Screen Media Use and Mental Health of Children and Adolescents: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Excessive screen media use has been associated with poorer mental health among children and adolescents in several observational studies. However, experimental evidence supporting this hypothesis is lacking. Objective: To investigate the effects of a 2-week screen media reduction intervention on children's and adolescents' mental health. Design, Setting, and Participants: This prespecified secondary analysis of a cluster randomized clinical trial with a 2-week follow-up included 89 families (with 181 children and adolescents) from 10 Danish municipalities in the region of Southern Denmark. All study procedures were carried out in the home of the participants. Enrollment began on June 6, 2019, and ended on March 30, 2021. This analysis was conducted between January 1 and November 30, 2023. Intervention: Families were randomly allocated to a screen media reduction group or a control group. The 2-week screen media reduction intervention was designed to ensure a high level of compliance to the reduction in leisure-time screen media use. Participants allocated to the intervention group had to reduce their leisure-time screen media use to 3 hours per week or less per person and hand over smartphones and tablets. Main Outcomes and Measures: The main outcome was the between-group mean difference in change in total behavioral difficulties, measured by the Strengths and Difficulties Questionnaire at 2-week follow-up. Results were estimated using mixed-effects tobit regression models. Analyses were carried out as both intention to treat and complete case. Results: In the sample of 89 families including 181 children and adolescents (intervention group [45 families]: 86 children; mean [SD] age, 8.6 [2.7] years; 42 girls [49%]; control group [44 families]: 95 children; mean [SD] age, 9.5 [2.5] years; 57 girls [60%]), there was a statistically significant between-group mean difference in the total difficulties score, favoring the screen media reduction intervention (-1.67; 95% CI, -2.68 to -0.67; Cohen d, 0.53). The greatest improvements were observed for internalizing symptoms (emotional symptoms and peer problems; between-group mean difference, -1.03; 95% CI, -1.76 to -0.29) and prosocial behavior (between-group mean difference, 0.84; 95% CI, 0.39-1.30). Conclusions and Relevance: This secondary analysis of a randomized clinical trial found that a short-term reduction in leisure-time screen media use within families positively affected psychological symptoms of children and adolescents, particularly by mitigating internalizing behavioral issues and enhancing prosocial behavior. More research is needed to confirm whether these effects are sustainable in the long term. Trial Registration: ClinicalTrials.gov Identifier: NCT04098913.

Facilitating ambulatory heart rate variability analysis using accelerometry-based classifications of body position and self-reported sleep.

Objective.This study aimed to examine differences in heart rate variability (HRV) across accelerometer-derived position, self-reported sleep, and different summary measures (sleep, 24 h HRV) in free-living settings using open-source methodology.Approach.HRV is a biomarker of autonomic activity. As it is strongly affected by factors such as physical behaviour, stress, and sleep, ambulatory HRV analysis is challenging. Beat-to-beat heart rate (HR) and accelerometry data were collected using single-lead electrocardiography and trunk- and thigh-worn accelerometers among 160 adults participating in the SCREENS trial. HR files were processed and analysed in the RHRV R package. Start time and duration spent in physical behaviours were extracted, and time and frequency analysis for each episode was performed. Differences in HRV estimates across activities were compared using linear mixed models adjusted for age and sex with subject ID as random effect. Next, repeated-measures Bland-Altman analysis was used to compare 24 h RMSSD estimates to HRV during self-reported sleep. Sensitivity analyses evaluated the accuracy of the methodology, and the approach of employing accelerometer-determined episodes to examine activity-independent HRV was described.Main results.HRV was estimated for 31 289 episodes in 160 individuals (53.1% female) at a mean age of 41.4 years. Significant differences in HR and most markers of HRV were found across positions [Mean differences RMSSD: Sitting (Reference) - Standing (-2.63 ms) or Lying (4.53 ms)]. Moreover, ambulatory HRV differed significantly across sleep status, and poor agreement between 24 h estimates compared to sleep HRV was detected. Sensitivity analyses confirmed that removing the first and last 30 s of accelerometry-determined HR episodes was an accurate strategy to account for orthostatic effects.Significance.Ambulatory HRV differed significantly across accelerometry-assigned positions and sleep. The proposed approach for free-living HRV analysis may be an effective strategy to remove confounding by physical activity when the aim is to monitor general autonomic stress.

Study protocol for the Screen-Free Time with Friends Feasibility Trial.

