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Funder: Manchester Cancer Research Centre, Funder: East of England Clinical Academic Reserve, In the UK, the National Institute for Health and Care Excellence (NICE) recommends that women at moderate or high risk of breast cancer be offered risk-reducing medication and enhanced breast screening/surveillance. In June 2022, NICE withdrew a statement recommending assessment of risk in primary care only when women present with concerns. This shift to the proactive assessment of risk substantially changes the role of primary care, in effect paving the way for a primary care-based screening programme to identify those at moderate or high risk of breast cancer. In this article, we review the literature surrounding proactive breast cancer risk assessment within primary care against the consolidated framework for screening. We find that risk assessment for women under 50 years currently satisfies many of the standard principles for screening. Most notably, there are large numbers of women at moderate or high risk currently unidentified, risk models exist that can identify those women with reasonable accuracy, and management options offer the opportunity to reduce breast cancer incidence and mortality in that group. However, there remain a number of uncertainties and research gaps, particularly around the programme/system requirements, that need to be addressed before these benefits can be realised.

BackgroundGestational diabetes mellitus (GDM) is an important risk factor for developing type 2 diabetes mellitus (T2DM) later in life. Postpartum screening provides an opportunity for early detection and management of T2DM, but uptake is poor.AimTo explore barriers to screening from clinicians’ perspectives to guide future interventions to increase uptake of postpartum screening.Design and settingSystematic review and qualitative synthesis.MethodQualitative studies included in a previous review were assessed, and then five electronic databases were searched from January 2013 to May 2019 for qualitative studies reporting clinicians’ perspectives on postpartum glucose screening after GDM. Study quality was assessed against the Critical Appraisal Skills Programmes checklist. Qualitative data from the studies were analysed using thematic synthesis.ResultsNine studies were included, containing views from 187 clinicians from both community and hospital care. Three main themes were identified: difficulties in handover between primary and secondary care (ambiguous roles and communication difficulties); short-term focus in clinical consultations (underplaying risk so as not to overwhelm patients and competing priorities); and patient-centric barriers such as time pressures.ConclusionBarriers to diabetes screening were identified at both system and individual levels. At the system level, clarification of responsibility for testing among healthcare professionals and better systems for recall are needed. These could be achieved through registers, improved clinical protocols, and automatic flagging and prompts within electronic medical records. At the individual level, clinicians should be supported to prioritise the importance of screening within consultations and better educational resources made available for women. Making it more convenient for women to attend may also facilitate screening.

Aim Many women do not attend recommended glucose testing following a pregnancy affected by gestational diabetes (GDM). We aimed to synthesize the literature regarding the views and experiences of women with a history of GDM on postpartum glucose testing, focusing on barriers and facilitators to attendance. Methods We systematically identified qualitative studies that examine women's experiences following GDM relating to glucose testing (diabetes screening) or experience of interventions to promote uptake of testing. We conducted a thematic synthesis to develop descriptive and then analytical themes, then developed recommendations to increase uptake based on the findings. We evaluated the quality of each study and the confidence that we had in the recommendations using published checklists. Results We included 16 articles after screening 23 160 citations and 129 full texts. We identified four themes of influences relating to the healthcare system and personal factors that affected both ability and motivation to attend: relationship with health care, logistics of appointments and tests, family‐related practicalities and concern about diabetes. We developed 10 recommendations addressing diabetes risk information and education, and changes to healthcare systems to promote increased attendance at screening in this population, most with high or moderate confidence. Conclusions We have identified a need to improve women's understanding about Type 2 diabetes and GDM, and to adjust healthcare provision during and after pregnancy to decrease barriers and increase motivation for testing. Encouraging higher uptake by incorporating these recommendations into practice will enable earlier management of diabetes and improve long‐term outcomes., What's new? There is a need to increase the number of women attending glucose testing after gestational diabetes. Higher attendance will enable earlier diagnosis and management of diabetes and improve long‐term outcomes.This is the first qualitative review focusing on barriers and facilitators to screening attendance.We found that factors could affect either mothers’ motivation or opportunity to attend.Some influences related to the healthcare system (relationship with health care and logistics of the appointment and test), whereas others were personal (concern about diabetes and family‐related practicalities).We developed 10 recommendations to increase screening attendance based on the barriers and facilitators identified.

Aims After gestational diabetes, many women exhibit behaviours that increase their risk of developing Type 2 diabetes. We aimed to systematically synthesize the literature that focuses on the views of women with a history of gestational diabetes on reducing their risk of developing diabetes postpartum through lifestyle and behaviour changes. Methods We identified qualitative studies that examined the views of women with a history of gestational diabetes towards healthy eating and physical activity, Type 2 diabetes risk management or their experience of a diabetes prevention programme, and conducted a thematic synthesis to develop descriptive and then analytical themes. We also evaluated the quality of each study and the confidence that we had in our findings. Results We included 21 articles after screening 23 160 citations and 129 full texts. We identified six themes of interacting influences on postpartum behaviour: role as mother and priorities; social support; demands of life; personal preferences and experiences; risk perception and information; and finances and resources (plus preferred format of interventions). These factors inhibited many women from addressing their own health, while they motivated others to persevere. We also developed 20 recommendations, most with high or moderate confidence, for effective promotion of healthy lifestyles in this population. Conclusions Many factors hinder healthy lifestyles after gestational diabetes, yet how women interpret them can motivate or prevent changes that reduce diabetes risk. As our recommendations emphasize, women's experiences and needs should be considered when designing strategies to promote healthier lifestyles in this population.

Background: Men have a greater risk of colorectal cancer (CRC) than women, but population screening currently starts at the same age for both sexes. Aim: This analysis investigates whether, in a resource‐constrained setting, it would be more effective and cost‐effective for men and women to start screening for CRC at different ages. Methods and results: An economic modeling analysis was carried out using the Microsimulation Model in Cancer of the Bowel to compare sex‐stratification against screening everyone from the same age, taking an English National Health Service perspective. Screening men from age 56 and women from age 60, rather than screening everyone from age 58 using a Fecal Immunochemical Test (FIT) threshold of 120 μg/g is expected to produce an additional 0.0004 QALYs for a cost of £0.55 per person at model start (Incremental Cost‐effectiveness Ratio = £1392), and to reduce CRC cases and mortality by 25 and 19 per 100 000 people respectively, while using a similar amount of screening resources. Probabilistic sensitivity analysis indicates a 61% probability that sex‐stratification is more cost‐effective than screening everyone at age 58. Similar benefits of sex‐stratification are found at other FIT thresholds, but become negligible if mean screening start age is reduced to 50. Conclusion: Where resources are constrained and it is not feasible to screen everyone from the age of 50, starting screening earlier in men than women is likely to be more cost‐effective and gain more health benefits overall than strategies where men and women start screening at the same age.

