Cross-Sectional Associations between Prenatal Per- and Poly-Fluoroalkyl Substances and Bioactive Lipids in Three Environmental Influences on Child Health Outcomes (ECHO) Cohorts.

Prenatal per- and poly-fluoroalkyl substances (PFAS) exposure may influence gestational outcomes through bioactive lipids─metabolic and inflammation pathway indicators. We estimated associations between prenatal PFAS exposure and bioactive lipids, measuring 12 serum PFAS and 50 plasma bioactive lipids in 414 pregnant women (median 17.4 weeks' gestation) from three Environmental influences on Child Health Outcomes Program cohorts. Pairwise association estimates across cohorts were obtained through linear mixed models and meta-analysis, adjusting the former for false discovery rates. Associations between the PFAS mixture and bioactive lipids were estimated using quantile g-computation. Pairwise analyses revealed bioactive lipid levels associated with PFDeA, PFNA, PFOA, and PFUdA (p < 0.05) across three enzymatic pathways (cyclooxygenase, cytochrome p450, lipoxygenase) in at least one combined cohort analysis, and PFOA and PFUdA (q < 0.2) in one linear mixed model. The strongest signature revealed doubling in PFOA corresponding with PGD2 (cyclooxygenase pathway; +24.3%, 95% CI: 7.3-43.9%) in the combined cohort. Mixture analysis revealed nine positive associations across all pathways with the PFAS mixture, the strongest signature indicating a quartile increase in the PFAS mixture associated with PGD2 (+34%, 95% CI: 8-66%), primarily driven by PFOS. Bioactive lipids emerged as prenatal PFAS exposure biomarkers, deepening insights into PFAS' influence on pregnancy outcomes.

Strategies for primary HPV test-based cervical cancer screening programme in resource-limited settings in India: Results from a quasi-experimental pragmatic implementation trial.

BACKGROUND: In order for low and middle income countries (LMIC) to transition to Human Papilloma Virus (HPV) test based cervical cancer screening, a greater understanding of how to implement these evidence based interventions (EBI) among vulnerable populations is needed. This paper documents outcomes of an implementation research on HPV screening among women from tribal, rural, urban slum settings in India. METHODS: A mixed-method, pragmatic, quasi-experimental trial design was used. HPV screening on self-collected cervical samples was offered to women aged 30-60 years. Implementation strategies were 1) Assessment of contextual factors using both qualitative and quantitative methods like key informant interviews (KII), focus group discussions (FGDs), pre-post population sample surveys, capacity assessment of participating departments 2) enhancing provider capacity through training workshops, access to HPV testing facility, colposcopy, thermal ablation/cryotherapy at the primary health care centers 3) community engagement, counselling for self-sampling and triage process by frontline health care workers (HCWs). Outcomes were assessed using the RE-AIM (Reach, Effectiveness, adoption, implementation, maintenance) framework. RESULTS: Screening rate in 8 months' of study was 31.0%, 26.7%, 32.9%, prevalence of oncogenic HPV was 12.1%, 3.1%, 5.5%, compliance to triage was 53.6%, 45.5%, 84.6% in tribal, urban slum, rural sites respectively. Pre-cancer among triage compliant HPV positive women was 13.6% in tribal, 4% in rural and 0% among urban slum women. Unique challenges faced in the tribal setting led to programme adaptations like increasing honoraria of community health workers for late-evening work and recalling HPV positive women for colposcopy by nurses, thermal ablation by gynaecologist at the outreach camp site. CONCLUSIONS: Self-collection of samples combined with HCW led community engagement activities, flexible triage processes and strengthening of health system showed an acceptable screening rate and better compliance to triage, highlighting the importance of identifying the barriers and developing strategies suitable for the setting. TRIAL REGISTRATION: CTRI/2021/09/036130.

Research priorities for children's cancer: a James Lind Alliance Priority Setting Partnership in the UK.

