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Background There is a high risk that young children who show early signs of mental health problems develop symptoms in the same or overlapping areas some years later. The Strengths and Difficulties Questionnaire (SDQ) is widely used to screen externalizing and internalizing problems early in life. In Sweden 80–90% of all children aged 1–5 years go to preschool and preschool is thus an appropriate context for finding early signs of mental health problems among children. Methods This study is part of a longitudinal project too investigate the frequency of emotional and behavioural problems for children between 1 and 5 years of age in Sweden. The SDQ including the impairment supplement questions were rated by preschool teachers too establish Swedish norms for SDQ in preschool children. Results The sample involved 815 children with a mean age of 42 months (SD = 16, range 13–71 months). 195 children were followed longitudinally for three years. There were significant differences between boys and girls on all subscales except for the Emotional subscale. The prevalence of behavioural problems was similar to other that in European countries, except for Prosocial behaviour, which was rated lower, and Conduct problems, rated higher. Swedish children were estimated to have more problems in the preschool setting, scored by preschool teachers. The development of behaviour over time differed for the different subscales of SDQ. Conclusions The teacher version of the SDQ, for 2–4 year-olds, can be used as a screening instrument to identify early signs of emotional distress/behavioural problems in young children. Preschool teachers seem to be able to identify children with problematic behaviour with the use of SDQ at an early age. The development of behaviour over time differs for the different subscales of SDQ. The Swedish norms for SDQ are to a large extent, similar to findings from other European countries.

Background In January 2017, the Dutch cervical cancer screening programme transitioned from cytomorphological to primary high-risk HPV (hrHPV) DNA screening, including the introduction of self-sampling, for women aged between 30 and 60 years. The Netherlands was the first country to switch to hrHPV screening at the national level. We investigated the health impact of this transition by comparing performance indicators from the new hrHPV-based programme with the previous cytology-based programme. Methods We obtained data from the Dutch nationwide network and registry of histo- and cytopathology (PALGA) for 454,573 women eligible for screening in 2017 who participated in the hrHPV-based programme between 1 January 2017 and 30 June 2018 (maximum follow-up of almost 21 months) and for 483,146 women eligible for screening in 2015 who participated in the cytology-based programme between 1 January 2015 and 31 March 2016 (maximum follow-up of 40 months). We compared indicators of participation (participation rate), referral (screen positivity; referral rate) and detection (cervical intraepithelial neoplasia (CIN) detection; number of referrals per detected CIN lesion). Results Participation in the hrHPV-based programme was significantly lower than that in the cytology-based programme (61% vs 64%). Screen positivity and direct referral rates were significantly higher in the hrHPV-based programme (positivity rate: 5% vs 9%; referral rate: 1% vs 3%). CIN2+ detection increased from 11 to 14 per 1000 women screened. Overall, approximately 2.2 times more clinical irrelevant findings (i.e. ≤CIN1) were found in the hrHPV-based programme, compared with approximately 1·3 times more clinically relevant findings (i.e. CIN2+); this difference was mostly due to a national policy change recommending colposcopy, rather than observation, of hrHPV-positive, ASC-US/LSIL results in the hrHPV-based programme. Conclusions This is the first time that comprehensive results of nationwide implementation of hrHPV-based screening have been reported using high-quality data with a long follow-up. We have shown that both benefits and potential harms are higher in one screening round of a well-implemented hrHPV-based screening programme than in an established cytology-based programme. Lower participation in the new hrHPV programme may be due to factors such as invitation policy changes and the phased roll-out of the new programme. Our findings add further to evidence from trials and modelling studies on the effectiveness of hrHPV-based screening.

To establish an optimal cutoff point for the National Comprehensive Cancer Network’s Distress Thermometer (DT) as a screening measure to identify and address psychological distress in individuals with cancer, and to examine whether distress as measured by the DT significantly changes across the treatment trajectory. Secondary analyses of baseline data from a longitudinal parent study examining a computerized psychosocial assessment. Three diverse comprehensive cancer centers across the United States. 836 patients with a current or past diagnosis of cancer. Study participants were selected from a randomized clinical trial. Patients during any stage of the cancer treatment trajectory were recruited during a chemotherapy infusion or routine oncology appointment. The Behavioral Health Status Index and the DT were administered and compared using receiver operating characteristic analyses. Results support a cutoff score of 3 on the DT to indicate patients with clinically elevated levels of distress. In addition, patients who received a diagnosis within the 1–4 weeks prior to the assessment indicated the highest levels of distress. Providers may wish to use a cutoff point of 3 to most efficiently identify distress in a large, diverse population of patients with cancer. In addition, results indicate that patients may experience a heightened state of distress within 1–4 weeks postdiagnosis compared to other stages of coping with cancer. Using a brief measure of distress can help streamline the process of screening for psychosocial distress.

