Comparative Efficacy and Safety of Standard and Biweekly Trifluridine/Tipiracil Regimen in Patients With Colorectal Cancer.

BACKGROUND/AIM: Trifluridine/tipiracil (FTD/TPI) is used to treat metastatic colorectal cancer (mCRC). Since the standard regimen of FTD/TPI features a complex dosing schedule and frequently results in severe hematological toxicities, a simplified regimen has emerged, in which FTD/TPI is orally administered biweekly. However, the survival benefits and potential adverse events associated with the biweekly FTD/TPI regimen have not been fully evaluated in previous reports. Therefore, in this study, the differences in efficacy and safety between the standard and biweekly FTD/TPI regimens were retrospectively investigated in patients with mCRC. PATIENTS AND METHODS: Data from 90 patients who received FTD/TPI for mCRC were extracted from the electronic medical records at the Osaka University Hospital. According to the inclusion and exclusion criteria, 85 of the 90 patients were enrolled in the study. We compared patient characteristics, overall survival (OS), progression-free survival (PFS), and adverse events between the standard (n=56) and biweekly groups (n=29). RESULTS: The biweekly group exhibited prolonged OS and PFS compared to patients in the standard group. Multivariate analysis for OS and PFS demonstrated that the biweekly regimen was the only significant factor that affected OS, and not PFS (HR=0.561, p=0.049). Kaplan-Meier analysis indicated that neutropenia (grade ≥3) in the biweekly group was significantly prolonged compared to the standard group (p=0.012). However, there were no significant differences in adverse events between the two groups (p>0.999). CONCLUSION: The biweekly FTD/TPI regimen, compared to the standard regimen, should enhance both OS and PFS in patients with mCRC without escalating any adverse event.

Model-Informed Vancomycin Dosing Optimization to Address Delayed Renal Maturation in Infants and Young Children with Critical Congenital Heart Disease.

Ensuring safe and effective drug therapy in infants and young children often requires accounting for growth and organ development; however, data on organ function maturation are scarce for special populations, such as infants with congenital diseases. Children with critical congenital heart disease (CCHD) often require multiple staged surgeries depending on their age and disease severity. Vancomycin (VCM) is used to treat postoperative infections; however, the standard pediatric dose (60-80 mg/kg/day) frequently results in overexposure in children with CCHD. In this study, we characterized the maturation of VCM clearance in pediatric patients with CCHD and determined the appropriate dosing regimen using population pharmacokinetic (PK) modeling and simulations. We analyzed 1,254 VCM serum concentrations from 152 postoperative patients (3 days-13 years old) for population PK analysis. The PK model was developed using a two-compartment model with allometrically scaled body weight, estimated glomerular filtration rate (eGFR), and postmenstrual age as covariates. The observed clearance in patients aged ≤ 1 year and 1-2 years was 33% and 40% lower compared with that of non-CCHD patients, respectively, indicating delayed renal maturation in patients with CCHD. Simulation analyses suggested VCM doses of 25 mg/kg/day (age ≤ 3 months, eGFR 40 mL/min/1.73 m2 ) and 35 mg/kg/day (3 months < age ≤ 3 years, eGFR 60 mL/min/1.73 m2 ). In conclusion, this study revealed delayed renal maturation in children with CCHD, could be due to cyanosis and low cardiac output. Model-informed simulations identified the lower VCM doses for children with CCHD compared with standard pediatric guidelines.

Proton Pump Inhibitors Ameliorate Oxaliplatin-induced Peripheral Neuropathy: Retrospective Analysis of Two Real-world Clinical Databases.

BACKGROUND/AIM: Chemotherapy-induced peripheral neuropathy (CIPN) due to oxaliplatin (L-OHP) is a major clinical problem. Effective and safe preventive strategies for CIPN are urgently needed. Although proton pump inhibitors (PPIs) have various off-target effects, their clinical impact on L-OHP-induced CIPN remains unclear. In the present study, we investigated the effects of PPIs on L-OHP-induced CIPN in patients using two real-world clinical databases. PATIENTS AND METHODS: We retrospectively analyzed the electronic medical records of Osaka University Hospital to examine the effect of PPIs on CIPN development in 217 patients who received XELOX (L-OHP plus capecitabine) therapy for colorectal cancer. In addition, the Japanese Adverse Drug Event Report (JADER) database was used to validate the effects of PPIs on L-OHP-induced CIPN. RESULTS: The incidences of CIPN (grade ≥2) and discontinuation of L-OHP were significantly lower in patients with PPIs than in those without PPIs. Multivariate analysis showed that concomitant PPIs use was an independent factor that significantly contributed to the prevention of grade ≥2 CIPN (odds ratio=0.054, p<0.001). Kaplan-Meier analysis showed that the time to onset of grade ≥2 CIPN was significantly prolonged in patients with PPIs without affecting the therapeutic efficacy of L-OHP (p=0.004). Moreover, JADER database analyses revealed that the reporting odds ratio of any PPI for L-OHP-induced CIPN was 0.485. CONCLUSION: Concomitant PPI use ameliorated L-OHP-induced CIPN in patients with colorectal cancer.