OBJECTIVES: To engage children who have experienced cancer, childhood cancer survivors, their families and professionals to systematically identify and prioritise research questions about childhood cancer to inform the future research agenda. DESIGN: James Lind Alliance Priority Setting Partnership. SETTING: UK health service and community. METHODS: A steering group oversaw the initiative. Potential research questions were collected in an online survey, then checked to ensure they were unanswered. Shortlisting via a second online survey identified the highest priority questions. A parallel process with children was undertaken. A final consensus workshop was held to determine the Top 10 priorities. PARTICIPANTS: Children and survivors of childhood cancer, diagnosed before age 16, their families, friends and professionals who work with this population. RESULTS: Four hundred and eighty-eight people submitted 1299 potential questions. These were refined into 108 unique questions; 4 were already answered and 3 were under active study, therefore, removed. Three hundred and twenty-seven respondents completed the shortlisting survey. Seventy-one children submitted questions in the children's surveys, eight children attended a workshop to prioritise these questions. The Top 5 questions from children were taken to the final workshop where 23 questions in total were discussed by 25 participants (young adults, carers and professionals). The top priority was 'can we find effective and kinder (less burdensome, more tolerable, with fewer short and long-term effects) treatments for children with cancer, including relapsed cancer?' CONCLUSIONS: We have identified research priorities for children's cancer from the perspectives of children, survivors, their families and the professionals who care for them. Questions reflect the breadth of the cancer experience, including diagnosis, relapse, hospital experience, support during/after treatment and the long-term impact of cancer. These should inform funding of future research as they are the questions that matter most to the people who could benefit from research.

Cross-sectional associations between prenatal maternal per- and poly-fluoroalkyl substances and bioactive lipids in three Environmental influences on Child Health Outcomes (ECHO) cohorts.

Background: Per- and poly-fluoroalkyl substances (PFAS) exposure can occur through ingestion of contaminated food and water, and inhalation of indoor air contaminated with these chemicals from consumer and industrial products. Prenatal PFAS exposures may confer risk for pregnancy-related outcomes such as hypertensive and metabolic disorders, preterm birth, and impaired fetal development through intermediate metabolic and inflammation pathways. Objective: Estimate associations between maternal pregnancy PFAS exposure (individually and as a mixture) and bioactive lipids. Methods: Our study included pregnant women in the Environmental influences on Child Health Outcomes Program: Chemicals in our Bodies cohort (CiOB, n=73), Illinois Kids Developmental Study (IKIDS, n=287), and the ECHO-PROTECT cohort (n=54). We measured twelve PFAS in serum and 50 plasma bioactive lipids (parent fatty acids and eicosanoids derived from cytochrome p450, lipoxygenase, and cyclooxygenase) during pregnancy (median 17 gestational weeks). Pairwise associations across cohorts were estimated using linear mixed models and meta-analysis. Associations between the PFAS mixture and individual bioactive lipids were estimated using quantile g-computation. Results: PFDeA, PFOA, and PFUdA were associated (p<0.05) with changes in bioactive lipid levels in all three enzymatic pathways (cyclooxygenase [n=6 signatures]; cytochrome p450 [n=5 signatures]; lipoxygenase [n=7 signatures]) in at least one combined cohort analysis. The strongest signature indicated that a doubling in PFOA corresponded with a 24.3% increase (95% CI [7.3%, 43.9%]) in PGD2 (cyclooxygenase pathway) in the combined cohort. In the mixtures analysis, we observed nine positive signals across all pathways associated with the PFAS mixture. The strongest signature indicated that a quartile increase in the PFAS mixture was associated with a 34% increase in PGD2 (95% CI [8%, 66%]), with PFOS contributing most to the increase. Conclusions: Bioactive lipids were revealed as biomarkers of PFAS exposure and could provide mechanistic insights into PFAS' influence on pregnancy outcomes, informing more precise risk estimation and prevention strategies.

Boom-bust cycles in gray whales associated with dynamic and changing Arctic conditions.

Climate change is affecting a wide range of global systems, with polar ecosystems experiencing the most rapid change. Although climate impacts affect lower-trophic-level and short-lived species most directly, it is less clear how long-lived and mobile species will respond to rapid polar warming because they may have the short-term ability to accommodate ecological disruptions while adapting to new conditions. We found that the population dynamics of an iconic and highly mobile polar-associated species are tightly coupled to Arctic prey availability and access to feeding areas. When low prey biomass coincided with high ice cover, gray whales experienced major mortality events, each reducing the population by 15 to 25%. This suggests that even mobile, long-lived species are sensitive to dynamic and changing conditions as the Arctic warms.

