Nfix regulates fetal-specific transcription in developing skeletal muscle.

Skeletal myogenesis, like hematopoiesis, occurs in successive developmental stages that involve different cell populations and expression of different genes. We show here that the transcription factor nuclear factor one X (Nfix), whose expression is activated by Pax7 in fetal muscle, in turn activates the transcription of fetal specific genes such as MCK and beta-enolase while repressing embryonic genes such as slow myosin. In the case of the MCK promoter, Nfix forms a complex with PKC theta that binds, phosphorylates, and activates MEF2A. Premature expression of Nfix activates fetal and suppresses embryonic genes in embryonic muscle, whereas muscle-specific ablation of Nfix prevents fetal and maintains embryonic gene expression in the fetus. Therefore, Nfix acts as a transcriptional switch from embryonic to fetal myogenesis.

Adjuvant Olaparib for Patients with BRCA1- or BRCA2-Mutated Breast Cancer.

BACKGROUND: Poly(adenosine diphosphate-ribose) polymerase inhibitors target cancers with defects in homologous recombination repair by synthetic lethality. New therapies are needed to reduce recurrence in patients with BRCA1 or BRCA2 germline mutation-associated early breast cancer. METHODS: We conducted a phase 3, double-blind, randomized trial involving patients with human epidermal growth factor receptor 2 (HER2)-negative early breast cancer with BRCA1 or BRCA2 germline pathogenic or likely pathogenic variants and high-risk clinicopathological factors who had received local treatment and neoadjuvant or adjuvant chemotherapy. Patients were randomly assigned (in a 1:1 ratio) to 1 year of oral olaparib or placebo. The primary end point was invasive disease-free survival. RESULTS: A total of 1836 patients underwent randomization. At a prespecified event-driven interim analysis with a median follow-up of 2.5 years, the 3-year invasive disease-free survival was 85.9% in the olaparib group and 77.1% in the placebo group (difference, 8.8 percentage points; 95% confidence interval [CI], 4.5 to 13.0; hazard ratio for invasive disease or death, 0.58; 99.5% CI, 0.41 to 0.82; P<0.001). The 3-year distant disease-free survival was 87.5% in the olaparib group and 80.4% in the placebo group (difference, 7.1 percentage points; 95% CI, 3.0 to 11.1; hazard ratio for distant disease or death, 0.57; 99.5% CI, 0.39 to 0.83; P<0.001). Olaparib was associated with fewer deaths than placebo (59 and 86, respectively) (hazard ratio, 0.68; 99% CI, 0.44 to 1.05; P = 0.02); however, the between-group difference was not significant at an interim-analysis boundary of a P value of less than 0.01. Safety data were consistent with known side effects of olaparib, with no excess serious adverse events or adverse events of special interest. CONCLUSIONS: Among patients with high-risk, HER2-negative early breast cancer and germline BRCA1 or BRCA2 pathogenic or likely pathogenic variants, adjuvant olaparib after completion of local treatment and neoadjuvant or adjuvant chemotherapy was associated with significantly longer survival free of invasive or distant disease than was placebo. Olaparib had limited effects on global patient-reported quality of life. (Funded by the National Cancer Institute and AstraZeneca; OlympiA ClinicalTrials.gov number, NCT02032823.).

Understanding service preferences among consensually non-monogamous individuals seeking sexual healthcare.

Despite consensually non-monogamous people being a minority population with specific healthcare needs, research on this group is minimal, especially in relation to sexual healthcare. This study explores the motivations behind consensually non-monogamous individuals' choices of sexual healthcare service options. Qualitative survey data was collected from 67 consensual non-monogamists and analysed using thematic analysis. Two key themes captured participants' perspectives on the selection of sexual healthcare services. 'Feeling Comfortable' highlighted preferences for sexually inclusive clinics and LGBT+- focused services due to perceived better quality of care and comfort. 'Practicalities' emphasised convenience, proximity and the availability of STI testing options as critical factors influencing service selection. Accordingly, this research provides insight into the specific sexual healthcare service needs, desires and motivations of those who are consensually non-monogamous. Suggestions are made for increased training and awareness when working with relationship diverse patients.

Adeno-Associated Virus 2 and Human Adenovirus F41 in Wastewater during Outbreak of Severe Acute Hepatitis in Children, Ireland.

