Short-Term Effects of Early Postoperative Celecoxib Administration for Pain, Sleep Quality, and Range of Motion After Total Knee Arthroplasty: A Randomized Controlled Trial.

BACKGROUND: We hypothesized that early postoperative administration of celecoxib would reduce pain scores and improve sleep quality and active range of motion after total knee arthroplasty (TKA) under general anesthesia. METHODS: Patients in the celecoxib group received 400 mg of celecoxib 2 hours after TKA, followed 6 hours later by 200 mg of celecoxib. Patients in the control group received 400 mg of celecoxib the second day after surgery. Patients in both group had access to patient-controlled analgesia fentanyl. The primary outcome measure was the patient-reported visual analog scale (VAS) pain score the second day after TKA. The secondary outcome measure was sleep quality (days 1, 2, and 7 postoperatively). Active knee joint range of motion was assessed on days 2 and 7 postoperatively, and VAS pain scores were evaluated on postoperative days 1 to 7. Total fentanyl consumption was also assessed. RESULTS: Compared to the control group, the celecoxib group had significantly lower median VAS pain scores on postoperative days 1 and 2, significantly less nocturnal awakening (in minutes) and frequency of body motion, and better sleep efficacy on postoperative day 1. The celecoxib group also had a significantly better median flexion angle (°) on postoperative days 2 and 7, and lower cumulative fentanyl consumption. CONCLUSION: Early administration of celecoxib after TKA was associated with significantly reduced early VAS pain scores and improved sleep quality and active knee flexion angles. Thus, the early administration of celecoxib after TKA under general anesthesia may reduce pain and improve sleep quality and functional recovery. LEVELS OF EVIDENCE: Level II, therapeutic study. TRIAL REGISTRATION: UMIN-CTR 000014624 (July 23, 2014).

The Possibility of Suppression of Increased Postprandial Blood Glucose Levels by Gamma-Polyglutamic Acid-Rich Natto in the Early Phase after Eating: A Randomized Crossover Pilot Study.

The natto containing high levels of gamma-polyglutamic acid (γ-PGA) was recently developed. We investigated the effect of γ-PGA-rich natto consumption on postprandial glycemic excursion in humans. A randomized crossover meal test study was performed on healthy volunteers aged 20-64 years using the following test meals: (1) white rice (WR), (2) low-γ-PGA natto meal (WR + low-γ-PGA natto), and (3) high-γ-PGA natto meal (WR + high-γ-PGA natto). Blood samples were obtained at each visit before and for 120 min after loading. The incremental area under the curve (IAUC) of blood glucose and insulin levels was calculated and compared among the test meals. The blood glucose's IAUC at 0-120 min, the primary endpoint, was 20.1% and 15.4% lower for the high- and low-γ-PGA natto meal than for the WR, with a significant difference only between the high-γ-PGA natto meal and WR (p < 0.05). The blood glucose's IAUC at 0-15, 0-30, and 0-45 min was lower for the high-γ-PGA natto meal than for the low-γ-PGA natto meal (all p < 0.05). The possibility that high-γ-PGA natto might suppress blood glucose elevations in the early phase after eating is indicated.

Prescription of potentially inappropriate medications in elderly outpatients: a survey using 2015 Japanese Guidelines.

