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PurposeThe majority of childhood, adolescent, and young adult cancer survivors (CAYACS) are at risk of late effects but may not receive long-term follow-up care for these. Here, we investigated (1) self-reported late effects, (2) long-term follow-up care, and (3) factors associated with receiving follow-up care in a population-based sample of Norwegian long-term CAYACS.MethodsSurvivors were identified by the Cancer Registry of Norway. All > 5-year survivors diagnosed between 1985 and 2009 with childhood cancer (CCS, 0–18 years old, excluding CNS), breast cancer (BC, stages I–III), colorectal cancer (CRC), leukemias (LEUK), non-Hodgkin lymphoma (NHL), or malignant melanoma (MM) at age 19–39 years were mailed a questionnaire (NOR-CAYACS study). Descriptive statistics and logistic regression models were used to analyze occurrence of late effects, long-term follow-up care for these, and associated factors.ResultsOf 2104 responding survivors, 1889 were eligible for analyses. Of these, 68% were females, with a mean age of 43 years at survey, on average 17 years since diagnosis, and diagnosed with CCS (31%), BC (26%), CRC (8%), NHL (12%), LEUK (7%), and MM (16%). Overall, 61.5% reported the experience of at least one late effect, the most common being concentration/memory problems (28.1%) and fatigue (25.2%). Sixty-nine percent reported not having received long-term follow-up care focusing on late effects. Lower age at survey (p = 0.001), higher education (p = 0.012), and increasing number of late effects (p = < 0.001) were associated with increased likelihood of follow-up care in the multivariate model.ConclusionsThe majority of survivors reported at least one late effect, but not receiving specific follow-up care for these. This indicates a need for structured models of long-term follow-up to ensure adequate access to care.

Background: Little is known about engagement in multiple health behaviours in childhood cancer survivors. Methods: Using latent class analysis, we identified health behaviour patterns in 835 adult survivors of childhood cancer (age 20–35 years) and 1670 age- and sex-matched controls from the general population. Behaviour groups were determined from replies to questions on smoking, drinking, cannabis use, sporting activities, diet, sun protection and skin examination. Results: The model identified four health behaviour patterns: ‘risk-avoidance’, with a generally healthy behaviour; ‘moderate drinking’, with higher levels of sporting activities, but moderate alcohol-consumption; ‘risk-taking’, engaging in several risk behaviours; and ‘smoking’, smoking but not drinking. Similar proportions of survivors and controls fell into the ‘risk-avoiding’ (42% vs 44%) and the ‘risk-taking’ cluster (14% vs 12%), but more survivors were in the ‘moderate drinking’ (39% vs 28%) and fewer in the ‘smoking’ cluster (5% vs 16%). Determinants of health behaviour clusters were gender, migration background, income and therapy. Conclusion: A comparable proportion of childhood cancer survivors as in the general population engage in multiple health-compromising behaviours. Because of increased vulnerability of survivors, multiple risk behaviours should be addressed in targeted health interventions.

Purpose Childhood cancer and its treatment may affect health-related quality of life (HRQoL) in childhood cancer survivors, but population-based studies in young survivors are scarce. We aimed to: (1) compare HRQoL between young survivors and population norms and (2) find factors that influence parent-reported HRQoL in survivors. Methods As part of the Swiss Childhood Cancer Survivor Study, a questionnaire was mailed to parents of survivors aged 8-16 years, registered in the Swiss Childhood Cancer Registry, ≥5 years after diagnosis. We used the KIDSCREEN-27 instrument to compare self- and parent-reported HRQoL between survivors (N = 425) and standardized norms in the five dimensions of physical well-being, psychological well-being, autonomy, peers and school environment (mean = 50, SD = 10). We then used multivariable linear regressions to test the influence of socio-demographic and cancer-related factors on HRQoL. Results Self-reported physical well-being was comparable to norms. Other HRQoL dimensions were higher than norms, with the highest mean = 52.2 (p < 0.001) for school environment. Parent-reported HRQoL in survivors was comparable to population norms; only physical well-being was lower (mean = 47.1, p < 0.001), and school environment was higher (mean = 51.1, p = 0.035). Parent-reported HRQoL was lower for survivors of CNS tumors (physical well-being: β = —5.27, p = 0.007; psychological well-being: β = -4.39, p = 0.044; peers β = -5.17, p = 0.028), survivors of neuroblastoma (psychological well-being β = —5.20, p = 0.047), and survivors who had had a relapse (physical well-being β = —5.41, p = 0.005). Conclusions Assessing HRQoL during follow-up care, with a focus on physical well-being, specific diagnoses (e.g., CNS tumor) and late complications (e.g., relapse) might help to early identify problems and offer support to survivors with reduced HRQoL.

