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Summary Background The use of prophylactic radiotherapy to prevent procedure-tract metastases (PTMs) in malignant pleural mesothelioma remains controversial, and clinical practice varies worldwide. We aimed to compare prophylactic radiotherapy with deferred radiotherapy (given only when a PTM developed) in a suitably powered trial. Methods We did a multicentre, open-label, phase 3, randomised controlled trial in 22 UK hospitals of patients with histocytologically proven mesothelioma who had undergone large-bore pleural interventions in the 35 days prior to recruitment. Eligible patients were randomised (1:1), using a computer-generated sequence, to receive immediate radiotherapy (21 Gy in three fractions within 42 days of the pleural intervention) or deferred radiotherapy (same dose given within 35 days of PTM diagnosis). Randomisation was minimised by histological subtype, surgical versus non-surgical procedure, and pleural procedure (indwelling pleural catheter vs other). The primary outcome was the incidence of PTM within 7 cm of the site of pleural intervention within 12 months from randomisation, assessed in the intention-to-treat population. This trial is registered with ISRCTN, number ISRCTN72767336. Findings Between Dec 23, 2011, and Aug 4, 2014, we randomised 203 patients to receive immediate radiotherapy (n=102) or deferred radiotherapy (n=101). The patients were well matched at baseline. No significant difference was seen in PTM incidence in the immediate and deferred radiotherapy groups (nine [9%] vs 16 [16%]; odds ratio 0·51 [95% CI 0·19–1·32]; p=0·14). The only serious adverse event related to a PTM or radiotherapy was development of a painful PTM within the radiotherapy field that required hospital admission for symptom control in one patient who received immediate radiotherapy. Common adverse events of immediate radiotherapy were skin toxicity (grade 1 in 50 [54%] and grade 2 in four [4%] of 92 patients vs grade 1 in three [60%] and grade 2 in two [40%] of five patients in the deferred radiotherapy group who received radiotherapy for a PTM) and tiredness or lethargy (36 [39%] in the immediate radiotherapy group vs two [40%] in the deferred radiotherapy group) within 3 months of receiving radiotherapy. Interpretation Routine use of prophylactic radiotherapy in all patients with mesothelioma after large-bore thoracic interventions is not justified. Funding Research for Patient Benefit Programme from the UK National Institute for Health Research.

Many patients with advanced non-small-cell lung cancer (NSCLC) receive only active supportive care because of poor performance status or presence of several comorbidities. We investigated whether erlotinib improves clinical outcome in these patients. TOPICAL was a double-blind, randomised, placebo-controlled, phase 3 trial, done at 78 centres in the UK. Eligibility criteria were newly diagnosed, pathologically confirmed NSCLC; stage IIIb or IV; chemotherapy naive; no symptomatic brain metastases; deemed unsuitable for chemotherapy because of poor (≥2) Eastern Cooperative Oncology Group performance status or presence of several comorbidities, or both; and estimated life expectancy of at least 8 weeks. Patients were randomly assigned (by phone call, in a 1:1 ratio, stratified by disease stage, performance status, smoking history, and centre, block size 10) to receive oral placebo or erlotinib (150 mg per day) until disease progression or unacceptable toxicity. Investigators, clinicians, and patients were masked to assignment. The primary endpoint was overall survival. Analyses were by intention to treat, and prespecified subgroup analyses included development of a rash due to erlotinib within 28 days of starting treatment. This study is registered, number ISRCTN 77383050. Between April 14, 2005, and April 1, 2009, we randomly assigned 350 patients to receive erlotinib and 320 to receive placebo. We followed up patients until March 31, 2011. 657 patients died; median overall survival did not differ between groups (erlotinib, 3·7 months, 95% CI 3·2–4·2, vs placebo, 3·6 months, 3·2–3·9; unadjusted hazard ratio [HR] 0·94, 95% CI 0·81–1·10, p=0·46). 59% (178 of 302) of patients assigned erlotinib and who were assessable at 1 month developed first-cycle rash, which was the only independent factor associated with overall survival. Patients with first-cycle rash had better overall survival (HR 0·76, 95% CI 0·63–0·92, p=0·0058), compared with placebo. Compared with placebo, overall survival seemed to be worse in the group that did not develop first-cycle rash (1·30, 1·05–1·61, p=0·017). Grade 3 or 4 diarrhoea was more common with erlotinib than placebo (8% [28 of 334] vs 1% [four of 313], p=0·0001), as was high-grade rash (23% [79 of 334] vs 2% [five of 313], p<0·0001); other adverse events were much the same between groups. Patients with NSCLC who are deemed unsuitable for chemotherapy could be given erlotinib. Patients who develop a first-cycle rash should continue to receive erlotinib, whereas those who do not have a rash after 28 days should discontinue erlotinib, because of the possibility of decreased survival. Cancer Research UK, Roche.