BACKGROUND: Children are spending less leisure time with their friends in person and an increasing amount of time with digital screens. These changes may negatively affect children's physical and mental health. The Screen-Free Time with Friends Feasibility Trial will test the feasibility, including acceptability and compliance, of an intervention designed to reduce screen media usage and encourage physical interaction with friends during leisure time in 9-11-year-old children. METHODS: A non-randomized single-group feasibility trial will be conducted from March to October 2023 including approximately 75 children (aged 9-11 years) and 75 parents (at least 1 per child) from 3 different schools recruited from 3 different municipalities in Denmark. The Screen-Free Time with Friends intervention is a multicomponent intervention targeting families, afterschool clubs, and local communities. It has been developed using a systematic process guided by the Medical Research Council UK's framework for developing and evaluating complex interventions. With a systems perspective in mind, the intervention and implementation approach has been designed to facilitate adaptation to the specific needs of diverse local communities while maintaining the core components of the intervention. Feasibility and acceptability of the intervention will be assessed during the intervention using process evaluation inspired by the RE-AIM framework including questionnaires and interviews with the municipality project managers, research team members, local ambassadors and stakeholders, parents and school, and afterschool club personnel. In addition, participation, recruitment, retention rate, and compliance to the outcome measurements will be investigated and presented. DISCUSSION: The trial will investigate the feasibility and acceptability of the Screen-Free Time with Friends intervention, the recruitment strategy, and the planned outcome measurements. This feasibility study will investigate necessary refinements before the implementation of the intervention program in a larger cluster randomized controlled trial to evaluate its impact. CLINICALTRIALS: gov, ID: NCT05480085. Registered 29 July 2022. https://clinicaltrials.gov/ct2/show/NCT05480085?cond=Screen+free+time+with+friends&draw=2&rank=1.

Probably the most active population in the world: accelerometer measurements of 72 school-children in Greenland.

Physical activity is the most important lifestyle factor to contribute to a healthy early life. International recommendations are that children should be vigorously physically active for at least 1 h per day, and in Greenland, authorities have claimed a goal of being the world's most active population. Since 1994, the Health Behaviour in School-aged Children (HBSC) has measured physical activity among school-children in Greenland by questionnaire data, but the measurement properties of self-reported data in comparison to more objectively measured accelerometer data are unknown. The present paper describes the first study using clinical measures of physical activity among Greenlandic youth. Seventy-two school-children (56% girls) with a mean age of 12 years (range 25%; 75% was 11.5; 12.25) wore accelerometers for seven consecutive days, and data produced significant and informative findings for both practice and future research. Fifty-two per cent of the school-children met the international recommendations of being physically active >1 h per day, when measured by accelerometers, but self-reported data reported a prevalence of 10% meeting the recommendations. A majority of this sample of Greenlandic school-children lives up to international recommendations, which indicates that the goal of being the world's most active population is within reach.

Recreational screen media use among Danish children aged 6-11 years: influence of parental screen media habits and attitudes.

AIMS: Little is known about the influence of parents' screen media habits and attitudes towards screen media on children's screen use. We investigated associations of parental screen use, their smartphone addiction and screen media attitudes, with children's recreational screen use. METHODS: This study was based on a population-based cross-sectional survey sent between May 2019 and November 2020 to a random sample of 6820 Danish parent-child dyads who answered questions regarding their screen media habits. Children were 6-11 years of age and had to reside with the parent. Multivariable adjusted regression analyses were conducted (in October 2021) separately for screen media use on weekdays and weekend days. RESULTS: The analyses included 5437 parents (41.0 years, 67.6% girls) and 5437 children (8.9 years, 48.2% girls). The adjusted relative odds of excessive amounts of screen use of children (>3 hours/weekday and >4 hours/weekend day) was 5.8 (95% confidence interval (CI) 4.6; 7.3) on weekdays and 7.2 (95% CI 5.9; 8.8) on weekend days comparing the fourth and first quartile of parental screen use. Children of parents in the fourth quartile of parental screen use had 2.1 (95% CI 1.7; 2.5) and 2.5 (95% CI 2.2; 3.0) greater odds of screen use before bedtime on all week and weekend days, respectively. Children of parents who had a positive attitude towards their child's screen use or were at high risk of smartphone addiction had significantly higher screen use and more frequent problematic screen use. CONCLUSIONS: Parent's screen media habits and attitudes were strongly associated with their children's recreational screen use.

