The optimal therapeutic approach for relapsed/refractory (R/R) Waldenström\'s Macroglobulinaemia (WM) has not been clearly defined, especially after treatment with chemoimmunotherapy (CIT) and covalent Bruton\'s tyrosine kinase inhibitors (cBTKi). The PembroWM trial is a multi-centre, phase II, single-arm study assessing the safety, tolerability and efficacy of rituximab with pembrolizumab in R/R WM patients who had received at least one prior line of treatment, with all having relapsed post-CIT and most also exposed to cBTKi. A total of 17 patients were enrolled, with a median age of 70, and median of three prior lines of therapy with 15 either refractory or intolerant of a cBTKi. A significant proportion was identified as genomically high risk with BTKC481, CXCR4 and MYD88 L265P wild-type aberrations. Twenty-four-week overall response rate was 50% (60% CI 39.3%-60.7%), and median duration of response was 11.6 months (IQR: 6.3-17). The median progression-free survival was 13.6 months (95% CI 3-19.8), and the median overall survival (OS) was not reached. Treatment was well tolerated, with minimal numbers of immune-mediated AEs typically seen with checkpoint inhibitors. PembroWM is the first study to evaluate the feasibility of PD-1 axis modulation in WM and has shown that in combination with Rituximab the combination is safe and deliverable.

BACKGROUND: In 2015, the results of the \'Small bites versus large bites for closure of abdominal midline incisions (STITCH) Trial\' were published in The Lancet. This demonstrated the superiority of small bite laparotomy closure over mass closure for the reduction of incisional hernias; despite this most surgeons have not changed their practice. Previous research has shown the time taken for the implementation of evidenced based practise within medicine takes an average of 17 years. This study aims to understand the reasons why surgeons have and have not changed their practice with regards to closure of midline laparotomy.
METHODS: Semi-structured interviews were completed with surgical consultants and registrars at a single institution in South West England. The interview topic guide was informed by a review of the published literature, which identified barriers to adopting evidence into surgical practice. Interview transcripts underwent thematic analysis with themes identified following discussions within the research team, exploring views on published data and clinical practise.
RESULTS: Nine interviews with general surgical and urological consultants as well as registrars in training were performed. Three themes were identified; \'Trusting the Evidence & Critical Appraisal\', \'Surgical Attitude to Risk\' and \'Adopting Evidence in Practise\', that reflected barriers to the introduction of evidenced based practise to clinical work.
CONCLUSIONS: Identification of the themes highlights possible areas for intervention to decrease the adoption time for evidence, for example from randomised controlled trials. The continued updating of clinical practise allows clinicians to provide best evidenced based care for patients and improve their outcomes.

BACKGROUND: Participants in research trials often disclose severe depression symptoms, including thoughts of self-harm and suicidal ideation, in validated self-administered questionnaires such as the Patient Health Questionnaire (PHQ-9). However, there is no standard protocol for responding to such disclosure, and the opportunity to support people at risk is potentially missed. We developed and evaluated a risk assessment protocol for the IBD-BOOST randomised controlled trial (ISRCTN71618461 09/09/2019).
METHODS: Participants completed the PHQ-9 at baseline and 6-month and 12-month follow-ups. The trial database automatically alerted the research team to risk assess participants. Trial researchers, trained in the protocol, contacted participants by telephone, completed the risk assessment, and signposted participants to appropriate professional services.
RESULTS: Seven hundred eighty participants were randomised in the trial; 41 required risk assessment. One participant declined assessment, so 40 risk assessments were completed. Twenty-four participants were assessed as low-risk and 16 participants as medium-risk, with 12 declaring previous suicide attempts. None were rated as high-risk. Trial participants expressed appreciation for being contacted, and all except two wished to receive information about professional support services. Trial risk assessors reported positive experiences of conducting the risk assessment with suggestions for improvement, which resulted in minor modifications to the protocol.
CONCLUSIONS: Our evaluation demonstrated that it was viable for a research trial team to successfully conduct a risk-assessment protocol for trial participants reporting thoughts of self-harm, with training and support from senior colleagues. Resources are required for training and delivery, but it is not unduly onerous. Trial participants appeared to find completing the assessment acceptable.

暂无摘要。

BACKGROUND: Low-intensity interventions targeting a range of mental health issues offer a scalable approach for young trauma survivors in low-middle income countries.
OBJECTIVE: Here, we present results from a proof-of-concept, randomized, waitlist-controlled trial evaluating MemFlex, an autobiographical memory-based intervention, for trauma-exposed Afghan youth residing in Iran. MemFlex seeks to reduce the negative and overgeneral memory biases which maintain and predict poor mental health.
METHODS: Young people aged 12-18 years (N = 40) with parents who had experienced forced migration from Afghanistan were recruited from high schools in Karaj City in Iran. All had experienced a traumatic event in the last year. Participants were randomized to receive four weeks of a group-based delivery of MemFlex or Waitlist. Our primary cognitive outcome was autobiographical memory flexibility, that is, the ability to deliberately retrieve any memory type on demand. Primary clinical outcome was emotional distress, measured on the Farsi version of the Hopkins Symptom Checklist.
RESULTS: Results indicated that MemFlex participants demonstrated large effect sizes for pre-to-post improvement in memory flexibility (d = 2.04) and emotional distress (d = 1.23). These improvements were significantly larger than Waitlist (ds < .49), and were maintained at three-month follow-up.
CONCLUSIONS: Positive benefits were observed for completion of MemFlex, and future comparison against an active intervention appears warranted.
CONCLUSIONS: Further evaluation of MemFlex in this context may offer a low-cost, and low-resource intervention to improve access to psychological intervention for young migrants in low-middle income countries.