Funder: NIHR School for Primary Care Research; Id: http://dx.doi.org/10.13039/501100013374, Funder: Cancer Research UK; Id: http://dx.doi.org/10.13039/501100000289, Funder: Action Medical Research; Id: http://dx.doi.org/10.13039/501100000317, Funder: European Foundation for the Study of Diabetes; Id: http://dx.doi.org/10.13039/501100001648, Funder: Medical Research Council; Id: http://dx.doi.org/10.13039/501100000265, Funder: Diabetes UK; Id: http://dx.doi.org/10.13039/501100000361, Aims: To explore the views of women with a history of gestational diabetes mellitus (GDM) on suggested practical approaches to support diabetes screening attendance after GDM, which is recommended but poorly attended. Methods: We conducted semi‐structured interviews with 20 participants in Cambridgeshire, UK who had been diagnosed with GDM and were 3–48 months postpartum. Interviews covered whether participants had been screened and why, plans for future screening and their views on potential interventions to facilitate attendance (at the first postpartum test and annual testing). Framework analysis was used to analyse the transcripts. The interview schedule, suggested interventions and thematic framework were based on a recent systematic review. Results: Sixteen participants had undergone screening since pregnancy, explaining that they had an appointment arranged and wanted reassurance that they did not have diabetes. The participants who had not been tested were not aware that it was recommended. Only 13 had planned to attend subsequent tests at the start of the interview. Eight themes to support future attendance were discussed. The majority of the participants agreed that changing the processes for arranging tests, offering choice in test location and combining appointments would facilitate attendance. Child‐friendly clinics, more opportunities to understand GDM and the role of postpartum testing, stopping self‐testing and increasing their GP’s awareness of their pregnancy received inconsistent feedback. The nature of the test used did not appear to influence attendance. Conclusions: The participants wanted to be screened for diabetes after GDM. We have identified interventions that could be relatively simply incorporated into routine practice to facilitate screening attendance, such as flexibility in the appointment location or time and sending invitations for tests.

Funder: Kidney Cancer UK, Funder: Renal Cancer Research Fund, Background: Using risk stratification approaches to determine eligibility has the potential to improve efficiency of screening. Objectives: To compare the public acceptability and potential impact on uptake of using different approaches to determine eligibility for screening. Design: An online population‐based survey of 668 adults in the UK aged 45‐79 including a series of scenarios in the context of a potential kidney cancer screening programme in which eligibility was determined by age, sex, age and sex combined, a simple risk score (age, sex, body mass index, smoking status), a complex risk score additionally incorporating family history and lifestyle, or a genetic risk score. Outcome measures: We used multi‐level ordinal logistic regression to compare acceptability and potential uptake within individuals and multivariable ordinal logistic regression differences between individuals. Results: Using sex, age and sex, or the simple risk score were less acceptable than age (P < .0001). All approaches were less acceptable to women than men. Over 70% were comfortable waiting until they were older if the complex risk score or genetics indicated a low risk. If told they were high risk, 85% would be more likely to take up screening. Being told they were low risk had no overall influence on uptake. Conclusions: Varying the starting age of screening based on estimated risk from models incorporating phenotypic or genetic risk factors would be acceptable to most individuals and may increase uptake. Patient or Public Contribution: Two members of the public contributed to the development of the survey and have commented on this paper.

ObjectiveTo determine the feasibility of a definitive trial in primary care of electronic clinical decision support (eCDS) for possible oesophago-gastric (O-G) cancer.Design and settingFeasibility study in 42 general practices in two regions of England, cluster randomised controlled trial design without blinding, nested qualitative and health economic evaluation.ParticipantsPatients aged 55 years or older, presenting to their general practitioner (GP) with symptoms associated with O-G cancer. 530 patients (mean age 68 years, 58% female) participated.InterventionPractices randomised 1:1 to usual care (control) or to receive a previously piloted eCDS tool for suspected cancer (intervention), for use at the discretion of the GPs, supported by a theory-based implementation package and ongoing support. We conducted semistructured interviews with GPs in intervention practices. Recruitment lasted 22 months.OutcomesPatient participation rate, use of eCDS, referrals and route to diagnosis, O-G cancer diagnoses; acceptability to GPs; cost-effectiveness. Participants followed up 6 months after index encounter.ResultsFrom control and intervention practices, we screened 3841 and 1303 patients, respectively; 1189 and 434 were eligible, 392 and 138 consented to participate. Ten patients (1.9%) had O-G cancer. eCDS was used eight times in total by five unique users. GPs experienced interoperability problems between the eCDS tool and their clinical system and also found it did not fit with their workflow. Unexpected restrictions on software installation caused major problems with implementation.ConclusionsThe conduct of this study was hampered by technical limitations not evident during an earlier pilot of the eCDS tool, and by regulatory controls on software installation introduced by primary care trusts early in the study. This eCDS tool needed to integrate better with clinical workflow; even then, its use for suspected cancer may be infrequent. Any definitive trial of eCDS for cancer diagnosis should only proceed after addressing these constraints.Trial registration numberISRCTN125595588.

Funder: Research Trainees Coordinating Centre; funder-id: http://dx.doi.org/10.13039/501100000659, Background: There is considerable heterogeneity in individuals’ risk of disease and thus the absolute benefits and harms of population-wide screening programmes. Using colorectal cancer (CRC) screening as an exemplar, we explored how people make decisions about screening when presented with information about absolute benefits and harms, and how those preferences vary with baseline risk, between screening tests and between individuals. Method: We conducted two linked studies with members of the public: a think-aloud study exploring decision making in-depth and an online randomised experiment quantifying preferences. In both, participants completed a web-based survey including information about three screening tests (colonoscopy, sigmoidoscopy, and faecal immunochemical testing) and then up to nine scenarios comparing screening to no screening for three levels of baseline risk (1%, 3% and 5% over 15 years) and the three screening tests. Participants reported, after each scenario, whether they would opt for screening (yes/no). Results: Of the 20 participants in the think-aloud study 13 did not consider absolute benefits or harms when making decisions concerning CRC screening. In the online experiment (n = 978), 60% expressed intention to attend at 1% risk of CRC, 70% at 3% and 77% at 5%, with no differences between screening tests. At an individual level, 535 (54.7%) would attend at all three risk levels and 178 (18.2%) at none. The 27% whose intention varied by baseline risk were more likely to be younger, without a family history of CRC, and without a prior history of screening. Conclusions: Most people in our population were not influenced by the range of absolute benefits and harms associated with CRC screening presented. For an appreciable minority, however, magnitude of benefit was important.

