Randomized feasibility trial of remote ischemic conditioning to enhance resuscitation (RICE).

RATIONALE: Restoration of blood flow after out-of-hospital cardiac arrest (OHCA) is associated with inflammation that causes cellular injury. The extent of this reperfusion injury (RI) is associated with the duration of ischemia and adequacy of resuscitation. Remote ischemic conditioning (RIC) consists of repeated application of non-lethal ischemia then reperfusion to a limb distal to the heart by inflating a blood pressure (BP) cuff. Trials in animal models in cardiac arrest and in humans with acute infarction show RIC reduces RI. OBJECTIVE: We sought to demonstrate the feasibility and safety of RIC in patients resuscitated from OHCA and transported to hospital. METHODS: This study was conducted under exception from informed consent (EFIC) for emergency research. Eligible subjects were randomized with masked allocation to control (standard care) versus intervention (standard care and RIC). Included were adults with non-traumatic OHCA. The primary outcome was attrition, the proportion of patients enrolled and not on allocated therapy for the study duration. Key secondary outcomes were survival to discharge, neurologic status at discharge, hospital-free survival, and adverse events. Results were summarized descriptively as recommended for pilot studies. RESULTS: N = 30 patients were enrolled (n = 14 control, n = 16 intervention). Mean age of enrolled patients was 52.5 ± 16.2 years. Eight (27%) were female gender and 7 (23%) had a shockable first recorded rhythm. 100% of enrolled patients completed their allocated study intervention (i.e., 0% attrition). The RIC group had 7 (44%) survival to discharge and median Rankin score of 6 (IQR 1, 6) at discharge as compared to the standard care group which had 6 (43%) survival to discharge and median Rankin score of 6 (IQR 1.5, 6) at discharge. A single patient (6%) in the intervention group had transient occlusion of their upper extremity intravenous line, which immediately resolved on repositioning of the blood pressure cuff. CONCLUSION: Application of RIC to patients resuscitated from CA and transported to an ED is feasible and safe. An adequately powered trial is required to assess whether RIC is effective at decreasing morbidity and mortality after CA.

Immediate smoking cessation support during lung cancer screening: long-term outcomes from two randomised controlled trials.

BACKGROUND: Immediate smoking cessation interventions delivered alongside targeted lung health checks (TLHCs) to screen for lung cancer increase self-reported abstinence at 3 months. The impact on longer term, objectively confirmed quit rates remains to be established. METHODS: We followed up participants from two clinical trials in people aged 55-75 years who smoked and took part in a TLHC. These randomised participants in the TLHC by day of attendance to either usual care (UC) (signposting to smoking cessation services) or an offer of immediate smoking cessation support including pharmacotherapy. In the QuLIT1 trial, this was delivered face to face and in QuLIT2, it was delivered remotely. Follow-up was conducted 12 months after the TLHC by telephone interview with subsequent biochemical verification of smoking cessation using exhaled CO. RESULTS: 430 people were enrolled initially (115 in QuLIT1 and 315 in QuLIT2), with 4 deaths before 12 months leaving 426 (62.1±5.27 years old and 48% women) participants for analysis. At 12 months, those randomised to attend on smoking cessation support intervention days had higher quit rates compared with UC adjusted for age, gender, deprivation, and which trial they had been in; self-reported 7-day point prevalence (20.0% vs 12.8%; adjusted OR (AOR)=1.78; 95% CI 1.04 to 2.89) and CO-verified quits (12.1% vs 4.7%; AOR=2.97; 95% CI 1.38 to 6.90). Those in the intervention arm were also more likely to report having made a quit attempt (30.2% vs UC 18.5%; AOR 1.90; 95% CI 1.15 to 3.15). CONCLUSION: Providing immediate smoking cessation support alongside TLHC increases long term, biochemically confirmed smoking abstinence. TRIAL REGISTRATION NUMBER: ISRCTN12455871.

Critical care delivery across health care systems in low-income and low-middle-income country settings: A systematic review.

