Nurse-Led Individualized Follow-Up Versus Regular Physician-Led Visits After Early Breast Cancer (MyHealth): A Phase III Randomized, Controlled Trial.

PURPOSE: Follow-up after breast cancer with regular visits has failed to detect recurrences, be cost-effective, and address patient needs. METHODS: MyHealth is a phase III randomized controlled trial (ClinicalTrials.gov identifier: NCT02949167). Patients, who recently completed primary treatment for stage I-II breast cancer, were randomly assigned in variable block sizes and stratified by age and human epidermal growth factor receptor 2 status to intervention or control follow-up. The nurse-led intervention comprised three to five individual self-management sessions, regular reporting of symptoms, and navigation to health care services. The control follow-up comprised regular outpatient visits with the physician. The primary outcome was breast cancer-specific quality of life (QoL) measured by the Trial Outcome Index-Physical/Functional/Breast summary score of the Functional Assessment of Cancer Therapy-Breast 2 years after random assignment. Secondary outcomes were fear of recurrence, anxiety, depression, and health care utilization. Analyses were intention-to-treat and P values were two-sided with 95% confidence level set at 0.005 because of multiple comparisons. RESULTS: Among 1,101 eligible patients, 875 were invited and 503 were randomly assigned to control (n = 252) or intervention (n = 251) follow-up. At 2 years, patients in the intervention group reported a significantly and clinically relevant higher QoL (mean, 75.69 [standard deviation [SD], 12.27]) than patients in the control group (71.26 [SD, 14.08]), with a mean difference of 5.05 (95% CI, 3.30 to 6.79; P < .001). The intervention group reported significantly less fear of recurrence, anxiety, and depression; they had fewer physician consultations but more nurse contacts and an unchanged diagnostic imaging pattern. The effect on all outcomes was stable through a 3-year follow-up. CONCLUSION: The MyHealth study suggested a new strategy for follow-up after early breast cancer as it provided significant improvements in QoL.

Characterizing Indicators of Engagement in HIV-Associated Healthcare and Clinical Outcomes among People with HIV and Mpox in Washington, DC: A Nested Case-Control Study of the DC Cohort.

The high proportion of people with HIV (PWH) in the 2022-2023 mpox outbreak has raised questions surrounding the association between HIV and mpox. The objectives of this study were to evaluate the association between engagement in HIV-associated healthcare and mpox diagnosis, as well as to characterize cases of mpox among PWH. The DC Cohort is a longitudinal cohort of PWH in Washington, DC. We conducted a 5:1 (controls:cases) nested case-cohort study on male participants, matching age and care site. Cases were participants with an identified mpox diagnosis. Conditional logistic regression was used to assess the impact of indicators of engagement in HIV-associated healthcare on mpox diagnosis. We identified 70 cases of mpox in DC Cohort participants randomly matched to 323 controls, for a total of 393 participants included in the analysis. Study participants were primarily non-Hispanic Black (72.3%) with a median age of 41 (IQR: 36, 50). There was no association between engagement in care and mpox diagnosis; however, low CD4 was associated with increased odds of mpox diagnosis (aOR: 4.60 (95% CI: 1.23, 17.11)). Among a cohort of PWH, engagement in care was not associated with mpox diagnosis, suggesting that the overrepresentation of PWH among mpox cases is not due to surveillance bias.

Mpox Awareness, Risk Reduction, and Vaccine Acceptance among People with HIV in Washington, DC.