Objectives To describe cervical cancer screening participation among women who have sex exclusively with women (WSEW) and women who have sex with women and men (WSWM) compared with women who have sex exclusively with men (WSEM), and women who have never had sex and compare this with bowel (colorectal) and breast screening participation. To explore whether there is evidence of differential stage 3 cervical intraepithelial neoplasia (CIN3) or cervical cancer risk. Methods We describe cervical, bowel and breast cancer screening uptake in age groups eligible for the national screening programmes, prevalent CIN3 and cervical cancer at baseline, and incident CIN3 and cervical cancer at five years follow-up, among 218,674 women in UK Biobank, a cohort of healthy volunteers from the UK. Results Compared with WSEM, in adjusted analysis [odds ratio (95% confidence interval)], WSEW 0.10 (0.08–0.13), WSWM 0.73 (0.58–0.91), and women who have never had sex 0.02 (0.01–0.02) were less likely to report ever having attended cervical screening. There were no differences when considering bowel cancer screening uptake ( p = 0.61). For breast cancer screening, attendance was lower among WSWM 0.79 (0.68 to 0.91) and women who have never had sex 0.47 (0.29–0.58), compared with WSEM. There were incident and prevalent cases of both CIN3 and cervical cancer among WSEW and WSWM. Compared with WSEM with a single male partner, among WSEW there was a twofold increase in CIN3 1.91 (1.01 to 3.59); among WSWM with only one male partner, this was 2.25 (1.19 to 4.24). Conclusions These findings highlight the importance of improving uptake of cervical screening among all women who have sex with women and breast screening among WSWM and women who have never had sex.

Population-based screening for colorectal cancer is an effective and cost-effective way of reducing colorectal cancer incidence and mortality. Many genetic and phenotypic risk factors for colorectal cancer have been identified, leading to development of colorectal cancer risk scores with varying discrimination. However, these are not currently used by population screening programs. We performed an economic analysis to assess the cost-effectiveness, clinical outcomes, and resource impact of using risk-stratification based on phenotypic and genetic risk, taking a UK National Health Service perspective. Biennial fecal immunochemical test (FIT), starting at an age determined through risk-assessment at age 40, was compared with FIT screening starting at a fixed age for all individuals. Compared with inviting everyone from age 60, using a risk score with area under the receiver operating characteristic curve of 0.721 to determine FIT screening start age, produces 418 QALYs, costs £247,000, and results in 218 fewer colorectal cancer cases and 156 fewer colorectal cancer deaths per 100,000 people, with similar FIT screening invites. There is 96% probability that risk-stratification is cost-effective, with net monetary benefit (based on £20,000 per QALY threshold) estimated at £8.1 million per 100,000 people. The maximum that could be spent on risk-assessment and still be cost-effective is £114 per person. Lower benefits are produced with lower discrimination risk scores, lower mean screening start age, or higher FIT thresholds. Risk-stratified screening benefits men more than women. Using risk to determine FIT screening start age could improve the clinical outcomes and cost effectiveness of colorectal cancer screening without using significant additional screening resources. Prevention Relevance: Colorectal cancer screening is essential for early detection and prevention of colorectal cancer, but implementation is often limited by resource constraints. This work shows that risk-stratification using genetic and phenotypic risk could improve the effectiveness and cost-effectiveness of screening programs, without using substantially more screening resources than are currently available.

Funder: Kidney Cancer UK, Funder: The Urology Foundation, Background: Kidney cancer is often asymptomatic, leading to proposals for a screening programme. The views of the public towards introducing a new screening programme for kidney cancer are unknown. The aim of this study was to explore attitudes towards kidney cancer screening and factors influencing intention to attend a future screening programme. Methods: We conducted an online population-based survey of 1021 adults aged 45–77 years. The main outcome measure was intention to attend four possible screening tests (urine, blood, ultrasound scan, low-dose CT) as well as extended low-dose CT scans within lung cancer screening programmes. We used multivariable regression to examine the association between intention and each screening test. Results: Most participants stated that they would be ‘very likely’ or ‘likely’ to undergo each of the screening tests [urine test: n = 961 (94.1%); blood test: n = 922 (90.3%); ultrasound: n = 914 (89.5%); low-dose CT: n = 804 (78.8%); lung CT: n = 962 (95.2%)]. Greater intention to attend was associated with higher general cancer worry and less perceived burden/inconvenience about the screening tests. Less worry about the screening test was also associated with higher intention to attend, but only in those with low general cancer worry (cancer worry scale ≤ 5). Compared with intention to take up screening with a urine test, participants were half as likely to report that they intended to undergo blood [OR 0.56 (0.43–0.73)] or ultrasound [OR 0.50 (0.38–0.67)] testing, and half as likely again to report that they intended to take part in a screening programme featuring a low dose CT scan for kidney cancer screening alone [OR 0.19 (0.14–0.27)]. Conclusion: Participants in this study expressed high levels of intention to accept an invitation to screening for kidney cancer, both within a kidney cancer specific screening programme and in conjunction with lung cancer screening. The choice of screening test is likely to influence uptake. Together these findings support on-going research into kidney cancer screening tests and the potential for combining kidney cancer screening with existing or new screening programmes.

Aim Complications of gestational diabetes (GDM) can be mitigated if the diagnosis is recognized. However, some at‐risk women do not complete antenatal diagnostic oral glucose tolerance testing (OGTT). We aimed to understand reasons contributing to non‐completion, particularly to identify modifiable factors. Methods Some 1906 women attending a tertiary UK obstetrics centre (2018–2019) were invited for OGTT based on risk‐factor assessment. Demographic information, test results and reasons for non‐completion were collected from the medical record. Logistic regression was used to analyse factors associated with non‐completion. Results Some 242 women (12.3%) did not complete at least one OGTT, of whom 32.2% (n = 78) never completed testing. In adjusted analysis, any non‐completion was associated with younger maternal age [≤ 30 years; odds ratio (OR) 2.3, 95% confidence interval (CI) 1.6–3.4; P, What’s new? Gestational diabetes is associated with significant complications if untreated, yet a proportion of at‐risk women invited for antenatal screening do not complete testing. There is a lack of evidence to guide improvements in antenatal screening completion.Younger women and those from minority ethnic groups were less likely to complete testing. Key barriers to completion cited by women related to the demands of the testing protocol, ability to attend appointments, and mental health or social issues.Modification of testing protocols, increased support for vulnerable groups, and fuller explanation regarding test indications and risk could improve screening rates.