The majority of targeted therapies for non-small-cell lung cancer (NSCLC) are directed against oncogenic drivers that are more prevalent in patients with light exposure to tobacco smoke 1 – 3 . As this group represents around 20% of all patients with lung cancer, the discovery of stratified medicine options for tobacco-associated NSCLC is a high priority. Umbrella trials seek to streamline the investigation of genotype-based treatments by screening tumours for multiple genomic alterations and triaging patients to one of several genotype-matched therapeutic agents. Here we report the current outcomes of 19 drug–biomarker cohorts from the ongoing National Lung Matrix Trial, the largest umbrella trial in NSCLC. We use next-generation sequencing to match patients to appropriate targeted therapies on the basis of their tumour genotype. The Bayesian trial design enables outcome data from open cohorts that are still recruiting to be reported alongside data from closed cohorts. Of the 5,467 patients that were screened, 2,007 were molecularly eligible for entry into the trial, and 302 entered the trial to receive genotype-matched therapy—including 14 that re-registered to the trial for a sequential trial drug. Despite pre-clinical data supporting the drug–biomarker combinations, current evidence shows that a limited number of combinations demonstrate clinically relevant benefits, which remain concentrated in patients with lung cancers that are associated with minimal exposure to tobacco smoke. Current outcomes are reported from the ongoing National Lung Matrix Trial, an umbrella trial for the treatment of non-small-cell lung cancer in which patients are triaged according to their tumour genotype and matched with targeted therapeutic agents.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Background: Short course neoadjuvant radiation has been shown to provide improved local control of rectal cancer in a clinical trial population even in the presence of standardized surgical techniques. However, this use of hypofractionated radiotherapy has been limited in North America owing to concerns over toxicity. Methods: Patients considered to have locally advanced rectal carcinoma received a radiation dose of 25 Gy given in five fractions to the posterior pelvis. Definitive surgery was then performed within 2 weeks. Retrospective analysis was performed Results: Sixty-three patients, of whom 60 were assessable, were treated with preoperative short course radiotherapy at the British Columbia Cancer Agency between 1991 and 1998, and 97% proceeded to R0 resection. Local recurrence developed in 3 patients (5%). Five-year actuarial overall and relapse-free survival rates for the group were 71% and 69%, respectively. The actuarial rates of relapse-free survival by stage at 5 years were stage 1 83%, stage II 75%, stage III 62%, and stage 4 0%. Eleven patients (18%) experienced a postoperative complication. Conclusion: Short course preoperative radiotherapy for operable rectal cancer can be delivered to a general population and produce high pelvic control rates with acceptable toxicity.

Chapter 5 discusses two main subtypes of lung cancer; small cell (SCLC) and nonsmall cell (NSCLC). However, the management is becoming increasingly similar so the general principles of lung cancer radiotherapy will be discussed first, followed by the specific features of management of the two pathological entities.

The purpose of this study was to test the information processing theory of organizational design (Galbraith, 1973; Tushman & Nadler, 1978) for effective decision making (Huber & McDaniel, 1986). Hypotheses tested the extent to which variations in information processing requirements (nursing unit context: nursing unit size and technological indeterminance) and information processing capacity (nursing unit structure: decentralization, nursing participation in decision making, formalization, and nursing care plans) corresponded with variations in nursing unit performance (medication error rate; patient fall rate; licensed staff vacancy rate; licensed staff turnover rate; patients' perception of supportive nursing behaviors; nurses' perception of the unit's ability to provide technical quality of care; and nurses' perception of the unit's ability to meet family member needs) while controlling for resource allocation (nurse-patient ratio). Forty-six medical-surgical nursing units (representing 15 hospitals) from four regions of the United States participated in this cross-sectional, correlational study. Hierarchical multiple regression was used to test the following hypotheses: (1) that resource allocation is related to nursing unit performance (supported for the three perceptual measures but not for the four objective measures of nursing unit performance); (2) that nursing unit context is related to nursing unit performance (supported for vacancy rate); (3) that nursing unit decision making structures are related to nursing unit performance (supported for meeting family member needs); (4) that nursing unit context and decision making structures are related to nursing unit performance (not supported); and (5) that the fit between nursing unit context and decision making structures is the best predictor ofnursing unit performance (not supported). Thus, the theory was not supported. The findings suggest a greater capacity for information processing than the demand for information processing warrants. The healthcare industry and professional organizations are pressuring hospitals and nurse administrators to conform to certain structural forms which may result in excess information processing capacity. Thus, nursing units are not structuring to meet their information processing demands but industry and professional norms.

Polymer membranes are attractive for molecular-scale separations such as hydrogen purification because of inherently low energy requirements. However, membrane materials with outstanding hydrogen separation performance in feed streams containing high-pressure carbon dioxide and impurities such as hydrogen sulfide and water are not available. We report highly permeable, reverse-selective membrane materials for hydrogen purification, as exemplified by molecularly engineered, highly branched, cross-linked poly(ethylene oxide). In contrast to the performance of conventional materials, we demonstrate that plasticization can be harnessed to improve separation performance.

IntroductionDespite unprecedented pressures on urgent and emergency care services, there is no clear consensus on how to provide acute medical care delivery in the UK. These pressures can lead to significant delays in care for patients presenting with emergencies when admitted via traditional routes through the emergency department. Historically, a separate pathway has existed where patients are directly admitted to acute medicine services without attending the emergency department. It is suspected that there is a significant variation in how these patients are selected, triaged and managed in the UK. This systematic review will assess the methods and evidence base used for direct patient admissions to acute medicine services compared with traditional admission pathways through the emergency department.Methods and analysisA systematic review of the literature will be conducted and a total of six databases will be searched: MEDLINE (Ovid), The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE in process, Web of Science, CINAHL and Embase. This will include studies from the period 01 January 1975 to 24 January 2024. Covidence software will be the platform for the extraction of data and paper screening with the selection process reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram. Both title and abstract screening and full-text screening will be done by two reviewers independently. The risk of bias of included studies will be assessed using the methods introduced in the Cochrane Handbook for Systematic Reviews of Interventions and the tool used will be dependent on the type of study. Where possible, outcomes will be dealt with as continuous variables. Change percentage will be assessed between any pathway characteristic or outcome. The χ² test and I² test will be used to evaluate the heterogeneity of included studies. Where appropriate, relevant meta-analysis techniques will be used to compare studies and forest plot produced.Ethics and disseminationThis systematic review does not require ethical approval. Findings will be disseminated widely in peer-reviewed publication and media, including conferences.PROSPERO registration numberCRD42023495786.