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Background The CheckMate 025 trial established nivolumab monotherapy as one of the standards of care in previously treated advanced or metastatic renal cell carcinoma (aRCC). However, supporting real-world data is lacking. This study investigated characteristics, treatment sequences and clinical outcomes of patients who received nivolumab monotherapy for previously treated aRCC in the UK. Methods This was a retrospective cohort study of aRCC patients treated with nivolumab at second line or later (2L +) at 4 UK oncology centres. Eligible patients commenced nivolumab (index date) between 01 March 2016 and 30 June 2018 (index period). Study data were extracted from medical records using an electronic case report form. Data cut-off (end of follow-up) was 31 May 2019. Results In total, 151 patients were included with median follow-up of 15.2 months. Mean age was 66.9 years, male preponderance (72.2%), and mostly Eastern Cooperative Oncology Group performance status grade 0–1 (71.5%). Amongst 112 patients with a known International Metastatic RCC Database Consortium score, distribution between favourable, intermediate, and poor risk categories was 20.5%, 53.6%, and 25.9% respectively. The majority of patients ( n  = 109; 72.2%) received nivolumab at 2L, and these patients had a median overall survival (OS) of 23.0 months [95% confidence interval: 17.2, not reached]. All patients who received nivolumab at 2L had received TKIs at 1L. Amongst the 42 patients (27.8%) who received nivolumab in third line or later (3L +) the median OS was 12.4 months [95% CI: 8.8, 23.2]. The most common reasons for nivolumab discontinuation were disease progression (2L: 61.2%; 3L: 68.8%) and adverse events (2L: 34.7%; 3L: 28.1%). Conclusion This study provides real-world evidence on the characteristics, treatment sequences, and outcomes of aRCC patients who received 2L + nivolumab monotherapy in the UK. Nivolumab-specific survival outcomes were similar to those achieved in the CheckMate 025 trial.

Imaging techniques, such as computed tomography (CT) and fluoroscopy, are essential for the diagnosis and treatment of urolithiasis. There is increasing concern regarding the cumulative radiation dose associated with medical imaging and its adverse effects. This study aimed to assess radiation exposure in patients undergoing endoscopic management of urolithiasis and to identify factors associated with increased exposure.A retrospective analysis of all consecutive symptomatic urolithiasis cases who underwent endoscopic surgery over a two-year period at a tertiary referral center was performed. The cumulative radiation dose was recorded per stone episode, and the effective dose (ED) then calculated. Multivariable regression analysis was performed to determine the association between ED and patient, stone, and procedural characteristics.Between January 2020 and December 2021, 250 patients underwent endoscopic intervention for urolithiasis; 71% (n = 178) were male with a median age of 48 years (IQR 35–59). The median stone size was 6 mm (IQR, 5–8 mm) and the median stone volume was 110 mm3 (IQR, 60–206 mm3). Most stones were located in the distal ureter (46%, n = 114). The median ED received per stone episode was 3.99 mSv (IQR 2.9–7 mSv). On multivariable analysis, BMI, number of CT scans performed, CT protocol used, and repeat procedures strongly predicted increased radiation dose (p < 0.01).It is important for urologists to consider the cumulative radiation dosage in patients with urolithiasis. Strategies to minimize exposure, such as avoiding re-imaging, low-dose CTs, and collimation of the region of interest with judicious magnification, should be considered during treatment.

