British Thoracic Society quality standards for the investigation and management of pulmonary nodules

IntroductionThe purpose of the quality standards document is to provide healthcare professionals, commissioners, service providers and patients with a guide to standards of care that should be met for the investigation and management of pulmonary nodules in the UK, together with measurable markers of good practice.MethodsDevelopment of British Thoracic Society (BTS) Quality Standards follows the BTS process of quality standard production based on the National Institute for Health and Care Excellence process manual for the development of quality standards.Results7 quality statements have been developed, each describing a key marker of high-quality, cost-effective care for the investigation and management of pulmonary nodules, and each statement is supported by quality measures that aim to improve the structure, process and outcomes of healthcare.DiscussionBTS Quality Standards for the investigation and management of pulmonary nodules form a key part of the range of supporting materials that the Society produces to assist in the dissemination and implementation of guideline recommendations.</jats:sec

Quantum Well Intermixing in 2 μm InGaAs Multiple Quantum Well structures

Quantum well intermixing in 2μm emitting structures is presented for the first time. A photoluminescence and electroluminescence differential shift of 160nm is achieved between SiNx and SiO2 capped regions demonstrating potential for monolithic integration

Caldera resurgence during the 2018 eruption of Sierra Negra volcano, Galápagos Islands.

Recent large basaltic eruptions began after only minor surface uplift and seismicity, and resulted in caldera subsidence. In contrast, some eruptions at Galápagos Island volcanoes are preceded by prolonged, large amplitude uplift and elevated seismicity. These systems also display long-term intra-caldera uplift, or resurgence. However, a scarcity of observations has obscured the mechanisms underpinning such behaviour. Here we combine a unique multiparametric dataset to show how the 2018 eruption of Sierra Negra contributed to caldera resurgence. Magma supply to a shallow reservoir drove 6.5 m of pre-eruptive uplift and seismicity over thirteen years, including an Mw5.4 earthquake that triggered the eruption. Although co-eruptive magma withdrawal resulted in 8.5 m of subsidence, net uplift of the inner-caldera on a trapdoor fault resulted in 1.5 m of permanent resurgence. These observations reveal the importance of intra-caldera faulting in affecting resurgence, and the mechanisms of eruption in the absence of well-developed rift systems

Use of a Cybex NORM dynamometer to assess muscle function in patients with thoracic cancer

<p>Abstract</p> <p>Background</p> <p>The cachexia-anorexia syndrome impacts on patients' physical independence and quality of life. New treatments are required and need to be evaluated using acceptable and reliable outcome measures, e.g. the assessment of muscle function. The aims of this study were to: (i) examine the acceptability and reliability of the Cybex NORM dynamometer to assess muscle function in people with non-small cell lung cancer or mesothelioma; (ii) compare muscle function in this group with healthy volunteers and; (iii) explore changes in muscle function over one month.</p> <p>Methods</p> <p>The test consisted of 25 repetitions of isokinetic knee flexion and extension at maximal effort while seated on a Cybex NORM dynamometer. Strength and endurance for the quadriceps and hamstrings were assessed as peak torque and total work and an endurance ratio respectively. Thirteen patients and 26 volunteers completed the test on three separate visits. Acceptability was assessed by questionnaire, reliability by intraclass correlation coefficients (ICC) and tests of difference compared outcomes between and within groups.</p> <p>Results</p> <p>All subjects found the test acceptable. Peak torque and work done were reliable measures (ICC >0.80), but the endurance ratio was not. Muscle function did not differ significantly between the patient and a matched volunteer group or in either group when repeated after one month.</p> <p>Conclusion</p> <p>For patients with non-small cell lung cancer or mesothelioma, the Cybex NORM dynamometer provides an acceptable and reliable method of assessing muscle strength and work done. Muscle function appears to be relatively well preserved in this group and it appears feasible to explore interventions which aim to maintain or even improve this.</p

Digital smartphone intervention to recognise and manage early warning signs in schizophrenia to prevent relapse : the EMPOWER feasibility cluster RCT