Emotional stress is associated with increased risk of cardiovascular disease. We imaged the amygdala, a brain region involved in stress, to determine whether its resting metabolic activity predicts risk of subsequent cardiovascular events. Individuals aged 30 years or older without known cardiovascular disease or active cancer disorders, who underwent 18F-fluorodexoyglucose PET/CT at Massachusetts General Hospital (Boston, MA, USA) between Jan 1, 2005, and Dec 31, 2008, were studied longitudinally. Amygdalar activity, bone-marrow activity, and arterial inflammation were assessed with validated methods. In a separate cross-sectional study we analysed the relation between perceived stress, amygdalar activity, arterial inflammation, and C-reactive protein. Image analyses and cardiovascular disease event adjudication were done by mutually blinded researchers. Relations between amygdalar activity and cardiovascular disease events were assessed with Cox models, log-rank tests, and mediation (path) analyses. 293 patients (median age 55 years [IQR 45·0–65·5]) were included in the longitudinal study, 22 of whom had a cardiovascular disease event during median follow-up of 3·7 years (IQR 2·7–4·8). Amygdalar activity was associated with increased bone-marrow activity (r=0·47; p<0·0001), arterial inflammation (r=0·49; p<0·0001), and risk of cardiovascular disease events (standardised hazard ratio 1·59, 95% CI 1·27–1·98; p<0·0001), a finding that remained significant after multivariate adjustments. The association between amygdalar activity and cardiovascular disease events seemed to be mediated by increased bone-marrow activity and arterial inflammation in series. In the separate cross-sectional study of patients who underwent psychometric analysis (n=13), amygdalar activity was significantly associated with arterial inflammation (r=0·70; p=0·0083). Perceived stress was associated with amygdalar activity (r=0·56; p=0·0485), arterial inflammation (r=0·59; p=0·0345), and C-reactive protein (r=0·83; p=0·0210). In this first study to link regional brain activity to subsequent cardiovascular disease, amygdalar activity independently and robustly predicted cardiovascular disease events. Amygdalar activity is involved partly via a path that includes increased bone-marrow activity and arterial inflammation. These findings provide novel insights into the mechanism through which emotional stressors can lead to cardiovascular disease in human beings. None.

Ovarian cancer continues to have a poor prognosis with the majority of women diagnosed with advanced disease. Therefore, we undertook the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) to determine if population screening can reduce deaths due to the disease. We report on ovarian cancer mortality after long-term follow-up in UKCTOCS. In this randomised controlled trial, postmenopausal women aged 50–74 years were recruited from 13 centres in National Health Service trusts in England, Wales, and Northern Ireland. Exclusion criteria were bilateral oophorectomy, previous ovarian or active non-ovarian malignancy, or increased familial ovarian cancer risk. The trial management system confirmed eligibility and randomly allocated participants in blocks of 32 using computer generated random numbers to annual multimodal screening (MMS), annual transvaginal ultrasound screening (USS), or no screening, in a 1:1:2 ratio. Follow-up was through national registries. The primary outcome was death due to ovarian or tubal cancer (WHO 2014 criteria) by June 30, 2020. Analyses were by intention to screen, comparing MMS and USS separately with no screening using the versatile test. Investigators and participants were aware of screening type, whereas the outcomes review committee were masked to randomisation group. This study is registered with ISRCTN, 22488978, and ClinicalTrials.gov, NCT00058032. Between April 17, 2001, and Sept 29, 2005, of 1 243 282 women invited, 202 638 were recruited and randomly assigned, and 202 562 were included in the analysis: 50 625 (25·0%) in the MMS group, 50 623 (25·0%) in the USS group, and 101 314 (50·0%) in the no screening group. At a median follow-up of 16·3 years (IQR 15·1–17·3), 2055 women were diagnosed with tubal or ovarian cancer: 522 (1·0%) of 50 625 in the MMS group, 517 (1·0%) of 50 623 in the USS group, and 1016 (1·0%) of 101 314 in the no screening group. Compared with no screening, there was a 47·2% (95% CI 19·7 to 81·1) increase in stage I and 24·5% (−41·8 to –2·0) decrease in stage IV disease incidence in the MMS group. Overall the incidence of stage I or II disease was 39·2% (95% CI 16·1 to 66·9) higher in the MMS group than in the no screening group, whereas the incidence of stage III or IV disease was 10·2% (−21·3 to 2·4) lower. 1206 women died of the disease: 296 (0·6%) of 50 625 in the MMS group, 291 (0·6%) of 50 623 in the USS group, and 619 (0·6%) of 101 314 in the no screening group. No significant reduction in ovarian and tubal cancer deaths was observed in the MMS (p=0·58) or USS (p=0·36) groups compared with the no screening group. The reduction in stage III or IV disease incidence in the MMS group was not sufficient to translate into lives saved, illustrating the importance of specifying cancer mortality as the primary outcome in screening trials. Given that screening did not significantly reduce ovarian and tubal cancer deaths, general population screening cannot be recommended. National Institute for Health Research, Cancer Research UK, and The Eve Appeal.