A systematic review of the theory of planned behaviour interventions for chronic diseases in low health-literacy settings.

Background: Due to their chronicity, prolonged morbidity, and high mortality, chronic respiratory diseases (CRDs) pose a huge burden of disease globally, primarily among low- and middle-income countries. Most of these diseases can be controlled by early diagnosis and treatment, correct practice of medications, regular follow-up, and avoidance of risk factors, which involves a change in health behaviour among patients. The theory of planned behaviour (TPB) has been proven to be effective and has been used increasingly as a behavioural framework for designing and evaluating behaviour change interventions, although most such studies were on affluent populations and from the global north. We aimed to collate evidence of TPB-based behavioural interventions in low health literacy settings for its effectiveness and feasibility by conducting a systematic review (SR). Methods: We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines in conducting and reporting this study. We selected interventional studies using at least two constructs of TPB for behaviour change in chronic disease patients and conducted in LMICs, used the PICO framework, and exported the retrieved studies through the Endnote software. We evaluated the studies using the Risk of Bias (RoB) 2 and Risk of Bias in Non-randomised Studies - of Interventions (ROBINS-I) tools. Results: We retrieved and reviewed the titles and abstracts 4281 titles and abstracts, identifying 186 articles for further detailed screening. Eleven studies met the criteria for a standardised independent full-text screening by two authors and four were selected for narrative synthesis. All studies were from urban settings, with established feasibility and fidelity; all interventions were effective in changing health behaviour and TPB constructs and provided structured education to participants in the intervention group (either face-to-face and through group education). Three studies had some concerns/moderate risk of bias and one had high risk of bias. Conclusions: All studies demonstrated effectiveness, feasibility, and fidelity of TPB interventions in LMIC settings, although most were of moderate quality. Further studies should gather definitive evidence and prove their feasibility and utility in LMICs. Registration: PROSPERO CRD42018104890.

Childhood health and educational disadvantage are associated with adult multimorbidity in the global south: findings from a cross-sectional analysis of nationally representative surveys in India and Brazil.

INTRODUCTION: Multimorbidity has emerged as a major healthcare challenge in low/middle-income countries (LMICs) such as India and Brazil. Life course epidemiology suggests that adverse events in early life contribute to an individual's later health in adulthood. However, little is known about the influence of early life health and social factors on the development of multimorbidity in adulthood in LMICs. We aimed to explore the association of adult multimorbidity with childhood health and social disadvantages among two LMICs, India and Brazil. METHODS: We conducted a secondary data analysis of older adults aged ≥50 years using nationally representative surveys from Longitudinal Ageing Study in India, 2017-2018 (n=51 481) and 'Estudo Longitudinal da Saude e Bem-Estar dos Idosos Brasileirous', 2015-2016 (n=8730). We estimated the prevalence of multimorbidity along with 95% CI as a measure of uncertainty for all weighted proportions. Log link in generalised linear model was used to assess the association between childhood health and disadvantages with multimorbidity, reported as adjusted prevalence ratio (APR). RESULTS: The prevalence of multimorbidity was 25.53% and 55.24% in India and Brazil, respectively. Participants who perceived their childhood health as poor and missed school for a month or more due to illness had the highest level of multimorbidity across both countries. After adjusting for age and gender, a significant association between adult multimorbidity and poor self-rated childhood health (APR: (India: 1.38, 1.16 to 1.65) and (Brazil: 1.19, 1.09 to 1.30)); and missed school for a month due to illness (AOR: (India: 1.73, 1.49 to 2.01) and (Brazil: 1.16, 1.08 to 1.25)) was observed. CONCLUSION: Early life health, educational and economic disadvantages are associated with adult multimorbidity and appear to contribute to the later course of life. A life course approach to the prevention of multimorbidity in adulthood in LMICs may be useful in health programmes and policies.

The impact of rurality on patient experience and diagnostic pathway intervals in Scotland's cancer patients: Further results from a national cancer diagnosis audit.

