Comparative profiles of lubiprostone, linaclotide, and elobixibat for chronic constipation: a systematic literature review with meta-analysis and number needed to treat/harm.

OBJECTIVE: To comprehensively evaluate the efficacy, safety, patient symptoms, and quality-of-life (QoL) of lubiprostone, linaclotide, and elobixibat as treatment for chronic constipation (CC). DESIGN: Systematic literature review (SLR) and meta-analysis (MA). Literature searches were conducted on PubMed and Embase using the Ovid platform. METHODS: SLR including randomized controlled trials (RCTs) and observational studies was conducted to identify the overall efficacy and safety of lubiprostone, linaclotide, and elobixibat. Thereafter, MA was performed using only RCTs. The number needed to treat (NNT) and number needed to harm (NNH) analyses were additionally conducted. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was efficacy regarding change in spontaneous bowel movements. Secondary outcomes included safety, constipation-related symptoms, and QoL. RESULTS: Twenty-four studies met the inclusion criteria for the SLR: 17 RCTs, 4 observational studies, and 3 single-arm trials. Feasibility assessment for the MA resulted in 14 studies available for safety data analysis, and 8 available for efficacy analysis, respectively. Three drugs showed similar efficacy in the MA and NNT analysis. However, the NNH analysis revealed distinct safety profiles: lubiprostone, linaclotide, and elobixibat were linked to the highest risk of nausea, diarrhea, and abdominal pain, respectively. CONCLUSION: The current study provides an updated overview of the efficacy, safety, patient symptoms, and QoL of the three drugs with different mechanisms of action for CC treatment.The findings could help physicians adopt an individualized approach for treating patients with CC in clinical practice.

Dietary therapy for patients with chronic pancreatitis in Japan: a cross-sectional online survey of physicians and registered dietitians.

Background: This study was aimed towards understanding the current status of dietary therapy for patients with pancreatic exocrine insufficiency (PEI) in Japan and its alignment with Japanese recommendations for high-fat intake and concomitant high-potency pancreatic enzyme replacement therapy (PERT) by surveying treating physicians and registered dietitians. Methods: The 19-item physicians' online questionnaire collected data about the number of patients with PEI treated, methods used to assess PEI and nutritional status in patients with PEI, as well as provision of dietary guidance and details of treatment with PERT. The 10-item registered dietitians' online questionnaire captured data about the provision of dietary guidance, including setting (inpatient or outpatient) and details of nutritional guidance provided to patients. Results: Overall, 35 physicians and 23 dietitians completed the respective questionnaires. The primary cause of PEI in patients treated by physicians during the previous month was chronic pancreatitis (80.5%). Of 30 (86%) physicians who reported implementing dietary guidance for patients with PEI, less than half (43%) followed national guidelines and most (83%) implemented a low-fat diet. The use of PERT in recently treated patients with PEI was low. Amongst 11 (48%) dietitians who reported providing dietary guidance to patients with chronic pancreatitis and PEI, 7 (64%) recommended restricting fat intake in patients with uncompensated chronic pancreatitis. Dietitians overall were more likely to provide guidance about alcohol avoidance (91%) than smoking cessation (48%) to appropriate patients. Conclusion: This survey suggests that additional educational efforts are required to align the management practices of physicians and registered dietitians with evidence-based clinical practice guidelines for Japanese patients with chronic pancreatitis and PEI.

Perioperative Analgesics and Anesthesia as Risk Factors for Postoperative Chronic Opioid Use in Patients Undergoing Total Knee Arthroplasty: A Retrospective Cohort Study Using Japanese Hospital Claims Data.

BACKGROUND: Patients with chronic postsurgical pain are commonly prescribed opioids chronically because of refractory pain although chronic opioid use can cause various severe problems. OBJECTIVE: We aimed to investigate postoperative chronic opioid use and its association with perioperative pain management in patients who underwent a total knee arthroplasty in a Japanese real-world clinical setting. METHODS: We conducted a retrospective cohort study using an administrative claims database. We used a multivariate logistic regression analysis to examine the association between perioperative analgesic and anesthesia prescriptions and postoperative chronic opioid use. We calculated all-cause medication and medical costs for each patient. RESULTS: Of the 23,537,431 patient records, 14,325 patients met the criteria and were included in the analyses. There were 5.4% of patients with postoperative chronic opioid use. Perioperative prescriptions of weak opioids, strong and weak opioids, and the α2δ ligand were significantly associated with postoperative chronic opioid use (adjusted odds ratio [95% confidence interval], 7.22 [3.89, 13.41], 7.97 [5.07, 12.50], and 1.45 [1.13, 1.88], respectively). Perioperative combined prescriptions of general and local anesthesia were also significantly associated with postoperative chronic opioid use (3.37 [2.23, 5.08]). These medications and local anesthesia were more commonly prescribed on the day following surgery, after routinely used medications and general anesthesia were prescribed. The median total direct costs were approximately 1.3-fold higher among patients with postoperative chronic opioid use than those without postoperative chronic opioid use. CONCLUSIONS: Patients who require supplementary prescription of analgesics for acute postsurgical pain are at high risk of postoperative chronic opioid use and these prescriptions should be given careful consideration to mitigate the patient burden.