Background A brief, inexpensive screening test for sarcopenia would be helpful for clinicians and their patients. To screen for persons with sarcopenia, we developed a simple five‐item questionnaire (SARC‐F) based on cardinal features or consequences of sarcopenia. Methods We investigated the utility of SARC‐F in the African American Health (AAH) study, Baltimore Longitudinal Study of Aging (BLSA), and National Health and Nutrition Examination Survey (NHANES). Internal consistency reliability for SARC‐F was determined using Cronbach's alpha. We evaluated SARC‐F factorial validity using principal components analysis and criterion validity by examining its association with exam‐based indicators of sarcopenia. Construct validity was examined using cross‐sectional and longitudinal differences among those with high (≥4) vs. low (<4) SARC‐F scores for mortality and health outcomes. Results SARC‐F exhibited good internal consistency reliability and factorial, criterion, and construct validity. AAH participants with SARC‐F scores ≥ 4 had more Instrumental Activity of Daily Living (IADL) deficits, slower chair stand times, lower grip strength, lower short physical performance battery scores, and a higher likelihood of recent hospitalization and of having a gait speed of <0.8 m/s. SARC‐F scores ≥ 4 in AAH also were associated with 6 year IADL deficits, slower chair stand times, lower short physical performance battery scores, having a gait speed of <0.8 m/s, being hospitalized recently, and mortality. SARC‐F scores ≥ 4 in the BLSA cohort were associated with having more IADL deficits and lower grip strength (both hands) in cross‐sectional comparisons and with IADL deficits, lower grip strength (both hands), and mortality at follow‐up. NHANES participants with SARC‐F scores ≥ 4 had slower 20 ft walk times, had lower peak force knee extensor strength, and were more likely to have been hospitalized recently in cross‐sectional analyses. Conclusions The SARC‐F proved internally consistent and valid for detecting persons at risk for adverse outcomes from sarcopenia in AAH, BLSA, and NHANES.

The NELSON (Nederlands Leuvens Longkanker Screenings Onderzoek) trial is, with 15,822 participants, the largest European lung cancer computer tomography screening trial. A volumetry-based screening strategy, stringent criteria for a positive screening, and an increasing length of screening interval are particular features of the NELSON trial. To determine the effect of stringent referral criteria and increasing screening interval on the characteristics of screen-detected lung cancers, and to compare this across screening rounds, between sexes, and with other screening trials. All NELSON participants with screen-detected lung cancer in the first three rounds were included. Lung cancer stage at diagnosis, histological subtype, and tumor localization were compared between the screening rounds, the sexes, and with other screening trials. In the first three screening rounds, 200 participants were diagnosed with 209 lung cancers. Of these lung cancers, 70.8% were diagnosed at stage I and 8.1% at stage IIIB-IV, and 51.2% were adenocarcinomas. There was no significant difference in cancer stage, histology, or tumor localization across the screening rounds. Women were diagnosed at a significantly more favorable cancer stage than men. Compared with other trials, the screen-detected lung cancers of the NELSON trial were relatively more often diagnosed at stage I and less often at stage IIIB-IV. Despite stringent criteria for a positive screening, an increasing length of screening interval, and few female participants, the screening strategy of the NELSON trial resulted in a favorable cancer stage distribution at diagnosis, which is essential for the effectiveness of our screening strategy. Clinical trial registered with www.trialregister.nl (ISRCTN63545820).

Background In Germany, all women aged 50–69 have been invited to biennial mammography screening since 2009. We aimed to assess longitudinal adherence over ten years in women aged 50 in 2009 and characterize the different adherence groups. Methods Using the German Pharmacoepidemiological Research Database (GePaRD, ~ 20% of the German population), we included women aged 50 in 2009 (baseline) with continuous health insurance coverage and without breast cancer or in-situ-carcinoma. We followed them until age 59 and categorized them according to mammography screening participation into the following groups: never, 1–2, 3–4, 5–6 times. We characterized these groups, inter alia, regarding the use of other preventive measures, non-screening mammography (i.e., mammography outside the organized screening program) and menopausal hormone therapy. Results Overall, 82,666 women were included. Of these, 27.6% never participated in the screening program, 15.1% participated 1–2 times, 31.7% participated 3–4 times and 25.6% participated regularly (5–6 times). Among regular participants, 91% utilized other preventive measures (e.g., cervical cancer screening, general health checkup) before baseline as compared to 66% among non-participants. Menopausal hormone therapy was least common among non-participants (11% vs. 18% among regular participants). Among non-participants, the proportions using ≥ 1, ≥ 2, and ≥ 3 non-screening mammographies between age 50–59 were 25%, 18%, and 15%, respectively. Conclusions Using a large cohort based on claims data, this study provides novel insights into longitudinal adherence to the mammography screening program and the use of mammography outside of the program in Germany. Between age 50–59, 57% of eligible women participated at least three times in the German mammography screening program and 28% (~ 3 in 10 women) never participated. Among non-participants, 15% had at least three non-screening mammographies during this period, indicating potential gray screening. Participants more often utilized other preventive measures as compared to non-participants.