During April-July 2022, outbreaks of severe acute hepatitis of unknown etiology (SAHUE) were reported in 35 countries. Five percent of cases required liver transplantation, and 22 patients died. Viral metagenomic studies of clinical samples from SAHUE cases showed a correlation with human adenovirus F type 41 (HAdV-F41) and adeno-associated virus type 2 (AAV2). To explore the association between those DNA viruses and SAHUE in children in Ireland, we quantified HAdV-F41 and AAV2 in samples collected from a wastewater treatment plant serving 40% of Ireland's population. We noted a high correlation between HAdV-F41 and AAV2 circulation in the community and SAHUE clinical cases. Next-generation sequencing of the adenovirus hexon in wastewater demonstrated HAdV-F41 was the predominant HAdV type circulating. Our environmental analysis showed increased HAdV-F41 and AAV2 prevalence in the community during the SAHUE outbreak. Our findings highlight how wastewater sampling could aid in surveillance for respiratory adenovirus species.

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.

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.

Acceptability of and barriers to human papillomavirus vaccination in China: A systematic review of the Chinese and English scientific literature.

INTRODUCTION: Widespread adoption of the human papillomavirus (HPV) vaccine will require population acceptance and tailoring of immunisation services to community needs and preferences. We examined peer-reviewed publications on the acceptability of and barriers to the HPV vaccine across China. METHODS: We searched English (MEDLINE, Embase, and Web of Science) and Chinese (CNKI, VIP, Wanfang data) databases between 1 January 2006 and 31 December 2017. We adopted a narrative approach for data synthesis. RESULTS: We identified 73 studies. The overall median acceptability of HPV vaccine was 71.8% (Q1-Q3: 58.6%-81%). Low levels of acceptability (<40%) of HPV vaccine were found in eastern regions of China. The largest differences of acceptability were observed between rural western regions (all >90%) and urban eastern regions (all <35%). Despite these regional variations, common barriers to HPV vaccine acceptance were concerns about vaccine safety, uncertainty over vaccine effectiveness, low perceived risk of cervical cancer and the price of the vaccine. The level of willingness to pay for the HPV vaccine (over 153 US dollars) was very low (<7%). CONCLUSION: The acceptability of and attitudes towards HPV vaccine vary by regions and populations across China. HPV vaccination programmes will need to tailor service delivery as well as information materials to take account of regional concerns.

Patient and GP experiences of pathways to diagnosis of a second primary cancer: a qualitative study.

BACKGROUND: More people are surviving a first primary cancer and experiencing a second, different cancer. However, little is known about the diagnostic journeys of patients with second primary cancer (SPC). This study explores the views of patients and general practitioners (GPs) on their experiences of pathways to diagnosis of SPC, including the influence of a previous diagnosis of cancer on symptom appraisal, help-seeking and referral decisions. METHODS: Qualitative interviews with patients with a SPC diagnosis and case-linked GP interviews in a Scottish primary care setting. In-depth face to face or telephone interviews were conducted, underpinned by a social constructionist approach. Interviews were transcribed and Braun and Clarke's thematic analysis undertaken. Three analysts from the research team read transcripts and developed the coding framework using QSR NVivo version 10, with input from a fourth researcher. Themes were developed from refined codes and interpreted in the context of existing literature and theory. RESULTS: Interviews were conducted with 23 patients (aged 43-84 years) with a SPC diagnosis, and 7 GPs. Five patient themes were identified: Awareness of SPC, symptom appraisal and help-seeking, pathways to diagnosis, navigating the healthcare system, and impact of SPC. GPs interviews identified: experience and knowledge of SPC and referrals and decision-making. CONCLUSIONS: Insights into the pathway to diagnosis of SPC highlights the need for increased awareness of and vigilance for SPC among patients and healthcare providers (HCPs), and emotional support to manage the psychosocial burden.

COVID-19 and cancer screening in Scotland: A national and coordinated approach to minimising harm.

