Clostridioides (Clostridium) difficile infection in Japanese hospitals 2008-2017: A real-world nationwide analysis of treatment pattern, incidence and testing density.

OBJECTIVE: To characterize treatment pattern, incidence and diagnosis of hospital-onset Clostridioides difficile infection (CDI) in Japan, cases were studied over a 9-year period using a large, administrative database. METHODS: This was a retrospective, cross-sectional analysis of inpatients at 320 Japanese Diagnosis-Procedure Combination (DPC) hospitals. Hospitalizations between April 2008 and March 2017 were extracted for patients aged ≥18 years. CDI was defined as CDI treatment plus CDI diagnosis or positive enzyme immunoassay (EIA) result. Endpoints included treatment (type, route, daily dose, duration), time to CDI onset from admission, and time to recurrence (rCDI) from the end of treatment. Chronological changes were reported for treatment pattern, CDI incidence and EIA testing. RESULTS: The analysis included 11,823 CDI hospitalizations, 1359 with rCDI. Overall, oral metronidazole (MNZ), oral vancomycin (VCM), and intravenous MNZ were used in 50.2%, 42.1% and 1.2% of CDI hospitalizations, respectively. From 2009 to 2017, CDI hospitalizations treated with MNZ more than doubled and VCM more than halved. Median (Q1-Q3) time to CDI and rCDI onset was 25 (11-52) days and 10 (6-17.5) days, respectively. Median treatment duration ranged from 8 to 10 days and median dose was 1 g/day for both MNZ and VCM. CDI incidence remained steady from 2010 until 2017 (0.99/10,000 patient-days) and EIA testing density doubled from 2008 to 2017 (24.46/10,000 patient-days). CONCLUSION: Oral MNZ has become the primary CDI treatment in Japanese DPC hospitals. The treatment duration and dose were aligned to the package insert. CDI diagnostic testing density increased over time, CDI incidence did not. CLINICAL TRIAL REGISTRATION NUMBER: N/A.

Risk stratification and clinical course of hepatitis B virus reactivation in rheumatoid arthritis patients with resolved infection: final report of a multicenter prospective observational study at Japanese Red Cross Hospital.

BACKGROUND: The prophylaxis for hepatitis B virus (HBV) reactivation assumes that hepatic injury after reactivation is often rapidly progressive and can evoke fulminant hepatitis. The incidence and prognosis of reactivation in patients with rheumatoid arthritis (RA) may be different from those receiving organ transplantation and cancer chemotherapy. This study aimed to investigate the incidence, risk factors, and clinical course of HBV reactivation and develop a scoring system for risk stratification in RA patients with resolved infection. METHODS: HBV DNA was measured using real-time polymerase chain reaction, and patient data were collected for 4 years in RA patients with resolved HBV infection who were treated with steroids or synthetic or biologic immunosuppressive drugs. RESULTS: Among 1127 patients, HBV DNA was detected in 57 patients (1.65/100 person-years); none of the reactivated patients exhibited worsening of hepatic function. Multivariate logistical analysis revealed that age > 70 years and HB core antibody (HBcAb) positivity alone were independent risk factors for HBV reactivation. HBV DNA ≥ 2.1 log copies/mL was observed in 15 patients (0.43/100 person-years); seven patients were treated with nucleic acid analogs (NAAs), whereas the remaining eight were observed without treatment. Among reactivated cases, 15 cases changed to HBV DNA-negative status spontaneously, whereas 24 cases remained HBV DNA positive < 2.1 log copies/mL during the observation period. We designed the following scoring system: HBV reactivation risk score = 1 × (age > 70 years) + 2 × (HBcAb positivity alone) + 1 × (treatment other than methotrexate monotherapy). This revealed that patients with the highest score had an odds ratio of 13.01 for HBV reactivation, compared to those with the lowest score. CONCLUSIONS: Rapid progression and poor outcomes after HBV reactivation were not frequent in RA patients with resolved infection. Our new risk scoring system might be useful for screening and optimization of prophylactic treatment by distinguishing patients with significantly lower reactivation risk.

Flexible alpha allocation strategies for confirmatory adaptive enrichment clinical trials with a prespecified subgroup.

Adaptive enrichment designs have recently received considerable attention as they have the potential to make drug development process for personalized medicine more efficient. Several statistical approaches have been proposed so far in the literature and the operating characteristics of these approaches are extensively investigated using simulation studies. In this paper, we improve on existing adaptive enrichment designs by assigning unequal weights to the significance levels associated with the hypotheses of the overall population and a prespecified subgroup. More specifically, we focus on the standard combination test, a modified combination test, the marginal combination test, and the partial conditional error rate approach and explore the operating characteristics of these approaches by a simulation study. We show that these approaches can lead to power gains, compared to existing approaches, if the weights are chosen carefully.