Preventive Effects of Bioabsorbable Anti-Adhesion Barriers on Bowel Obstruction After Colectomy in Colon Cancer Patients: A Retrospective Cohort Study Using an Insurance Claims Database.

PURPOSE: Postoperative adhesions can be prevented by the use of bioabsorbable anti-adhesion barriers. Although the occurrence of postoperative bowel obstruction is an important concern for patients, at the time of approval of anti-adhesion barriers, its effectiveness in preventing postoperative bowel obstruction had not been evaluated. We aimed to retrospectively evaluate the incidence of bowel obstruction after colectomy in patients with colon cancer using an insurance claims database. METHODS: This retrospective cohort study analyzed the data of colon cancer patients (between 2005 and 2017 from a national insurance claims database) who underwent colectomies to compare the proportion of individuals with postoperative bowel obstruction between the barrier and no barrier groups. RESULTS: Of the 587 patients who met the inclusion criteria, 308 and 279 patients were identified as the barrier and no barrier groups, respectively. The incidence of postoperative bowel obstruction was significantly lower in the barrier group (log-rank test, P = 0.0483). The cumulative incidence of postoperative bowel obstruction 37 months after the initial colectomy was 6.1% and 10.9% in the barrier and no barrier groups, respectively. Moreover, consistent results were obtained in the matched cohort. CONCLUSION: In colectomies for patients with colon cancer, the use of anti-adhesion barriers could significantly reduce the incidence of postoperative bowel obstruction. Evaluations using insurance claims databases could provide important information on outcomes following implementation of medical devices.

Increased risk of hypocalcemia with decreased kidney function in patients prescribed bisphosphonates based on real-world data from the MID-NET® in Japan: a new-user cohort study.

BACKGROUND: In the post-marketing stage, cases of hypocalcemia associated with bisphosphonate preparations (BPs) have been reported in patients with decreased kidney function, despite warning against use of BPs in such patients in the package insert (PI) of Japan. The purpose of this study was to investigate the safety of BPs in patients with decreased kidney function. METHODS: The cohort study was conducted in patients with osteoporosis and newly prescribed bisphosphonate utilizing real-world data from MID-NET® in Japan. The adjusted hazard ratios (aHRs) for hypocalcemia (a corrected serum Ca level < 8.00 mg/dL) relative to the normal group were calculated in each decreased kidney function group (mild, moderate or severe group). RESULTS: A total of 14,551 patients were included in the analysis, comprising 2,601 (17.88%) with normal (eGFR ≥ 90 mL/min/1.73m2), 7,613 (52.32%) with mild (60 ≤ eGFR < 90 mL/min/1.73m2), 3,919 (26.93%) with moderate (30 ≤ eGFR < 60 mL/min/1.73m2), and 418 (2.87%) with severe kidney function (eGFR < 30 mL/min/1.73m2). The aHRs (95% confidence interval) for hypocalcemia were 1.85 (0.75-4.57), 2.30 (0.86-6.21), and 22.74 (8.37-61.78) in the mild, moderate, and severe groups, respectively. The increased risk of hypocalcemia depending on kidney function was also observed even when calculating the aHR for each specific BP such as alendronate sodium hydrate, minodronic acid hydrate, and sodium risedronate hydrate. Furthermore, similar results were obtained in the sensitivity analysis by altering the outcome definition to a 20% or more reduction in corrected serum Ca level from the baseline, as well as when focusing on patients with more than one laboratory test result per 30 days during the follow-up period. CONCLUSIONS: These findings suggest that the risk of hypocalcemia during BP prescription is higher in patients with decreased kidney function, particularly those with severely decreased kidney function. The quantitative real-world evidence on the safety risk of BPs obtained in this study has led to the PI revision describing a relationship between hypocalcemia risk and decreased kidney function as a regulatory action in Japan and will contribute to promoting the proper use of BPs with appropriate risk management in clinical practice.

Lower Risks of Gastrointestinal Perforation and Intestinal Obstruction in Patients with Atypical Antipsychotics in Comparison with Typical Antipsychotics Based on Real-World Data from the MID-NET® in Japan.