Screening is an important component of cancer control internationally. In Scotland, the National Health Service Scotland provides screening programmes for cervical, bowel and breast cancers. The COVID-19 pandemic resulted in the suspension of these programmes in March 2020. We describe the integrated approach to managing the impact of the pandemic on cancer screening programmes in Scotland throughout 2020. We outline the policy context and decision-making process leading to suspension, and the criteria and framework informing the subsequent, staggered, restart in subsequent months. The decision to suspend screening services in order to protect screening invitees and staff, and manage NHS capacity, was made after review of numbers of screening participants likely to be affected, and the potential number of delayed cancer diagnoses. Restart principles and a detailed route map plan were developed for each programme, seeking to ensure broad consistency of approach across the programmes and nationally. Early data indicates bowel, breast and cervical screening participation has increased since restart. Primary care has had to adapt to new infection prevention control measures for delivery of cervical screening. Cancer charities provided cancer intelligence and policy briefs to national bodies and Scottish Government, as well as supporting the public, patients and screening invitees through information and awareness campaigns. Emerging from the pandemic, there is recognition of the need and the opportunity to transform and renew both cancer and screening services in Scotland, and in particular to address long-standing workforce capacity problems through innovation and investment, and to continue to prioritise addressing health inequalities.

Early assessment of the first wave of the COVID-19 pandemic on cancer screening services: The International Cancer Screening Network COVID-19 survey.

Screening can decrease the burden of breast, cervical, and colorectal cancers. The COVID-19 pandemic led many countries to suspend cancer screening services as part of their response to the pandemic. The International Cancer Screening Network (ICSN) carried out an online survey to assess the effects of the first wave of the COVID-19 pandemic on cancer screening. A 33-item survey was distributed to 834 email addresses to gather information about settings and assess decision-making processes that led to cancer screening suspension. Information about communication, impact on resources, and patient follow-up was collected. Quantitative data was analyzed as frequencies overall and by setting, while a comment section under each survey item captured nuanced details. Responses were recategorized into 66 settings, representing 35 countries. Most settings suspended cancer screening services (n = 60, 90.9%) in March 2020 (n = 45, 68.2%), guided by a government decision (n = 51, 77.3%). Few settings made the decision whether to suspend services based on a preparedness plan (n = 17, 25.8%). In most settings, professionals were reassigned (n = 41, 62.1%) and infrastructure repurposed (n = 35, 53.0%). The first wave of the COVID-19 pandemic has had profound effects on cancer screening worldwide, including the suspension of services in almost all settings. Most settings were unprepared to deal with the scale of the pandemic but demonstrated flexibility in the response. These results contribute to inform, through experiences and lessons learned, the next steps for the global cancer screening community to further evaluate the impact of COVID-19 and prepare for future disruptions.

Experiences of cervical screening participation and non-participation in women from minority ethnic populations in Scotland.

BACKGROUND: The introduction of screening in the UK and other high-income countries led to a significant decrease in the incidence of cervical cancer and increase in survival rates. Minority ethnic groups are often underrepresented in screening participation for reasons that are poorly understood. OBJECTIVE: To explore experiences of cervical screening participation and non-participation of women from minority ethnic populations in Scotland and gain insights to support the development of interventions that could potentially support screening participation and thereby reduce inequalities. DESIGN: Qualitative comparison group study using in-depth, semi-structured individual interviews that were thematically analysed. SETTING AND PARTICIPANTS: This study took place in Scotland. Fifty women were purposively sampled from four ethnic minority groups: South Asian; East European; Chinese; and Black African or Caribbean. White Scottish women were also interviewed. RESULTS: Many experiences described were common regardless of ethnicity, such as difficulties managing competing priorities, including work and care responsibilities. However, important differences existed across the groups. These included going abroad for more frequent screening, delayed introduction to screening and not accessing primary care services, language difficulties in health-care settings despite proficiency in English and not being sexually active at screening commencement. Experiences of racism, ignorance and feeling shamed were also reported. CONCLUSIONS: Key differences exist in the experience of minority ethnic groups in Scotland. These offer potential opportunities to reduce disparity and support screening participation including maximizing co-incidental interactions and developing outreach work.

Cervical cancer incidence by ethnic group in Scotland from 2008 to 2017: A population-based study.