Administration of lipid emulsion reduced the hypnotic potency of propofol more than that of thiamylal in mice.

Administration in a lipid emulsion can modify the pharmacodynamics of drugs via a process known as lipid resuscitation. However, the detailed mechanism remains unclear. We studied the volume and another pharmacodynamic effect, the lipid sink, using propofol and thiamylal. Male adult mice (ddY) were intravenously administered 10 ml/kg propofol or thiamylal diluted with physiological saline, 10% soybean oil, or 20% soybean oil. The 50% effective dose (ED50) for achieving hypnosis was calculated using probit analysis. To investigate the volume effect, 0, 10, or 20 ml/kg of saline or soybean oil was administered, either simultaneously or beforehand. Next, a two- or three-fold dose of the anesthetics was administered and the durations of anesthesia were measured. Finally, at 30 s after the first injection, supplemental soybean oil was administered. The mean (± SE) ED50 values of propofol and thiamylal were 5.79 mg/kg (0.61) and 8.83 mg/kg (0.84), respectively. Lipid dilution increased the ED50 values of both anesthetics. After injection of a dose two-fold the ED50 value, the respective mean (± SD) durations of anesthesia were 125 ± 35 s and 102 ± 38 s. Supplemental administration of soybean oil significantly shortened the duration of anesthesia of propofol, but not that of thiamylal. The results indicate that administration of a lipid emulsion vitiated the anesthetic effect of propofol by reducing the non-emulsified free fraction in the aqueous phase, which may elucidate the lipid resuscitation likely caused by the lipid sink mechanism.

A Case of Surgery Cancellation Following the Discovery of Anisocoria After Induction of General Anesthesia.

Anisocoria after induction of general anesthesia may indicate a severe cerebrovascular disorder. We encountered a case in which anisocoria in the left and right eyes was noticed after induction of general anesthesia, and the surgery was canceled. The patient was a 53-year-old woman with a history of hypertension. She received general anesthesia 10 years ago, but the details were unknown. Anesthesia was induced with propofol, remifentanil, and rocuronium, followed by nasal intubation. No significant change was observed in vital signs during the induction of anesthesia. After intubation, the pupils were checked according to the protocol for observing pupil diameter. The pupil size was found to be unequal, measuring 1 mm in the left eye and 4 mm in the right eye. A cerebrovascular disorder was suspected; thus, the surgery was canceled, and the patient was awakened and extubated. Neurological symptoms such as limb movements were checked after awakening, and no disorientation or motor dysfunction was detected in the patient. However, her pupils remained unequal, measuring 2 mm in the left eye and 4 mm in the right eye. Regarding light reflex, the left eye was miotic, but the right eye remained mydriatic. The pupillary symptom persisted even during discharge the next day. Since our hospital is a solely dental hospital, following discharge, after consulting the ophthalmology department of a nearby medical university hospital, the patient was diagnosed with pupillotonia, as she had been experiencing light dazzling in only her right eye for seven years, had no light reflex but near reflex, and was miotic due to the use of pilocarpine hydrochloride eye drops, which promotes miosis. The patient has had these symptoms in the right eye for seven years, and it is possible that she had anisocoria during the preoperative examination at this time. If anisocoria had been detected and examined carefully during the preoperative examination, there would have been no need to cancel the surgery. In this case, we strongly felt that the pupils must be checked during the preoperative examination.

3M microfoam™ surgical tape prevents nasal pressure injury associated with nasotracheal intubation: A randomized double-blind trial.

