Effectiveness and safety of pegylated liposomal doxorubicin versus epirubicin as neoadjuvant or adjuvant chemotherapy for breast cancer: a real-world study

Background Pegylated liposomal doxorubicin (PLD) is an improved formulation of doxorubicin with comparable effectiveness but significantly lower cardiotoxicity than conventional anthracycline. This study aimed to evaluate the real-world effectiveness and safety of PLD versus epirubicin as neoadjuvant or adjuvant treatment for breast cancer. Methods Clinical data of invasive breast cancer patients who received neoadjuvant or adjuvant chemotherapy with PLD or epirubicin were retrospectively collected. Propensity score matching (PSM) was performed to reduce the risk of selection bias. The molecular typing of these patients included Luminal A, Luminal B, HER2-positive, and basal-like/triple-negative. The primary outcome was pathological complete response (pCR) rate for neoadjuvant chemotherapy and 3-year disease-free survival (DFS) rate for adjuvant chemotherapy. Noninferiority was suggested if the lower limit of the 95% CI for the 3-year DFS rate difference was greater than − 10%. The secondary outcome was adverse reactions. Results A total of 1213 patients were included (neoadjuvant, n = 274; adjuvant, n = 939). pCR (ypT0/Tis ypN0) rates of patients who received neoadjuvant chemotherapy were 11.6% for the PLD group and 7.0% for the epirubicin group, but the difference was not statistically significant (P = 0.4578). The 3-year DFS rate of patients who received adjuvant chemotherapy was 94.9% [95%CI, 91.1–98.6%] for the PLD group and 95.4% [95%CI, 93.0–97.9%] for the epirubicin group (P = 0.5684). Rate difference between the two groups and its 95% CI was - 0.55 [− 5.02, 3.92]. The lower limit of the 95% CI was − 5.0% > − 10.0%, suggesting that PLD is not be inferior to epirubicin in adjuvant chemotherapy for breast cancer. The incidences of myelosuppression, decreased appetite, alopecia, gastrointestinal reactions, and cardiotoxicity were lower in the PLD group than in the epirubicin group, while the incidence of nausea was higher in the PLD group. Conclusions In the neoadjuvant and adjuvant treatment of breast cancer, effectiveness is similar but toxicities are different between the PLD-containing regimen and epirubicin-containing regimen. Therefore, further study is warranted to explore PLD-based neoadjuvant and adjuvant chemotherapy for breast cancer.

Monitoring the Effectiveness and Safety of ARNI vs. Angiotensin Receptor Blocker by Frailty Status

Using Medicare data 2015-2017, we conducted 5 sequential 1-to-1 propensity score-matched analyses of ARNI initiators and angiotensin receptor blockers (ARB) initiators, mimicking the accrual of new data every 6 months. Primary effectiveness endpoint was a composite of heart failure hospitalization or all-cause mortality and primary safety endpoint was a composite of hospitalization or emergency department visits for hypotension, acute kidney injury, hyperkalemia, and angioedema. Among non-frail patients (n=5,014), the rates (per 100 person-years) for ARNI vs ARB were 12.7 and 9.2 (rate difference: 3.4, 95% CI: 0.8 to 6.1), respectively, for the effectiveness endpoint and 5.2 and 3.6 (rate difference: 1.5, 95% CI: -0.1 to 3.2), respectively, for the safety endpoint. Among frail patients (n=2,694), the corresponding rates were 19.8 and 21.6 (rate difference: -1.8, 95% CI: -7.0 to 3.4) for the effectiveness endpoint and 10.9 and 8.0 (rate difference: 2.9, 95% CI: -0.6 to 6.4) for the safety endpoint.

Patient Health Outcomes following Dialysis Facility Closures in the United States