Relationship of Annual Health Checkups with the Subject's Subsequent Behavior of Cardiovascular Risk Management in a Real-World Setting in Japan: A Retrospective Cohort Study on Changes in Antihypertensive Drug Prescription and Blood Pressure from 2015 to 2017.

BACKGROUND: In Japan, workers receive a health checkup annually, and based on the results, a follow-up health guidance or intervention is provided when deemed necessary. However, it remains unclear whether the current real-world health checkup and guidance programs in Japan successfully lead to behavioral changes or improvement of clinical outcomes in individuals who require cardiovascular (CV) risk management. OBJECTIVE: This study aimed to explore the association between health checkup and the subsequent behavior change in CV risk management in subjects with uncontrolled blood pressure (BP) without antihypertensive drug prescription, who can have increased risk of CV events. PATIENTS AND METHODS: This was a retrospective cohort study that used health-checkup and claims data from a Japanese healthcare database managed by MinaCare Co., Ltd. Of those aged 20-74 years with available data on systolic and diastolic BP from 2015 to 2017, data from individuals with uncontrolled BP who were not prescribed antihypertensive drugs within 6 months before their baseline health checkup in 2015 were extracted and analyzed. The primary outcome measures were changes in antihypertensive drug prescription and BP control status based on health-checkup results from the baseline year (2015) to 2017. CV risk-management behavior was also assessed using body mass index (BMI) and smoking status, as these are the major modifiable CV risk factors. RESULTS: Among 39,242 subjects with uncontrolled BP without antihypertensive drug prescription at baseline, 88.9% remained without prescription in 2016. Of the subjects without prescription, 62.9% continued to have uncontrolled BP. Both statuses of the major modifiable CV risk factors remained unchanged in 2016: 92.1% of obese subjects (BMI ≥ 25 kg/m2) at baseline remained obese, and 93.8% of smokers at baseline aged ≥ 40 years continued to smoke. Logistic regression analysis revealed that age 60-69 years (vs. 40-49 years), hypertension (HT) stage II (vs. stage I), HT stage III (vs. stage I), and BMI ≥ 25.0 kg/m2 (vs. < 25.0 kg/m2) were factors associated with uncontrolled BP in 2016 (subsequent year), regardless of antihypertensive drug prescription. CONCLUSIONS: Untreated HT for years increases the risk of CV events. These results suggest that current health-checkup and guidance programs are inadequately effective for behavioral change. Further practices for committing to lifestyle modifications and seeking medical advice based on their health-checkup results need to be undertaken to improve health behavior.

Role of disulphide bonds in a thermophilic serine protease aqualysin I from Thermus aquaticus YT-1.

A thermophilic serine protease, Aqualysin I, from Thermus aquaticus YT-1 has two disulphide bonds, which are also found in a psychrophilic serine protease from Vibrio sp. PA-44 and a proteinase K-like enzyme from Serratia sp. at corresponding positions. To understand the significance of these disulphide bonds in aqualysin I, we prepared mutants C99S, C194S and C99S/C194S (WSS), in which Cys69-Cys99, Cys163-Cys194 and both of these disulphide bonds, respectively, were disrupted by replacing Cys residues with Ser residues. All mutants were expressed stably in Escherichia coli. The C99S mutant was 68% as active as the wild-type enzyme at 40 degrees C in terms of k(cat) value, while C194S and WSS were only 6 and 3%, respectively, as active, indicating that disulphide bond Cys163-Cys194 is critically important for maintaining proper catalytic site conformation. Mutants C194S and WSS were less thermostable than wild-type enzyme, with a half-life at 90 degrees C of 10 min as compared to 45 min of the latter and with transition temperatures on differential scanning calorimetry of 86.7 degrees C and 86.9 degrees C, respectively. Mutant C99S was almost as stable as the wild-type aqualysin I. These results indicate that the disulphide bond Cys163-Cys194 is more important for catalytic activity and conformational stability of aqualysin I than Cys67-Cys99.