Objectives To review the evidence for an association of white matter hyperintensities with risk of stroke, cognitive decline, dementia, and death.Design Systematic review and meta-analysis.Data sources PubMed from 1966 to 23 November 2009.Study selection Prospective longitudinal studies that used magnetic resonance imaging and assessed the impact of white matter hyperintensities on risk of incident stroke, cognitive decline, dementia, and death, and, for the meta-analysis, studies that provided risk estimates for a categorical measure of white matter hyperintensities, assessing the impact of these lesions on risk of stroke, dementia, and death.Data extraction Population studied, duration of follow-up, method used to measure white matter hyperintensities, definition of the outcome, and measure of the association of white matter hyperintensities with the outcome.Data synthesis 46 longitudinal studies evaluated the association of white matter hyperintensities with risk of stroke (n=12), cognitive decline (n=19), dementia (n=17), and death (n=10). 22 studies could be included in a meta-analysis (nine of stroke, nine of dementia, eight of death). White matter hyperintensities were associated with an increased risk of stroke (hazard ratio 3.3, 95% confidence interval 2.6 to 4.4), dementia (1.9, 1.3 to 2.8), and death (2.0, 1.6 to 2.7). An association of white matter hyperintensities with a faster decline in global cognitive performance, executive function, and processing speed was also suggested.Conclusion White matter hyperintensities predict an increased risk of stroke, dementia, and death. Therefore white matter hyperintensities indicate an increased risk of cerebrovascular events when identified as part of diagnostic investigations, and support their use as an intermediate marker in a research setting. Their discovery should prompt detailed screening for risk factors of stroke and dementia.

Li-Fraumeni syndrome, caused primarily by pathogenic or likely pathogenic germline TP53 variants, is a rare, variably penetrant, cancer predisposition syndrome with very high risks of cancer starting in childhood, including the risk of multiple primary malignancies over an individual's lifespan. We aimed to characterise and quantify cancer incidence, patterns, and genotype–phenotype associations in individuals with pathogenic or likely pathogenic germline TP53 variants. This observational cohort study was done in 480 carriers of pathogenic or likely pathogenic germline TP53 variants enrolled in the National Cancer Institute's referral-based longitudinal Li-Fraumeni syndrome study between Aug 1, 2011, and March 24, 2020. Data on personal and family history of cancer were obtained through study questionnaires and validated by medical records. Variants were categorised on the basis of both loss-of-function (LOF) and dominant-negative effect (DNE) properties. Cancer incidence associated with Li-Fraumeni syndrome was compared with that of the general population using the Surveillance, Epidemiology, and End Results (SEER) 1975–2017 registry. Cancer incidence was evaluated with family-clustered Cox regression models and competing risk methods. This study is registered with ClinicalTrials.gov, NCT01443468. Individuals with Li-Fraumeni syndrome had a nearly 24 times higher incidence of any cancer than the general population (standardised incidence ratio 23·9; 95% CI 21·9–26·0), with the highest comparative incidence from childhood to 30 years of age. The overall cancer incidence remained 10·3 (95% CI 7·9–13·2) times higher than that of the general population after age 50 years. In women, when considering breast cancer as a competing risk, the probability of a first diagnosis of a non-breast cancer malignancy was substantially lower than that of any first cancer (24·4% [95% CI 19·6–30·5] vs 50·4% [43·5–56·5] by age 33·7 years). Overall, DNE_LOF and notDNE_LOF variants were associated with earlier age at first and second cancer compared with notDNE_notLOF and DNE_notLOF variants. The time interval from first to second cancer was shorter among carriers whose first cancer diagnoses were later in life. Multiple cancers were diagnosed within a short timeframe in some individuals, regardless of the order of cancer occurrence. This study adds granularity to the understanding of cancer incidence and patterns in individuals with pathogenic or likely pathogenic germline TP53 variants. Integration of age range-specific cancer incidence estimates, cancer-free survival by functional variant group, the potential impact of risk-reducing mastectomy on female cancer incidence, and data on subsequent malignancies will be important for the development of strategies to optimise cancer screening and management for these individuals. Intramural Research Program, Division of Cancer Epidemiology and Genetics, National Institutes of Health.