BACKGROUND: In Scotland 17 % of the population reside rurally and previous research has demonstrated worse cancer outcomes in this group. The underlying reason for this is unclear. This study aims to determine whether patient presenting factors, GP consultation factors or the diagnostic pathways differ between urban and rural patients within Scotland. METHODS: This study combined two Scottish National Cancer Diagnosis Audits. Participating GPs collected data on the diagnostic pathway from primary to secondary care for cancer patients diagnosed during the audit period. Using the Scottish Government Urban Rural Classification, patients were designated as rural or urban dwellers and compared in descriptive analyses. Key cancer intervals (primary, diagnostic, secondary and treatment interval) were compared between urban and rural dwellers with an additional adjusted analysis for the main cancer sites. RESULTS: A total of 4309 cancer diagnoses were included in the study; 22 % were in patients from rural locations. Rural patients had significantly more consultations and investigations prior to referral than their urban counterparts. There was no difference in prolonged cancer pathways between the two groups except in lung cancer patients where rural patients had a significantly increased odds of a diagnostic interval of >90 days. CONCLUSION: Our findings suggest differences in the interaction between patients and GPs prior to referral in urban and rural settings. However, this does not appear to lead to prolonged patient pathways, except in lung cancer. Further research is needed to determine whether this delay is clinically significant and contributing to poorer outcomes in Scottish rural dwellers with lung cancer.

Symptoms and signs of urogenital cancer in primary care.

BACKGROUND: Urogenital cancers are common, accounting for approximately 20% of cancer incidence globally. Cancers belonging to the same organ system often present with similar symptoms, making initial management challenging. In this study, 511 cases of cancer were recorded after the date of consultation among 61,802 randomly selected patients presenting in primary care in six European countries: a subgroup analysis of urogenital cancers was carried out in order to study variation in symptom presentation. METHODS: Initial data capture was by completion of standardised forms containing closed questions about symptoms recorded during the consultation. The general practitioner (GP) provided follow-up data after diagnosis, based on medical record data made after the consultation. GPs also provided free text comments about the diagnostic procedure for individual patients. RESULTS: The most common symptoms were mainly associated with one or two specific types of cancer: 'Macroscopic haematuria' with bladder or renal cancer (combined sensitivity 28.3%), 'Increased urinary frequency' with bladder (sensitivity 13.3%) or prostatic (sensitivity 32.1%) cancer, or to uterine body (sensitivity 14.3%) cancer, 'Unexpected genital bleeding' with uterine cancer (cervix, sensitivity 20.0%, uterine body, sensitivity 71.4%). 'Distended abdomen, bloating' had sensitivity 62.5% (based on eight cases of ovarian cancer). In ovarian cancer, increased abdominal circumference and a palpable tumour also were important diagnostic elements. Specificity for 'Macroscopic haematuria' was 99.8% (99.7-99.8). PPV > 3% was noted for 'Macroscopic haematuria' and bladder or renal cancer combined, for bladder cancer in male patients. In males aged 55-74, PPV = 7.1% for 'Macroscopic haematuria' and bladder cancer. Abdominal pain was an infrequent symptom in urogenital cancers. CONCLUSIONS: Most types of urogenital cancer present with rather specific symptoms. If the GP considers ovarian cancer, increased abdominal circumference should be actively determined. Several cases were clarified through the GP's clinical examination, or laboratory investigations.

Joint Asian Pacific Association of Gastroenterology (APAGE)-Asian Pacific Society of Digestive Endoscopy (APSDE) clinical practice guidelines on the use of non-invasive biomarkers for diagnosis of colorectal neoplasia.

Screening for colorectal cancer (CRC) is effective in reducing CRC related mortality. Current screening methods include endoscopy based and biomarker based approaches. This guideline is a joint official statement of the Asian Pacific Association of Gastroenterology (APAGE) and the Asian Pacific Society of Digestive Endoscopy (APSDE), developed in response to the increasing use of, and accumulating supportive evidence for the role of, non-invasive biomarkers for the diagnosis of CRC and its precursor lesions. A systematic review of 678 publications and a two stage Delphi consensus process involving 16 clinicians in various disciplines was undertaken to develop 32 evidence based and expert opinion based recommendations for the use of faecal immunochemical tests, faecal based tumour biomarkers or microbial biomarkers, and blood based tumour biomarkers for the detection of CRC and adenoma. Comprehensive up-to-date guidance is provided on indications, patient selection and strengths and limitations of each screening tool. Future research to inform clinical applications are discussed alongside objective measurement of research priorities. This joint APAGE-APSDE practice guideline is intended to provide an up-to-date guide to assist clinicians worldwide in utilising non-invasive biomarkers for CRC screening; it has particular salience for clinicians in the Asia-Pacific region.