BACKGROUND: 3M microfoam™ surgical tape (3ST: 3M Japan Limited) is used for pressure wound control of medical equipment. It is cushioned and can be fitted to any body part. Here we investigated whether 3ST prevents nasal pressure injury associated with nasotracheal intubation (NTI). METHODS: We conducted a prospective, randomized double-blind study, enrolling 63 patients aged 20 to 70 years, who underwent general anesthesia with NTI. They were divided into 2 groups; those treated with 3ST (group S; n = 31) and control (group C; n = 31). After NTI and before securing the nasotracheal tube, a 35 × 25 mm 3ST was used to protect the nasal wing in group S, and the nasotracheal tube was fixed in place after NTI without protection in group C. The primary outcome was the presence or absence of nasal pressure injury after extubation. The Chi-Square test was used to assess the association between the 2 categorical variables. RESULTS: Nasal pressure injury was observed in 7 and 19 patients from groups S and C, respectively, representing a significant difference between the 2 groups (24.1% vs 67.8%, P = .001). Remarkably, none of the patients developed ulcers. CONCLUSION: 3ST prevents nasal pressure injury associated with NTI.

Sequestration of Antimicrobial Agents in Xcoating and Heparin-Coated Extracorporeal Membrane Oxygenation Circuits: An In Vitro Study.

Limited data exist to guide antimicrobial therapy commonly prescribed to patients undergoing extracorporeal membrane oxygenation (ECMO). This study aimed to describe the kinetics of the cefazolin, doripenem, daptomycin, and levofloxacin in heparin-coated and Xcoating ECMO circuits. Circuits were primed with bovine whole blood and maintained at a physiological pH and temperature for 24 h. Each antimicrobial agent was added to the whole blood before priming. Equivalent doses of these drugs were added to glass jars containing fresh bovine whole blood as a control. Serial blood samples were collected from the ECMO circuits and controls over 24 h, and drug concentrations were quantified using validated assays. The concentrations of cefazolin, doripenem, daptomycin, and levofloxacin did not decrease significantly over 24 h. Collectively, these antimicrobial agents can be administered without the need to consider sequestration when using either heparin-coated or Xcoating circuits.

A doxycycline-inducible CYP3A4-Caco-2 cell line as a model for evaluating safety of aflatoxin B1 in the human intestine.

Exposure of humans to aflatoxin B1 (AFB1) via ingestion of contaminated agricultural products is a major concern for human health throughout the world because epoxidized AFB1, biotransformed from AFB1 by hepatic CYP3A4, is strongly hepatotoxic and hepatocarcinogenic. Intestinal epithelial cells serve as a physical and physiological barrier against xenobiotics via their intercellular tight junction (TJ) seals and the metabolizing enzyme CYP3A4. However, the effect of AFB1 on the intestinal barrier remains unclear. Here, we investigated the influence of AFB1 on these physical and physiological intestinal barriers by means of an in vitro human intestinal model utilizing doxycycline-inducible CYP3A4-expressing Caco-2 cells, in which CYP3A4 activity is comparable to that in the adult human intestine. Cellular toxicity of AFB1 in induced Caco-2 cells (i.e., cells in which expression of CYP3A4 is induced by doxycycline) was approximately 5 times that of uninduced Caco-2 cells. Exposure to 16 µM AFB1 did not decrease the transepithelial electric resistance (TEER; a measure of TJ barrier integrity) in monolayers of uninduced Caco-2 cells to 95.8 % of that in vehicle-treated cells; in contrast, in induced Caco-2 cells, TEER was reduced to 28.8 %. Exposure to 16 µM AFB1 increased paracellular permeation of 4- and 20-kDa dextrans (paracellular permeation markers) through monolayers of induced Caco-2 cells to 5.4 and 5.2 times that through uninduced Caco-2 cells. These results together show that ingested AFB1 can modulate the intestinal barrier, and that inducible CYP3A4-expressing Caco-2 cells are a promising tool for evaluating the safety of food contaminants in the human intestine.

Repositioning of Lansoprazole as a Protective Agent Against Cisplatin-Induced Ototoxicity.