Funding Information: Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 27. See the NIHR Journals Library website for further project information. Funding in Australia was provided by the National Health and Medical Research Council (APP1095879). Funding Information: The research reported in this issue of the journal was funded by the HTA programme as project number 13/154/04. The contractual start date was in April 2016. The draft report began editorial review in September 2019 and was accepted for publication in March 2020. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors’ report and would like to thank the reviewers for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report. Funding Information: Declared competing interests of authors: Andrew I Gumley reports personal fees from the University of Manchester, the University of Exeter and the British Association for Behavioural & Cognitive Psychotherapies (BABCP) (Accrington, UK), and other interests with NHS Education for Scotland outside the submitted work. John Ainsworth reports other interests with Affigo CIC (Manchester, UK) outside the submitted work. Sandra Bucci is a director of Affigo CIC, a not-for-profit social enterprise company spun out of the University of Manchester in December 2015 to enable access to social enterprise funding and to promote ClinTouch, a symptom-monitoring app, to the NHS and public sector. Andrew Briggs reports personal fees from Bayer (Leverkusen, Germany), Merck Sharp & Dohme (Kenilworth, NJ, USA), Janssen Pharmaceutica (Beerse, Belgium), Novartis (Basel, Switzerland), SWORD Health (Porto, Portugal), Amgen Inc. (Thousand Oaks, CA, USA) and Daiichi Sankyo (Tokyo, Japan) outside the submitted work. John Farhall reports grants from the National Health and Medical Research Council (Australia) during the conduct of the study and other interests with Melbourne Health (NorthWestern Mental Health, Parkville, VIC, Australia) outside the submitted work. Shôn Lewis reports grants from the Medical Research Council, non-financial support from Affigo CIC and personal fees from XenZone plc (Manchester, UK) outside the submitted work. Cathy Mihalopoulos reports grants from National Health and Medical Research Council (Australia) during the conduct of the study. John Norrie reports grants from the University of Aberdeen and the University of Edinburgh during the conduct of the study and declares membership of the following NIHR boards: CPR Decision Making Committee (2016), HTA Commissioning Board (2010–16), HTA Commissioning Sub-Board (EOI) (2012–16), HTA Funding Boards Policy Group (2016), HTA General Board (2016–19), HTA Post-Board funding teleconference (2016–19), NIHR CTU Standing Advisory Committee (2017–present), NIHR HTA and EME Editorial Board (2014–19) and Pre-exposure Prophylaxis Impact Review Panel (2017–present). Paul French is a member of the HTA Mental Health Prioritisation Panel (2017–present). Chris Williams reports grants from NIHR during the conduct of the study (HTA 10/104/34 BEAT-IT: a randomised controlled trial comparing a behavioural activation treatment for depression in adults with learning disabilities with attention control; NIHR multicentre RCT of a group psychological intervention for postnatal depression in British mothers of South Asian Origin: RP-PG-0514-20012: Integrated therapist and online CBT for depression in primary care); other from Five Areas Ltd (Clydebank, UK) outside the submitted work; and that he has twice been president of the British Association for Behavioural & Cognitive Psychotherapies, the lead body for cognitive–bahavioural therapy in the UK. This body aims to advocate use of evidence-based delivery of cognitive–bahavioural therapy. Publisher Copyright: © Queen’s Printer and Controller of HMSO 2022.Peer reviewedPublisher PD

Early Signs Monitoring to Prevent Relapse in Psychosis and Promote Well-Being, Engagement, and Recovery:Protocol for a Feasibility Cluster Randomized Controlled Trial Harnessing Mobile Phone Technology Blended With Peer Support

BACKGROUND: Relapse in schizophrenia is a major cause of distress and disability and is predicted by changes in symptoms such as anxiety, depression, and suspiciousness (early warning signs [EWSs]). These can be used as the basis for timely interventions to prevent relapse. However, there is considerable uncertainty regarding the implementation of EWS interventions. OBJECTIVE: This study was designed to establish the feasibility of conducting a definitive cluster randomized controlled trial comparing Early signs Monitoring to Prevent relapse in psychosis and prOmote Well-being, Engagement, and Recovery (EMPOWER) against treatment as usual (TAU). Our primary outcomes are establishing parameters of feasibility, acceptability, usability, safety, and outcome signals of a digital health intervention as an adjunct to usual care that is deliverable in the UK National Health Service and Australian community mental health service (CMHS) settings. We will assess the feasibility of candidate primary outcomes, candidate secondary outcomes, and candidate mechanisms for a definitive trial. METHODS: We will randomize CMHSs to EMPOWER or TAU. We aim to recruit up to 120 service user participants from 8 CMHSs and follow them for 12 months. Eligible service users will (1) be aged 16 years and above, (2) be in contact with local CMHSs, (3) have either been admitted to a psychiatric inpatient service or received crisis intervention at least once in the previous 2 years for a relapse, and (4) have an International Classification of Diseases-10 diagnosis of a schizophrenia-related disorder. Service users will also be invited to nominate a carer to participate. We will identify the feasibility of the main trial in terms of recruitment and retention to the study and the acceptability, usability, safety, and outcome signals of the EMPOWER intervention. EMPOWER is a mobile phone app that enables the monitoring of well-being and possible EWSs of relapse on a daily basis. An algorithm calculates changes in well-being based on participants' own baseline to enable tailoring of well-being messaging and clinical triage of possible EWSs. Use of the app is blended with ongoing peer support. RESULTS: Recruitment to the trial began September 2018, and follow-up of participants was completed in July 2019. Data collection is continuing. The database was locked in July 2019, followed by analysis and disclosing of group allocation. CONCLUSIONS: The knowledge gained from the study will inform the design of a definitive trial including finalizing the delivery of our digital health intervention, sample size estimation, methods to ensure successful identification, consent, randomization, and follow-up of participants, and the primary and secondary outcomes. The trial will also inform the final health economic model to be applied in the main trial. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN): 99559262; http://isrctn.com/ISRCTN99559262. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/15058