BackgroundWomen with a history of gestational diabetes mellitus (GDM) are at high risk of developing type 2 diabetes mellitus (T2DM). They are therefore recommended to follow a healthy diet and be physically active in order to reduce that risk. However, achieving and maintaining these behaviours in the postpartum period is challenging. This study sought to explore women’s views on suggested practical approaches to achieve and maintain a healthy diet and physical activity to reduce T2DM risk.MethodsSemi-structured interviews with 20 participants in Cambridgeshire, UK were conducted at three to 48 months after GDM. The participants’ current diet and physical activity, intentions for any changes, and views on potential interventions to help manage T2DM risk through these behaviours were discussed. Framework analysis was used to analyse the transcripts. The interview schedule, suggested interventions, and thematic framework were based on a recent systematic review.ResultsMost of the participants wanted to eat more healthily and be more active. A third of the participants considered that postpartum support for these behaviours would be transformative, a third thought it would be beneficial, and a third did not want additional support. The majority agreed that more information about the impact of diet and physical activity on diabetes risk, support to exercise with others, and advice about eating healthily, exercising with a busy schedule, monitoring progress and sustaining changes would facilitate a healthy diet and physical activity. Four other suggested interventions received mixed responses. It would be acceptable for this support to be delivered throughout pregnancy and postpartum through a range of formats. Clinicians were seen to have important roles in giving or signposting to support.ConclusionsMany women would appreciate more support to reduce their T2DM risk after GDM and believe that a variety of interventions to integrate changes into their daily lives would help them to sustain healthier lifestyles.

This study aimed to assess the association between achievement, and within-person change in achievement, of lifestyle recommendations in middle-age and incidence of the most common potentially preventable cancers. We used data from 44,572 participants from the Swedish Västerbotten Intervention Programme who had attended at least two health checks 9–11 years apart. We assessed the association between the mean number of healthy lifestyle recommendations achieved (lifestyle score), and change in lifestyle score between the health checks, and risk of one or more of the eight most common potentially preventable cancers using Cox regression. Participants were followed-up for 11.0 (SD 4.9) years. A higher mean lifestyle score was associated with a lower hazard of cancer in men (HR 0.81 (95%CI 0.74–0.90) per unit increase) and women (HR 0.90 (0.84–0.96)). There was no evidence of a linear association between change in lifestyle score and risk (HR 0.93 (0.85–1.03) and HR 1.004 (0.94–1.07) per unit change for men and women respectively). When comparing those with an increase in lifestyle score of ≥2 with those who improved less or declined in achievement the HR was 0.74 (0.54–1.00) and 1.02 (0.84–1.24) for men and women respectively. These findings support the inclusion of lifestyle recommendations in cancer prevention guidelines. They further suggest that interventions to change health behaviours in middle-age may reduce risk of the most common preventable cancers in men, but this association was not observed in women. Strategies to encourage healthy lifestyles earlier in the life course may be more effective., Highlights • Meeting more lifestyle recommendations in middle-age reduces cancer incidence. • Each additional recommendation met is associated with a 10–19% decrease in rate. • Change in middle-age to achieve ≥2 more recommendations may reduce cancer rate in men. • Up to 23% of chosen cancers might be prevented if all men achieved ≥2 more recommendations. • Change in middle-age is not associated with incident cancer in women.

Background: This study aimed to compare and externally validate risk scores developed to predict incident colorectal cancer (CRC) that include variables routinely available or easily obtainable via self-completed questionnaire. Methods: External validation of fourteen risk models from a previous systematic review in 373 112 men and women within the UK Biobank cohort with 5-year follow-up, no prior history of CRC and data for incidence of CRC through linkage to national cancer registries. Results: There were 1719 (0.46%) cases of incident CRC. The performance of the risk models varied substantially. In men, the QCancer10 model and models by Tao, Driver and Ma all had an area under the receiver operating characteristic curve (AUC) between 0.67 and 0.70. Discrimination was lower in women: the QCancer10, Wells, Tao, Guesmi and Ma models were the best performing with AUCs between 0.63 and 0.66. Assessment of calibration was possible for six models in men and women. All would require country-specific recalibration if estimates of absolute risks were to be given to individuals. Conclusions: Several risk models based on easily obtainable data have relatively good discrimination in a UK population. Modelling studies are now required to estimate the potential health benefits and cost-effectiveness of implementing stratified risk-based CRC screening.

The aim of this study was to compare and externally validate risk scores developed to predict incident colorectal cancer that include common genetic variants (SNPs), with or without established lifestyle/environmental (questionnaire-based/classical/phenotypic) risk factors. We externally validated 23 risk models from a previous systematic review in 443,888 participants ages 37 to 73 from the UK Biobank cohort who had 6-year prospective follow-up, no prior history of colorectal cancer, and data for incidence of colorectal cancer through linkage to national cancer registries. There were 2,679 (0.6%) cases of incident colorectal cancer. We assessed model discrimination using the area under the operating characteristic curve (AUC) and relative risk calibration. The AUC of models including only SNPs increased with the number of included SNPs and was similar in men and women: the model by Huyghe with 120 SNPs had the highest AUC of 0.62 [95% confidence interval (CI), 0.59–0.64] in women and 0.64 (95% CI, 0.61–0.66) in men. Adding phenotypic risk factors without age improved discrimination in men but not in women. Adding phenotypic risk factors and age increased discrimination in all cases (P < 0.05), with the best performing models including SNPs, phenotypic risk factors, and age having AUCs between 0.64 and 0.67 in women and 0.67 and 0.71 in men. Relative risk calibration varied substantially across the models. Among middle-aged people in the UK, existing polygenic risk scores discriminate moderately well between those who do and do not develop colorectal cancer over 6 years. Consideration should be given to exploring the feasibility of incorporating genetic and lifestyle/environmental information in any future stratified colorectal cancer screening program.