Background: Prior research has demonstrated that low- and low-middle-income countries (LLMICs) bear a higher burden of critical illness and have a higher rate of mortality from critical illness than high-income countries (HICs). There is a pressing need for improved critical care delivery in LLMICs to reduce this inequity. This systematic review aimed to characterise the range of critical care interventions and services delivered within LLMIC health care systems as reported in the literature. Methods: A search strategy using terms related to critical care in LLMICs was implemented in multiple databases. We included English language articles with human subjects describing at least one critical care intervention or service in an LLMIC setting published between 1 January 2008 and 1 January 2020. Results: A total of 1620 studies met the inclusion criteria. Among the included studies, 45% of studies reported on pediatric patients, 43% on adults, 23% on infants, 8.9% on geriatric patients and 4.2% on maternal patients. Most of the care described (94%) was delivered in-hospital, with the remainder (6.2%) taking place in out-of-hospital care settings. Overall, 49% of critical care described was delivered outside of a designated intensive care unit. Specialist physicians delivered critical care in 60% of the included studies. Additional critical care was delivered by general physicians (40%), as well as specialist physician trainees (22%), pharmacists (16%), advanced nursing or midlevel practitioners (8.9%), ambulance providers (3.3%) and respiratory therapists (3.1%). Conclusions: This review represents a comprehensive synthesis of critical care delivery in LLMIC settings. Approximately 50% of critical care interventions and services were delivered outside of a designated intensive care unit. Specialist physicians were the most common health care professionals involved in care delivery in the included studies, however generalist physicians were commonly reported to provide critical care interventions and services. This study additionally characterised the quality of the published evidence guiding critical care practice in LLMICs, demonstrating a paucity of interventional and cost-effectiveness studies. Future research is needed to understand better how to optimise critical care interventions, services, care delivery and costs in these settings. Registration: PROSPERO CRD42019146802.

ERS/ESTS/ESTRO/ESR/ESTI/EFOMP statement on management of incidental findings from low dose CT screening for lung cancer.

BACKGROUND: Screening for lung cancer with low radiation dose computed tomography has a strong evidence base, is being introduced in several European countries and is recommended as a new targeted cancer screening programme. The imperative now is to ensure that implementation follows an evidence-based process that will ensure clinical and cost effectiveness. This European Respiratory Society (ERS) task force was formed to provide an expert consensus for the management of incidental findings which can be adapted and followed during implementation. METHODS: A multi-European society collaborative group was convened. 23 topics were identified, primarily from an ERS statement on lung cancer screening, and a systematic review of the literature was conducted according to ERS standards. Initial review of abstracts was completed and full text was provided to members of the group for each topic. Sections were edited and the final document approved by all members and the ERS Science Council. RESULTS: Nine topics considered most important and frequent were reviewed as standalone topics (interstitial lung abnormalities, emphysema, bronchiectasis, consolidation, coronary calcification, aortic valve disease, mediastinal mass, mediastinal lymph nodes and thyroid abnormalities). Other topics considered of lower importance or infrequent were grouped into generic categories, suitable for general statements. CONCLUSIONS: This European collaborative group has produced an incidental findings statement that can be followed during lung cancer screening. It will ensure that an evidence-based approach is used for reporting and managing incidental findings, which will mean that harms are minimised and any programme is as cost-effective as possible.

ERS/ESTS/ESTRO/ESR/ESTI/EFOMP statement on management of incidental findings from low dose CT screening for lung cancer.

BACKGROUND: Screening for lung cancer with low radiation dose computed tomography has a strong evidence base, is being introduced in several European countries and is recommended as a new targeted cancer screening programme. The imperative now is to ensure that implementation follows an evidence-based process that will ensure clinical and cost effectiveness. This European Respiratory Society (ERS) task force was formed to provide an expert consensus for the management of incidental findings which can be adapted and followed during implementation. METHODS: A multi-European society collaborative group was convened. 23 topics were identified, primarily from an ERS statement on lung cancer screening, and a systematic review of the literature was conducted according to ERS standards. Initial review of abstracts was completed and full text was provided to members of the group for each topic. Sections were edited and the final document approved by all members and the ERS Science Council. RESULTS: Nine topics considered most important and frequent were reviewed as standalone topics (interstitial lung abnormalities, emphysema, bronchiectasis, consolidation, coronary calcification, aortic valve disease, mediastinal mass, mediastinal lymph nodes and thyroid abnormalities). Other topics considered of lower importance or infrequent were grouped into generic categories, suitable for general statements. CONCLUSIONS: This European collaborative group has produced an incidental findings statement that can be followed during lung cancer screening. It will ensure that an evidence-based approach is used for reporting and managing incidental findings, which will mean that harms are minimised and any programme is as cost-effective as possible.