Prepregnancy Body Mass Index and Risk of Differentiated Thyroid Cancer: A Prospective Cohort Study of More than 440,000 Danish Women.

Background: High body mass index (BMI) has previously been associated with increased risk of differentiated thyroid cancer (DTC); however, only few studies have investigated the association with BMI in a large cohort assessed at a young age and with sufficient data on confounding factors. We assessed the association between excess body weight and the risk of DTC and papillary thyroid cancer (PTC) in a large cohort of young Danish women with substantial confounder control. Methods: We included all parous Danish women registered with a prepregnancy BMI ≥18.5 kg/m2 during 2004-2016 in the Danish Medical Birth Registry in the study population. Cox proportional hazards regression models were used to estimate the hazard ratios (HRs) with confidence intervals (CIs) of DTC according to BMI. In subanalyses, we investigated PTC as a separate group. Analyses were adjusted for calendar time, education, smoking status, benign thyroid disease (BTD), type II diabetes, parity, and oral contraceptive use. In addition, we examined the association with increasing BMI stratified for previous BTD. Results: A total of 443,403 women were included in the study population, and the median age at baseline was 30.0 years. Altogether, 463 women were diagnosed with DTC during follow-up. Excess body weight was associated with a higher rate of DTC (overweight, BMI 25-29.9 kg/m2: HR = 1.54; CI 1.25-1.90. Obese, BMI ≥30 kg/m2: HR = 1.32; CI 1.00-1.75) compared with normal weight. Results were similar in PTC. In addition, we found an increased rate of DTC with increasing BMI, when investigating BMI as a continuous variable per 5 kg/m2 increase (HR = 1.17; CI 1.07-1.27). The results were similar in women without previous BTD. Conclusions: Our study confirms that excess body weight is associated with an increased incidence of DTC and PTC in women.

Effects of Limiting Recreational Screen Media Use on Physical Activity and Sleep in Families With Children: A Cluster Randomized Clinical Trial.

Importance: Children and adults spend large amounts of their leisure time using screen media, which may affect their health and behavior. Objective: To investigate the effect of reducing household recreational screen media use on physical activity and sleep in children and adults. Design, Setting, and Participants: This was a cluster randomized clinical trial with a 2-week follow-up. Enrollment began on June 6, 2019, and ended on March 30, 2021. This study included a population-based sample from 10 Danish municipalities. A total of 89 families (181 children and 164 adults) were recruited based on a population-based survey on screen media habits in families with children. To be eligible, the responding parent had to list self-reported recreational screen use greater than the 40th percentile of recreational screen time use in the source population (>2.4 hours per day). In addition, the parent had to be full-time employed (with no regular night shifts) or enrolled in full-time education. Interventions: Families were randomly assigned to the screen media reduction intervention (45 families, 86 children, 82 adults) designed to ensure participant compliance to a maximum use of screen media (≤3 hours per week) for a 2-week period. Families randomly assigned to the control group (44 families, 95 children, 82 adults) were instructed to carry on as usual. Main Outcomes and Measures: The primary outcome was between-group difference in leisure nonsedentary activity (in minutes per day) measured by combined thigh and waist accelerometry. Secondary outcomes included other physical activity and sleep parameters measured by single-channel electroencephalography. Results: Among the 89 randomized families (intervention group [45 families]: 86 children; mean [SD] age, 8.6 [2.7] years; 44 boys [51%]; 42 girls [49%]; control group [44 families]: 95 children, mean [SD] age, 9.5 [2.5] years; 38 boys [40%]; 57 girls [60%]), 157 children (87%) had complete data on the primary outcome. Eighty-three children (97%) in the intervention group were compliant to the screen use reduction during the intervention. The mean (SD) change in leisure nonsedentary activity in the intervention group was 44.8 (63.5) minutes per day and in the control group was 1.0 (55.1) minute per day (intention-to-treat between-group mean difference, 45.8 minutes per day; 95% CI, 27.9-63.6 minutes per day; P < .001). No significant between-group mean differences were observed between intervention and control for the electroencephalography-based sleep outcomes. Conclusions and Relevance: In this cluster randomized clinical trial, a recreational screen media reduction intervention resulted in a substantial increase in children's engagement in physical activity. The large effect size suggests that the high levels of recreational screen media use seen in many children should be a public health concern. Trial Registration: ClinicalTrials.gov Identifier: NCT04098913.