UNASSIGNED: Transfemoral access is predominantly used for mechanical thrombectomy in patients with stroke with a large vessel occlusion. Following the interventional cardiology guidelines, routine transradial access has been proposed as an alternative, although its safety and efficacy remain controversial. We aim to explore the noninferiority of radial access in terms of final recanalization.
UNASSIGNED: The study was an investigator-initiated, single-center, evaluator-blinded, noninferiority randomized clinical trial. Patients with stroke undergoing mechanical thrombectomy, with a patent femoral artery and a radial artery diameter ≥2.5 mm, were randomly assigned (1:1) to either transradial (60 patients) or transfemoral access (60 patients). The primary binary outcome was the successful recanalization (expanded Treatment in Cerebral Ischemia score, 2b-3) assigned by blinded evaluators. We established a noninferiority margin of -13.2%, considering an acceptable reduction of 15% in the expected recanalization rates.
UNASSIGNED: From September 2021 to July 2023, 120 patients were randomly assigned and 116 (58 transradial access and 58 transfemoral access) with confirmed intracranial occlusion on the initial angiogram were included in the intention-to-treat analysis. Successful recanalization was achieved in 51 (87.9%) patients assigned to transfemoral access and in 56/58 (96.6%) patients assigned to transradial (adjusted 1 side risk difference [RD], -5.0% [95% CI, -6.61% to +13.1%]) showing noninferiority of transradial access. Median time from angiosuite arrival to first pass (femoral, 30 [interquartile range, 25-37] minutes versus radial: 41 [interquartile range, 33-62] minutes; P<0.001) and from angiosuite arrival to recanalization (femoral: 42 (IQR, 28-74) versus radial: 59.5 (IQR, 44-81) minutes; P<0.050) were longer in the transradial access group. Both groups presented 1 severe access complication and there was no difference in the rate of access conversion: transradial 7 (12.1%) versus transfemoral 5 (8.6%) (P=0.751).
UNASSIGNED: Among patients who underwent mechanical thrombectomy, transradial access was noninferior to transfemoral access in terms of final recanalization. Procedural delays may favor transfemoral access as the default first-line approach.
UNASSIGNED: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05225636.

Esophagectomy is a complex and complication laden procedure. Despite centralization, variations in perioparative strategies reflect a paucity of evidence regarding optimal routines. The use of nasogastric (NG) tubes post esophagectomy is typically associated with significant discomfort for the patients. We hypothesize that immediate postoperative removal of the NG tube is non-inferior to current routines. All Nordic Upper Gastrointestinal Cancer centers were invited to participate in this open-label pragmatic randomized controlled trial (RCT). Inclusion criteria include resection for locally advanced esophageal cancer with gastric tube reconstruction. A pretrial survey was undertaken and was the foundation for a consensus process resulting in the Kinetic trial, an RCT allocating patients to either no use of a NG tube (intervention) or 5 days of postoperative NG tube use (control) with anastomotic leakage as primary endpoint. Secondary endpoints include pulmonary complications, overall complications, length of stay, health related quality of life. A sample size of 450 patients is planned (Kinetic trial: https://www.isrctn.com/ISRCTN39935085). Thirteen Nordic centers with a combined catchment area of 17 million inhabitants have entered the trial and ethical approval was granted in Sweden, Norway, Finland, and Denmark. All centers routinely use NG tube and all but one center use total or hybrid minimally invasive-surgical approach. Inclusion began in January 2022 and the first annual safety board assessment has deemed the trial safe and recommended continuation. We have launched the first adequately powered multi-center pragmatic controlled randomized clinical trial regarding NG tube use after esophagectomy with gastric conduit reconstruction.