Multiple Receptors Contribute to the Attractive Response of Caenorhabditis elegans to Pathogenic Bacteria.

Nematodes feed mainly on bacteria and sense volatile signals through their chemosensory system to distinguish food from pathogens. Although nematodes recognizing bacteria by volatile metabolites are ubiquitous, little is known of the associated molecular mechanism. Here, we show that the antinematode bacterium Paenibacillus polymyxa KM2501-1 exhibits an attractive effect on Caenorhabditis elegans via volatile metabolites, of which furfural acetone (FAc) acts as a broad-spectrum nematode attractant. We show that the attractive response toward FAc requires both the G-protein-coupled receptors STR-2 in AWC neurons and SRA-13 in AWA and AWC neurons. In the downstream olfactory signaling cascades, both the transient receptor potential vanilloid channel and the cyclic nucleotide-gated channel are necessary for FAc sensation. These results indicate that multiple receptors and subsequent signaling cascades contribute to the attractive response of C. elegans to FAc, and FAc is the first reported ligand of SRA-13. Our current work discovers that P. polymyxa KM2501-1 exhibits an attractive effect on nematodes by secreting volatile metabolites, especially FAc and 2-heptanone, broadening our understanding of the interactions between bacterial pathogens and nematodes. IMPORTANCE Nematodes feed on nontoxic bacteria as a food resource and avoid toxic bacteria; they distinguish them through their volatile metabolites. However, the mechanism of how nematodes recognize bacteria by volatile metabolites is not fully understood. Here, the antinematode bacterium Paenibacillus polymyxa KM2501-1 is found to exhibit an attractive effect on Caenorhabditis elegans via volatile metabolites, including FAc. We further reveal that the attractive response of C. elegans toward FAc requires multiple G-protein-coupled receptors and downstream olfactory signaling cascades in AWA and AWC neurons. This study highlights the important role of volatile metabolites in the interaction between nematodes and bacteria and confirms that multiple G-protein-coupled receptors on different olfactory neurons of C. elegans can jointly sense bacterial volatile signals.

Variation in suspected cancer referral pathways in primary care: comparative analysis across the International Benchmarking Cancer Partnership.

BACKGROUND: International variations in cancer outcomes persist and may be influenced by differences in the accessibility and organisation of cancer patient pathways. More evidence is needed to understand to what extent variations in the structure of primary care referral pathways for cancer investigation contribute to differences in the timeliness of diagnoses and cancer outcomes in different countries. AIM: To explore the variation in primary care referral pathways for the management of suspected cancer across different countries. DESIGN AND SETTING: Descriptive comparative analysis using mixed methods across the International Cancer Benchmarking Partnership (ICBP) countries. METHOD: Schematics of primary care referral pathways were developed across 10 ICBP jurisdictions. The schematics were initially developed using the Aarhus statement (a resource providing greater insight and precision into early cancer diagnosis research) and were further supplemented with expert insights through consulting leading experts in primary care and cancer, existing ICBP data, a focused review of existing evidence on the management of suspected cancer, published primary care cancer guidelines, and evaluations of referral tools and initiatives in primary care. RESULTS: Referral pathway schematics for 10 ICBP jurisdictions were presented alongside a descriptive comparison of the organisation of primary care management of suspected cancer. Several key areas of variation across countries were identified: inflexibility of referral pathways, lack of a managed route for non-specific symptoms, primary care practitioner decision-making autonomy, direct access to investigations, and use of emergency routes. CONCLUSION: Analysing the differences in referral processes can prompt further research to better understand the impact of variation on the timeliness of diagnoses and cancer outcomes. Studying these schematics in local contexts may help to identify opportunities to improve care and facilitate discussions on what may constitute best referral practice.