Background In recent years, rapid increase of elderly population has become a major social problem in developed countries. They tend to receive an increasing number of prescibed drugs due to multiple illnesses, which might include inappropriate medications, in turn leading to health hazards and rising healthcare cost. Objective To evaluate the current status of potentially inappropriate medications prescribed for elderly outpatients and filled by dispensing pharmacies using the recent Japanese Guidelines, and to determine factors that are related to prescribing potentially inappropriate medications. Setting A cross-sectional study of older patients (≥ 75 years) who visited dispensing pharmacies in the Ibaraki Prefecture, Japan. Method We identified patients prescribed potentially inappropriate medications using the "List of Medications that Require Particularly Careful Administration" in the Guidelines (Guideline List). We explored patient's factors related to polypharmacy (≥ 5 medications) and prescription of inappropriate medications through multivariate analysis, and a cutoff value for predicting potentially inappropriate medications through receiver operating characteristic curve analysis. Main outcome measure Prevalence of polypharmacy and potentially inappropriate medications, and patient's factors associated with them. Results Of 8080 patients (39,252 medications) who visited pharmacies during the study period, 43.1% (3481) were prescribed ≥ 5 medications. In total, 2157 patients (26.7%) were prescribed at least one potentially inappropriate medication. The most prescribed inappropriate medication class was (benzodiazepine) sedatives and hypnotics. Potentially inappropriate medications were 7.11 times (95% CI 6.29-8.03) and 1.51 times (1.34-1.71) more likely to be prescribed for patients with ≥ 5 medications and those prescribed by multiple physicians, respectively. A cutoff value for potentially inappropriate medications was found to be five for the total number of medications and four for the number of chronic medications with a systemic effect. Conclusion Prescription of potentially inappropriate medications was increased among patients with ≥ 5 medications and those chronically prescribed ≥ 4 medications with a systemic effect. The Guideline List should be actively used to screen such patients, and to carefully examine prescriptions. Particular care should be exercised when patients are visiting multiple physicians.

Olive leaf tea is beneficial for lipid metabolism in adults with prediabetes: an exploratory randomized controlled trial.

Olive leaves are rich in oleuropein, which has been shown to have beneficial effects on dyslipidemia, type 2 diabetes, and obesity. However, we previously found no significant health benefits of olive leaf tea (OLT) on nonobese and nondiabetic individuals. Thus, we performed this study to further explore the health benefits of OLT in individuals with prediabetes and compare the health benefits between low-concentration OLT (LOLT) and OLT. We hypothesized that OLT will have a more pronounced effect on abdominal obesity as well as glucose and lipid metabolism in prediabetic individuals. Individuals between 40 and 70 years of age with a body mass index of 23.0-29.9 kg/m2 and prediabetes status were recruited and randomly assigned to the OLT or the LOLT group. The intervention, which was the consumption of 330 mL of the test beverage 3 times daily during mealtime, lasted for 12 weeks. After the intervention, serum levels of log-transformed triglycerides (P < .05) and low-density lipoprotein cholesterol (P < .01) decreased significantly in the OLT group (n = 28), with the reductions higher in the OLT group than those in the LOLT group (n = 29, log-transformed triglycerides: P = .079, low-density lipoprotein cholesterol: P < .05). Whereas body weight, waist circumference, and insulin levels were not significantly changed in both groups, fasting plasma glucose levels in the OLT group were significantly decreased compared to those in the LOLT group (P < .05). In conclusion, although the effect of OLT on abdominal obesity and glucose metabolism remains unclear, OLT has been found to have lipid-lowering effects.

Comparison of glucose monitoring between Freestyle Libre Pro and iPro2 in patients with diabetes mellitus.

AIMS/INTRODUCTION: Flash and continuous glucose monitoring systems are becoming prevalent in clinical practice. We directly compared a flash glucose monitoring system (FreeStyle Libre Pro [FSL-Pro]) with a continuous glucose monitoring system (iPro2) in patients with diabetes mellitus. MATERIALS AND METHODS: Glucose concentrations were simultaneously measured using the FSL-Pro, iPro2 and self-monitoring blood glucose in 10 patients with diabetes mellitus, and agreement among them was assessed. RESULTS: Parkes error grid analysis showed that the 92.9 and 7.1% of glucose values measured using the FSL-Pro fell into areas A and B, respectively, and that 96.3, 2.8 and 0.9% of those determined using iPro2 fell into areas A, B and C, respectively. The median absolute relative differences compared with self-monitoring blood glucose were 8.1% (3.9-12.7%) and 5.0% (2.6-9.1%) for the FSL-Pro and iPro2, respectively. Analysis of 5,555 paired values showed a close correlation between FSL-Pro and iPro2 glucose values (ρ = 0.96, P < 0.01). Notably, 65.3% of all glucose values were lower for the FSL-Pro than the iPro2. Median glucose values also decreased by 3.3% for the FSL-Pro compared with the iPro2 (177.0 [133.0-228.0] vs 183.0 [145.0-230.0] mg/dL, P < 0.01). The difference in glucose values between the two systems was more pronounced in hypoglycemia. The median absolute relative difference between FSL-Pro and iPro2 during hypoglycemia was much larger than that during euglycemia and hyperglycemia. CONCLUSIONS: Both the FSL-Pro and iPro2 systems are clinically acceptable, but glucose values tended to be lower when measured using the FSL-Pro than the iPro2. Agreement was not close between these systems during hypoglycemia.