Cisplatin (CDDP) is a well-known chemotherapeutic drug approved for various cancers. However, CDDP accumulates in the inner ear cochlea via organic cation transporter 2 (OCT2) and causes ototoxicity, which is a major clinical limitation. Since lansoprazole (LPZ), a proton pump inhibitor, is known to inhibit OCT2-mediated transport of CDDP, we hypothesized that LPZ might ameliorate CDDP-induced ototoxicity (CIO). To test this hypothesis, we utilized in vivo fluorescence imaging of zebrafish sensory hair cells. The fluorescence signals in hair cells in zebrafish treated with CDDP dose-dependently decreased. Co-treatment with LPZ significantly suppressed the decrease of fluorescence signals in zebrafish treated with CDDP. Knockout of a zebrafish homolog of OCT2 also ameliorated the reduction of fluorescence signals in hair cells in zebrafish treated with CDDP. These in vivo studies suggest that CDDP damages the hair cells of zebrafish through oct2-mediated accumulation and that LPZ protects against CIO, possibly inhibiting the entry of CDDP into the hair cells via oct2. We also evaluated the otoprotective effect of LPZ using a public database containing adverse event reports. The analysis revealed that the incidence rate of CIO was significantly decreased in patients treated with LPZ. We then retrospectively analyzed the medical records of Mie University Hospital to examine the otoprotective effect of LPZ. The incidence rate of ototoxicity was significantly lower in patients co-treated with LPZ compared to those without LPZ. These retrospective findings suggest that LPZ is also protective against CIO in humans. Taken together, co-treatment with LPZ may reduce the risk of CIO.

Comparison of Emergence Agitation Scale Scores and Creatine Kinase Levels After General Anesthesia in Children: A Prospective Cohort Study.

Introduction A simple indicator of muscle damage is creatine kinase (CK). Although CK elevation is informative for malignant hyperthermia, no study has examined the relationship between the anesthetically awake state and CK in children. We aimed to prospectively examine the relationship between the awakening state and CK on the day after surgery in children who have undergone anesthesia with volatile inhalation anesthetics. Methods The study included 119 patients aged 0-15 years and scheduled to undergo general anesthesia for cleft lip and palate-related surgery. Emergence agitation (EA) was assessed after completion of general anesthesia using the five-point EA scale, and patients were divided into the following five groups according to the EA score: EA1, EA2, EA3, EA4, and EA5. The primary outcome was ΔCK (comparison of CK values one week prior to surgery to CK values on the day after surgery) in each EA group. The secondary outcome was ΔCK when the EA score was divided into the following two groups: EA ≤2 (EA score of 1 or 2) and EA ≥3 (EA score of 3, 4, or 5). Results The median ΔCK values in the EA1 to EA5 groups were 3 (quartile -19~9), 5 (-32~88), 99.5 (-18~190.5), 121 (29~219.5), and 144 (41~340.5), respectively, indicating a statistically significant difference overall. Statistically significant differences were also observed between the EA1 and EA4 groups and between the EA2 and EA4 groups. The median ΔCK values in the EA ≤2 and EA ≥3 groups were 3 (quartile -27~85) and 108 (23.5~206.7), respectively, indicating a statistically significant difference. Conclusion The results of this study revealed that a higher EA score at the time of anesthesia awakening is associated with a larger ΔCK, indicating that a high CK level on the day after surgery is highly related to the state of the patient upon awakening.

Concomitant palonosetron ameliorates cisplatin-induced nephrotoxicity, nausea, and vomiting: a retrospective cohort study and pharmacovigilance analysis.

BACKGROUND: Cisplatin (CDDP)-induced nephrotoxicity is the most important complication of CDDP treatment. 5-Hydroxytryptamine type 3 receptor antagonists (5-HT3RAs) are widely used to prevent chemotherapy-induced nausea and vomiting (CINV). However, in patients with the triple antiemetic (neurokinin-1 receptor antagonist, 5-HT3RA, and dexamethasone) therapy, the advantage of palonosetron in comparison with other 5-HT3RAs on CDDP-induced nephrotoxicity and CINV remains unclear. In the present study, we investigated the effect of palonosetron on CDDP-induced nephrotoxicity and CINV in patients with the triple antiemetic therapy by a retrospective cohort study and a pharmacovigilance analysis. METHODS: We retrospectively analyzed the effect of 5-HT3RAs on the development of nephrotoxicity and CINV in 110 patients who received CDDP, fluorouracil, and triple antiemetic therapy for the treatment of esophageal cancer. Moreover, the effect of 5-HT3RAs on CDDP-induced nephrotoxicity was validated in patients with the triple antiemetic therapy using the Japanese Adverse Drug Event Report (JADER) database. RESULTS: In a retrospective study, the incidence of nephrotoxicity (≥ grade 1) in patients receiving palonosetron (18%) was significantly lower than that in patients receiving ramosetron (another 5-HT3RA) (36%, p = 0.044). Moreover, severe nephrotoxicity ≥ grade 3 was observed in one patient treated with ramosetron, whereas hematological toxicity was comparable between the two groups (p = 0.553). Furthermore, the incidence rate of CINV within 120 h following CDDP administration in patients treated with palonosetron (18%) was significantly lower than that in patients receiving ramosetron (39%, p = 0.026). JADER database analyses revealed that the reporting odds ratio of palonosetron for CDDP-induced acute kidney injury was 0.282 (95% confidence interval: 0.169-0.472). CONCLUSIONS: The findings of the present study suggested a greater potential of palonosetron against CDDP-induced nephrotoxicity and CINV than other 5-HT3RAs in patients with the triple antiemetic therapy.