Intestinal perforation and obstruction are known to be one of the adverse events caused by antipsychotics; however, warning information on package inserts varies among antipsychotics. To investigate the risks of gastrointestinal perforation and intestinal obstruction in patients prescribed atypical antipsychotics compared with those in patients prescribed typical antipsychotics, a nested case-control study was conducted utilizing real-world data from the MID-NET® medical information database in Japan. The study period spanned from January 1, 2009, to December 31, 2018. We found that the risks of gastrointestinal perforation and intestinal obstruction in patients prescribed atypical antipsychotics were significantly lower than those in patients prescribed typical antipsychotics (adjusted odds ratio, 0.48; 95% confidence interval, 0.29-0.80). This finding was supported with prolonged periods for the exposure definition in the sensitivity analyses. In addition, no major differences in the risks of atypical antipsychotics, such as risperidone, quetiapine, olanzapine, and aripiprazole, were identified in this study. The safety profile regarding the lower risks of gastrointestinal perforation and intestinal obstruction in patients prescribed atypical antipsychotics should be considered when choosing antipsychotics in clinical practice in terms of the proper use of such drugs.

Assessing the Risk of Decrease in Kidney Function in Patients Prescribed Direct-Acting Antivirals for Hepatitis C Utilizing the MID-NET® Medical Information Database Network in Japan.

An association between kidney disease and direct-acting antivirals against hepatitis C (DAAs) has been suggested, however the warning on the package insert (PI) of the drug varies among DAAs. In this study, the risk of decreased kidney function associated with DAAs marketed in Japan was investigated to determine whether the risk of kidney disease is a common adverse event and class effect of DAAs. Data for patients who were new users of DAAs marketed in Japan, with eGFR ≥ 45 mL/min/1.73 m2 and without specific risk factors, were extracted from the MID-NET® medical information database network in Japan. Changes from the baseline on estimated glomerular filtration rate (eGFR) categories (eGFR ≥ 90, 90 > eGFR ≥ 60, 60 > eGFR ≥ 45, 45 > eGFR ≥ 30, 30 > eGFR ≥ 15, 15 > eGFR; unit: mL/min/1.73 m2) were used for evaluating the risk of decreased kidney function. Exposure groups for DAAs and relevant concomitant drugs were categorized into 10 patterns based on the PI. Among the 10 patterns, a significant increase in the incidence rate ratio (P < 0.01) was observed in the prescription patterns of concomitant use of telaprevir with peginterferon alpha and ribavirin, concomitant use of daclatasvir hydrochloride with asunaprevir, and ombitasvir hydrate combined with paritaprevir hydrate and ritonavir, which were concomitantly used with ribavirin; such an increase was not observed in the other prescription patterns. The effects of DAAs on kidney function may differ among drugs, suggesting the possibility that the risk of kidney disease is not a class effect of DAAs and should be evaluated individually for each DAA.

Predictors of increase in pacing threshold after transcatheter pacing system implantation due to micro-dislodgement.

BACKGROUND: Achieving a favorable pacing threshold with a Micra transcatheter pacing system (Micra-TPS) is needed to reduce battery depletion. In some cases, the threshold increases shortly after the device is implanted, and a higher pacing threshold may be required. This study aims to identify the causes and predictors of the increase in pacing threshold observed shortly after Micra-TPS implantation. METHODS: The study included 64 consecutive patients who underwent Micra-TPS implantation between 2017 and 2020. The patients were divided into two groups depending on their pacing threshold: the increased pacing threshold (IPT) group (threshold increased by ≥0.5 V/0.24 ms within 1 month of implantation) and the stable pacing threshold (SPT) group. RESULTS: Excluding four patients who could not be followed up, of the 60 remaining patients, nine (15%) were in the IPT group and 51 (85%) were in the SPT group. The IPT group had significantly lower implant impedance values and higher implant thresholds than the SPT group (582 ± 59 vs 755 ± 167 Ω [P < .001] and 1.29 ± 0.87 vs 0.71 ± 0.40 V/0.24 ms [P = .014]). Implant impedance and threshold may serve as predictors of a threshold increase after implantation (area under the curve: 0.737-0.943 and 0.586-0.926, respectively). CONCLUSIONS: An IPT was noted shortly after Micra-TPS implantation owing to micro-dislodgement because of insufficient anchoring of the device to the myocardium. Impedance >660 Ω and threshold <1.0 V/0.24 ms may predict an increase in pacing threshold.