Background: Cancer is the second leading cause of death worldwide. Lifestyle choices play an important role in the aetiology of cancer with up to 4 in 10 cases potentially preventable. Interventions delivered by healthcare professionals (HCPs) that incorporate risk information have the potential to promote behaviour change. Our aim was to develop a very brief intervention incorporating cancer risk, which could be implemented within primary care. Methods: Guided by normalisation process theory (NPT), we developed a prototype intervention using literature reviews, consultation with patient and public representatives and pilot work with patients and HCPs. We conducted focus groups and interviews with 65 HCPs involved in delivering prevention activities. Findings were used to refine the intervention before 22 HCPs completed an online usability test and provided further feedback via a questionnaire incorporating a modified version of the NoMAD checklist. Results: The intervention included a website where individuals could provide information on lifestyle risk factors view their estimated 10-year risk of developing one or more of the five most common preventable cancers and access lifestyle advice incorporating behaviour change techniques. Changes incorporated from feedback from the focus groups and interviews included signposting to local services and websites, simplified wording and labelling of risk information. In the usability testing, all participants felt it would be easy to collect the risk information. Ninety-one percent felt the intervention would enable discussion about cancer risk and believed it had potential to be easily integrated into National Health Service (NHS) Health Checks. However, only 36% agreed it could be delivered within 5 min. Conclusions: With the use of NPT, we developed a very brief intervention that is acceptable to HCPs in primary care and could be potentially integrated into NHS Health Checks. However, further work is needed to assess its feasibility and potential effectiveness.

Update to this article In October 2022, three years after the initial publication of this guideline, the first trial of the effect of colonoscopy screening was published. The implications of this new evidence for the current recommendations were evaluated by the guideline panel in January 2023. The guideline panel judged that this new evidence did not alter the current recommendations, and therefore that an update of the following guideline was not needed (see table 2 for details). Clinical question Recent 15-year updates of sigmoidoscopy screening trials provide new evidence on the effectiveness of colorectal cancer screening. Prompted by the new evidence, we asked: “Does colorectal cancer screening make an important difference to health outcomes in individuals initiating screening at age 50 to 79? And which screening option is best?” Current practice Numerous guidelines recommend screening, but vary on recommended test, age and screening frequency. This guideline looks at the evidence and makes recommendations on screening for four screening options: faecal immunochemical test (FIT) every year, FIT every two years, a single sigmoidoscopy, or a single colonoscopy. Recommendations These recommendations apply to adults aged 50-79 years with no prior screening, no symptoms of colorectal cancer, and a life expectancy of at least 15 years. For individuals with an estimated 15-year colorectal cancer risk below 3%, we suggest no screening (weak recommendation). For individuals with an estimated 15-year risk above 3%, we suggest screening with one of the four screening options: FIT every year, FIT every two years, a single sigmoidoscopy, or a single colonoscopy (weak recommendation). With our guidance we publish the linked research, a graphic of the absolute harms and benefits, a clear description of how we reached our value judgments, and linked decision aids. How this guideline was created A guideline panel including patients, clinicians, content experts and methodologists produced these recommendations using GRADE and in adherence with standards for trustworthy guidelines. A linked systematic review of colorectal cancer screening trials and microsimulation modelling were performed to inform the panel of 15-year screening benefits and harms. The panel also reviewed each screening option’s practical issues and burdens. Based on their own experience, the panel estimated the magnitude of benefit typical members of the population would value to opt for screening and used the benefit thresholds to inform their recommendations. The evidence Overall there was substantial uncertainty (low certainty evidence) regarding the 15-year benefits, burdens, and harms of screening. Best estimates suggested that all four screening options resulted in similar colorectal cancer mortality reductions. FIT every two years may have little or no effect on cancer incidence over 15 years, while FIT every year, sigmoidoscopy, and colonoscopy may reduce cancer incidence, although for FIT the incidence reduction is small compared with sigmoidoscopy and colonoscopy. Screening related serious gastrointestinal and cardiovascular adverse events are rare. The magnitude of the benefits is dependent on the individual risk, while harms and burdens are less strongly associated with cancer risk. Understanding the recommendation Based on benefits, harms, and burdens of screening, the panel inferred that most informed individuals with a 15-year risk of colorectal cancer of 3% or higher are likely to choose screening, and most individuals with a risk of below 3% are likely to decline screening. Given varying values and preferences, optimal care will require shared decision making.

Background: Screening for renal cell carcinoma (RCC) has been identified as a key research priority; however, no randomised control trials have been performed. Value of information analysis can determine whether further research on this topic is of value. Objective: To determine (1) whether current evidence suggests that screening is potentially cost-effective and, if so, (2) in which age/sex groups, (3) identify evidence gaps, and (4) estimate the value of further research to close those gaps. Design, setting, and participants: A decision model was developed evaluating screening in asymptomatic individuals in the UK. A National Health Service perspective was adopted. Intervention: A single focused renal ultrasound scan compared with standard of care (no screening). Outcome measurements and statistical analysis: Expected lifetime costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER), discounted at 3.5% per annum. Results and limitations: Given a prevalence of RCC of 0.34% (0.18–0.54%), screening 60-yr-old men resulted in an ICER of £18 092/QALY (€22 843/QALY). Given a prevalence of RCC of 0.16% (0.08–0.25%), screening 60-yr-old women resulted in an ICER of £37 327/QALY (€47 129/QALY). In the one-way sensitivity analysis, the ICER was

Background A significant proportion of the worldwide population is at risk of social isolation and loneliness as a result of the COVID-19 pandemic. We aimed to identify effective interventions to reduce social isolation and loneliness that are compatible with COVID-19 shielding and social distancing measures. Methods and findings In this rapid systematic review, we searched six electronic databases (Medline, Embase, Web of Science, PsycINFO, Cochrane Database of Systematic Reviews and SCOPUS) from inception to April 2020 for systematic reviews appraising interventions for loneliness and/or social isolation. Primary studies from those reviews were eligible if they included: 1) participants in a non-hospital setting; 2) interventions to reduce social isolation and/or loneliness that would be feasible during COVID-19 shielding measures; 3) a relevant control group; and 4) quantitative measures of social isolation, social support or loneliness. At least two authors independently screened studies, extracted data, and assessed risk of bias using the Downs and Black checklist. Study registration: PROSPERO CRD42020178654. We identified 45 RCTs and 13 non-randomised controlled trials; none were conducted during the COVID-19 pandemic. The nature, type, and potential effectiveness of interventions varied greatly. Effective interventions for loneliness include psychological therapies such as mindfulness, lessons on friendship, robotic pets, and social facilitation software. Few interventions improved social isolation. Overall, 37 of 58 studies were of “Fair” quality, as measured by the Downs & Black checklist. The main study limitations identified were the inclusion of studies of variable quality; the applicability of our findings to the entire population; and the current poor understanding of the types of loneliness and isolation experienced by different groups affected by the COVID-19 pandemic. Conclusions Many effective interventions involved cognitive or educational components, or facilitated communication between peers. These interventions may require minor modifications to align with COVID-19 shielding/social distancing measures. Future high-quality randomised controlled trials conducted under shielding/social distancing constraints are urgently needed.