Temporal Trends in Papillary and Follicular Thyroid Cancer Incidence from 1995 to 2019 in Adults in Denmark According to Education and Income.

Background: Thyroid cancer incidence has increased over the past decades. Differences in incidence trends have been observed depending on socioeconomic status. Here, we describe trends in the incidence of papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC) in Denmark by level of education and income. Methods: All PTC and FTC cases registered in the Danish Cancer Registry from 1995 to 2019 were identified. Individual-level information on education and income was obtained from nationwide registries. We calculated age-standardized incidence rates according to sex, tumor size, education and income, and estimated incidence trends by average annual percentage change (AAPC) and corresponding confidence intervals [CIs] for the periods 1995 to 2004 and 2005 to 2019 by using Poisson regression models. Results: We identified 3454 cases of PTC and 972 cases of FTC. From 2005 to 2019 among women, the incidence of PTC increased across all levels of education (AAPCshort education = 12.5% [CI 9.8 to 15.3]; AAPCmedium education = 8.1% [CI 6.4 to 9.9]; AAPClong education = 7.3% [CI 5.4 to 9.2]). The same pattern was seen for income. The incidence of FTC increased in all levels of education (AAPCshort education = 10.5% [CI 5.8 to 15.4]; AAPCmedium education = 4.0% [CI 0.9 to 7.3]; AAPClong education = 4.3% [CI 0.6 to 8.1]), with the same pattern for income. Similar trends were observed among men, in both small (≤2 cm) and large (>2 cm) PTCs and from 1995 to 2004 in both sexes. Conclusions: Enhanced detection of thyroid cancer among all levels of education and income cannot be ruled out, and in addition, our results may suggest a true increase in the incidence of differentiated thyroid cancer.

Nutrition and preparation of blenderized tube feeding in children and adolescents with neurological impairment: A scoping review.

BACKGROUND: The use of homemade tube feeding formula has become increasingly popular for children requiring enteral nutrition. This project aimed to investigate nutrition and preparation of blenderized tube feeding in the field of children and adolescents with neurological impairment. METHODS: A scoping review was performed using established methodologies. In January 2021, we searched PubMed, Embase, CINAHL Complete, the Cochrane Central Register of Controlled Trials, and gray literature to identify relevant articles. MAJOR FINDINGS: Twenty-two papers were included describing the composition of food items, preparation procedures, and food safety. No randomized controlled trials and only a few prospective studies were included. A broad variety of food items from all food groups and many examples of recipes were presented. Most recipes provided 1.0 kcal/ml but tended to contain less energy and nutrients than expected, which could be due to preparation issues, such as sieving and the high viscosity of the blend. Preparation requires a commercial-grade household blender and diligence to ensure thorough household hygiene for adequate food safety. CONCLUSIONS: This review revealed practical experience in the nutrition and preparation aspects of blenderized tube feeding but minimal empirical evidence. Multiple examples of the composition of food items and preparation procedures for blenderized tube feeding were found, but uncertainty regarding the ideal composition or preparation was also exposed. The future of blenderized tube feeding would benefit from clinically tested recipes that include an evaluation of nutrients, viscosity, and microbial contamination, as well as the effect of the food's appearance and scent on the target group.

Residual tumor and primary debulking surgery vs interval debulking surgery in stage IV epithelial ovarian cancer.

INTRODUCTION: It is debated whether women with FIGO (International Federation of Gynecology and Obstetrics) Stage IV epithelial ovarian cancer should be offered primary debulking surgery (PDS) or interval debulking surgery (IDS). Furthermore, the impact of complete resection of intra-abdominal disease (R0) despite their extra-abdominal metastases is questioned. The objective of this study was to investigate the impact of intra-abdominal residual tumor, Stage IVA vs IVB, the localization and number of metastases defining Stage IV disease on overall survival (OS) comparing PDS and IDS in FIGO Stage IV epithelial ovarian cancer. MATERIAL AND METHODS: We included 2091 women registered with Stage IIIC-IV ovarian cancer in the Danish Gynecological Cancer Database during 2009-2016. The impact of residual tumor was evaluated using univariate and multivariate analyses. RESULTS: In total, 681 patients had stage IV disease, of whom 26% underwent PDS, 38% IDS, and 36% chemotherapy only. Overall survival for PDS and IDS were similar. Patients achieving R0 at PDS showed a tendency towards a higher OS than patients achieving R0 at IDS, though the difference was non-significant. In women with Stage IVA and IVB disease there was a survival benefit in achieving R0 both when treated with PDS and IDS. Women with Stage IVB disease treated with chemotherapy only had a significantly lower OS than patients achieving R0 at both PDS and IDS. Malignant pleural effusion and having five metastatic sites compared with having one was associated with a poorer OS. CONCLUSIONS: Our study shows similar OS in patients with Stage IV disease treated with IDS compared with PDS. Complete intra-abdominal tumor resection improves the prognosis in both PDS and IDS in Stage IV ovarian cancer. Malignant pleural effusion seems to be a negative prognostic factor and should have more focus in future studies.