Usefulness of Continuous Low-Dose Fentanyl in Combination with Dexmedetomidine and Midazolam for Intravenous Sedation: A Randomised Controlled Trial.

Intravenous dexmedetomidine (DEX) and midazolam (MZ) are currently used to achieve sedation in dental surgery under local anaesthesia. However, the efficacy of low-dose fentanyl (FEN) in combination with DEX and MZ sedation remains unclear. Therefore, we implemented a prospective randomised controlled trial to investigate the intra- and postoperative analgesic effects, intraoperative respiratory and circulatory dynamics, and frequency of intra- and postoperative adverse events of continuous low-dose fentanyl administration with DEX and MZ sedation. Patients aged 20-64 years scheduled for dental surgery under sedation were randomly assigned to the DEX+MZ (DM) or DEX+MZ+FEN (DMF) group. DEX was administered at 4 µg/kg/h for 10 min and then reduced to 0.7 µg/kg/h until the end of surgery. MZ was administered at 0.04 mg/kg upon the initial administration of DEX and 0.02 mg/kg every hour thereafter. In the DMF group, FEN infusion was administered at 2 µg/kg/h during the initial administration of DEX and then reduced to 1 µg/kg/h after 10 min until the end of surgery. Primary outcomes were intra- and postoperative analgesic efficacies, whereas secondary outcomes were intraoperative respiratory and circulatory dynamics. The total amount of intraoperative local anaesthetic administered and the heart rate were significantly lower in the DMF group than in the DM group (P = 0.044 and P < 0.01, respectively). No significant difference was observed in the frequency of postoperative administration of analgesics and intra- and postoperative adverse events. These findings demonstrated that low-dose FEN infusion in combination with DEX and MZ sedation in dental surgery provides intraoperative analgesia and suppresses tachycardia with little effect on blood pressure and respiratory dynamics and without effect on postoperative analgesia.

Perioperative Management of a Patient With von Recklinghausen's Disease With Anticipated Difficult Airway Management: A Case Report.

Von Recklinghausen's disease is characterized by skin pigmentation, multiple neurofibromatosis, and osseous changes. In the anesthetic management of patients with von Willebrand's disease, it is important to provide appropriate airway management, taking into account the cutaneous laxity caused by neurofibromatosis of Recklinghausen's disease. This case describes the perioperative management of a patient with Recklinghausen's disease with suspected difficulty in airway management.

Proton Pump Inhibitors Ameliorate Capecitabine-induced Hand-Foot Syndrome in Patients With Breast Cancer: A Retrospective Study.

BACKGROUND/AIM: Hand-foot syndrome (HFS) is the most common adverse event associated with capecitabine, and its pathogenesis is known to be associated with inflammation. Proton pump inhibitors (PPIs) reportedly exert anti-inflammatory effects; however, the impact of PPIs on capecitabine-induced HFS needs to be clarified in the clinical setting. In the present study, we retrospectively investigated the efficacy and safety of PPIs in patients with breast cancer receiving capecitabine. PATIENTS AND METHODS: We analyzed the effects of PPIs on the development of severe HFS (grade ≥2), progression-free survival (PFS), and overall survival (OS) in 195 patients who received capecitabine chemotherapy for breast cancer. RESULTS: In total, 50 patients (26%) were treated with PPIs, while 145 patients (74%) did not receive PPIs. The incidence of severe HFS was significantly lower in patients who received PPIs (18%) than in patients who did not receive PPIs (43%, p=0.001), and the discontinuation rate of capecitabine therapy due to HFS was also lower in patients receiving PPIs than in those who did not receive PPIs (p=0.003). Multivariate analysis revealed that concomitant PPIs use was an independent factor that significantly contributed to the prevention of severe HFS (odds ratio (OR)=0.265, p=0.003). Meanwhile, no significant difference in median PFS and OS values was observed between patients treated with and without PPIs. CONCLUSION: Concomitant use of PPIs could ameliorate capecitabine-induced HFS in patients with breast cancer.