Understanding patient barriers and facilitators to uptake of lung screening using low dose computed tomography: a mixed methods scoping review of the current literature.

BACKGROUND: Targeted lung cancer screening is effective in reducing mortality by upwards of twenty percent. However, screening is not universally available and uptake is variable and socially patterned. Understanding screening behaviour is integral to designing a service that serves its population and promotes equitable uptake. We sought to review the literature to identify barriers and facilitators to screening to inform the development of a pilot lung screening study in Scotland. METHODS: We used Arksey and O'Malley's scoping review methodology and PRISMA-ScR framework to identify relevant literature to meet the study aims. Qualitative, quantitative and mixed methods primary studies published between January 2000 and May 2021 were identified and reviewed by two reviewers for inclusion, using a list of search terms developed by the study team and adapted for chosen databases. RESULTS: Twenty-one articles met the final inclusion criteria. Articles were published between 2003 and 2021 and came from high income countries. Following data extraction and synthesis, findings were organised into four categories: Awareness of lung screening, Enthusiasm for lung screening, Barriers to lung screening, and Facilitators or ways of promoting uptake of lung screening. Awareness of lung screening was low while enthusiasm was high. Barriers to screening included fear of a cancer diagnosis, low perceived risk of lung cancer as well as practical barriers of cost, travel and time off work. Being health conscious, provider endorsement and seeking reassurance were all identified as facilitators of screening participation. CONCLUSIONS: Understanding patient reported barriers and facilitators to lung screening can help inform the implementation of future lung screening pilots and national lung screening programmes.

Diagnostic pathways for breast cancer in 10 International Cancer Benchmarking Partnership (ICBP) jurisdictions: an international comparative cohort study based on questionnaire and registry data.

OBJECTIVES: A growing body of evidence suggests longer time between symptom onset and start of treatment affects breast cancer prognosis. To explore this association, the International Cancer Benchmarking Partnership Module 4 examined differences in breast cancer diagnostic pathways in 10 jurisdictions across Australia, Canada, Denmark, Norway, Sweden and the UK. SETTING: Primary care in 10 jurisdictions. PARTICIPANT: Data were collated from 3471 women aged >40 diagnosed for the first time with breast cancer and surveyed between 2013 and 2015. Data were supplemented by feedback from their primary care physicians (PCPs), cancer treatment specialists and available registry data. PRIMARY AND SECONDARY OUTCOME MEASURES: Patient, primary care, diagnostic and treatment intervals. RESULTS: Overall, 56% of women reported symptoms to primary care, with 66% first noticing lumps or breast changes. PCPs reported 77% presented with symptoms, of whom 81% were urgently referred with suspicion of cancer (ranging from 62% to 92%; Norway and Victoria). Ranges for median patient, primary care and diagnostic intervals (days) for symptomatic patients were 3-29 (Denmark and Sweden), 0-20 (seven jurisdictions and Ontario) and 8-29 (Denmark and Wales). Ranges for median treatment and total intervals (days) for all patients were 15-39 (Norway, Victoria and Manitoba) and 4-78 days (Sweden, Victoria and Ontario). The 10% longest waits ranged between 101 and 209 days (Sweden and Ontario). CONCLUSIONS: Large international differences in breast cancer diagnostic pathways exist, suggesting some jurisdictions develop more effective strategies to optimise pathways and reduce time intervals. Targeted awareness interventions could also facilitate more timely diagnosis of breast cancer.

Optimizing the implementation of lung cancer screening in Scotland: Focus group participant perspectives in the LUNGSCOT study.