Bolus fibrinolytic therapy facilitates early efficient institution of reperfusion therapy. Tenecteplase is a genetically engineered variant of alteplase with slower plasma clearance, better fibrin specificity, and high resistance to plasminogen-activator inhibitor-1. We did a double-blind, randomised, controlled trial to assess the efficacy and safety of tenecteplase compared with alteplase. In 1021 hospitals, we randomly assigned 16 949 patients with acute myocardial infarction of less than 6 h duration rapid infusion of alteplase (≥100 mg) or single-bolus injection of tenecteplase (30–50 mg according to bodyweight). All patients received aspirin and heparin (target activated partial thromboplastin time 50–75 s). The primary outcome was equivalence in all-cause mortality at 30 days. Covariate-adjusted 30-day mortality rates were almost identical for the two groups—6·18% for tenecteplase and 6·15% for alteplase. The 95% one-sided upper boundaries of the absolute and relative differences in 30-day mortality were 0·61% and 10·00%, respectively, which met the prespecified criteria of equivalence (1% absolute or 14% relative difference in 30-day mortality, whichever difference proved smaller). Rates of intracranial haemorrhage were similar (0·93% for tenecteplase and 0·94% for alteplase), but fewer non-cerebral bleeding complications (26·43 vs 28·95%, p=0·0003) and less need for blood transfusion (4·25 vs 5·49%, p=0·0002) were seen with tenecteplase. The rate of death or non-fatal stroke at 30 days was 7·11% with tenecteplase and 7·04% with alteplase (relative risk 1·01 [95% Cl 0·91–1·13]). Tenecteplase and alteplase were equivalent for 30-day mortality. The ease of administration of tenecteplase may facilitate more rapid treatment in and out of hospital.

PurposeTransanal minimally invasive surgery (TAMIS) is a surgical alternative to transanal endoscopic microsurgery (TEM), transanal excision and proctectomy in the management of benign rectal polyps and early rectal cancers. Low anterior resection syndrome (LARS) describes the constellation of symptoms which result from and are common after distal colorectal resection. Symptoms include incontinence, frequency, urgency and evacuatory dysfunction. The aim of the current study was to prospectively evaluate pre- and post-operative LARS in patients who undergo TAMIS.MethodsWe conducted a prospective analysis of a consecutive series of patients who underwent TAMIS at our institution between January 2021 and February 2022. A LARS questionnaire was undertaken preoperatively, at 1 month and at 6 months post-operatively.ResultsTwenty patients were recruited to this pilot study. The mean age was 63 ± 12 years, 11 of the patients were male, mean pre-operative BMI was 29 ± 6 kg/m2, and 30% (n = 6) of patients underwent TAMIS for an invasive rectal cancer, with all patients receiving an R0 resection. Mean distance from the anal verge was 5.7 ± 3.2 cm, and mean lesion diameter was 46 ± 20.5 mm. A statistically significant interval reduction was observed between preoperative (20.3 ± 12.9) and 6-month post-operative (12.6 ± 9.7) LARS scores (p = 0.02) and also between 1-month (18.2 ± 10.6) and 6-month post-operative scores (p = 0.01).ConclusionsWe noted a high prevalence of LARS across our cohort preoperatively, and this had improved significantly at 6-month review post-TAMIS. This study reaffirms the safety and efficacy of TAMIS for the treatment of early rectal neoplasia.

Abstract Despite a significant reduction in tuberculosis (TB) mortality over the past decade, TB remains a leading cause of death worldwide. Food insecurity—through pathways such as malnutrition, mental health impact, and high-risk health behaviors—affects the risk of TB disease, treatment failure, and mortality. We searched the literature for studies reporting on the links between food insecurity and TB. In contrast to the well-documented interactions between food insecurity and HIV/AIDS, we found that the association between food insecurity and TB remains largely understudied—this is especially true with regard to non-nutritional correlations. Mental health and behavioral linkages between TB and food insecurity deserve further attention. An improved understanding of the pathways through which food insecurity impacts TB is crucial to inform evidence-based integration of interventions such as psychological counseling, psychiatric care, harm reduction programs, and efforts to address social determinants of disease within current TB programs.

