan-San (Japanese herbal medicine) with antipsychotics in hospitalized older patients with pneumonia.

AIM: Behavioral and psychological symptoms and delirium frequently occur in hospitalized older patients with pneumonia and are associated with longer hospital stays. Yokukan-San (YKS, traditional Japanese [Kampo] medicine) and antipsychotics are often used to treat delirium and behavioral and psychological symptoms in Japan. Hence, this study aimed to assess the effectiveness and safety of the co-administration of YKS with atypical antipsychotics in older patients with pneumonia. METHODS: We used the Japanese Diagnosis Procedure Combination inpatient database to retrospectively identify older patients (≥65 years) hospitalized for pneumonia who received antipsychotics within 3 days of hospitalization. The patients were divided into two groups: those who received atypical antipsychotics alone (control group) and those who received both atypical antipsychotics and YKS (YKS group). We compared length of hospital stay, in-hospital mortality, bone fractures, and administration of potassium products between the two groups using propensity score overlap weighting. RESULT: We identified 4789 patients in the YKS group and 61 641 in the control group. After propensity score overlap weighting, length of hospital stay was statistically significantly shorter in the YKS group (percentage difference -3.0%; 95% confidence interval -5.8% to -0.3%). The proportion of patients who received potassium products was higher in the YKS group (odds ratio 1.34; 95% confidence interval 1.15-1.55). In-hospital death and bone fractures were not significantly different. CONCLUSION: Co-administration of YKS with atypical antipsychotics could be a reasonable treatment option for hospitalized older patients with pneumonia and aggressive psychiatric symptoms. Geriatr Gerontol Int 2023; 23: 849-854.

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.

Effects of the supplementation of a calcium soap containing medium-chain fatty acids on the fecal microbiota of pigs, lactating cows, and calves.

Medium-chain fatty acids (MCFAs) have antialgal, antibacterial, antifungal, antiprotozoan, and antiviral activities. However, antibacterial activities of MCFAs in the hindgut of pigs and cattle are still unknown. We report the effects of the supplementation of MCFAs on fecal bacteria of pigs, lactating cows, and Japanese Black calves. Lactobacillus spp., Bifidobacterium spp., eaeA(+) Escherichia coli, Salmonella spp., Campylobacter jejuni, and Clostridium perfringens in the feces of animals were quantified by real-time PCR assay. There was no significant increase or decrease in Lactobacillus spp. and Bifidobacterium spp. in the three animals. In the pig feces, eaeA(+) E. coli was reduced to less than a third in the treatment group (P < 0.01). C. jejuni in the pig feces was also significantly less in the treatment group compared with the control (P < 0.01). In the lactating cow, eaeA(+) E. coli was reduced to one fifth of that in the control (P < 0.01). Salmonella spp. was halved in calf feces (P < 0.01). Thus, a reduction in Gram-negative pathogenic bacteria was observed. In conclusion, supplementation of a MCFA calcium soap in the diet would be beneficial to growing pigs, lactating cow, and calves by reducing pathogenic bacteria.

Effect of Daikenchuto for Mechanically Ventilated Patients With Enteral Feeding Intolerance: A Propensity Score-Matched Analysis Using a Nationwide Administrative Inpatient Database.

BACKGROUND: Daikenchuto, a Japanese herbal Kampo medicine, is used to improve gastrointestinal motility in critically ill patients with enteral feeding intolerance (EFI) in Japan. The present study aimed to investigate the effect of Daikenchuto for critically ill patients with EFI. METHODS: Using the Japanese Diagnosis Procedure Combination inpatient database from July 2010 to March 2018, we identified mechanically ventilated patients in intensive care units (ICUs) who had EFI during mechanical ventilation. We defined EFI as receipt of intravenous metoclopramide during mechanical ventilation. Patients who started Daikenchuto within 2 days of EFI onset were defined as the Daikenchuto group, and the remaining patients were defined as the control group. Propensity score-matched analyses were performed to compare the outcomes between the 2 groups. RESULTS: A total of 61,454 patients were included. Of these, 8842 patients (14%) were in the Daikenchuto group. One-to-one propensity score matching created 8701 matched pairs. After propensity score matching, the total number of days receiving enteral nutrition within 28 days of EFI onset was significantly longer in the Daikenchuto group than in the control group (risk difference, 0.9 days; 95% CI, 0.5-1.3 days). There were no significant differences in 28-day in-hospital mortality, hospital-acquired pneumonia, ventilator-free days, length of ICU stay, time to discharge alive, and adverse complications. CONCLUSION: This nationwide observational study suggested that use of Daikenchuto may increase the total number of days receiving enteral nutrition in mechanically ventilated patients with EFI.