Aims To estimate development of type 2 diabetes (T2DM) in women with previous gestational diabetes (GDM) and investigate characteristics associated with higher diagnoses, building on previous meta-analyses and exploring heterogeneity. Methods Systematic literature review of studies published up to October 2019. We included studies reporting progression to T2DM ≥6 months after pregnancy, if diagnostic methods were reported and ≥50 women with GDM participated. We conducted random-effects meta-analyses and meta-regression of absolute and relative T2DM risk. PROSPERO ID: CRD42017080299. Results In 129 included studies, the percentage diagnosed with T2DM was 12% (95% confidence interval 8–16%) higher for each additional year after pregnancy, with a third developing diabetes within 15 years. Development was 18% (5–34%) higher per unit BMI at follow-up, and 57% (39–70%) lower in White European populations compared to others (adjusted for ethnicity and follow-up). Women with GDM had a relative risk of T2DM of 8.3 (6.5–10.6). 17.0% (15.1–19.0%) developed T2DM overall, although heterogeneity between studies was substantial (I2 99.3%), and remained high after accounting for various study-level characteristics. Conclusions Percentage developing T2DM after GDM is highly variable. These findings highlight the need for sustained follow-up after GDM through screening, and interventions to reduce modifiable risk factors.

ObjectiveTo determine whether provision of web-based lifestyle advice and coronary heart disease risk information either based on phenotypic characteristics or phenotypic plus genetic characteristics affects changes in objectively measured health behaviours.MethodsA parallel-group, open randomised trial including 956 male and female blood donors with no history of cardiovascular disease (mean [SD] age=56.7 [8.8] years) randomised to four study groups: control group (no information provided); web-based lifestyle advice only (lifestyle group); lifestyle advice plus information on estimated 10-year coronary heart disease risk based on phenotypic characteristics (phenotypic risk estimate) (phenotypic group) and lifestyle advice plus information on estimated 10-year coronary heart disease risk based on phenotypic (phenotypic risk estimate) and genetic characteristics (genetic risk estimate) (genetic group). The primary outcome was change in physical activity from baseline to 12 weeks assessed by wrist-worn accelerometer.Results928 (97.1%) participants completed the trial. There was no evidence of intervention effects on physical activity (difference in adjusted mean change from baseline): lifestyle group vs control group 0.09 milligravity (mg) (95% CI −1.15 to 1.33); genetic group vs phenotypic group −0.33 mg (95% CI −1.55 to 0.90); phenotypic group and genetic group vs control group −0.52 mg (95% CI −1.59 to 0.55) and vs lifestyle group −0.61 mg (95% CI −1.67 to 0.46). There was no evidence of intervention effects on secondary biological, emotional and health-related behavioural outcomes except self-reported fruit and vegetable intake.ConclusionsProvision of risk information, whether based on phenotypic or genotypic characteristics, alongside web-based lifestyle advice did not importantly affect objectively measured levels of physical activity, other health-related behaviours, biological risk factors or emotional well-being.Trial registration numberISRCTN17721237; Pre-results.

Background: Most risk models for cancer are either specific to individual cancers or include complex or predominantly non-modifiable risk factors. Methods: We developed lifestyle-based models for the five cancers for which the most cases are potentially preventable through lifestyle change in the UK (lung, colorectal, bladder, kidney, and esophageal for men and breast, lung, colorectal, endometrial, and kidney for women). We selected lifestyle risk factors from the European Code against Cancer and obtained estimates of relative risks from meta-analyses of observational studies. We used mean values for risk factors from nationally representative samples and mean 10-year estimated absolute risks from routinely available sources. We then assessed the performance of the models in 23,768 participants in the EPIC-Norfolk cohort who had no history of the five selected cancers at baseline. Results: In men, the combined risk model showed good discrimination [AUC, 0.71; 95% confidence interval (CI), 0.69–0.73] and calibration. Discrimination was lower in women (AUC, 0.59; 95% CI, 0.57–0.61), but calibration was good. In both sexes, the individual models for lung cancer had the highest AUCs (0.83; 95% CI, 0.80–0.85 for men and 0.82; 95% CI, 0.76–0.87 for women). The lowest AUCs were for breast cancer in women and kidney cancer in men. Conclusions: The discrimination and calibration of the models are both reasonable, with the discrimination for individual cancers comparable or better than many other published risk models. Impact: These models could be used to demonstrate the potential impact of lifestyle change on risk of cancer to promote behavior change.

Background Cancer is a leading cause of mortality and morbidity worldwide. Prevention is recognised by many, including the World Health Organization, to offer the most cost-effective long-term strategy for the control of cancer. One approach that focuses on individuals is the provision of personalised risk information. However, whether such information motivates behaviour change and whether the effect is different with varying formats of risk presentation is unclear. We aim to assess the short-term effect of providing information about personalised risk of cancer in three different formats alongside lifestyle advice on health-related behaviours, risk perception and risk conviction. Methods In a parallel group, randomised controlled trial 1000 participants will be recruited through the online platform Prolific. Participants will be allocated to either a control group receiving cancer-specific lifestyle advice alone or one of three intervention groups receiving the same lifestyle advice alongside their estimated 10-year risk of developing one of the five most common preventable cancers, calculated from self-reported modifiable behavioural risk factors, in one of three different formats (bar chart, pictograph or qualitative scale). The primary outcome is change from baseline in computed risk relative to an individual with a recommended lifestyle at three months. Secondary outcomes include: perceived risk of cancer; anxiety; cancer-related worry; intention to change behaviour; and awareness of cancer risk factors. Discussion This study will provide evidence on the short-term effect of providing online information about personalised risk of cancer alongside lifestyle advice on risk perception and health-related behaviours and inform the development of interventions. Trial registration ISRCTN17450583. Registered 30 January 2018.

