BackgroundTrials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to determine if daily fluoxetine for 6 months after stroke improves functional outcome in Australasian and Vietnamese patients. MethodsAFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial conducted in 43 hospital stroke units in Australia (n=29), New Zealand (4), and Vietnam (10). Eligible patients were adults with a clinical diagnosis of stroke in the previous 2-15 days and a persisting neurological deficit. Patients were randomised via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20mg or matching placebo for 6 months. Patients, investigators and outcome assessors were masked to the treatment allocation. The primary outcome was functional outcome, measured by the modified Rankin scale (mRS), at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Analyses were according to the patient's treatment allocation. The trial is registered with the ACTRN registry, number 12611000774921. FindingsPowered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation 1280 patients were recruited in Australia (n=532), New Zealand (n=42) and Vietnam (n=706) between 11 January 2013 and 30 June 2019; 642 were allocated fluoxetine and 638 placebo. Adherence to trial medication (mean 167 [SD 48] days) was similar between groups. At 6 months, mRS data were available in 624 (97.2%) patients allocated fluoxetine and 632 (99.1%) placebo. The distribution of mRS categories at 6 months was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0.936, 95% CI 0.762-1.150; p=0.53), and consistent among all pre-defined subgroups. Compared to placebo, patients allocated fluoxetine had more falls (20 [3.12%] vs 7 [1.10%]; p=0.02), bone fractures (19 [2•96%] vs 6 [0.94%]; p=0.01) and epileptic seizures (10 [1.56%] vs 2 [0.31%]; p=0.04) at 6 months. InterpretationFluoxetine 20mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and seizures. These results do not support the use of fluoxetine to improve outcome after stroke.

Moderate quality evidence indicates that intramuscular methotrexate at a dose of 15 mg/week is superior to placebo for maintenance of remission in Crohn's disease. Intramuscular methotrexate appears to be safe. Low dose oral methotrexate (12.5 to 15 mg/week) does not appear to be effective for maintenance of remission in Crohn's disease. Combination therapy (methotrexate and infliximab) does not appear to be any more effective for maintenance of remission than infliximab monotherapy. The results for efficacy outcomes between methotrexate and 6-mercaptopurine and methotrexate and 5-aminosalicylic acid were uncertain. Large-scale studies of methotrexate given orally at higher doses for maintenance of remission in Crohn's disease may provide stronger evidence for the use of methotrexate in this manner.

Intramuscular methotrexate at a dose of 15 mg/week is safe and effective for maintenance of remission in Crohn's disease. Oral methotrexate (12.5 to 15 mg/week) does not appear to be effective for maintenance of remission in Crohn's disease.

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Background Neonatal portal vein thrombosis (PVT) is uncommon with potentially serious complications that may manifest in infancy and childhood. Objective The primary aim of our study was to describe the short‐term and long‐term outcomes of neonatal PVT. Methods A retrospective chart review was conducted from 2008 to 2016 of neonates diagnosed with PVT. A systematic review was also performed from 2000 to 2018 to evaluate anticoagulant therapy (ACT) in neonatal PVT. Results Forty‐four premature and 30 term infants (mean gestational age 30.7 vs 39.1 weeks, respectively) had PVT. Sixty‐eight involved the left portal vein, one involved only the main portal vein, and 5 involved ≥1 vein. PVT was catheter associated in 46 (62%); none of the 7 neonates tested had thrombophilia. Of 74 neonates, 19 (26%) received ACT and 55 (74%) were untreated. The mean follow‐up duration was 16.6 months (SD = 17.62; range, 0–89.6); 59.5% were followed for ≥6 months. On last ultrasound examination, thrombus resolution was documented in treated (ACT; n = 19) and nontreated (n = 55) neonates: 12 (63%) versus 32 (58%) with complete resolution, 1 (5%) versus 6 (11%) partial, 0 versus 1 (2%) extension, and 6 (32%) versus 16 (29%) had nonprogressive lesions, respectively. Seventy‐one (96%) had no complications. Seventy‐one articles met inclusion criteria for the systematic review and 19 were retained for analysis after assessment. Conclusions PVT resolution rate was similar to previous reports. Although a low complication rate was detected, longer follow‐up is necessary to determine the need for early treatment and the precise incidence of outcomes such as portal hypertension.

SUMMARY BackgroundMethotrexate (MTX) is administered subcutaneously to Crohn's Disease (CD) patients. There are very few studies evaluating the use of oral (PO) MTX in CD. A drug and its pharmaceutical alternative are equivalent (bioequivalence) when the bioavailability of the alternative falls within 80-125% of the bioavailability of the standard (US Food and Drug Administration -FDA).

