In the CREDIBLE-CR and APEKS-NP studies, cefiderocol treatment was effective against Gram-negative bacteria producing metallo-beta-lactamases; rates of clinical cure (70.8% [17/24]), microbiological eradication (58.3% [14/24]), and Day-28 all-cause mortality (12.5% [3/24]) compared favorably with comparators of best available therapy and high-dose meropenem (40.0% [4/10]; 30.0% [3/10]; 50.0% [5/10]), respectively.

Summary For marginal structural models, which play an important role in causal inference, we consider a model selection problem within a semiparametric framework using inverse-probability-weighted estimation or doubly robust estimation. In this framework, the modelling target is a potential outcome that may be missing, so there is no classical information criterion. We define a mean squared error for treating the potential outcome and derive an asymptotic unbiased estimator as a $C_{p}$ criterion using an ignorable treatment assignment condition. Simulation shows that the proposed criterion outperforms a conventional one by providing smaller squared errors and higher frequencies of selecting the true model in all the settings considered. Moreover, in a real-data analysis we found a clear difference between the two criteria.

AimTo evaluate the efficacy and safety of an oral, once‐daily, 14‐day treatment course of zuranolone in Japanese patients with major depressive disorder (MDD).MethodsThis multicenter, randomized, double‐blind, placebo‐controlled study randomized eligible patients (1:1:1) to receive oral zuranolone 20 mg, zuranolone 30 mg, or placebo once daily for 14 days (treatment‐period), followed by two 6‐week follow‐up periods. The primary endpoint was change from baseline in the 17‐item Hamilton Depression Rating Scale (HAMD‐17) total score on Day 15.ResultsOverall, 250 patients (enrolled: 07/07/2020–05/26/2021) were randomized to receive placebo (n = 83), zuranolone 20 mg (n = 85), or zuranolone 30 mg (n = 82). The demographic and baseline characteristics were balanced between groups. The adjusted mean (standard error) change from baseline in the HAMD‐17 total score on Day 15 was −6.22 (0.62), −8.14 (0.62), and − 8.31 (0.63) in the placebo, zuranolone 20‐mg, and zuranolone 30‐mg groups, respectively. Significant differences in the adjusted mean (95% confidence interval [CI]) for zuranolone 20 mg versus placebo (−1.92; [−3.65, −0.19]; P = 0.0296) and zuranolone 30 mg versus placebo (−2.09; [−3.83, −0.35]; P = 0.0190) groups were observed on Day 15, and also as early as Day 3. A nonsignificant yet distinct drug‐placebo separation was observed during follow‐up. Somnolence (placebo [3.7%], zuranolone 20 mg [10.6%], and zuranolone 30 mg [20.7%]) and dizziness (3.7%, 9.4%, and 9.8%, respectively) were more common with zuranolone.ConclusionOral zuranolone was safe and demonstrated significant improvements in depressive symptoms, as assessed by HAMD‐17 total score change from baseline over 14 days in Japanese patients with MDD.

Introduction: A post hoc, descriptive analysis of three prospective, randomised, controlled clinical studies investigating cefiderocol in gram-negative bacterial infections was conducted to assess its efficacy in patients with baseline bacteraemia. Methods: Data from APEKS-cUTI (NCT02321800), APEKS-NP (NCT03032380) and CREDIBLE-CR (NCT02714595) studies were assessed individually. Patients received cefiderocol 2g, q8h, for 7-14 days or comparators (imipenem/cilastatin [APEKS-cUTI], meropenem [APEKS-NP] or best available therapy [BAT; CREDIBLE-CR]). Bacteraemia and clinical outcomes were assessed at early assessment (EA), end of treatment (EOT) and test of cure (TOC) for patients in the intention-to-treat populations with baseline blood samples positive for aerobic gram-negative species. Eradication, persistence or recurrence of baseline blood pathogen was confirmed from follow-up blood cultures; in the absence of follow-up blood cultures, clinical response, administration of additional antibiotics and vital status were used to assess bacteraemia outcome. Results: Of 885 patients randomised, 84 had bacteraemia and 89 (cefiderocol: 55, comparators: 34) gram-negative pathogens were isolated, namely Enterobacterales (n = 62) and non-fermenters (n = 27). At EA, on-therapy bacteraemia eradication rates in APEKS-cUTI, APEKS-NP and CREDIBLE-CR were 100% (19/ 19), 50.0% (4/8) and 72.0% (18/25) with cefiderocol. Corresponding rates for comparators were 77.8% (7/9), 100% (10/10) and 69.2% (9/13), respectively. Persistence in blood at EA was seen in six patients overall (cefiderocol: 3, comparators: 3); indeterminate responses were common (cefiderocol: 8, comparators: 3), usually due to lack of blood cultures. Clinical cure/ improvement rates at EA in APEKS-cUTI, APEKS-NP and CREDIBLE-CR were 100% (19/19), 62.5% (5/8) and 64.0% (16/25) with cefiderocol. Corresponding rates for comparators were 77.8% (7/9), 90.0% (9/10) and 30.8% (4/13), respectively. Bacteraemia eradication rates with cefiderocol in APEKS-cUTI, APEKS-NP and

Background Influenza is a public health issue that needs to be addressed strategically. The assessment of detailed infectious profiles is an important part of this effort. Household transmission data play a key role in estimating such profiles. We used diagnostic and questionnaire-based data on influenza patients at a Japanese clinic to estimate the detailed infectious period (as well as incubation period, symptomatic and infectious periods, and extended infectious period after recovery) and the secondary attack ratio (SAR) of influenza for households of various sizes based on a modified Cauchemez-type model. Results The data were from enrolled patients with confirmed influenza who were treated at the Hirotsu Clinic (Kawasaki, Japan) with a neuraminidase inhibitor (NAI) during six northern hemisphere influenza seasons between 2010 and 2016. A total of 2342 outpatients, representing 1807 households, were included. For influenza type A, the average incubation period was 1.43 days (95% probability interval, 0.03–5.32 days). The estimated average symptomatic and infective period was 1.76 days (0.33–4.62 days); the extended infective period after recovery was 0.25 days. The estimated SAR rose from 20 to 32% as household size increased from 3 to 5. For influenza type B, the average incubation period, average symptomatic and infective period, and extended infective period were estimated as 1.66 days (0.21–4.61), 2.62 days (0.54–5.75) and 1.00 days, respectively. The SAR increased from 12 to 21% as household size increased from 3 to 5. Conclusion All estimated periods of influenza type B were longer than the corresponding periods for type A. However, the SAR for type B was less than that for type A. These results may reflect Japanese demographics and treatment policy. Understanding the infectious profiles of influenza is necessary for assessing public health measures.