People with HIV (PWH) are disproportionally affected by mpox and at risk of severe complications. We assessed mpox knowledge, adoption of preventive behaviors, and vaccination attitudes among PWH enrolled in a longitudinal HIV cohort in Washington, DC, the DC Cohort. We conducted uni- and multivariable analyses comparing participants by vaccination status and HIV risk group, and multinomial regression to identify factors associated with vaccine acceptance. Among 430 PWH, 378 (87.9%) were aware of mpox. Among 373 participants with vaccination status data, 101 (27.1%) were vaccinated, 129 (34.6%) planned to vaccinate, and 143 (38.3%) did not plan to vaccinate. The three vaccination groups differed significantly by age, race, education, HIV risk group, recent STI status, and level of mpox worry (all p < 0.05). A higher proportion of men who have sex with men (MSM) reported limiting their number of sexual partners compared to non-MSM (p < 0.0001). Multinomial regression models comparing vaccinated to unvaccinated PWH found age, education, mode of HIV transmission/gender, and survey period were significantly associated with vaccination status (all p < 0.05). High levels of mpox awareness were observed among this cohort of PWH with more MSM employing risk reduction behaviors and being vaccinated. Ensuring that PWH, regardless of gender, sexual orientation, or age, understand the risks of mpox may improve vaccination uptake.

Cumulative incidence of second primary cancers in a large nationwide cohort of Danish cancer survivors: a population-based retrospective cohort study.

BACKGROUND: A new primary cancer is a serious late effect of a pre-existing cancer diagnosis, and can be attributed to hereditary cancer syndromes, immune or hormonal factors, cancer treatment, or modifiable lifestyle or environmental factors. We investigated the absolute and relative incidence of second primary cancers in a large cohort of Danish cancer survivors. Furthermore, we examined the association between alcohol-related, smoking-related, virus-related, and hormone-related first and second primary cancers. METHODS: In this retrospective cohort study, we identified a cohort of Danish adults (aged ≥40 years) diagnosed with cancer from Jan 1, 1997, to Dec 31, 2014 and alive 1 year after diagnosis. Follow-up was from date of first cancer diagnosis and lasted up to 24 years, ending on Dec 31, 2020. Cohort identification and information on second primary cancers was obtained from the Danish Cancer Registry, and comorbidity and sociodemographic information was obtained from Danish population-based registries. Overall, and for 27 cancer types, cumulative incidence functions and Cox proportional hazard regression models were used to estimate the incidence of second primary cancer and death, and hazard ratios (HRs) and 95% CIs of second primary cancer adjusted for sex, age and year of diagnosis, cohabitation status, income, and comorbidity. FINDINGS: 457 334 Danish adults were included in our study (230 150 [50·3%] male individuals and 227 184 [49·7%] female individuals; median age at diagnosis 68·3 years, IQR 59·7-76·6; median follow-up 3·6 years, IQR 0·6-9·3). The cumulative incidence of second primary cancer increased over time from 6·3% (95% CI 6·2-6·4) 5 years after diagnosis to 10·5% (10·4-10·6) 10 years after diagnosis and to 13·5% (13·4-13·7) 15 years after diagnosis. The highest cumulative incidence of second primary cancer 10 years after diagnosis was observed in survivors of cancers in the larynx (21·8%, 20·5-23·1), oropharynx and oral cavity (19·5%, 18·7-20·3), and bladder and urinary tract (18·5%, 18·0-19·0). Survivors of cancers related to alcohol (HR 1·09, 95% CI 1·06-1·13), smoking (1·73, 1·68-1·78), diet high in red or processed meat (1·32, 1·24-1·39), or virus (1·23, 1·13-1·35) were at increased risk of developing a second cancer with the same aetiology, whereas having had a hormone-related first cancer was associated with lower risk of a second hormone-related cancer (0·77, 0·73-0·81). INTERPRETATION: Our results could help optimise prevention efforts targeting modifiable risk factors to reduce risk of developing a second primary cancer. FUNDING: Nordic Cancer Union and The Health Foundation (Helsefonden).

Maternal use of hormonal contraception and risk of childhood autism spectrum disorders: A Parental Exposures and Child Health (PECH) cohort study.