BACKGROUND: The epidemiology of type 1 diabetes mellitus (T1DM) suggests diagnostic delays may contribute to children developing diabetic ketoacidosis at diagnosis. We sought to quantify opportunities for earlier diagnosis of T1DM in primary care. METHODS: A matched case-control study of children (0-16 years) presenting to UK primary care, examining routinely collected primary care consultation types and National Institute for Health and Care Excellence (NICE) warning signs in the 13 weeks before diagnosis. RESULTS: Our primary analysis included 1920 new T1DM cases and 7680 controls. In the week prior to diagnosis more cases than controls had medical record entries (663, 34.5% vs 1014, 13.6%, odds ratio 3.46, 95% CI 3.07-3.89; p

Background Physical activity (PA) and fruit and vegetable intake (FVI) are two key modifiable risk factors for cardiovascular disease (CVD). Achieving change in these behaviours is challenging and affected by many variables including psychosocial factors. We aimed to investigate the association between social support, stress and mood, and change in PA and FVI following provision of CVD risk information and web-based lifestyle advice. Methods Seven hundred sixteen blood donors (56% male; mean age 57 years) from the intervention arms of the Information and Risk Modification (INFORM) trial, a randomised controlled trial to assess the impact of providing CVD risk and web-based lifestyle information, were analysed as a prospective cohort. We used linear and logistic regression analyses to quantify the association between social support, stress and mood at baseline and behaviour change following the intervention. We modelled objective (average acceleration measured by Axivity AX3 wrist-worn accelerometers and plasma carotenoid levels) and subjective (self-reported recreational PA and FVI) outcomes as change between baseline and 12 weeks follow-up. Results There was no clear association between social support and change in objective or subjective PA. Higher levels of stress and, to a lesser extent, depression symptoms were associated with smaller improvement in self-reported PA (β -1.53 h/week vigorous PA, 95% confidence interval (CI) -2.30 to -0.75, p

Background It is estimated that nearly 600,000 cancer cases in the UK could have been avoided in the past five years if people had healthier lifestyles. A number of theories of behaviour change suggest that before people will change health behaviours, they must accept that a risk applies to them. This study aimed to explore the views of the public on receiving personalised cancer risk information and the potential for that information to motivate behaviour change. Methods We conducted 27 interviews with members of the public (mean age 49 ± 23 years). Each participant completed a questionnaire to allow calculation of their risk of developing the most common cancers (10 for women, 8 for men). During the interviews we presented their risk using a web-based tool developed for the study and discussions covered their views on receiving that information. Each interview was audio-recorded and then analysed using thematic analysis. Results Participants generally viewed the concept of personalised cancer risk positively. The first reaction of almost all when presented with their 10-year risk of an individual cancer without any further context was that it was low and not concerning. Views on what constituted a high risk ranged widely, from 0.5 to 60%. All felt seeing the impact of changes in lifestyle was helpful. For some this led to intentions to change behaviour, but reductions in risk were not always motivating as the risks were considered low and differences small. Conclusions Provision of personalised cancer risk was well received and may be a useful addition to other cancer prevention initiatives. Further work is needed in particular to develop ways to present cancer risk that reflect the general perception of what constitutes a risk high enough to motivate behaviour change and help patients contextualise a less well known health risk by providing a frame of reference. Electronic supplementary material The online version of this article (10.1186/s12889-017-4985-1) contains supplementary material, which is available to authorized users.

Several multivariable risk prediction models have been developed to asses an individual's risk of developing specific cancers. Such models can be used in a variety of settings for prevention, screening, and guiding investigations and treatments. Models aimed at predicting future disease risk that contains lifestyle factors may be of particular use for targeting health promotion activities at an individual level. This type of cancer risk prediction is not yet available in the UK. We have adopted the approach used by the well-established U.S.-derived "YourCancerRisk" model for use in the UK population, which allow users to quantify their individual risk of developing individual cancers relative to the population average risk. The UK version of “YourCancerRisk" computes 10-year cancer risk estimates for 11 cancers utilizing UK figures for prevalence of risk factors and cancer incidence. Because the prevalence of risk factors and the incidence rates for cancer are different between the U.S. and the UK population, this UK model provides more accurate estimates of risks for a UK population. Using an example of breast cancer and data from UK Biobank cohort, we demonstrate that the individual risk factor estimates are similar for the U.S. and UK populations. Assessment of the performance and validation of the multivariate model predictions based on a binary score confirm the model's applicability. The model can be used to estimate absolute and relative cancer risk for use in Primary Care and community settings and is being used in the community to guide lifestyle change. Cancer Prev Res; 10(7); 421–30. ©2017 AACR.

BACKGROUND: Melanoma incidence is rising rapidly worldwide among white populations. Defining higher-risk populations using risk prediction models may help targeted screening and early detection approaches. OBJECTIVES: To assess the feasibility of identifying people at higher risk of melanoma using the Williams self-assessed clinical risk estimation model in U.K. primary care. METHODS: We recruited participants from the waiting rooms of 22 general practices covering a total population of > 240 000 in three U.K. regions: Eastern England, North East Scotland and North Wales. Participants completed an electronic questionnaire using tablet computers. The main outcome was the mean melanoma risk score using the Williams melanoma risk model. RESULTS: Of 9004 people approached, 7742 (86%) completed the electronic questionnaire. The mean melanoma risk score for the 7566 eligible participants was 17·15 ± 8·51, with small regional differences [lower in England compared with Scotland (P = 0·001) and Wales (P < 0·001), mainly due to greater freckling and childhood sunburn among Scottish and Welsh participants]. After weighting to the age and sex distribution, different potential cut-offs would allow between 4% and 20% of the population to be identified as higher risk, and those groups would contain 30% and 60%, respectively of those likely to develop melanoma. CONCLUSIONS: Collecting data on the melanoma risk profile of the general population in U.K. primary care is both feasible and acceptable for patients in a general practice setting, and provides opportunities for new methods of real-time risk assessment and risk stratified cancer interventions.