Means to an End: An Assessment of the Status-blind Approach to Protecting Undocumented Worker Rights

This article applies the tenets of bureaucratic incorporation theory to an investigation of bureaucratic decision making in labor standards enforcement agencies (LSEAs), as they relate to undocumented workers. Drawing on 25 semistructured interviews with high-level officials in San Jose and Houston, I find that bureaucrats in both cities routinely evade the issue of immigration status during the claims-making process, and directly challenge employers’ attempts to use the undocumented status of their workers to deflect liability. Respondents offer three institutionalized narratives for this approach: (1) to deter employer demand for undocumented labor, (2) the conviction that the protection of undocumented workers is essential to the agency’s ability to regulate industry standards for all workers, and (3) to clearly demarcate the agency’s jurisdictional boundaries to preserve institutional autonomy and scarce resources. Within this context, enforcing the rights of undocumented workers becomes simply an institutional means to an end

Digital smartphone intervention to recognise and manage early warning signs in schizophrenia to prevent relapse: the EMPOWER feasibility cluster RCT.

BACKGROUND: Relapse is a major determinant of outcome for people with a diagnosis of schizophrenia. Early warning signs frequently precede relapse. A recent Cochrane Review found low-quality evidence to suggest a positive effect of early warning signs interventions on hospitalisation and relapse. OBJECTIVE: How feasible is a study to investigate the clinical effectiveness and cost-effectiveness of a digital intervention to recognise and promptly manage early warning signs of relapse in schizophrenia with the aim of preventing relapse? DESIGN: A multicentre, two-arm, parallel-group cluster randomised controlled trial involving eight community mental health services, with 12-month follow-up. SETTINGS: Glasgow, UK, and Melbourne, Australia. PARTICIPANTS: Service users were aged > 16 years and had a schizophrenia spectrum disorder with evidence of a relapse within the previous 2 years. Carers were eligible for inclusion if they were nominated by an eligible service user. INTERVENTIONS: The Early signs Monitoring to Prevent relapse in psychosis and prOmote Wellbeing, Engagement, and Recovery (EMPOWER) intervention was designed to enable participants to monitor changes in their well-being daily using a mobile phone, blended with peer support. Clinical triage of changes in well-being that were suggestive of early signs of relapse was enabled through an algorithm that triggered a check-in prompt that informed a relapse prevention pathway, if warranted. MAIN OUTCOME MEASURES: The main outcomes were feasibility of the trial and feasibility, acceptability and usability of the intervention, as well as safety and performance. Candidate co-primary outcomes were relapse and fear of relapse. RESULTS: We recruited 86 service users, of whom 73 were randomised (42 to EMPOWER and 31 to treatment as usual). Primary outcome data were collected for 84% of participants at 12 months. Feasibility data for people using the smartphone application (app) suggested that the app was easy to use and had a positive impact on motivations and intentions in relation to mental health. Actual app usage was high, with 91% of users who completed the baseline period meeting our a priori criterion of acceptable engagement (> 33%). The median time to discontinuation of > 33% app usage was 32 weeks (95% confidence interval 14 weeks to ∞). There were 8 out of 33 (24%) relapses in the EMPOWER arm and 13 out of 28 (46%) in the treatment-as-usual arm. Fewer participants in the EMPOWER arm had a relapse (relative risk 0.50, 95% confidence interval 0.26 to 0.98), and time to first relapse (hazard ratio 0.32, 95% confidence interval 0.14 to 0.74) was longer in the EMPOWER arm than in the treatment-as-usual group. At 12 months, EMPOWER participants were less fearful of having a relapse than those in the treatment-as-usual arm (mean difference -4.29, 95% confidence interval -7.29 to -1.28). EMPOWER was more costly and more effective, resulting in an incremental cost-effectiveness ratio of £3041. This incremental cost-effectiveness ratio would be considered cost-effective when using the National Institute for Health and Care Excellence threshold of £20,000 per quality-adjusted life-year gained. LIMITATIONS: This was a feasibility study and the outcomes detected cannot be taken as evidence of efficacy or effectiveness. CONCLUSIONS: A trial of digital technology to monitor early warning signs that blended with peer support and clinical triage to detect and prevent relapse is feasible. FUTURE WORK: A main trial with a sample size of 500 (assuming 90% power and 20% dropout) would detect a clinically meaningful reduction in relapse (relative risk 0.7) and improvement in other variables (effect sizes 0.3-0.4). TRIAL REGISTRATION: This trial is registered as ISRCTN99559262. FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 27. See the NIHR Journals Library website for further project information. Funding in Australia was provided by the National Health and Medical Research Council (APP1095879)