Effects of limiting digital screen use on well-being, mood, and biomarkers of stress in adults.

Studies have linked higher digital screen use with poorer mental health. However, there is limited experimental evidence to suggest a causal relationship. In this trial, we aimed to investigate the effects of limiting recreational digital screen use on mental well-being, mood, and biomarkers of stress in healthy young and middle-aged adults. We randomly allocated 89 families (including 164 adults) to participate in an extensive screen media reduction intervention or control. Participants in the intervention group were instructed to decrease their recreational screen use to less than 3 hours/week/person. Intervention compliance was assessed using applications and tv-monitors. Overall subjective mental well-being and mood, and collected daily biomarkers of stress (salivary cortisol and cortisone) was assessed at baseline and 2-week follow-up. Reducing recreational digital screen use resulted in significantly improved self-reported well-being and mood in adults allocated to the intervention compared to control. We observed no intervention effects for biomarkers of stress. (ClinicalTrials.gov: NCT04098913, 23/09/2019).

Feasibility of home-based sampling of salivary cortisol and cortisone in healthy adults.

OBJECTIVE: Salivary cortisol and cortisone are used as biomarkers of physiological stress. Careful sampling of saliva for profiling of awakening response and the diurnal slope can be challenging in free-living environments, and validated sampling protocols are lacking. Therefore, we investigated (1) the level of compliance to a three-day home-based salivary sampling protocol, and (2) the within subject day-to-day variability of cortisol and cortisone outcomes and the required measuring days to obtain high reproducibility. RESULTS: Nineteen healthy adults (mean age: 42, 50% females) participated. Participants collected in total 434 salivary samples out of 456 scheduled (four samples per day over three consecutive days at two time points). We found high level of compliance to the proposed free-living salivary sampling protocol with 18 (95%) and 16 (84%) participants being compliant to numbers and timing of samples, respectively. The area under the curve for the morning salivary samples and peak-to-bed slope had moderate reproducibility for cortisol and cortisone (intraclass correlation coefficient: 0.51-0.68, and mean coefficient of variation: 14.7%-75.3%). Three-to-four measuring days were required for high reproducibility of the area under the curve for the morning salivary samples and peak-to-bed slope using this free-living salivary sampling protocol. Trial registration Clinical trial registered with www.clinicaltrials.gov (NCT03788525).

Nutritional screening of children and adolescents with cerebral palsy: a scoping review.

AIM: To examine nutritional screening methods for children and adolescents with cerebral palsy. METHOD: A scoping review was performed using established methodologies. In June 2020 we searched PubMed, Embase, CINAHL Complete, and the Cochrane Central Register of Controlled Trials to identify articles on tools/methods for nutritional screening of our target groups. RESULTS: Thirty studies were included, containing various tools/methods used to identify under- and/or overnutrition by weight/height, circumferences, skinfolds, questionnaires, and/or technically advanced or invasive methods. Questionnaires, weight/height, circumferences, and skinfolds were considered feasible based on clinical utility, whereas bioelectrical impedance analysis and blood samples were not. INTERPRETATION: We identified two screening tools for undernutrition that include no physical measurements, but did not find any screening tools for overweight and obesity. Most of the studies recommended one or more methods, indicating that determining nutritional status most likely includes a combination of methods, not all of which may be feasible in clinical practice. What this paper adds No nutritional screening tool using anthropometry or body composition was discovered. Heterogenous methods to identify under- and/or overnutrition are recommended. Preferable methods for nutritional screening include assessment of body composition. A validated nutritional screening tool for identification of overweight is warranted.