Comparison of hemostatic effect and safety between epinephrine and tramazoline during nasotracheal intubation: a double-blind randomized trial.

BACKGROUND: Nasal bleeding is the most common complication during nasotracheal intubation (NTI). To reduce nasal bleeding, the nasal mucosa is treated with vasoconstrictors (epinephrine [E] or tramazoline [T]) prior to NTI. This study aimed to determine whether E or T is more effective and safe for reducing nasal bleeding during NTI. METHODS: This study was preregistered on UMIN-CTR after being approved by the IRB of the School of Dentistry at Aichi Gakuin University. Written consent was received from all the patients. Total 206 patients aged 20-70 years and classified as 1-2 on American Society of Anesthesiologists-physical status were scheduled to undergo general anesthesia with NTI. At last, 197 patients were randomly divided into two groups and treated with either E (n = 99; 3 patients were discontinued) or T (n = 98; 2 patient were discontinued). After induction of general anesthesia, each patient's nasal mucosa was treated using either E or T. The E used in this study was BOSMIN® SOLUTION 0.1% (Daiichi-Sankyo Co., Ltd., Tokyo), and the T used in this study was TRAMAZOLIN Nasal Solution 0.118% AFP, (Alfresa Pharma Corporation, Osaka). E was diluted five times according to the package insert (final concentration of E = 0.02%), and T was used in its original solution. After 2 min, NTI was performed via the right nostril. Primary outcome were the presence of nasal bleeding (if bleeding was recognized at the posterior pharyngeal wall via nasal cavity during intubation, it was defined as bleeding) and the degree of bleeding (classified as none, mild, moderate, or severe). Secondary outcomes were arrhythmia, and hemodynamic (mean atrial pressure and heart rate) changes associated with vasoconstrictors. RESULTS: The presence of bleeding was comparable in both groups (12.5%, E; 14.5%, T; P = 0.63). No significant difference between the groups regarding the degree of bleeding (P = 0.78) was observed, with most patients having no bleeding (n = 84, E; n = 82, T). No severe bleeding and no arrhythmias induced by vasoconstrictor were observed in the two groups. CONCLUSIONS: Nasal treatment with E or T shows no difference in nasal bleeding during NTI. Although no arrhythmia associated with E was observed in this study, it has been reported in literature. Therefore, as frequency and degree of nasal bleeding were comparable, nasal treatment with T could reduce the risk of NTI. TRIAL REGISTRATION: UMIN-CTR (Registration No. UMIN000037907 ). Registered (05/09/2019).

A Case of Childhood-Onset Basedow-Graves' Disease Diagnosed as a Result of the Fourth Time of General Anesthesia for Oral and Maxillofacial Surgery.

The incidence of childhood-onset Basedow's (Graves') disease is approximately 5% of all cases. Herein, we report a teenage female patient diagnosed with childhood-onset Graves' disease immediately following general anesthesia. Her signs and symptoms included tachycardia immediately prior to general anesthesia, delirium upon emerging from anesthesia, persistent postoperative tachycardia and anxiety, and prolonged nausea and vomiting.

Effect of number of medications and complexity of regimens on medication adherence and blood pressure management in hospitalized patients with hypertension.