UNASSIGNED: Transfemoral access is predominantly used for mechanical thrombectomy in patients with stroke with a large vessel occlusion. Following the interventional cardiology guidelines, routine transradial access has been proposed as an alternative, although its safety and efficacy remain controversial. We aim to explore the noninferiority of radial access in terms of final recanalization.
UNASSIGNED: The study was an investigator-initiated, single-center, evaluator-blinded, noninferiority randomized clinical trial. Patients with stroke undergoing mechanical thrombectomy, with a patent femoral artery and a radial artery diameter ≥2.5 mm, were randomly assigned (1:1) to either transradial (60 patients) or transfemoral access (60 patients). The primary binary outcome was the successful recanalization (expanded Treatment in Cerebral Ischemia score, 2b-3) assigned by blinded evaluators. We established a noninferiority margin of -13.2%, considering an acceptable reduction of 15% in the expected recanalization rates.
UNASSIGNED: From September 2021 to July 2023, 120 patients were randomly assigned and 116 (58 transradial access and 58 transfemoral access) with confirmed intracranial occlusion on the initial angiogram were included in the intention-to-treat analysis. Successful recanalization was achieved in 51 (87.9%) patients assigned to transfemoral access and in 56/58 (96.6%) patients assigned to transradial (adjusted 1 side risk difference [RD], -5.0% [95% CI, -6.61% to +13.1%]) showing noninferiority of transradial access. Median time from angiosuite arrival to first pass (femoral, 30 [interquartile range, 25-37] minutes versus radial: 41 [interquartile range, 33-62] minutes; P<0.001) and from angiosuite arrival to recanalization (femoral: 42 (IQR, 28-74) versus radial: 59.5 (IQR, 44-81) minutes; P<0.050) were longer in the transradial access group. Both groups presented 1 severe access complication and there was no difference in the rate of access conversion: transradial 7 (12.1%) versus transfemoral 5 (8.6%) (P=0.751).
UNASSIGNED: Among patients who underwent mechanical thrombectomy, transradial access was noninferior to transfemoral access in terms of final recanalization. Procedural delays may favor transfemoral access as the default first-line approach.
UNASSIGNED: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05225636.

Based on the results of randomized clinical trials (RCT) assessing direct oral anticoagulants (DOACs) for the treatment of patients with cancer-associated thrombosis (CAT), DOACs have been proposed as alternative to low molecular weight heparin by several international guidelines. However, the proportion of CAT patients who would have not been eligible for such trials is currently unknown. Our primary aim was to assess the proportion of patients seen in clinical practice for acute CAT who would not have been eligible for CARAVAGGIO or HOKUSAI-VTE RCT. Secondary aim was to describe patients outcomes according to eligibility. In a multicenter, observational study, all patients consecutively admitted from January 2017 to December 2019 for an acute CAT event were retrospectively analyzed. Patients were classified according to the presence or absence of non-inclusion criteria for CARAVAGGIO or HOKUSAI-VTE RCT. Event free survival during a 6-month follow-up were analyzed as secondary endpoints. Among the 302 patients (women: 53 %, mean age: 67.9 ± 13.2) analyzed, 138 (46 %) for HOKUSAI-VTE cancer and 161 (53 %) for CARAVAGGIO met one or more non-inclusion criteria. Main criteria were upper limb and unsual site thrombosis (n = 63, 18.5 %), anemia/thrombopenia (n = 43, 14.2 %), brain tumors (n = 33, 10.9 %), ECOG PS >2 (n = 28, 9.3 %), severe renal failure (n = 16, 5.3 %). At 6 months, the event-free survival rate was not statistically different between the two groups. Almost half of CAT patients would have not been able to participate to a modern DOAC RCT. Evaluation of DOACs safety and efficacy in this subset of patients deserves further research.

BACKGROUND: The LOw RISk DCIS (LORIS) study was set up to compare conventional surgical treatment with active monitoring in women with ductal carcinoma in situ (DCIS). Recruitment to trials with a surveillance arm is known to be challenging, so strategies to maximise patient recruitment, aimed at both patients and recruiting centres, were implemented.
METHODS: Women aged ≥ 46 years with a histologically confirmed diagnosis of non-high-grade DCIS were eligible for 1:1 randomisation to either surgery or active monitoring. Prior to randomisation, all eligible women were invited to complete: (1) the Clinical Trials Questionnaire (CTQ) examining reasons for or against participation, and (2) interviews exploring in depth opinions about the study information sheets and film. Women agreeing to randomisation completed validated questionnaires assessing health status, physical and mental health, and anxiety levels. Hospital site staff were invited to communication workshops and refresher site initiation visits to support recruitment. Their perspectives on LORIS recruitment were collected via surveys and interviews.
RESULTS: Eighty percent (181/227) of eligible women agreed to be randomised. Over 40% of participants had high anxiety levels at baseline. On the CTQ, the most frequent most important reasons for accepting randomisation were altruism and belief that the trial offered the best treatment, whilst worries about randomisation and the influences of others were the most frequent most important reasons for declining. Most women found the study information provided clear and useful. Communication workshops for site staff improved knowledge and confidence but only about half said they themselves would join LORIS if eligible. The most common recruitment barriers identified by staff were low numbers of eligible patients and patient preference.
CONCLUSIONS: Recruitment to LORIS was challenging despite strategies aimed at both patients and site staff. Ensuring that recruiting staff support the study could improve recruitment in similar future trials.
BACKGROUND: ISRCTN27544579, prospectively registered on 22 May 2014.