BACKGROUND: There is limited information on cervical cancer incidence among different ethnic groups. This study used a name classification system to describe recent patterns of cervical cancer by ethnic group in Scotland. METHODS: Data on incident cases of cancer of the cervix and carcinoma in situ diagnosed in Scotland from 2008 to 2017 were extracted from the Scottish Cancer Registry. Onomap was applied to ascribe ethnicity to each patient. Ethnic groups were categorised as White, Black, South-Asian, Chinese and Other. Age-standardised rates (ASRs) were calculated for each year, as well as cumulatively for the 10-year time period. RESULTS: The Cumulative Age-standardised rate (CASR) of invasive cancer was 2.45 times higher in the White ethnic group (CASR 125.45 (95% CI 121.2-129.8) per 1,00,000) compared to the non-white ethnic groups combined (CASR 51.16 (95% CI 31.05-77.36) per 1,00,000). The highest age-specific rates within the White patients were in the 30-34 age group (18.34 per 1,00,000), whereas the highest age specific rates for the non-white patients were in the 60-64 age group (9.59 per 1,00,000). CONCLUSION: Ethnic minority populations in Scotland had lower incidence of cervical cancer compared to the White population between 2008 and 2017.

Symptoms and signs of colorectal cancer, with differences between proximal and distal colon cancer: a prospective cohort study of diagnostic accuracy in primary care.

BACKGROUND: In an abdominal symptom study in primary care in six European countries, 511 cases of cancer were recorded prospectively among 61,802 patients 16 years and older in Norway, Denmark, Sweden, Netherlands, Belgium and Scotland. Colorectal cancer is one of the main types of cancer associated with abdominal symptoms; hence, an in-depth subgroup analysis of the 94 colorectal cancers was carried out in order to study variation in symptom presentation among cancers in different anatomical locations. METHOD: Initial data capture was by completion of standardised forms containing closed questions about symptoms recorded during the consultation. Follow-up data were provided by the GP after diagnosis, based on medical record data made after the consultation. GPs also provided free text comments about the diagnostic procedure for individual patients. Fisher's exact test was used to analyse differences between groups. RESULTS: Almost all symptoms recorded could indicate colorectal cancer. 'Rectal bleeding' had a specificity of 99.4% and a PPV of 4.0%. Faecal occult blood in stool (FOBT) or anaemia may indicate gastrointestinal bleeding: when these symptoms and signs were combined, sensitivity reached 57.5%, with 69.2% for cancer in the distal colon. For proximal colon cancers, none of 18 patients had 'Rectal bleeding' at the initial consultation, but three of the 18 did so at a later consultation. 'Abdominal pain, lower part', 'Constipation' and 'Distended abdomen, bloating' were less specific and also less sensitive than 'Rectal bleeding', and with PPV between 0.7% and 1.9%. CONCLUSIONS: Apart from rectal bleeding, single symptoms did not reach the PPV 3% NICE threshold. However, supplementary information such as a positive FOBT or persistent symptoms may revise the PPV upwards. If a colorectal cancer is suspected by the GP despite few symptoms, the total clinical picture may still reach the NICE PPV threshold of 3% and justify a specific referral.

Pregnancies during and after trastuzumab and/or lapatinib in patients with human epidermal growth factor receptor 2-positive early breast cancer: Analysis from the NeoALTTO (BIG 1-06) and ALTTO (BIG 2-06) trials.

BACKGROUND: Limited data exist on the safety of using anti-human epidermal growth factor receptor 2 (HER2) targeted agents during pregnancy. To date, only retrospective studies have assessed the prognosis of patients with a pregnancy after prior early breast cancer, with no data in HER2-positive patients. METHODS: The Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimization (NeoALTTO) trial and the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization (ALTTO) trial were randomized phase 3 trials for patients with HER2-positive early breast cancer. In both trials, pregnancy information was prospectively collected. Pregnancy outcomes were compared between patients unintentionally exposed to trastuzumab and/or lapatinib during gestation (the exposed group) and those who became pregnant after trastuzumab and/or lapatinib completion (the unexposed group). In the ALTTO trial, disease-free survival (DFS) was compared between pregnant patients and those aged 40 years or younger without a subsequent pregnancy via an extended Cox model with time-varying covariates to account for a guarantee-time bias. RESULTS: Ninety-two patients (12 in the exposed group and 80 in the unexposed group) had a pregnancy: 7 in the NeoALTTO trial and 85 in the ALTTO trial. Seven patients (58.3%) in the exposed group and 10 patients (12.5%) in the unexposed group opted for an induced abortion; in the unexposed group, 10 patients (12.5%) had a spontaneous abortion. No pregnancy/delivery complications were reported for the remaining cases, who successfully completed their pregnancy, with the exception of 1 fetus with trisomy 21 (Down syndrome). No significant difference in DFS (adjusted hazard ratio, 1.12; 95% confidence interval, 0.52-2.42) was observed between young patients with a pregnancy (n = 85) and young patients without a pregnancy (n = 1307). CONCLUSIONS: For patients with HER2-positive early breast cancer, having a pregnancy after treatment completion appears to be safe without compromising fetal outcome or maternal prognosis.