Defining the road map to a UK national lung cancer screening programme.

Lung cancer screening with low-dose CT was recommended by the UK National Screening Committee (UKNSC) in September, 2022, on the basis of data from trials showing a reduction in lung cancer mortality. These trials provide sufficient evidence to show clinical efficacy, but further work is needed to prove deliverability in preparation for a national roll-out of the first major targeted screening programme. The UK has been world leading in addressing logistical issues with lung cancer screening through clinical trials, implementation pilots, and the National Health Service (NHS) England Targeted Lung Health Check Programme. In this Policy Review, we describe the consensus reached by a multiprofessional group of experts in lung cancer screening on the key requirements and priorities for effective implementation of a programme. We summarise the output from a round-table meeting of clinicians, behavioural scientists, stakeholder organisations, and representatives from NHS England, the UKNSC, and the four UK nations. This Policy Review will be an important tool in the ongoing expansion and evolution of an already successful programme, and provides a summary of UK expert opinion for consideration by those organising and delivering lung cancer screenings in other countries.

Immediate, Remote Smoking Cessation Intervention in Participants Undergoing a Targeted Lung Health Check: Quit Smoking Lung Health Intervention Trial, a Randomized Controlled Trial.

BACKGROUND: Lung cancer screening programs provide an opportunity to support people who smoke to quit, but the most appropriate model for delivery remains to be determined. Immediate face-to-face smoking cessation support for people undergoing screening can increase quit rates, but it is not known whether remote delivery of immediate smoking cessation counselling and pharmacotherapy in this context also is effective. RESEARCH QUESTION: Does an immediate telephone smoking cessation intervention increase quit rates compared with usual care among a population enrolled in a targeted lung health check (TLHC)? STUDY DESIGN AND METHODS: In a single-masked randomized controlled trial, people 55 to 75 years of age who smoke and attended a TLHC were allocated by day of attendance to receive either immediate telephone smoking cessation intervention (TSI) support (starting immediately and lasting for 6 weeks) with appropriate pharmacotherapy or usual care (UC; very brief advice to quit and signposting to smoking cessation services). The primary outcome was self-reported 7-day point prevalence smoking abstinence at 3 months. Differences between groups were assessed using logistic regression. RESULTS: Three hundred fifteen people taking part in the screening program who reported current smoking with a mean ± SD age of 63 ± 5.4 years, 48% of whom were women, were randomized to TSI (n = 152) or UC (n = 163). The two groups were well matched at baseline. Self-reported quit rates were higher in the intervention arm, 21.1% vs 8.9% (OR, 2.83; 95% CI, 1.44-5.61; P = .002). Controlling for participant demographics, neither baseline smoking characteristics nor the discovery of abnormalities on low-dose CT imaging modified the effect of the intervention. INTERPRETATION: Immediate provision of an intensive telephone-based smoking cessation intervention including pharmacotherapy, delivered within a targeted lung screening context, is associated with increased smoking abstinence at 3 months. TRIAL REGISTRY: ISRCTN registry; No.: ISRCTN12455871; URL: www.IRSCN.com.

COVID-protected pathways for image-guided lung cancer intervention during the COVID-19 pandemic: A cohort study.

OBJECTIVES: To compare the experience of COVID-protected and mixed cohort pathways in COVID-19 transmission at a tertiary referral hospital for elective CT-guided lung biopsy and ablation during the COVID-19 pandemic. METHODS: From September 2020 to August 2021, patients admitted for elective thoracic intervention were treated at a tertiary hospital (Site 1). Site 1 received patients for extracorporeal membrane oxygenation (ECMO) and invasive ventilation in the treatment of COVID-19. Shared imaging, theater, and hallway facilities were used.From April 2020 to August 2020, patients admitted for elective thoracic intervention were treated at a COVID-protected hospital (Site 2). No patients with suspected or confirmed COVID-19 were treated at Site 2.Patients were surveyed for clinical and laboratory signs of COVID-19 infection up to 30 days post-procedure. RESULTS: At Sites 1 and 2, patients (2.4%) were tested positive for COVID-19 at 10 and 14 days post-procedure.At Site 2, there were no COVID-19 positive cases within 30 days of undergoing elective thoracic intervention. CONCLUSION: A mixed-site method for infection control could represent a pragmatic approach to the management of elective procedures during the COVID-19 pandemic or for similar illnesses. ADVANCES IN KNOWLEDGE: Mixed-cohort infection control is possible in the prevention of nosocomial COVID-19 infection.