Physical activity (PA) is a cornerstone in disease prevention and varies throughout life. A pooled analysis of cohort studies and a meta-analysis of cohort studies found positive associations between PA and melanoma risk. However, previous studies focused on PA at specific ages and often lacked information on ultraviolet radiation (UVR) exposure. Using the population-based Norwegian Women and Cancer (NOWAC) cohort, including information on PA and UVR exposure, we estimated life-course PA trajectories from adolescence to adulthood and their associations with melanoma. Total PA across different domains (recreation, occupation, transport, household) was reported for ages 14 and 30 years, and when responding to the questionnaire (31-76 years) using a 10-point scale, validated to rank PA levels in Norwegian females. We estimated life-course PA trajectories using a latent class mixed model in 152,248 women divided into three subcohorts depending on age at questionnaire completion: 31-39 (n = 27,098), 40-49 (n = 52,515) and ≥50 years (n = 72,635). The unique 11-digit identity number of Norwegian citizens was used to link NOWAC to the Cancer Registry of Norway for information on cancer diagnoses, emigration and death. Associations between PA trajectories and melanoma risk were estimated in each subcohort using multivariable Cox regression. Five classes of individual life-course PA trajectories were identified in subcohort 31-39 years (low, moderate, high, decreasing, increasing PA) and four in subcohorts 40-49 and ≥50 years (low, moderate, high, decreasing PA). No significant association was found between life-course PA trajectories and melanoma risk in any subcohort. Hazard ratios (95% confidence intervals) for the high versus moderate trajectory were 0.92 (0.66-1.29), 1.15 (0.97-1.37) and 0.90 (0.78-1.05) for subcohorts 31-39, 40-49 and ≥50 years, respectively. Our results do not support a positive association between PA and melanoma risk found in previous studies, which is important for public health guidelines promoting regular PA.

Background Human papillomaviruses are common in the urogenital tract amongst women of childbearing age. A few studies indicate a possible association between human papillomavirus infections in pregnancy and adverse pregnancy outcomes whilst other studies find no such association. We aimed to investigate the association between human papillomavirus infections during pregnancy and adverse pregnancy outcomes linked to placental dysfunction, including hypertensive disorders of pregnancy, gestational diabetes mellitus and newborns small for gestational age. Materials and methods Pregnant women from the general population in Norway and Sweden were enrolled at the time of routine mid-gestational ultrasound examination. Urine samples collected at mid-gestation in 950 and at delivery in 753 participants, were analyzed for 28 human papillomavirus genotypes, including 12 high-risk genotypes. Participants completed electronic questionnaires at enrollment and medical records were reviewed for background characteristics and for the following adverse pregnancy outcomes: hypertensive disorders of pregnancy including gestational hypertension, preeclampsia, superimposed preeclampsia, eclampsia and Hemolysis Elevated Liver enzymes and Low Platelets (HELLP) syndrome, gestational diabetes mellitus, and newborns small for gestational age. Associations between adverse pregnancy outcomes and (a) any human papillomavirus, high-risk human papillomavirus and human papillomavirus genotype 16 infection at mid-gestation, (b) multiple genotype infections at mid-gestation, and (c) persisting infections during pregnancy were assessed with univariable and multivariable logistic regression models. Missing covariates were imputed using multiple imputation. Results At mid-gestation, 40% (377/950) of women were positive for any of the 28 genotypes, 24% (231/950) for high-risk genotypes and human papillomavirus 16 was found in 6% (59/950) of the women. Hypertensive disorders of pregnancy was observed in 9% (83/950), gestational diabetes mellitus in 4% (40/950) and newborns small for gestational age in 7% (67/950). Human papillomavirus infection with any genotype, high-risk or human papillomavirus genotype 16 at mid-gestation was not associated with adverse pregnancy outcomes. No associations were found for multiple genotype infections at mid-gestation or persisting infections. Conclusion In a general population of pregnant women, we found no evidence of human papillomavirus infections during pregnancy being associated with hypertensive disorders of pregnancy, gestational diabetes mellitus, or newborns small for gestational age. Trial registration Trial registration The study is registered at ClincialTrials.gov; NCT02449850 on May 19th, 2015. Graphical Abstract

Host-directed-therapy strategies are warranted to fight tuberculosis. Here we assess the safety and immunogenicity of adjunctive vaccination with the H56:IC31 candidate and cyclooxygenase-2-inhibitor treatment (etoricoxib) in pulmonary and extra-pulmonary tuberculosis patients in a randomized open-label phase I/II clinical trial (TBCOX2, NCT02503839). A total of 222 patients were screened, 51 enrolled and randomized; 13 in the etoricoxib-group, 14 in the H56:IC31-group, 12 in the etoricoxib+H56:IC31-group and 12 controls. Three Serious Adverse Events were reported in the etoricoxib-groups; two urticarial rash and one possible disease progression, no Serious Adverse Events were vaccine related. H56:IC31 induces robust expansion of antigen-specific T-cells analyzed by fluorospot and flow cytometry, and higher proportion of seroconversions. Etoricoxib reduced H56:IC31-induced T-cell responses. Here, we show the first clinical data that H56:IC31 vaccination is safe and immunogenic in tuberculosis patients, supporting further studies of H56:IC31 as a host-directed-therapy strategy. Although etoricoxib appears safe, our data do not support therapy with adjunctive cyclooxygenase-2-inhibitors. Modulating the host immune response during tuberculosis is an emerging and critical advance in the therapeutic approach. Here the authors present data from a first-in-human phase I/II randomised trial on the safety and immunogenicity of adjuvant therapy of the H56:IC31 vaccine and cyclooxygenase-2 inhibitors in patients with tuberculosis.