Reappraisal of the clinical implications of adenosine triphosphate in terms of the prediction of reconnection sites in cases with electrical isolation of the pulmonary veins.

PURPOSE: Dormant conduction (DC) induced by intravenous adenosine triphosphate (ATP) after pulmonary vein (PV) isolation (PVI) could predict subsequent PV reconnection (RC) sites. This study aimed to investigate the relationship between the DC and RC sites during the long-term follow-up. METHODS: Ninety-one consecutive patients (62 males; mean age, 62 ± 11 years) with symptomatic persistent (n = 18) or paroxysmal (n = 73) atrial fibrillation (AF) who underwent PVI were included in this study. After a successful PVI, we administered ATP to reveal the DC sites. In total, DC sites were observed in 46 (51%) patients, and all were left un-ablated after marking or tagging all of them using fluoroscopic images and a three-dimensional (3D) mapping system. After the follow-up period (14.8 ± 3.6 months), AF recurred in 29 (32%) patients, all of whom had a DC in the initial ablation session, and underwent redo sessions. We divided the DC sites into three groups; in group A, the RC sites differed from the DC sites, in group B, the RC sites were identical to the DC sites, and in group C, the RC sites involved both DC and other sites. RESULTS: As a result, 20 (69%), 3 (11.5%), and 6 (19.5%) patients belonged to groups A, B, and C, respectively. Statistical analyses comparing the agreement between DC and the RC sites yielded a weak relationship. CONCLUSIONS: DC sites implying RC sites had a weak agreement, and other options to predict RC sites will be required to improve the clinical benefit of CA of AF.

Novel use of the ultra-short-acting intravenous ß1-selective blocker landiolol for supraventricular tachyarrhythmias in patients with congestive heart failure.

The purpose of this study was to find a safe dosing regimen for landiolol, an ultra-short-acting ß-adrenergic blocking agent, to rapidly control supraventricular tachyarrhythmias (SVTs) in patients with heart failure (HF). Landiolol is reported to have good effects in the treatment of SVTs after cardiac surgery. We evaluated 52 patients with SVT and symptoms of HF (NYHA class III/IV, 10/42; EF 32 ± 12 %) on admission because of ischaemic disease (n = 10), non-ischaemic cardiomyopathy (n = 32), or valvular disease (n = 10). Paroxysmal/persistent atrial fibrillation and atrial tachycardia were present in 16 (30 %), 23 (45 %), and 13 (25 %) patients, respectively. The patients first underwent conventional therapy with carperitide, dobutamine, or milrinone. Intravenous landiolol was administered at an infusion rate of 1 µg/kg/min and, if no adverse effects developed, the maintenance dose, titrated to HR and blood pressure response, was increased. At an average dose of 10.8 ± 9.4 µg/kg/min, mean HR significantly decreased significantly from 133 ± 27 to 82 ± 15 beats/min (P < 0.01), whereas systolic blood pressure did not differ from baseline to attainment of an effective dose level (105 ± 21 vs. 101 ± 19 mmHg, P = ns). Within 60 min after initiation of therapy, all patients had achieved a 20 % reduction in HR at the maintenance dose. Transient asymptomatic hypotension requiring cessation of landiolol therapy occurred in three patients. Intravenous administration of landiolol was both effective in rapidly controlling HR for up to 24 h and useful as bridging treatment to additional therapy of oral ß blockade, pulmonary vein catheter ablation, or cardiac resynchronisation therapy in patients with HF.