INTRODUCTION: Good adherence of antihypertensives is recommended for the accomplishment of hypertension therapy. The number of medications and characteristics contributing to medication regimen complexity, such as dosage forms and dosing frequency, are known to influence medication adherence. However, the effect of medication regimen complexity on the therapeutic efficacy of medicines remains to be clarified. In the present study, we retrospectively investigated the effect of number of medications and medication regimen complexity on medication adherence and therapeutic efficacy in patients with hypertension. METHODS: According to the inclusion and exclusion criteria, 1,057 patients, who were on medications including antihypertensives on admission at the Mie University Hospital between July 2018 and December 2018, were enrolled in this study. Poor blood pressure management was defined if the systolic or diastolic blood pressure were ≥140 mmHg or ≥ 90 mmHg. Medication regimen complexity was quantified using the medication regimen complexity index (MRCI) score. RESULTS: Among 1,057 patients, 164 and 893 patients were categorized into poor and good adherence groups, respectively. The multivariate analyses revealed that age ≥ 71 years and oral MRCI score ≥ 19.5 but not number of oral medications were extracted as risk factors for poor medication adherence. Medication adherence and blood pressure management were poor in the group with oral MRCI score ≥ 19.5, regardless of the age. The rate of readmission was similar. CONCLUSION: Our study is the first to demonstrate that medication regimen complexity rather than number of medications is closely related to medication adherence and blood pressure management. Hence, physicians and/or pharmacists should consider the complexity of medication regimens while modifying them.

Opioid therapy duration before naldemedine treatment is a significant independent risk of diarrhea: a retrospective cohort study.

BACKGROUND: The most common adverse event (AE) associated with opioid analgesics is opioid-induced constipation (OIC). Naldemedine (NAL) is widely used for the treatment of OIC. However, diarrhea has been reported as the most common treatment-emergent AE of NAL, and little is known about the risk factors associated with the development of diarrhea during NAL administration. This study examined the risk factors for NAL-induced diarrhea via a retrospective chart review of hospitalized patients. METHODS: The data of 101 hospitalized adult patients who received NAL for the first time for the treatment of OIC at Mie University Hospital between June 2017 and December 2018 were extracted from electronic medical records. According to the inclusion and exclusion criteria, 70 of the 101 patients were enrolled in this study. Diarrhea was defined as "diarrhea" on the medical record within 2 weeks of NAL administration. Univariate and multivariate analyses were performed to identify risk factors for the development of diarrhea in patients receiving NAL. RESULTS: Twenty-two of the 70 patients enrolled (31%) developed diarrhea within 2 weeks of NAL administration. The median duration (range) of NAL treatment before diarrhea onset was 3 (1-12) days. Patients with diarrhea had a significantly longer duration of opioid therapy before NAL administration than patients without diarrhea (P=0.002). Multivariate logistic regression analysis indicated that the independent risk factors for the development of NAL-induced diarrhea were NAL administration after more than 17 days of opioid therapy (odds ratio [OR]=7.539; P=0.016) and pancreatic cancer (OR=6.217; P=0.025). In fact, the incidence of diarrhea in patients who were administered NAL within a day of opioid therapy was significantly lower than that in patients who were administered NAL after more than 17 days of opioid therapy (13% vs. 54%, P=0.030). CONCLUSIONS: These results suggested that a prolonged duration of opioid therapy prior to NAL initiation is associated with increased incidence of diarrhea.

Evaluation of patients suffered from burning mouth syndrome and persistent idiopathic facial pain using Japanese version PainDETECT questionnaire and depression scales.

BACKGROUND/PURPOSE: Various questionnaires have been validated as methods for screening of neuropathic pain, but none have been established for the orofacial region. Although chronic pain and depression are likely to comorbid, few studies have examined the relationship between orofacial chronic pain and depression. Therefore, we evaluated the potential of the Japanese Version of PainDETECT as an assessment tool for neuropathic pain associated with burning mouth syndrome (BMS) and persistent idiopathic facial pain (PIFP). We also evaluated the depression scale such as Beck's Depression Inventory (BDI: a subjective index) and Hamilton Depression Rating Scale (HDRS: an objective index) with BMS or PIFP. MATERIALS AND METHODS: As a target, we administered the Japanese version of the PainDETECT questionnaire to the BMS (29 patients) and PIFP (17 patients). As a control, patients with post-extraction pain (typical nociceptive pain, (EXT) 16 patients) were also participated. We performed BDI and HDRS with BMS or PIFP. RESULTS: Although PainDETECT final score was significantly higher in BMS [median: 10] compared with PIFP [6] and EXT [5] (p < 0.05), PainDETECT final scores for all groups were lower than the cutoff value for the possibility of neuropathic pain. HDRS was significantly higher in the BMS than the PIFP. There were no significant differences between the BMS and PIFP in BDI. CONCLUSION: Under the limitations of current research design, the Japanese version of the PainDETECT questionnaire does not show sufficient potential as pain assessment tool for patients with BMS and PIFP. BMS is comorbid with depression objectively when compared with PIFP.