First report of Colletotrichum fructicola, C. perseae, and C. siamense causing anthracnose disease of avocado (Persea americana) in New Zealand.

In January and March 2019, an inspection of 11 commercial 'Hass' avocado orchards in mid-North and Tauranga (New Zealand) was conducted by NZ Avocado Growers Association Inc. (NZAGA) and the samples were sent to Plant Diagnostics Limited for investigation of a newly observed fruit staining symptom termed "tannin stain". Fruit symptoms consisted of areas of minute small spots which coalesced into areas of tear staining associated with water movement over the fruit's surface (Supplementary Fig. 1). Up to seven trees per orchard were sampled targeting symptomatic fruit with the aim of determining the cause of the problem. Fruit was surface disinfected for 4 minutes in 1% sodium hypochlorite solution and sections from lesions were plated on agar medium (prune extract agar) to isolate any plant pathogens. The predominant fungi isolated, represented species in the Colletotrichum acutatum, C. gloeosporioides, and C. boninense species complexes. Since the morphological characters within these complexes overlap (see Supplementary Fig. 2 for examples), the isolates were differentiated by amplification and sequencing of the glyceraldehyde-3-phosphate dehydrogenase (GPDH) gene and, where necessary, the calmodulin (CAL) gene and/or the Apn2-Mat1-2 intergenic spacer region (ApMat) locus (Weir et al., 2012; Rojas et al., 2010). The sequence analysis revealed eight Colletotrichum species comprising C. alienum, C. aotearoa, C. cigarro, C. fioriniae, C. fructicola, C. karstii, C. perseae, and C. siamense. This range included three species that have not previously been recorded in New Zealand: C. fructicola (Cf), C. perseae (Cp), and C. siamense (Cs). Colonies for all these three fungi were white to grey with salmon-coloured and black acervuli. Conidia were aseptate, hyaline, straight, cylindrical, with broadly rounded ends, forming on cylindrical conidiogenous cells. The respective GPDH, CAL, and/or ApMat sequences of the Cf, Cp, and Cs isolates were identical to reference sequences of representative isolates in GenBank (e.g. ApMat: Cf - KX620181, Cp - KX620177, Cs - KP703788). An isolate for each species is stored in the International Collection of Microorganisms from Plants (Cf - ICMP22409, Cp - ICMP22431, Cs - ICMP22411) and sequences are deposited in GenBank (accession numbers MT522858-MT522865). Pathogenicity of each of the newly recorded species was confirmed on freshly picked 'Hass' avocado fruit. After surface disinfection with 1% sodium hypochlorite solution for 5 minutes, fruit was triple washed with sterile water and air dried. Five fruits per species were pin-pricked and inoculated with 10µL of conidial suspension (7 x 106 to 1 x 107 conidia/mL) prepared with sterile water containing Tween 20 (1µL/mL H2O) from 6-day-old cultures grown on PDA. Control fruit was pin-pricked and mock-inoculated with sterile water containing Tween 20 (1µL/mL H2O). All fruit was incubated in moist chambers at 25°C for 7 days. The three Colletotrichum species produced anthracnose symptoms on inoculated fruit whereas no symptoms were observed on control fruit (Supplementary Fig. 3). Each one of the species was successfully re-isolated from symptomatic tissue and identified using the methods described above, fulfilling Koch's postulates. While Cf and Cs have been reported from several hosts and countries to date (Weir et al. 2012), Cp has only been found from avocado in Israel (Sharma et al. 2017) and grape in Japan (Yokosawa et al. 2020). Although a number of species from the C. gloeosporioides species complex, i.e. C. alienum, C. aotearoa, C. cigarro, and C. gloeosporioides have been previously associated with avocado diseases in New Zealand, the detections of Cf, Cp, and Cs represent first records. In this study, eight Colletotrichum species were associated with the "tannin stain" fruit symptoms in New Zealand avocado orchards. The individual contribution of the newly recorded pathogens Cf, Cp, and Cs to the observed disease symptoms was not determined, but their detection highlights the importance of sequence-based identification of Colletotrichum species, as morphology is insufficiently robust to separate cryptic species. Accurate identification of pathogens provides knowledge of species biodiversity that may be useful in biosecurity decision making. Since it has been reported that fungicide treatment efficiencies differ for some closely related Colletotrichum species on grape (Yokosawa et al. 2020), accurate identification might also contribute to establishing effective management strategies.