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Background: The RRMM treatment landscape has increased in complexity in recent years due to the availability of novel agents. In this study, we evaluated treatment patterns over 3 years in real-world RRMM pts treated with regimens containing one or more of the following agents: carfilzomib (K), bortezomib (V), lenalidomide (R), pomalidomide (P), ixazomib (I), daratumumab (D), and elotuzumab (E). Methods: We retrospectively analysed data from a German longitudinal database (TherapyMonitor) for pts receiving RRMM treatment (2nd-line [2L] and beyond) between January 2016 and December 2018. Patient demographics, treatment details and clinical characteristics were described by line of treatment and regimen for a patients most recent treatment. Treatment patterns were described by year of treatment initiation (2016, 2017 or 2018). Results: Of the total study population of 2033 RRMM pts, the most recent treatment line was 2L for 1047 and 3L+ for 986 pts. 2L/3L+ pts had a median age of 70/71 years (22%/27% >75 years; most were aged 66-75 years); 57%/61% had ISS stage III; 43%/50% had ECOG ≥2; 10%/9% had renal dysfunction; 56%/56% had ≥1 comorbidity and 14%/17% had received stem cell transplantation at 1L, respectively. In 2L pts, across 2016-2018, R non-triplet (24%) was the most common treatment regimen, with 18% and 10% of pts receiving K+R and D+R triplets, respectively. In 3L+ pts, the most common treatment regimens were D-based (29% [12% non-triplet, 9% D+V triplet and 8% D+R triplet]), P non-triplet (9%), K non-triplet or I/R triplet (both 8%), and R non-triplet (7%). In 2L pts, the most frequent prior treatments were V triplets/non-triplets (45%/19%) and R non-triplets (15%). In 3L+ pts, the most frequent prior treatments were R non-triplets (27%) and K non-triplets (16%). Triplet regimens were mostly administered in 2L to pts ≤65 years. Age had no clear impact on 3L+ treatment patterns. ECOG status impacted treatment patterns in 2L (doublet therapy more frequent in ECOG ≥2) but not in 3L+ (most pts had ECOG ≥2 but were frequently treated with E/D/I triplets). Regarding trends over time (2016 to 2018), considering all treatments, V triplet+ was the most frequently used regimen prior to 2L (37 to 43%), while V-non-triplet use decreased (32% to 19%) and R-based non-triplet use doubled (7% to 16%). In 2L, K-based regimen use increased from 25% to 38%, mainly due to increased use of K non-triplet (10% to 19%). 2L D-based triplet use increased from 0% to 15% and use of R non-triplet halved (55% to 27%). Patients receiving K- or D-based triplet or R non-triplet at 2L predominantly received V triplet regimens at 1L. Most 2L pts receiving non-triplet regimens also received V or R non-triplets at 1L. These trends suggest a shift in use of R non-triplets from 2L to 1L, replacing 1L V non-triplets and resulting in greater use of 2L K non-triplets. Specifically, for 2L in 2018, of the 27% of pts treated with R non-triplets (Figure), the most common 1L regimens were V-triplet (44%), V non-triplet (29%) and other non-novel agent containing regimens (15%). For the 19% of pts receiving 2L K+R triplet regimen, the most common 1L regimens were V-triplet+ (66%), other regimens containing novel agents (24%) and V and R non-triplets (5% each). Of the 19% of pts receiving 2L K non-triplet regimens, R non-triplet (35%), V non-triplet (28%) and V-triplet+ (24%) were the most common 1L treatments. For the 11% of pts receiving 2L DR-triplet regimens, V-triplet+ (57%), other regimens containing novel agents (20%), R non-triplet (14%), and V non-triplet (6%) were the most common 1L treatments. Conclusions: Multiple approvals of novel RRMM agents in Europe resulted in changes in the treatment landscape, with a more immediate impact in countries with earlier access to new drugs. In this RRMM population we found increased 1L use of R non-triplets and decreased V non-triplet use between 2016-2018. Use of D-based regimens increased in 2L; P-, I-, and E-based regimens were infrequently used in 2L (≤4% in 2018). Pts receiving 1L non-triplets generally received 2L non-triplet treatment; those receiving 1L triplet generally also received 2L triplet treatment. 3L pts were mostly R-pretreated due to high use of 2L R-based triplets. Germany may serve as an example for the adoption of novel treatments as there is adoption of all RRMM agents approved since 2016. Figure Disclosures Merz: Takeda Vertrieb GmbH: Other: Travel grants, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Other: Travel grants; Janssen: Other: Travel grants; Abbvie: Other: Travel grants; Celgene: Other: Travel grants. Patel:Amgen: Employment. Kutikova:Amgen: Employment. Lebioda:Amgen: Employment. Schoehl:Amgen: Employment. Kellermann:Takeda: Research Funding; Amgen: Research Funding; BMS: Research Funding; Celgene: Research Funding; Janssen: Research Funding; Sanofi: Research Funding. Goldschmidt:Dietmar-Hopp-Stiftung: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Research Funding; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Chugai: Honoraria, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Molecular Partners: Research Funding; MSD: Research Funding; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Mundipharma: Research Funding; Janssen: Consultancy, Research Funding; John-Hopkins University: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive Biotechnology: Membership on an entity's Board of Directors or advisory committees; John-Hopkins University: Research Funding.