Indigenous Health Inequities Arising From Inadequate Transfer Systems for Patients With Critical Illness.

This Viewpoint describes how the systems for delivering emergency care for Indigenous and rural communities were strained during the COVID-19 pandemic and proposes policy solutions to advance health care equity.

Imaging of Lung Disease Associated with Connective Tissue Disease.

There is a well-known association between the connective tissue disorders (CTDs) and lung disease. In addition to interstitial lung disease, the CTDs may affect the air spaces and pulmonary vasculature. Imaging tests are important not only in diagnosis but also in management of these complex disorders. In the present review, key aspects of the imaging of CTD-reated diseases are discussed.

Lung cancer screening provides an opportunity for early diagnosis and treatment of interstitial lung disease.

Interstitial lung abnormalities (ILA) can be incidentally detected in patients undergoing low-dose CT screening for lung cancer. In this retrospective study, we explore the downstream impact of ILA detection on interstitial lung disease (ILD) diagnosis and treatment. Using a targeted approach in a lung cancer screening programme, the rate of de novo ILD diagnosis was 1.5%. The extent of abnormality on CT and severity of lung function impairment, but not symptoms were the most important factors in differentiating ILA from ILD. Disease modifying therapies were commenced in 39% of ILD cases, the majority being antifibrotic therapy for idiopathic pulmonary fibrosis.

Immediate smoking cessation support versus usual care in smokers attending a targeted lung health check: the QuLIT trial.

OBJECTIVES: Lung cancer screening programmes offer an opportunity to address tobacco dependence in current smokers. The effectiveness of different approaches to smoking cessation in this context has not yet been established. We investigated if immediate smoking cessation support, including pharmacotherapy, offered as part of a lung cancer screening programme, increases quit rates compared to usual care (Very Brief Advice to quit and signposting to smoking cessation services). MATERIALS AND METHODS: We conducted a single-blind randomised controlled trial of current smokers aged 55-75 years attending a Targeted Lung Health Check. On randomly allocated days smokers received either (1) immediate support from a trained smoking cessation counsellor with appropriate pharmacotherapy or (2) usual care. The primary outcome was self-reported quit rate at 3 months. We performed thematic analysis of participant interview responses. RESULTS: Of 412 people attending between January and March 2020, 115 (27.9%) were current smokers; 46% female, mean (SD) 62.4 (5.3) years. Follow-up data were available for 84 smokers. At 3 months, quit rates in the intervention group were higher 14/48 (29.2%) vs 4/36 (11%) (χ2 3.98, p=0.04). Participant interviews revealed four smoking-cessation related themes: (1) stress and anxiety, (2) impact of the COVID-19 pandemic, (3) CT scans influencing desire to quit and (4) individual beliefs about stopping smoking. CONCLUSION: The provision of immediate smoking cessation support is associated with a substantial increase in quit rates at 3 months. Further research is needed to investigate longer-term outcomes and to refine future service delivery. TRIAL REGISTRATION NUMBER: ISRCTN12455871.

Defining growth in small pulmonary nodules using volumetry: results from a "coffee-break" CT study and implications for current nodule management guidelines.