Here, we randomized 53 patients hospitalized with coronavirus disease 2019 (COVID-19) to hydroxychloroquine therapy (at a dose of 400 mg twice daily for seven days) in addition to standard care or standard care alone (ClinicalTrials.gov Identifier, NCT04316377). All severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive patients 18 years of age or older were eligible for study inclusion if they had moderately severe COVID-19 at admission. Treatment with hydroxychloroquine did not result in a significantly greater rate of decline in SARS-CoV-2 oropharyngeal viral load compared to standard care alone during the first five days. Our results suggest no important antiviral effect of hydroxychloroquine in humans infected with SARS-CoV-2. The use of hydroxychloroquine therapy for the treatment of Covid-19 is controversial. In this study, Lyngbakken and colleagues present a randomized controlled trial and show that the drug has no antiviral effects in humans infected with SARS-CoV-2.

BackgroundThis randomised controlled trial (RCT) assessed the effect of a 1-year, partially supervised, physical activity (PA) intervention on a cardiovascular disease (CVD) risk score in adult survivors of childhood cancer.MethodsWe included childhood cancer survivors ≥16 y at enrolment, <16 y at diagnosis and ≥5 y in remission. The intervention group was asked to perform an additional ≥2.5 h of intense physical activity/week, controls continued exercise as usual; assessments were performed at baseline, 6 months (T6) and 12 months (T12). The primary endpoint was change in a CVD risk score (average z-score of waist circumference, blood pressure, fasting glucose, inverted high-density lipoprotein cholesterol, triglycerides, and inverted cardiorespiratory fitness) from baseline to T12. We performed intention-to-treat (ITT, primary) and 3 per protocol analyses.ResultsWe randomised 151 survivors (44% females, 30.4 ± 8.6 years). We found a significant and robust reduction of the CVD risk score in the intervention compared to the control group at T6 and T12 across all analyses; with a difference in the reduction of the CVD risk z-score of −0.18 (95% confidence interval −0.29 to −0.06, P = 0.003) at T12 in favour of the intervention group (ITT analysis).ConclusionsThis RCT showed that a long-term PA intervention can reduce CVD risk in long-term survivors of childhood cancer.Trial registrationClinicaltrials.gov: NCT02730767.

In a recently published paper in BMC Public Health we read about a randomized trial on Covid-19 transmission performed in five fitness centers in Oslo, Norway, during the spring of 2020. In our opinion, this study has major shortcomings in design and methodology, which have not been addressed by the authors.

Background Beyond survival of nowadays >80%, modern childhood cancer treatment strives to preserve long-term health and quality of life. However, the majority of today’s survivors suffer from short- and long-term adverse effects such as cardiovascular and pulmonary diseases, obesity, osteoporosis, fatigue, depression, and reduced physical fitness and quality of life. Regular exercise can play a major role to mitigate or prevent such late-effects. Despite this, there are no data on the effects of regular exercise in childhood cancer survivors from randomized controlled trials (RCTs). Primary outcome of the current RCT is therefore the effect of a 12-months exercise program on a composite cardiovascular disease risk score in childhood cancer survivors. Secondary outcomes are single cardiovascular disease risk factors, glycaemic control, bone health, body composition, physical fitness, physical activity, quality of life, mental health, fatigue and adverse events (safety). Methods A total of 150 childhood cancer survivors aged ≥16 years and diagnosed ≥5 years prior to the study are recruited from Swiss paediatric oncology clinics. Following the baseline assessments patients are randomized 1:1 into an intervention and control group. Thereafter, they are seen at month 3, 6 and 12 for follow-up assessments. The intervention group is asked to add ≥2.5 h of intense physical activity/week, including 30 min of strength building and 2 h of aerobic exercises. In addition, they are told to reduce screen time by 25%. Regular consulting by physiotherapists, individual web-based activity diaries, and pedometer devices are used as motivational tools for the intervention group. The control group is asked to keep their physical activity levels constant. Discussion The results of this study will show whether a partially supervised exercise intervention can improve cardiovascular disease risk factors, bone health, body composition, physical activity and fitness, fatigue, mental health and quality of life in childhood cancer survivors. If the program will be effective, all relevant information of the SURfit physical activity intervention will be made available to interested clinics that treat and follow-up childhood cancer patients to promote exercise in their patients. Trial registration Prospectively registered in clinicaltrials.gov [ NCT02730767 ], registration date: 10.12.2015.