Comparing uptake across breast, cervical and bowel screening at an individual level: a retrospective cohort study.

BACKGROUND: We investigated demographic and clinical predictors of lower participation in bowel screening relative to breast and cervical screening. METHODS: Data linkage study of routinely collected clinical data from 430,591 women registered with general practices in the Greater Glasgow & Clyde Health Board. Participation in the screening programmes was measured by attendance at breast or cervical screening or the return of a bowel screening kit. RESULTS: 72.6% of 159,993 women invited attended breast screening, 80.7% of 309,899 women invited attended cervical screening and 61.7% of 180,408 women invited completed bowel screening. Of the 68,324 women invited to participate in all three screening programmes during the study period, 52.1% participated in all three while 7.2% participated in none. Women who participated in breast (OR = 3.34 (3.21, 3.47), p < 0.001) or cervical (OR = 3.48 (3.32, 3.65), p < 0.001) were more likely to participate in bowel screening. CONCLUSION: Participation in bowel screening was lower than breast or cervical for this population although the same demographic factors were associated with uptake, namely lower social deprivation, increasing age, low levels of comorbidity and prior non-malignant neoplasms. As women who complete breast and cervical are more likely to also complete bowel screening, interventions at these procedures to encourage bowel screening participation should be explored.

Dissecting the effect of hormone receptor status in patients with HER2-positive early breast cancer: exploratory analysis from the ALTTO (BIG 2-06) randomized clinical trial.

PURPOSE: Limited evidence exists on the impact of hormone receptor (HR) status to counsel HER2-positive early breast cancer patients receiving adjuvant anti-HER2 therapy. METHODS: ALTTO (BIG 2-06) was an international, intergroup, open-label, randomized phase III trial in HER2-positive early breast cancer patients randomized to receive 1 year of trastuzumab and/or lapatinib. HER2, estrogen and progesterone receptors were centrally tested for all patients. We investigated the impact of HR status on prognosis, risk of disease-free survival (DFS) events over time, patterns of first DFS events, and factors associated with risk of DFS events overall, in years 0-5 and 6-8. RESULTS: Out of 6273 patients included in this analysis, 3603 (57.4%) had HR-positive tumors. Median follow-up was 6.93 years. Five-year and 8-year DFS were 86% and 80% in patients with HR-positive disease, and 83% and 79% in those with HR-negative tumors, respectively. Mean annual hazards of recurrence in years 0-5 were 3% in patients with HR-positive disease and 4% in those with HR-negative tumors, while in years 6-8 they were 3% and 2%, respectively. Distribution of first DFS event in years 6-8 (P = 0.005) and type of first distant recurrence (P < 0.001) were significantly different between the two groups. Risk factors for DFS events overall, in years 0-5, and 6-8 were different in patients with HR-positive and HR-negative tumors. CONCLUSIONS: HER2-positive early breast cancer is characterized by the presence of two diseases with distinct natural history based on HR status requiring the development of different follow-up strategies and future de-escalation and escalation clinical trials.

Cardiac biomarkers for early detection and prediction of trastuzumab and/or lapatinib-induced cardiotoxicity in patients with HER2-positive early-stage breast cancer: a NeoALTTO sub-study (BIG 1-06).