Aspirin lowers risks of death and myocardial infarction in patients with acute coronary syndromes. Intravenous glycoprotein IIb/IIIa receptor antagonists further reduce the rates of ischaemic events in these patients, but the efficacy of long-term oral glycoprotein IIb/IIIa receptor blockade has not been established. We tested whether the oral glycoprotein IIb/IIIa receptor antagonist sibrafiban would prevent more cardiovascular events than aspirin, when given within 7 days of, and sustained for 90 days after, an acute coronary syndrome event. 9233 patients who had stabilised after an acute coronary syndrome event were randomly assigned aspirin (80 mg orally twice daily) or low-dose or high-dose sibrafiban. Sibrafiban doses (3·0 mg, 4·5 mg, or 6·0 mg) were based on a model accounting for weight and serum creatinine and designed to achieve at least 25% steady-state inhibition of platelet aggregation (low dose) or at least 50% inhibition (high dose). The primary endpoint was the composite of death, non-fatal infarction or reinfarction, or severe recurrent ischaemia at 90 days. Analysis was by intention to treat. The 90-day rate of the primary endpoint did not differ significantly between the groups assigned aspirin (302 [9·8%]), low-dose sibrafiban (310 [10·1%]; odds ratio 1·03 [95% Cl 0·87–1·21]), and high-dose sibrafiban (303 [10·1%]; 1·03 [0·87–1·21]). The groups did not differ significantly in the rates of the component events or secondary efficacy endpoints. Major bleeding was more common with high-dose sibrafiban (171 [5·7%]) than with aspirin (120 [3·9%]) or low-dose sibrafiban (159 [5·2%]). Sibrafiban showed no additional benefit over aspirin for secondary prevention of major ischaemic events after an acute coronary syndrome, and was associated with more dose-related bleeding.

OBJECTIVE To examine the management and outcome of an unselected consecutive series of patients admitted with acute myocardial infarction to a tertiary referral centre. DESIGN A historical cohort study over a three year period (1992–94) of consecutive unselected admissions with acute myocardial infarction identified using the HIPE (hospital inpatient enquiry) database and validated according to MONICA criteria for definite or probable acute myocardial infarction. SETTING University teaching hospital and cardiac tertiary referral centre. RESULTS 1059 patients were included. Mean age was 67 years; 60% were male and 40% female. Rates of coronary care unit (CCU) admission, thrombolysis, and predischarge angiography were 70%, 28%, and 32%, respectively. Overall in-hospital mortality was 18%. Independent predictors of hospital mortality by multivariate analysis were age, left ventricular failure, ventricular arrhythmias, cardiogenic shock, management outside CCU, and reinfarction. Hospital mortality in a small cohort from a non-tertiary referral centre was 14%, a difference largely explained by the lower mean age of these patients (64 years). Five year survival in the cohort was 50%. Only age and left ventricular failure were independent predictors of mortality at follow up. CONCLUSIONS In unselected consecutive patients the hospital mortality of acute myocardial infarction remains high (18%). Age and the occurrence of left ventricular failure are major determinants of short and long term mortality after acute myocardial infarction.