A comparison of nephrotoxicity between patients with a solitary-functioning kidney and those with bilateral-functioning kidneys in cisplatin-based chemotherapy for advanced urothelial carcinoma: a Japanese retrospective multi-institutional study.

BACKGROUND: To compare the prevalence of nephrotoxicity between patients with a solitary-functioning kidney versus those with bilateral-functioning kidneys during the administration of cisplatin-based chemotherapy for advanced urothelial carcinoma. METHODS: We retrospectively analyzed 244 advanced urothelial carcinoma patients treated with cisplatin-based chemotherapy between 2004 and 2010 at 17 institutes in Japan. The 24 h creatinine clearance, Cockcroft-Gault formula, and estimated glomerular filtration rate equation (eGFR), were compared before all chemotherapies. The urinary tract function status was determined based on the data of nephroureterectomy, hydronephrosis, and relief of upper urinary tract obstruction. A total of 244 patients were divided into four groups according to their urinary tract functioning status and eGFR results, including bilateral-functioning kidneys with pretreatment eGFR ≥60 mL/min/1.73 m2 group (n = 83, 34.0%); a solitary-functioning kidney with pretreatment eGFR ≥60 mL/min/1.73 m2 group (n = 36, 14.8%); bilateral-functioning kidneys with pretreatment eGFR < 60 mL/min/1.73 m2 group (n = 45, 18.4%); and a solitary-functioning kidney with pretreatment eGFR < 60 mL/min/1.73 m2 group (n = 80, 32.8%). RESULTS: The prevalence of nephrotoxicity with impaired eGFR of > 10% and 30% from baseline in the post-third-course of chemotherapy was significantly higher in patients with bilateral-functioning kidneys than in those with a solitary-functioning kidney, among patients with pretreatment eGFR < 60 mL/min/1.73 m2 (p = 0.023 and p = 0.026). During all courses of chemotherapy, the prevalence of nephrotoxicity with impaired eGFR of > 20% from baseline were significantly higher in patients with bilateral-functioning kidneys than those with a solitary-functioning kidney among patients with pretreatment eGFR < 60 mL/min/1.73 m2 (p = 0.034), whereas no significant difference was observed among patients with pretreatment eGFR ≥60 mL/min/1.73 m2. CONCLUSIONS: The results suggest that cisplatin-based chemotherapy may have more nephrotoxicity in patients with bilateral-functioning kidneys than in those with a solitary-functioning kidney.

Current status of systemic chemotherapy for octogenarians with advanced urothelial cancer in Japan: a Japanese multi-institutional study (CURE study).

BACKGROUND: The standard regimen of systemic chemotherapy for patients with advanced urothelial cancer (UC) changed from methotrexate, vinblastine, adriamycin, and cisplatin (MVAC) to gemcitabine and cisplatin (GC) in 2008 when the use of gemcitabine for UC began to be reimbursed by public health insurance in Japan. We examined its influence on the chemotherapy trend in elderly patients aged ≥80 years. METHODS: Among 345 patients included in our previous multicenter retrospective cohort study (chemotherapy for urothelial carcinoma: renal function and efficacy study; CURE study), the outcome of 30 patients aged ≥80 years was reviewed before and after 2008 and compared with 315 young patients. RESULTS: There were only 7 (4.6 %) elderly individuals among all registered patients before 2008, whereas the number increased to 23 (12 %) after 2008. Before 2008, only one elderly patient received MVAC, while GC (whose rate was similar to the rate in young patients) was administered to 13 patients (56.5 %) after 2008. The chemotherapeutic effect and overall survival (OS) rate was not significantly different between young and elderly patients. In the elderly treated with the GC regimen, the renal impairment rate after the first cycle was significantly higher, and the presence of distant metastases and renal impairment were independent prognostic factors in a multivariate analysis. CONCLUSION: Since GC was approved as the standard regimen for first-line chemotherapy in UC, selected elderly patients have been able to safely receive systemic chemotherapy like young patients. The clinical response rate and OS rate were similar to the young, but we need to monitor changes in renal function more closely in the elderly treated with GC.