INTRODUCTION: Targeted lung cancer screening is effective in reducing lung cancer and all-cause mortality according to major trials in the United Kingdom and Europe. However, the best ways of implementing screening in local communities requires an understanding of the population the programme will serve. We undertook a study to explore the views of those potentially eligible for, and to identify potential barriers and facilitators to taking part in, lung screening, to inform the development of a feasibility study. METHODS: Men and women aged 45-70, living in urban and rural Scotland, and either self-reported people who smoke or who recently quit, were invited to take part in the study via research agency Taylor McKenzie. Eleven men and 14 women took part in three virtual focus groups exploring their views on lung screening. Focus group transcripts were transcribed and analysed using thematic analysis, assisted by QSR NVivo. FINDINGS: Three overarching themes were identified: (1) Knowledge, awareness and acceptability of lung screening, (2) Barriers and facilitators to screening and (3) Promoting screening and implementation ideas. Participants were largely supportive of lung screening in principle and described the importance of the early detection of cancer. Emotional and psychological concerns as well as system-level and practical issues were discussed as posing barriers and facilitators to lung screening. CONCLUSIONS: Understanding the views of people potentially eligible for a lung health check can usefully inform the development of a further study to test the feasibility and acceptability of lung screening in Scotland. PATIENT OR PUBLIC CONTRIBUTION: The LUNGSCOT study has convened a patient advisory group to advise on all aspects of study development and implementation. Patient representatives commented on the focus group study design, study materials and ethics application, and two representatives read the focus group transcripts.

Theory of planned behaviour-based interventions in chronic diseases among low health-literacy population: protocol for a systematic review.

BACKGROUND: Health behaviour can change outcomes in both healthy and unhealthy populations and are particularly useful in promoting compliance to treatment and maintaining fidelity to care seeking and follow-up options in chronic diseases. Interventions to change health behaviour based on psychological theory are more often successful than those without any underlying theory. The theory of planned behaviour (TPB) is one such psychological theory which had been found to predict human behaviour with respect to disease prevention and when applied to interventions can change the outcomes of diseases. Most of the research evidence of TPB-based interventions have been from developed world. Evidence is required whether TPB-based interventions can be applied and works in low-resource, low health-literacy settings of low- and middle-income countries (LMICs). METHODS: The protocol has been developed as per PRISMA-P guidelines and incorporates PICO (population, intervention, comparison, outcomes) framework for describing the methodology. Population above 18 years of age and having any chronic disease (as defined for this systematic review) will be selected, while any health or educational intervention based on constructs of TPB will be included. Comparison will be with non-TPB-based interventions or treatment as usual without any intervention, and the primary outcome will be the behaviour change effected by the TPB-based intervention. Intervention studies will be considered, and relevant databases like MEDLINE, Embase, Cochrane Library and ProQuest will be explored. Data extraction will done in a standardised form, and risk-of-bias assessment will be done using the Cochrane Collaboration's tools for such assessment. Narrative synthesis of the selected studies will be done to draw the conclusions, and meta-analysis will be done to calculate the effect estimates with I-squared statistics to describe the heterogeneity. DISCUSSION: This systematic review will provide new evidence on fidelity and effectiveness of the TPB-based interventions among chronic disease patients from low health literacy, resource-poor background. It will inform of how to plan and use such interventions to change health behaviour in chronic disease patients, particularly in LMIC settings. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018104890 .

Diagnostic routes and time intervals for ovarian cancer in nine international jurisdictions; findings from the International Cancer Benchmarking Partnership (ICBP).

BACKGROUND: International Cancer Benchmarking Partnership Module 4 reports the first international comparison of ovarian cancer (OC) diagnosis routes and intervals (symptom onset to treatment start), which may inform previously reported variations in survival and stage. METHODS: Data were collated from 1110 newly diagnosed OC patients aged >40 surveyed between 2013 and 2015 across five countries (51-272 per jurisdiction), their primary-care physicians (PCPs) and cancer treatment specialists, supplement by treatment records or clinical databases. Diagnosis routes and time interval differences using quantile regression with reference to Denmark (largest survey response) were calculated. RESULTS: There were no significant jurisdictional differences in the proportion diagnosed with symptoms on the Goff Symptom Index (53%; P = 0.179) or National Institute for Health and Care Excellence NG12 guidelines (62%; P = 0.946). Though the main diagnosis route consistently involved primary-care presentation (63-86%; P = 0.068), onward urgent referral rates varied significantly (29-79%; P < 0.001). In most jurisdictions, diagnostic intervals were generally shorter and other intervals, in particular, treatment longer compared to Denmark. CONCLUSION: This study highlights key intervals in the diagnostic pathway where improvements could be made. It provides the opportunity to consider the systems and approaches across different jurisdictions that might allow for more timely ovarian cancer diagnosis and treatment.