BACKGROUND: Biomarkers of cardiac damages, such as troponin T (TnT) and the amino-terminal fragment of brain natriuretic peptide (NT-proBNP), may be useful as early predictors of cardiac dysfunction. The role of these biomarkers in patients receiving lapatinib and/or trastuzumab before anthracyclines is unknown. This study explores TnT and NT-proBNP as predictors of early cardiac toxicity in neoadjuvant breast cancer patients. METHODS: This sub-study of the NEOALTTO trial tested if changes in the levels of TnT and NT-proBNP occurred after 2 weeks of anti-HER2 therapy (lapatinib, trastuzumab or their combination) alone and/or after 18 weeks of anti-HER2 therapy plus weekly paclitaxel. RESULTS: 173 and 172 were tested at all three timepoints for NT-proBNP and TnT, respectively. The incidence of biomarker elevation was overall low at all timepoints for all the three treatment arms. A total of 13 CEs in 11 patients occurred. Biomarker elevations in patients with CEs were very rare; only one patient with subsequent CE had a NT-proBNP elevation at baseline and at week 2. CONCLUSION: These results suggest that TnT and proBNP may not be useful as early predictors of cardiac toxicity in anthracycline-naïve patients receiving trastuzumab and/or lapatinib.

Deaths Related to Hurricane Irma - Florida, Georgia, and North Carolina, September 4-October 10, 2017.

Three powerful and devastating hurricanes from the 2017 Atlantic hurricane season (Harvey [August 17-September 1], Irma [August 30-September 13], and Maria [September 16-October 2]) resulted in the deaths of hundreds of persons. Disaster-related mortality surveillance is critical to an emergency response because it provides government and public health officials with information about the scope of the disaster and topics for prevention messaging. CDC's Emergency Operations Center collaborated with state health departments in Florida, Georgia, and North Carolina to collect and analyze Hurricane Irma-related mortality data to understand the main circumstances of death. The most common circumstance-of-death categories were exacerbation of existing medical conditions and power outage. Further analysis revealed two unique subcategories of heat-related and oxygen-dependent deaths in which power outage contributed to exacerbation of an existing medical condition. Understanding the need for subcategorization of disaster-related circumstances of death and the possibility of overlapping categories can help public health practitioners derive more effective public health interventions to prevent deaths in future disasters.

The contribution of a negative colorectal screening test result to symptom appraisal and help-seeking behaviour among patients subsequently diagnosed with an interval colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) screening programmes using a guaiac faecal occult blood test (gFOBt) reduce CRC mortality. Interval cancers are diagnosed between screening rounds: reassurance from a negative gFOBt has the potential to influence the pathway to diagnosis of an interval colorectal cancer. METHODS: Twenty-six semi-structured face-to-face interviews were carried out in Scotland and England, with individuals diagnosed with an interval colorectal cancer following a negative gFOBt result. RESULTS: Participants reported they were reassured by a negative gFOBt, interpreting their result as an "all clear". Therefore, most did not suspect cancer as a possible cause of symptoms and many did not recall their screening result during symptom appraisal. Among those who did consider cancer, and did think about their screening test result, reassurance from a negative gFOBt led some to "downplay" the seriousness of their symptoms with some interviewees explicitly stating that their negative test result contributed to a delayed decision to seek help. CONCLUSION: Screening participants need to be informed of the limitations of screening and the ongoing risk of developing colorectal cancer even when in receipt of a negative result: the importance of minimizing delay in seeking medical advice for colorectal symptoms should be emphasized.

The Aarhus statement on cancer diagnostic research: turning recommendations into new survey instruments.

BACKGROUND: Over recent years there has been a growth in cancer early diagnosis (ED) research, which requires valid measurement of routes to diagnosis and diagnostic intervals. The Aarhus Statement, published in 2012, provided methodological guidance to generate valid data on these key pre-diagnostic measures. However, there is still a wide variety of measuring instruments of varying quality in published research. In this paper we test comprehension of self-completion ED questionnaire items, based on Aarhus Statement guidance, and seek input from patients, GPs and ED researchers to refine these questions. METHODS: We used personal interviews and consensus approaches to generate draft ED questionnaire items, then a combination of focus groups and telephone interviews to test comprehension and obtain feedback. A framework analysis approach was used, to identify themes and potential refinements to the items. RESULTS: We found that many of the questionnaire items still prompted uncertainty in respondents, in both routes to diagnosis and diagnostic interval measurement. Uncertainty was greatest in the context of multiple or vague symptoms, and potentially ambiguous time-points (such as 'date of referral'). CONCLUSIONS: There are limits on the validity of self-completion questionnaire responses, and refinements to the wording of questions may not be able to completely overcome these limitations. It's important that ED researchers use the best identifiable measuring instruments, but accommodate inevitable uncertainty in the interpretation of their results. Every effort should be made to increase clarity of questions and responses, and use of two or more data sources should be considered.