Effects of postoperative administration of celecoxib on pain management in patients after total knee arthroplasty: study protocol for an open-label randomized controlled trial.

BACKGROUND: Multimodal analgesia is achieved by combining different analgesics and different methods of analgesic administration, synergistically providing superior pain relief when compared with conventional analgesia. Multimodal analgesia can also result in reductions in the side effects and complications of analgesia, thereby improving patient safety. Preventive analgesia, treatment before initiation of the surgical procedure, has a potential to be more effective in reducing pain sensitization than treatment initiated after surgery. Multimodal analgesia that includes prophylactic administration of selective cyclooxygenase-2 (COX-2) inhibitors can improve postoperative pain and reduce opioid analgesic consumption after total knee arthroplasty (TKA). However COX-2 inhibitors are not approved for use as preventive analgesia in Japan. Thus, assessing the effectiveness of COX-2 inhibitors during the early postoperative period is important to establish clinical practice guidelines in Japan. This study was designed to examine the effects of celecoxib administration immediately after surgery, in addition to multimodal analgesia, on postoperative pain management after TKA. METHODS/DESIGN: This randomized, prospective, open-label controlled study will include 120 patients undergoing unilateral TKA. All patients will routinely receive single injections of femoral and sciatic nerve blocks, along with postoperative patient-controlled analgesia (PCA) with fentanyl. Patients will be randomly assigned to receive or not receive immediate postoperative administration of celecoxib. The primary outcome is a visual analog scale (VAS) pain score the second day after surgery. Secondary outcomes include opioid consumption, VAS pain score for 7 days after surgery, range of knee motion, evaluation of sleep quality, overall evaluations by patients and physicians, rates of postoperative nausea and vomiting, and consumption of rescue analgesics. DISCUSSION: The objective of this study is to evaluate the effects of celecoxib administration immediately after surgery on pain after TKA surgery. A randomized controlled trial design will address the hypothesis that administration of oral celecoxib immediately after surgery, along with multimodal analgesia that includes peripheral nerve block and PCA, could reduce VAS pain score after TKA surgery. TRIAL REGISTRATION: UMIN-CTR 000014624 (23 July 2014).

Do dispatcher instructions facilitate bystander-initiated cardiopulmonary resuscitation and improve outcomes in patients with out-of-hospital cardiac arrest? A comparison of family and non-family bystanders.

OBJECTIVES: Bystander-initiated cardiopulmonary resuscitation (CPR) has been reported to increase the possibility of survival in patients with out-of-hospital cardiopulmonary arrest (OHCA). We evaluated the effects of CPR instructions by emergency medical dispatchers on the frequency of bystander CPR and outcomes, and whether these effects differed between family and non-family bystanders. METHODS: We conducted a retrospective cohort study, using Utstein-style records of OHCA taken in a rural area of Japan between January 2004 and December 2009. RESULTS: Of the 559 patients with non-traumatic OHCA witnessed by laypeople, 231 (41.3%) were given bystander CPR. More OHCA patients received resuscitation when the OHCA was witnessed by non-family bystanders than when it was witnessed by family members (61.4% vs. 34.2%). The patients with non-family-witnessed OHCA were more likely to be given conventional CPR (chest compression plus rescue breathing) or defibrillation with an AED than were those with family-witnessed OHCA. Dispatcher instructions significantly increased the provision of bystander CPR regardless of who the witnesses were. Neurologically favorable survival was increased by CPR in non-family-witnessed, but not in family-witnessed, OHCA patients. No difference in survival rate was observed between the cases provided with dispatcher instructions and those not provided with the instructions. CONCLUSIONS: Dispatcher instructions increased the frequency of bystander CPR, but did not improve the rate of neurologically favorable survival in patients with witnessed OHCA. Efforts to enhance the frequency and quality of resuscitation, especially by family members, are required for dispatcher-assisted CPR.