BackgroundHeart murmurs are common in children. The majority are detected incidentally, and congenital heart disease is rare. There are no published United Kingdom guidelines for management of children with murmurs in primary care. Common practice is to refer all children for specialist assessment.AimTo review outcomes of children with heart murmurs who were referred by general practitioners to a clinic conducted by a paediatrician with expertise in cardiology.Design and settingA retrospective review of children referred by general practitioners to a paediatrician with expertise in cardiology.MethodsHospital records of all children under 17 years of age who attended the clinic during 2011 were reviewed. We excluded children previously seen by any cardiology service.ResultsThere were 313 new primary care referrals, with complete records available for 310 children. Of them, 186 (60%) were referred with a murmur: 154 for an asymptomatic murmur alone, and 32 for a murmur plus additional symptoms or family history of congenital heart disease. All underwent echocardiography. Of the patients, 38 (20%) had congenital heart disease. Younger children were more likely to have congenital heart disease. There was no difference between rates of congenital heart disease in children with or without symptoms or a family history.ConclusionThe finding that a large proportion of children referred by general practitioners with asymptomatic heart murmurs have congenital heart disease supports current referral practice on clinical grounds.

To identify the proportion of individuals with an accurate perception of their risk of type 2 diabetes (T2D) prior to, immediately after and eight weeks after receiving a personalised risk estimate. Additionally, we aimed to explore what factors are associated with underestimation and overestimation immediately post-intervention.Cohort study based on the data collected in the Diabetes Risk Communication Trial. We included 379 participants (mean age 48.9 (SD 7.4) years; 55.1% women) who received a genotypic or phenotypic risk estimate for T2D.While only 1.3% of participants perceived their risk accurately at baseline, this increased to 24.7% immediately after receiving a risk estimate and then dropped to 7.3% at eight weeks. Those who overestimated their risk at baseline continued to overestimate it, whereas those who underestimated their risk at baseline improved their risk accuracy. We did not identify any other characteristics associated with underestimation or overestimation immediately after receiving a risk estimate.Understanding a received risk estimate is challenging for most participants with many continuing to have inaccurate risk perception after receiving the estimate.Individuals who overestimate or underestimate their T2D risk before receiving risk information might require different approaches for altering their risk perception.

BACKGROUND: In 2014 the UK National Institute for Health and Care Excellence recommended reducing the threshold for offering statin therapy to patients from a 10-year modelled risk of cardiovascular disease (CVD) of 20% to 10%. AIM: To describe the response of patients in UK primary care with a CVD risk between 10% and 20% to an invitation to attend a consultation to discuss statins. DESIGN AND SETTING: Review of electronic medical records at one GP practice in the East of England. METHOD: We invited all patients who had attended an NHS Health Check at the practice, had a QRisk(®) score between 10% and 20%, and were not prescribed statins to attend designated clinics in the practice to discuss starting statins. We reviewed the medical records to identify those who had attended the clinics and those who had chosen to start a statin. RESULTS: Of 410 patients invited, 100 (24.4%) patients attended the designated clinics and 45 (11%) chose to start a statin. Those who chose to start a statin were older and with a higher QRisk(®) than those who did not. Among those who attended, individuals who started a statin had a higher QRisk(®) than those who did not and were more likely to be current or ex-smokers. CONCLUSIONS: The proportion choosing to start a statin was substantially lower than previously estimated. Large population-based studies with long-term follow-up are needed to assess the impact on health and workload of this change in guidance.

OBJECTIVES: To review existing cardiovascular risk models applicable to South Asian populations. METHODS: A systematic review of the literature using a combination of search terms for "South Asian", "cardiovascular", "risk"/"score" and existing risk models for inclusion. South Asian was defined as those residing in or with ancestry belonging to the Indian subcontinent. RESULTS: The literature search including MEDLINE and EMBASE identified 7560 papers. After full-text review, 4 papers met the inclusion criteria. Only 1 reported formal measures of model performance. In that study, both a modified Framingham model and QRISK2 showed similar good discrimination with AUROCs of 0.73-0.77 with calibration also reasonable in men (0.71-0.93) but poor in women (0.43-0.52). CONCLUSIONS: Considering the number of South Asians and prevalence of cardiovascular disease, very few studies have reported performance of risk scores in South Asian populations. Furthermore, it was difficult to make comparisons, as many did not provide measures of discrimination, accuracy and calibration. There is a need for further research to evaluate risk models in South Asians, and ideally derive and validate cardiovascular risk models within South Asian populations.

Objective To explore the pathway to diagnosis of type 1 diabetes (T1D) in children. Design Questionnaire completed by parents. Participants Parents of children aged 1 month to 16 years diagnosed with T1D within the previous 3 months. Setting Children and parents from 11 hospitals within the East of England. Results 88/164 (54%) invited families returned the questionnaire. Children had mean±SD age of 9.41±4.5 years. 35 (39.8%) presented with diabetic ketoacidosis at diagnosis. The most common symptoms were polydipsia (97.7%), polyuria (83.9%), tiredness (75.9%), nocturia (73.6%) and weight loss (64.4%) and all children presented with at least one of those symptoms. The time from symptom onset to diagnosis ranged from 2 to 315 days (median 25 days). Most of this was the appraisal interval from symptom onset until perceiving the need to seek medical advice. Access to healthcare was good but one in five children presenting to primary care were not diagnosed at first encounter, most commonly due to waiting for fasting blood tests or alternative diagnoses. Children diagnosed at first consultation had a shorter duration of symptoms (p=0.022) and children whose parents suspected the diagnosis were 1.3 times more likely (relative risk (RR) 1.3, 95% CI 1.02 to 1.67) to be diagnosed at first consultation. Conclusions Children present with the known symptoms of T1D but there is considerable scope to improve the diagnostic pathway. Future interventions targeted at parents need to address the tendency of parents to find alternative explanations for symptoms and the perceived barriers to access, in addition to symptom awareness.

OBJECTIVE: To identify the factors associated with diabetic ketoacidosis at diagnosis of type 1 diabetes in children and young adults. DESIGN: Systematic review. DATA SOURCES: PubMed, EMBASE, Web of Science, Scopus, and Cinahl and article reference lists. STUDY SELECTION: Cohort studies including unselected groups of children and young adults presenting with new onset type 1 diabetes that distinguished between those who presented in diabetic ketoacidosis and those who did not and included a measurement of either pH or bicarbonate in the definition of diabetic ketoacidosis. There were no restrictions on language of publication. RESULTS: 46 studies involving more than 24,000 children in 31 countries were included. Together they compared 23 different factors. Factors associated with increased risk were younger age (for