Impact of PD-L1 and T-cell inflamed gene expression profile on survival in advanced ovarian cancer.

OBJECTIVE: Programmed death ligand 1 (PD-L1) expression affects tumor evasion of immune surveillance. The prognostic value and relationship of PD-L1 expression to T-cell-inflamed immune signatures in ovarian cancer are unclear. The purpose of this study is to evaluate the impact of PD-L1 on overall survival and its correlation with an immune-mediated gene expression profile in patients with advanced ovarian cancer. METHODS: PD-L1 expression in tumor and immune cells was assessed by immunohistochemistry, and PD-L1-positive expression was defined as a combined positive score ≥1; a T-cell-inflamed gene expression profile containing interferon γ response genes was evaluated using extracted RNA from surgical samples. Associations between PD-L1 expression, gene expression profile status, and overall survival were analyzed using the Kaplan-Meier method, log-rank test, and multivariate Cox proportional hazards regression models. RESULTS: A total of 376 patients with advanced epithelial ovarian, primary peritoneal, or fallopian tube cancer treated by cytoreductive surgery and platinum-based therapy were included. PD-L1-positive expression was observed in 50.5% of patients and associated with more advanced stage (p=0.047), more aggressive histologic subtype (p=0.001), and platinum sensitivity defined by increasing treatment-free interval from first platinum-based chemotherapy to next systemic treatment (p=0.027). PD-L1-positive expression was associated with longer overall survival in multivariate analyses (adjusted HR 0.72, 95% CI 0.56 to 0.93). In subgroup analyses, this association was most pronounced in patients with partially platinum-sensitive disease (treatment-free interval ≥6 to <12 months). T-cell-inflamed gene expression profile status correlated with PD-L1 expression (Spearman, ρ=0.712) but was not an independent predictor of overall survival. CONCLUSION: PD-L1 expression is associated with longer overall survival among advanced ovarian cancer patients. PD-L1 expression may be an independent prognostic biomarker.

Impact of residual disease on overall survival in women with Federation of Gynecology and Obstetrics stage IIIB-IIIC vs stage IV epithelial ovarian cancer after primary surgery.

INTRODUCTION: The objective of this study was to determine the impact of intra-abdominal residual disease size, type (carcinomatosis, tumor mass or both), and location (upper/lower abdominal/both) on overall survival in women with Federation of Gynecology and Obstetrics (FIGO) stage IIIB-IIIC vs stage IV epithelial ovarian cancer who underwent primary debulking surgery. MATERIAL AND METHODS: Altogether 2092 women diagnosed with advanced epithelial ovarian cancer undergoing primary debulking surgery in Denmark during 2005-2016 were identified in the Danish Gynecological Cancer Database. The impact of residual disease size, type, and location were evaluated using univariate and multivariate analyses. RESULTS: Complete cytoreduction (residual disease = 0) was achieved in 47.3% and 38.4% of women with stage IIIB-IIIC and IV epithelial ovarian cancer, respectively. A benefit in overall survival was observed in women with residual disease = 0 compared with women with residual disease, and among women with residual disease ≤1 cm compared with residual disease >2 cm in both stages IIIB-IIIC and stage IV in multivariate analyses. Multivariate analyses showed an inferior overall survival for women with both residual carcinomatosis and residual tumor mass compared with those with residual tumor mass or residual carcinomatosis only for stage IIIB-IIIC and IV, and an inferior overall survival for women with residual disease located in both the upper and lower abdomen compared with residual disease in the upper abdomen only in stages IIIB-IIIC. CONCLUSIONS: Our results confirm the positive prognostic impact of both complete cytoreduction and residual disease ≤1 cm in stages IIIB-IIIC as well as stage IV epithelial ovarian cancer. Women with stage IV do benefit from cytoreductive surgery and should be considered for primary debulking surgery, if residual disease = 0 can initially be expected.

Danish Gynecological Cancer Database.