Hyperbaric oxygen therapy and mortality from carbon monoxide poisoning: A nationwide observational study.

BACKGROUND: The effects of hyperbaric oxygen therapy (HBOT) on mortality or morbidity in patients with carbon monoxide (CO) poisoning remain unknown. We examined the effects of HBOT on CO poisoning and further strived to delineate its inherent effects on specific subgroups of patients using a nationwide inpatient database. METHODS: We identified adult patients with CO poisoning who were registered in the Japanese Diagnosis Procedure Combination inpatient database from 2010 to 2016. Propensity score-matching was performed to compare patients who received HBOT within 1 day of admission (HBOT group) with those who did not receive HBOT (control group). The primary outcome was in-hospital mortality. The secondary outcomes were a depressed mental status and reduced activities of daily living (ADL) at discharge. We also performed subgroup analyses divided according to severity of CO poisoning. RESULTS: Eligible patients were categorized into the HBOT group (n = 2034) or the control group (n = 4701). One-to-one propensity score-matching created 2034 pairs. In-hospital mortality was not significantly different between the HBOT and control groups (0.8% vs. 1.2%, risk difference: -0.4%, 95% confidence interval: -1.0 to 0.2). Patients in the HBOT group had significantly lower proportions of a depressed mental status and reduced ADL at discharge than did those in the control group. Similar associations were shown in the non-severe poisoning subgroup. CONCLUSIONS: Although HBOT was not significantly associated with reduced mortality, it was significantly associated with a favorable consciousness level and ADL in patients with CO poisoning. HBOT may be beneficial even for patients with non-severe CO poisoning.

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.

Differences in effect of early enteral nutrition on mortality among ventilated adults with shock requiring low-, medium-, and high-dose noradrenaline: A propensity-matched analysis.

BACKGROUND & AIMS: Despite extensive research on early enteral nutrition (EEN), it remains unclear whether EEN is effective for patients with shock requiring vasopressors. This study aimed to compare outcomes between EEN and late enteral nutrition (LEN) in ventilated patients with shock requiring low-, medium-, or high-dose noradrenaline. METHODS: Using a national inpatient database in Japan, we identified ventilated patients admitted to intensive care units who had shock requiring catecholamines (noradrenaline or dobutamine) from July 2010 to March 2016. We defined patients who started enteral nutrition within 2 days after starting mechanical ventilation as EEN group and the others as LEN group. Propensity score matching was performed between patients undergoing EEN and LEN in each of the low- (<0.1 µg/kg/min), medium- (0.1-0.3 µg/kg/min), and high-dose (≥0.3 µg/kg/min) noradrenaline groups. RESULTS: We identified 52,563 eligible patients during the 69-month study period, including 38,488, 11,042, and 3033 patients in the low-, medium-, and high-dose noradrenaline groups, respectively. One-to-two propensity score matching created 5,969, 2,162, and 477 one-to-two matched pairs in the low-, medium-, and high-dose noradrenaline groups, respectively. The 28-day mortality rate was significantly lower in the EEN than LEN group in the low-dose noradrenaline group (risk difference, -2.9%; 95% confidence interval [CI], -4.5% to -1.3%) and in the medium-dose noradrenaline group (risk difference, -6.8%; 95% CI, -9.6% to -4.0%). In the high-dose noradrenaline group, 28-day mortality did not differ significantly between the EEN and LEN groups (absolute risk difference, -1.4%; 95% CI, -7.4%-4.7%). CONCLUSIONS: Although the size of the subgroup requiring high-dose noradrenaline may have been too small to demonstrate a significant difference, the results suggest that EEN was associated with a reduction in mortality in ventilated adults treated with low- or medium-dose noradrenaline but not in those requiring high-dose noradrenaline.