OBJECTIVES: An increase in lung nodule volume on serial CT may represent true growth or measurement variation. In nodule guidelines, a 25% increase in nodule volume is frequently used to determine that growth has occurred; this is based on previous same-day, test-retest (coffee-break) studies examining metastatic nodules. Whether results from prior studies apply to small non-metastatic nodules is unknown. This study aimed to establish the interscan variability in the volumetric measurements of small-sized non-metastatic nodules. METHODS: Institutional review board approval was obtained for this study. Between March 2019 and January 2021, 45 adults (25 males; mean age 65 years, range 37-84 years) with previously identified pulmonary nodules (30-150 mm3) requiring surveillance, without a known primary tumour, underwent two same-day CT scans. Non-calcified solid nodules were measured using commercial volumetry software, and interscan variability of volume measurements was assessed using a Bland-Altman method and limits of agreement. RESULTS: One hundred nodules (range 28-170 mm3; mean 81.1 mm3) were analysed. The lower and upper limits of agreement for the absolute volume difference between the two scans were - 14.2 mm3 and 12.0 mm3 respectively (mean difference 1.09 mm3, range - 33-12 mm3). The lower and upper limits of agreement for relative volume difference were - 16.4% and 14.6% respectively (mean difference 0.90%, range - 24.1-32.8%). CONCLUSIONS: The interscan volume variability in this cohort of small non-metastatic nodules was smaller than that in previous studies involving lung metastases of varying sizes. An increase of 15% in nodule volume on sequential CT may represent true growth, and closer surveillance of these nodules may be warranted. KEY POINTS: • In current pulmonary nodule management guidelines, a threshold of 25% increase in volume is required to determine that true growth of a pulmonary nodule has occurred. • This test-retest (coffee break) study has demonstrated that a smaller threshold of 15% increase in volume may represent true growth in small non-metastatic nodules. • Closer surveillance of some small nodules growing 15-25% over a short interval may be appropriate.

Critical care service delivery across healthcare systems in low-income and low-middle-income countries: protocol for a systematic review.

INTRODUCTION: Critical care in low-income and low-middle income countries (LLMICs) is an underdeveloped component of the healthcare system. Given the increasing growth in demand for critical care services in LLMICs, understanding the current capacity to provide critical care is imperative to inform policy on service expansion. Thus, our aim is to describe the provision of critical care in LLMICs with respect to patients, providers, location of care and services and interventions delivered. METHODS AND ANALYSIS: We will search PubMed/MEDLINE, Web of Science and EMBASE for full-text original research articles available in English describing critical care services that specify the location of service delivery and describe patients and interventions. We will restrict our review to populations from LLMICs (using 2016 World Bank classifications) and published from 1 January 2008 to 1 January 2020. Two-reviewer agreement will be required for both title/abstract and full text review stages, and rate of agreement will be calculated for each stage. We will extract data regarding the location of critical care service delivery, the training of the healthcare professionals providing services, and the illnesses treated according to classification by the WHO Universal Health Coverage Compendium. ETHICS AND DISSEMINATION: Reviewed and exempted by the Stanford University Office for Human Subjects Research and IRB on 20 May 2020. The results of this review will be disseminated through scholarly publication and presentation at regional and international conferences. This review is designed to inform broader WHO, International Federation for Emergency Medicine and partner efforts to strengthen critical care globally. PROSPERO REGISTRATION NUMBER: CRD42019146802.

Implications of incidental findings from lung screening for primary care: data from a UK pilot.

Regional lung cancer screening (LCS) is underway in England, involving a "lung health check" (LHC) and low-dose CT scan for those at high risk of cancer. Incidental findings from LHCs or CTs are usually referred to primary care. We describe the proportion of participants referred from the West London LCS pilot to primary care, the indications for referral, the number of general practitioner (GP) attendances and consequent changes to patient management, and provide an estimated cost-burden analysis for primary care. A small proportion (163/1542, 10.6%) of LHC attendees were referred to primary care, primarily for suspected undiagnosed chronic obstructive pulmonary disease (55/163, 33.7%) or for QRISK® (63/163, 38.7%) assessment. Ninety one of 159 (57.2%) participants consenting to follow-up attended GP appointments; costs incurred by primary care were estimated at £5.69/LHC participant. Patient management changes occurred in only 36/159 (22.6%) referred participants. LHCs result in a small increase to primary care workload provided a strict referral protocol is adhered to. Changes to patient management arising from incidental findings referrals are infrequent.

False-Negative Results in Lung Cancer Screening-Evidence and Controversies.