Homologous recombination DNA repair defects in PALB2- associated breast cancers

Abstract: Mono-allelic germline pathogenic variants in the Partner And Localizer of BRCA2 (PALB2) gene predispose to a high-risk of breast cancer development, consistent with the role of PALB2 in homologous recombination (HR) DNA repair. Here, we sought to define the repertoire of somatic genetic alterations in PALB2-associated breast cancers (BCs), and whether PALB2-associated BCs display bi-allelic inactivation of PALB2 and/or genomic features of HR-deficiency (HRD). Twenty-four breast cancer patients with pathogenic PALB2 germline mutations were analyzed by whole-exome sequencing (WES, n = 16) or targeted capture massively parallel sequencing (410 cancer genes, n = 8). Somatic genetic alterations, loss of heterozygosity (LOH) of the PALB2 wild-type allele, large-scale state transitions (LSTs) and mutational signatures were defined. PALB2-associated BCs were found to be heterogeneous at the genetic level, with PIK3CA (29%), PALB2 (21%), TP53 (21%), and NOTCH3 (17%) being the genes most frequently affected by somatic mutations. Bi-allelic PALB2 inactivation was found in 16 of the 24 cases (67%), either through LOH (n = 11) or second somatic mutations (n = 5) of the wild-type allele. High LST scores were found in all 12 PALB2-associated BCs with bi-allelic PALB2 inactivation sequenced by WES, of which eight displayed the HRD-related mutational signature 3. In addition, bi-allelic inactivation of PALB2 was significantly associated with high LST scores. Our findings suggest that the identification of bi-allelic PALB2 inactivation in PALB2-associated BCs is required for the personalization of HR-directed therapies, such as platinum salts and/or PARP inhibitors, as the vast majority of PALB2-associated BCs without PALB2 bi-allelic inactivation lack genomic features of HRD

Comparative Accuracy and Cost-Effectiveness of Dynamic Contrast Enhanced Computed Tomography and Positron Emission Tomography in the Characterisation of Solitary Pulmonary Nodules

Abstract Introduction: Dynamic contrast-enhanced computed tomography (DCE-CT) and Positron Emission Tomography/Computed Tomography (PET/CT) have a high reported accuracy for the diagnosis of malignancy in solitary pulmonary nodules. The aim of this study was to compare the accuracy and cost-effectiveness of these. Methods: In this prospective multicentre trial, 380 participants with a solitary pulmonary nodule (8-30mm) and no recent history of malignancy underwent DCE-CT and PET/CT. All patients underwent either biopsy with histological diagnosis or completed CT follow-up. Primary outcome measures were sensitivity, specificity, and overall diagnostic accuracy for PET/CT and DCE-CT. Costs and cost-effectiveness were estimated from a healthcare provider perspective using a decision-model. Results: 312 participants (47% female, 68.1±9.0 years) completed the study, with 61% rate of malignancy at 2 years. The sensitivity, specificity, positive predictive value and negative predictive values for DCE-CT were 95.3% [95% CI 91.3;97.5], 29.8% [95% CI 22.3;38.4], 68.2% [95% CI 62.4%;73.5%] and 80.0% [95% CI 66.2;89.1] respectively, and for PET/CT were 79.1% [95% CI 72.7;84.2], 81.8% [95% CI 74.0;87.7], 87.3%[95% CI 81.5;91.5) and 71·2% [95% CI 63.2;78.1]. The area under the receiver operator characteristic curve (AUROC) for DCE-CT and PET/CT was 0.62 [95%CI 0.58;0.67] and 0.80 [95%CI 0.76;0.85] respectively (p<0.001). Combined results significantly increased diagnostic accuracy over PET/CT alone (AUROC=0.90 [95%CI 0.86;0.93], p<0.001). DCE-CT was preferred when the willingness to pay per incremental cost per correctly treated malignancy was below £9000. Above £15500 a combined approach was preferred. Conclusions: PET/CT has a superior diagnostic accuracy to DCE-CT for the diagnosis of solitary pulmonary nodules. Combining both techniques improves the diagnostic accuracy over either test alone and could be cost-effective. (Clinical trials.gov - NCT02013063)