Effect of high-dose vitamin C therapy on severe burn patients: a nationwide cohort study.

BACKGROUND: Vitamin C is a well-documented antioxidant that reduces oxidative stress and fluid infusion in high doses; however, the association between high-dose vitamin C and reduced mortality remains unclear. This study evaluates the effect of high-dose vitamin C in severe burn patients under two varying thresholds. METHODS: We enrolled adult patients with severe burns (burn index ≥ 15) who were registered in the Japanese Diagnosis Procedure Combination national inpatient database from 2010 to 2016. Propensity score matching was performed between patients who received high-dose vitamin C within 1 day of admission (vitamin C group) and those who did not (control group). High-dose vitamin C was defined as a dosage in excess of 10 g or 24 g within 2 days of admission. The primary outcome was in-hospital mortality. RESULTS: Eligible patients (n = 2713) were categorized into the vitamin C group (n = 157) or control group (n = 2556). After 1:4 propensity score matching, we compared 157 and 628 patients who were administered high-dose vitamin C (> 10-g threshold) and controls, respectively. Under this particular threshold, high-dose vitamin C therapy was associated with reduced in-hospital mortality (risk ratio, 0.79; 95% confidence interval, 0.66-0.95; p = 0.006). In contrast, in-hospital mortality did not differ between the control and high-dose vitamin C group under the > 24-g threshold (risk ratio, 0.83; 95% confidence interval, 0.68-1.02; p = 0.068). CONCLUSIONS: High-dose vitamin C therapy was associated with reduced mortality in patients with severe burns when used under a minimum threshold of 10 g within the first 2 days of admission. While "high-dose" vitamin C therapy lacks a universal definition, the present study reveals that different "high-dose" regimens may yield improved outcomes.

Early Enteral Nutrition in Patients Undergoing Sustained Neuromuscular Blockade: A Propensity-Matched Analysis Using a Nationwide Inpatient Database.

OBJECTIVES: Whether enteral nutrition should be postponed in patients undergoing sustained treatment with neuromuscular blocking agents remains unclear. We evaluated the association between enteral nutrition initiated within 2 days of sustained neuromuscular blocking agent treatment and in-hospital mortality. DESIGN: Retrospective administrative database study from July 2010 to March 2016. SETTING: More than 1,200 acute care hospitals covering approximately 90% of all tertiary-care emergency hospitals in Japan. PATIENTS: Mechanically ventilated patients, who had undergone sustained treatment with neuromuscular blocking agents in an ICU, were retrospectively reviewed. We defined patients who received sustained treatment with neuromuscular blocking agents as those who received either rocuronium at greater than or equal to 250 mg/d or vecuronium at greater than or equal to 50 mg/d for at least 2 consecutive days. INTERVENTIONS: Enteral nutrition started within 2 days from the initiation of neuromuscular blocking agents (defined as early enteral nutrition). MEASUREMENTS AND MAIN RESULTS: We identified 2,340 eligible patients during the 69-month study period. Of these, 378 patients (16%) had received early enteral nutrition. One-to-three propensity score matching created 374-1,122 pairs. The in-hospital mortality rate was significantly lower in the early than late enteral nutrition group (risk difference, -6.3%; 95% CI, -11.7% to -0.9%). There was no significant difference in the rate of hospital pneumonia between the two groups (risk difference, 2.8%; 95% CI, -2.7% to 8.3%). Length of hospital stay among survivors was significantly shorter in the early compared with the late enteral nutrition group (risk difference, -11.4 d; 95% CI, -19.1 to -3.7 d). There was no significant difference between the two groups in length of ICU stay or length of mechanical ventilation among survivors. CONCLUSIONS: According to this retrospective database study, early enteral nutrition may be associated with lower in-hospital mortality with no increase in-hospital pneumonia in patients undergoing sustained treatment with neuromuscular blocking agents.

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.

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.

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.

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.