AIM OF DATABASE: The Danish Gynecological Cancer Database (DGCD) is a nationwide clinical cancer database and its aim is to monitor the treatment quality of Danish gynecological cancer patients, and to generate data for scientific purposes. DGCD also records detailed data on the diagnostic measures for gynecological cancer. STUDY POPULATION: DGCD was initiated January 1, 2005, and includes all patients treated at Danish hospitals for cancer of the ovaries, peritoneum, fallopian tubes, cervix, vulva, vagina, and uterus, including rare histological types. MAIN VARIABLES: DGCD data are organized within separate data forms as follows: clinical data, surgery, pathology, pre- and postoperative care, complications, follow-up visits, and final quality check. DGCD is linked with additional data from the Danish "Pathology Registry", the "National Patient Registry", and the "Cause of Death Registry" using the unique Danish personal identification number (CPR number). DESCRIPTIVE DATA: Data from DGCD and registers are available online in the Statistical Analysis Software portal. The DGCD forms cover almost all possible clinical variables used to describe gynecological cancer courses. The only limitation is the registration of oncological treatment data, which is incomplete for a large number of patients. CONCLUSION: The very complete collection of available data from more registries form one of the unique strengths of DGCD compared to many other clinical databases, and provides unique possibilities for validation and completeness of data. The success of the DGCD is illustrated through annual reports, high coverage, and several peer-reviewed DGCD-based publications.

Identification of high-risk patients by human epididymis protein 4 levels during follow-up of ovarian cancer.

The majority of ovarian cancer patients with advanced disease at diagnosis will relapse following primary treatment, with a dismal prognosis. Monitoring the levels of serum markers in patients under follow-up may be essential for the early detection of relapse, and for distinguishing high-risk patients from those with less aggressive disease. The aim of the present study was to investigate the possible predictive value of human epididymis protein 4 (HE4) and carbohydrate antigen 125 (CA125) in relation to recurrence of epithelial ovarian cancer by measuring the two markers during follow-up subsequent to surgery and adjuvant first-line carboplatin/paclitaxel chemotherapy. Serum HE4 and CA125 were analyzed in 88 epithelial ovarian cancer patients at the end of treatment and consecutively during follow-up. The patients were divided into a high-risk and a low-risk group based on having an increase in HE4 and CA125 levels above or below 50% during follow-up, relative to the baseline (end-of-treatment) level. Disease recurrence was detected in 55 patients during follow-up. Patients with an increase in HE4 of >50% at 3- and 6-month follow-up compared to the end-of-treatment sample had significantly poorer progression-free survival (PFS) [hazard ratio (HR), 2.82 (95% CI, 0.91-8.79; P=0.0052) and HR, 7.71 (95% CI, 3.03-19.58; P<0.0001), respectively]. The corresponding 3- and 6-month biomarker assessments for increased CA125 levels (>50%) showed HRs of 1.86 (95% CI, 0.90-3.80; P=0.0512) and 2.55 (95% CI, 1.39-4.68; P=0.0011), respectively. Multivariate analysis confirmed HE4 as a predictor of short PFS, with an HR of 8.23 (95% CI, 3.28-20.9; P<0.0001) at 6-month follow-up. The increase of CA125 was not a significant prognostic factor in multivariate analysis for PFS. In conclusion, HE4 appears to be a sensitive marker of recurrence and instrumental in risk assessment during the first 6 months of follow-up.

The return-to-work process of individuals sick-listed because of whiplash-associated disorder: a three-year follow-up study in a Danish cohort of long-term sickness absentees.

BACKGROUND: The chronic course of whiplash-associated disorder (WAD) has implications for both the individual and society. It has been shown that up to 50% of patients have not yet returned to work six months after a whiplash injury. We wanted to study the return-to-work (RTW) process in individuals sick-listed for more than eight weeks in six Danish municipalities. RTW in individuals sick-listed due to WAD was compared to that in those sick-listed for other musculoskeletal disorders (MSD). METHODS: Information about long-term sick-listed individuals in six Danish municipalities was retrieved from an existing database. Data on public transfer income were collected and the RTW process was followed on a weekly basis. Multivariate logistic regression analysis of RTW was done four times during the first three years after the start of sick-listing. RESULTS: One hundred and four individuals were sick-listed due to WAD and 3,204 individuals were sick-listed due to other MSDs. After 6 months, the RTW was significantly lower in the WAD group. OR for RTW in the WAD group was 0.29 (0.18-0.49) compared to the MSD group. The RTW process for both groups stabilised after two years of follow-up; 44% returned to work in the WAD group as compared to 58% in the MSD group. CONCLUSION: Sick-listed individuals with whiplash-associated disorder are less likely to return to work than individuals who are sick-listed because of other musculoskeletal disorders. In both groups, RTW stabilised after two years of follow-up.