Identifying false-negative cases is an important quality metric in lung cancer screening, but it has been infrequently and variably reported in previous studies. Although as a proportion of all screening participants, false-negative cases are uncommon, such cases may constitute a substantial proportion of all lung cancers diagnosed (up to 15%) within a screening program. This article reviews the impact and causes of false-negative lung cancer screening tests, including those related to radiologic evaluation, nodule management protocols, and management decisions made by multidisciplinary teams. Following a review of data from international screening studies, this article discusses the controversies within the screening literature surrounding the definition and classification of a false-negative lung cancer screening test and how data on false-negative rates should be captured and recorded. Challenges, such as avoiding overly cautious surveillance of lung nodules while minimizing overdiagnosis and investigation of indolent or benign lesions, are considered. Finally, the advantages and disadvantages of different approaches to dealing with false-negative results in lung cancer screening are discussed.

Public knowledge of cardiovascular disease and response to acute cardiac events in three municipalities in Brazil.

OBJECTIVE: To conduct a landscape assessment of public knowledge of cardiovascular disease risk factors and acute myocardial infarction symptoms, cardiopulmonary resuscitation (CPR) and automated external defibrillator (AED) awareness and training in three underserved communities in Brazil. METHODS: A cross-sectional, population-based survey of non-institutionalised adults age 30 or greater was conducted in three municipalities in Eastern Brazil. Data were analysed as survey-weighted percentages of the sampled populations. RESULTS: 3035 surveys were completed. Overall, one-third of respondents was unable to identify at least one cardiovascular disease risk factor and 25% unable to identify at least one myocardial infarction symptom. A minority of respondents had received training in CPR or were able to identify an AED. Low levels of education and low socioeconomic status were consistent predictors of lower knowledge levels of cardiovascular disease risk factors, acute coronary syndrome symptoms and CPR and AED use. CONCLUSIONS: In three municipalities in Eastern Brazil, overall public knowledge of cardiovascular disease risk factors and symptoms, as well as knowledge of appropriate CPR and AED use was low. Our findings indicate the need for interventions to improve public knowledge and response to acute cardiovascular events in Brazil as a first step towards improving health outcomes in this population. Significant heterogeneity in knowledge seen across sites and socioeconomic strata indicates a need to appropriately target such interventions.

Baseline Results of the West London lung cancer screening pilot study - Impact of mobile scanners and dual risk model utilisation.

OBJECTIVES: The West London lung screening pilot aimed to identify early-stage lung cancer by targeting low-dose CT (LDCT) to high risk participants. Successful implementation of screening requires maximising participant uptake and identifying those at highest risk. As well as reporting pre-specified baseline screening metrics, additional objectives were to 1) compare participant uptake between a mobile and hospital-based CT scanner and 2) evaluate the impact on cancer detection using two lung cancer risk models. METHODS: From primary care records, ever-smokers aged 60-75 were invited to a lung health check at a hospital or mobile site. Participants with PLCOM2012 6-yr risk ≥1.51 % and/or LLPv2 5-yr risk ≥2.0 % were offered a LDCT. Lung cancer detection rate, stage, and recall rates are reported. Participant uptake was compared at both sites (chi-squared test). LDCT eligibility and cancer detection rate were compared between those recruited under each risk model. RESULTS: Of 8366 potential participants invited, 1047/5135 (20.4 %) invitees responded to an invitation to the hospital site, and 702/3231 (21.7 %) to the mobile site (p = 0.14). The median distance travelled to the hospital site was less than to the mobile site (3.3 km vs 6.4 km, p < 0.01). Of 1159 participants eligible for a scan, 451/1159 (38.9 %) had a LLPv2 ≥2.0 % only, 71/1159 (6.1 %) had a PLCOM2012 ≥1.5 % only; 637/1159 (55.0 %) met both risk thresholds. Recall rate was 15.9 %. Lung cancer was detected in 29/1145 (2.5 %) participants scanned (stage 1, 58.6 %); 5/29 participants with lung cancer did not meet a PLCOM2012 threshold of ≥1.51 %; all had a LLPv2 ≥2.0 %. CONCLUSION: Targeted screening is effective in detecting early-stage lung cancer. Similar levels of participant uptake at a mobile and fixed site scanner were demonstrated, indicating that uptake was driven by factors in addition to scanner location. The LLPv2 model was more permissive; recruitment with PLCOM2012 alone would have missed several cancers.