BackgroundOngoing changes to reimbursement of United States dialysis care may increase the risk of dialysis facility closures. Closures may be particularly detrimental to the health of patients receiving dialysis, who are medically complex and clinically tenuous.MethodsWe used two separate analytic strategies—one using facility-based matching and the other using propensity score matching—to compare health outcomes of patients receiving in-center hemodialysis at United States facilities that closed with outcomes of similar patients who were unaffected. We used negative binomial and Cox regression models to estimate associations of facility closure with hospitalization and mortality in the subsequent 180 days.ResultsWe identified 8386 patients affected by 521 facility closures from January 2001 through April 2014. In the facility-matched model, closures were associated with 9% higher rates of hospitalization (relative rate ratio [RR], 1.09; 95% confidence interval [95% CI], 1.03 to 1.16), yielding an absolute annual rate difference of 1.69 hospital days per patient-year (95% CI, 0.45 to 2.93). Similarly, in a propensity-matched model, closures were associated with 7% higher rates of hospitalization (RR, 1.07; 95% CI, 1.00 to 1.13; P=0.04), yielding an absolute rate difference of 1.08 hospital days per year (95% CI, 0.04 to 2.12). Closures were associated with nonsignificant increases in mortality (hazard ratio [HR], 1.08; 95% CI, 1.00 to 1.18; P=0.05 for the facility-matched comparison; HR, 1.08; 95% CI, 0.99 to 1.17; P=0.08 for the propensity-matched comparison).ConclusionsPatients affected by dialysis facility closures experienced increased rates of hospitalization in the subsequent 180 days and may be at increased risk of death. This highlights the need for effective policies that continue to mitigate risk of facility closures.

913Factors of premature atrial contractions among general Japanese men

Background Premature atrial contractions (PACs) are known predictor of atrial fibrillation; however very little has been revealed on its factors among Asian general population. We assessed the frequency of higher PAC counts and its association with relevant factors in general Japanese men. Methods We have conducted a population based cross sectional study among 517 healthy men from Kusatsu, Japan, aged between 40 and 79 years. 24 hours Holter electrocardiogram was performed to assess the PAC frequency. We divided participants into quartiles based on number of PACs/hour to compare the characteristics by using Cochran–Mantel–Hanzal test and ANOVA. We defined the highest quartile as event and multivariable logistic regression was performed to assess the significance with relevant factors. Results Median number of PACs was 2.84 PACs/hour. The highest quartile of PAC counts was >7.86PACs/hour. Age, triglycerides, blood pressure, ventricular contractions and heart rates were different among quartiles. In multivariable logistic regression analysis, higher age (OR, 95% CI: 1.35, 1.01-1.67), lower mean heart rates (OR, 95% CI: 0.97, 0.94-0.99), higher heart rate difference in a day (OR, 95% CI: 1.40, 1.12-1.75) and lower triglyceride (OR, 95% CI: 0.53, 0.33-0.82) were independently, significantly associated with highest quartile of PACs. Conclusions Higher PACs evaluated by Holter ECG was associated with higher age, lower heart rate, higher heart rate difference, and lower triglyceride in general Japanese men. Key messages The PAC frequency was high. Age, mean heart rates, difference between maximum and resting heart rates, triglycerides are possible risk factors for frequent PAC counts.

Effect of different commercial enzymes on the clotting of milk and certain properties of curd

More researches published data about the milk curd properties, evaluated the importance in the cheese making, but an analysis of importance of these properties in practical applications is usually lacking. We investigate the milk curd behaviour using different enzyme preparations at the cutting of curd. We focused on the well measurable properties as clotting time, viscosity of curd, texture properties an whey separation rate of cur at cutting time. Approximately five minutes difference was determined between the clotting times. Investigated the curd properties we found significant differences between the hardness on samples clotted with CHY MAX® M 1000 and NATUREN® Premium 145 enzymes. Other properties did not show significant differences, but in some case differences were remarkable. Discovered differences e.g. approx. 5% whey separation rate difference and the different trends of adhesive force and adhesiveness confirm that such studies should be carried out. Summarized effect of different enzymes can alter the cheese making technology in the practice, significantly. Considering every aspect, in our investigation the CHY MAX® M 1000 enzyme seemed the best.

Mucosal Healing Effectiveness and Safety of Anaprazole, a Novel PPI, vs. Rabeprazole in Patients With Duodenal Ulcers: A Randomized Double-Blinded Multicenter Phase II Clinical Trial