Background:Patients with moderate to severe active rheumatoid arthritis (RA) may be treated with biological disease-modifying antirheumatic drugs (bDMARDs), such as abatacept, after treatment failure with conventional synthetic DMARDs (csDMARDs). Abatacept has shown equivalent efficiency with other targeted therapies for RA in clinical trials and network meta-analyses. However, there is limited real-world evidence on patient outcomes associated with abatacept treatment in UK routine clinical practice.Objectives:To describe the clinical outcomes of RA patients treated with abatacept in UK real-world clinical practice.Methods:A multi-centre, retrospective observational study was undertaken in RA patients treated with abatacept at any line of therapy (LOT). Data were extracted from medical records at four UK hospitals. Patients aged 18 years or older who received abatacept between 1 January 2013 and 31 December 2017 were included. The index date was the date of first bDMARD initiation, with follow-up from index date to latest RA clinic visit, death or 31 December 2017, whichever occurred first.Clinical outcomes (disease activity and response to treatment) were measured using the 28-joint Disease Activity Score based on erythrocyte sedimentation rate (DAS28-ESR) and European League Against Rheumatism (EULAR) response criteria1-3.Results:The study included 213 patients (mean age 55.2 years, 71.4% female, 7.0 years mean duration of RA at index date). Where ACPA and RF status were recorded, 66.1% of patients were anti-citrullinated protein antibodies (ACPA) and rheumatoid factor (RF) positive at index. Mean DAS28-ESR at index was 6.2 (SD 1.0) and 80.9% of patients were categorised with high disease activity.Irrespective of LOT, changes in DAS28-ESR (where recorded) from LOT initiation among patients treated with abatacept versus other bDMARDs were -1.59 vs -1.56 (LS mean (SE): -0.04; 95% CI: -0.45,0.38; p=0.86) at 6 months and -1.98 vs -1.42 (LS mean (SE): -0.56; 95% CI: -1.04,-0.07; p=0.03) at 12 months, respectively. Table 1 shows that compared with other bDMARDs, patients treated with abatacept at any LOT experienced good response to treatment at 6 months (22.8%, n= 21/92 vs 15.9%, n= 24/151) and 12 months (27.9%, n= 17/61 vs 20.5%, n= 24/117) according to EULAR criteria.Table1.Treatment response at 6 and 12 months after initiation of any LOT*EULAR response6 months12 monthsAbatacept,n = 92Other bDMARDs,n = 151Abatacept,n = 61Other bDMARDs,n = 117Good21 (22.8%)24 (15.9%)17 (27.9%)24 (20.5%)Moderate38 (41.3%)60 (39.7%)22 (36.1%)40 (34.2%)None33 (35.9%)67 (44.4%)22 (36.1%)53 (45.3%)n = number of unique LOTs in which a patient has both a DAS28-ESR collected at initiation and 6 and/or 12 months (a patient may be included in this analysis multiple times)Patients who received abatacept remained on treatment for significantly longer than patients who received other bDMARDs at LOT1 (median 53.4 vs 17.4 months; p<0.01) (Figure 1) and at LOT2 (median 40.1 vs 17.1 months; p<0.01).Figure 1.Time on treatment from first LOT initiation, abatacept versus other bDMARDsConclusion:RA patients who received bDMARDs, including abatacept, experienced reduced disease activity. These findings are comparable with those from a European, multicentre, observational study on patients receiving abatacept4. The mechanisms associated with such clinical benefit should be elucidated in future research.References:[1]Prevoo et al. Arthritis Rheum 1995;38:44–8.[2]Fransen & van Riel. Clin Exp Rheumatol 2005;23:S93–9.[3]van Gestel et al. Arthritis Rheum 1998;41:1845–50.[4]Alten et al. Clin Rheumatol (2019) 38: 1413.Acknowledgments:Yusuf PatelSrinivasan VenkatachalamJames MaxwellUsman FarooquiKevin PollockDisclosure of Interests:Sadie Henning Shareholder of: Sadie Henning is a shareholder for Bristol-Myers Squibb Pharmaceuticals Ltd., Employee of: Sadie Henning is employed by Bristol-Myers Squibb Pharmaceuticals Ltd., Lara Groves Grant/research support from: Lara Groves is an employee of Health Economics and Outcomes Research Ltd., Cardiff, UK, who received fees from Bristol-Myers Squibb Pharmaceuticals Ltd in relation to this study., Michael Hurst Grant/research support from: Michael Hurst is an employee of Health Economics and Outcomes Research Ltd., Cardiff, UK, who received fees from Bristol-Myers Squibb Pharmaceuticals Ltd in relation to this study., Daniel Sugrue Grant/research support from: Daniel Sugrue is an employee of Health Economics and Outcomes Research Ltd., Cardiff, UK, who received fees from Bristol-Myers Squibb Pharmaceuticals Ltd in relation to this study., Jason Gordon Grant/research support from: Jason Gordon is an employee of Health Economics and Outcomes Research Ltd., Cardiff, UK, who received fees from Bristol-Myers Squibb Pharmaceuticals Ltd in relation to this study., Ernest Choy Grant/research support from: Amgen, Bio-Cancer, Chugai Pharma, Ferring Pharmaceuticals, Novimmune, Pfizer, Roche, UCB, Consultant of: AbbVie, Amgen, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Chelsea Therapeutics, Chugai Pharma, Daiichi Sankyo, Eli Lilly, Ferring Pharmaceuticals, GlaxoSmithKline, Hospita, Ionis, Janssen, Jazz Pharmaceuticals, MedImmune, Merck Sharp & Dohme, Merrimack Pharmaceutical, Napp, Novartis, Novimmune, ObsEva, Pfizer, R-Pharm, Regeneron Pharmaceuticals, Inc., Roche, SynAct Pharma, Sanofi Genzyme, Tonix, UCB, Speakers bureau: Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai Pharma, Eli Lilly, Hospira, Merck Sharp & Dohme, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Roche, Sanofi-Aventis, UCB