Background: Proton pump inhibitors (PPIs) are validated gastric acid suppressors and have been widely used to treat patients with active duodenal ulcers. Although existing PPIs have shown great efficacy, many scientists are still devoted to developing more effective PPIs with better safety profile. Herein, we aimed to compare the safety and efficacy of anaprazole in duodenal mucosal healing, a novel PPI, to that of rabeprazole.Methods: In this multicenter, randomized, positive-controlled, double-blinded, parallel-group phase II clinical trial, a total of 150 qualified patients with endoscopically confirmed active duodenal ulcers were randomized (1:1:1) to receive rabeprazole 10 mg, anaprazole 20 mg or anaprazole 40 mg for 4 weeks. The ulcer healing rates after 4 weeks of treatment were compared between groups by independent central review and investigator review. In addition, symptoms and safety were evaluated.Results: Based on the independent central review, the ulcer healing rates of the 10 mg rabeprazole, 20 mg anaprazole and 40 mg anaprazole groups were 88.0, 85.1, and 87.5%, respectively, in the FAS population and 88.9, 86.0, and 90.9%, respectively, in the PPS population. The ulcer healing rate difference between anaprazole 20 mg and Rabeprazole 10 mg is −2.9% (95% CI, −16.5–10.7%), and −0.5% (95% CI, −13.5–12.5%) between anaprazole 40 mg and Rabeprazole 10 mg, in the FAS population. Based on the investigator review, the ulcer healing rates of the 10 mg rabeprazole, 20 mg anaprazole, and 40 mg anaprazole groups were 72.0, 70.2, and 77.1%, respectively, in the FAS population and 75.6, 72.1, and 79.5%, respectively, in the PPS population. The ulcer healing rate difference between anaprazole 20 mg and Rabeprazole 10 mg is −1.8% (95% CI, −19.8–16.3%), and 5.1% (95% CI, −12.2–22.3%) between anaprazole 40 mg and Rabeprazole 10 mg, in the FAS population. Most patients (>90%) eventually achieved complete symptom relief. The incidence rates of adverse events were of no significant differences among the treatment groups. Potential possible better liver tolerance was observed in two anaprazole dose groups than rabeprazole 10 mg group.Conclusion: Both at a dosage of 20 and 40 mg daily, anaprazole, is effective with good safety profile in the treatment of active duodenal ulcers in this Phase 2 study, which allows anaprazole to be advanced to a phase III clinical trial.Clinical Trial Registration:https://www.clinicaltrials.gov/ct2/results?cond=&term=NCT04503629&cntry=&state=&city=&dist=, Identifier: CTR20181464, NCT04503629.

Use of incretin-based drugs and risk of cholangiocarcinoma: Scandinavian cohort study

Aims/hypothesis Concerns have been raised regarding a potential association of use of the incretin-based drugs dipeptidyl peptidase 4 (DPP4) inhibitors and glucagon-like peptide-1 (GLP-1)-receptor agonists with risk of cholangiocarcinoma. We examined this association in nationwide data from three countries. Methods We used data from nationwide registers in Sweden, Denmark and Norway, 2007–2018, to conduct two cohort studies, one for DPP4 inhibitors and one for GLP-1-receptor agonists, to investigate the risk of incident cholangiocarcinoma compared with an active-comparator drug class (sulfonylureas). The cohorts included patients initiating treatment episodes with DPP4 inhibitors vs sulfonylureas, and GLP-1-receptor agonists vs sulfonylureas. We used Cox regression models, adjusted for potential confounders, to estimate hazard ratios from day 366 after treatment initiation to account for cancer latency. Results The main analyses of DPP4 inhibitors included 1,414,144 person-years of follow-up from 222,577 patients receiving DPP4 inhibitors (median [IQR] follow-up time, 4.5 [2.6–7.0] years) and 123,908 patients receiving sulfonylureas (median [IQR] follow-up time, 5.1 [2.9–7.8] years) during which 350 cholangiocarcinoma events occurred. Use of DPP4 inhibitors, compared with sulfonylureas, was not associated with a statistically significant increase in risk of cholangiocarcinoma (incidence rate 26 vs 23 per 100,000 person-years; adjusted HR, 1.15 [95% CI 0.90, 1.46]; absolute rate difference 3 [95% CI -3, 10] events per 100,000 person-years). The main analyses of GLP-1-receptor agonists included 1,036,587 person-years of follow-up from 96,813 patients receiving GLP-1-receptor agonists (median [IQR] follow-up time, 4.4 [2.4–6.9] years) and 142,578 patients receiving sulfonylureas (median [IQR] follow-up time, 5.5 [3.2–8.1] years) during which 249 cholangiocarcinoma events occurred. Use of GLP-1-receptor agonists was not associated with a statistically significant increase in risk of cholangiocarcinoma (incidence rate 26 vs 23 per 100,000 person-years; adjusted HR, 1.25 [95% CI 0.89, 1.76]; absolute rate difference 3 [95% CI -5, 13] events per 100,000 patient-years). Conclusions/interpretation In this analysis using nationwide data from three countries, use of DPP4 inhibitors and GLP-1-receptor agonists, compared with sulfonylureas, was not associated with a significantly increased risk of cholangiocarcinoma. Graphical abstract