A recent hypothesis suggests that maternal hormonal contraception use has contributed to the increasing incidence of autism spectrum disorders (ASD). We used a nationwide population-based cohort (the PECH cohort) including 1,056,149 Danish children born in the period January 1, 1998, to December 31, 2014, to assess associations between maternal hormonal contraception use and childhood ASD (end of follow-up: December 31, 2017). Maternal hormonal contraception use was grouped as "recent use" (≤ 3 months before pregnancy start or during pregnancy), "previous use" (>3 months before pregnancy start) and "never use", except for few products. Incidence rate ratios (IRRs) were estimated using Poisson regression. During follow-up of nearly 12 million person-years, 19,996 children were diagnosed with ASD. A slightly higher IRR was observed for maternal recent use of any hormonal contraception, compared to previous use. This association was largely driven by the non-oral progestin-only products, and associations were especially seen for infantile autism and other/unspecified ASD. An increased IRR of infantile autism was also observed for recent use of the oral progestin-only products, compared to previous use. Our results suggest that maternal use of hormonal contraception may be associated with ASD risk in children, especially for the progestin-only products.

Impact of multimorbidity and polypharmacy on mortality after cancer: a nationwide registry-based cohort study in Denmark 2005-2017.

BACKGROUND: Concurrent chronic diseases and treatment hereof in patients with cancer may increase mortality. In this population-based study we examined the individual and combined impact of multimorbidity and polypharmacy on mortality, across 20 cancers and with 13-years follow-up in Denmark. MATERIALS AND METHODS: This nationwide study included all Danish residents with a first primary cancer diagnosed between 1 January 2005 and 31 December 2015, and followed until the end of 2017. We defined multimorbidity as having one or more of 20 chronic conditions in addition to cancer, registered in the five years preceding diagnosis, and polypharmacy as five or more redeemed medications 2-12 months prior to cancer diagnosis. Cox regression analyses were used to estimate the effects of multimorbidity and polypharmacy, as well as the combined effect on mortality. RESULTS: A total of 261,745 cancer patients were included. We found that patients diagnosed with breast, prostate, colon, rectal, oropharynx, bladder, uterine and cervical cancer, malignant melanoma, Non-Hodgkin lymphoma, and leukemia had higher mortality when the cancer diagnosis was accompanied by multimorbidity and polypharmacy, while in patients with cancer of the lung, esophagus, stomach, liver, pancreas, kidney, ovarian and brain & central nervous system, these factors had less impact on mortality. CONCLUSION: We found that multimorbidity and polypharmacy was associated with higher mortality in patients diagnosed with cancer types that typically have a favorable prognosis compared with patients without multimorbidity and polypharmacy. Multimorbidity and polypharmacy had less impact on mortality in cancers that typically have a poor prognosis.

Scalable production of tissue-like vascularized liver organoids from human PSCs.

The lack of physiological parity between 2D cell culture and in vivo culture has led to the development of more organotypic models, such as organoids. Organoid models have been developed for a number of tissues, including the liver. Current organoid protocols are characterized by a reliance on extracellular matrices (ECMs), patterning in 2D culture, costly growth factors and a lack of cellular diversity, structure, and organization. Current hepatic organoid models are generally simplistic and composed of hepatocytes or cholangiocytes, rendering them less physiologically relevant compared to native tissue. We have developed an approach that does not require 2D patterning, is ECM independent, and employs small molecules to mimic embryonic liver development that produces large quantities of liver-like organoids. Using single-cell RNA sequencing and immunofluorescence, we demonstrate a liver-like cellular repertoire, a higher order cellular complexity, presenting with vascular luminal structures, and a population of resident macrophages: Kupffer cells. The organoids exhibit key liver functions, including drug metabolism, serum protein production, urea synthesis and coagulation factor production, with preserved post-translational modifications such as N-glycosylation and functionality. The organoids can be transplanted and maintained long term in mice producing human albumin. The organoids exhibit a complex cellular repertoire reflective of the organ and have de novo vascularization and liver-like function. These characteristics are a prerequisite for many applications from cellular therapy, tissue engineering, drug toxicity assessment, and disease modeling to basic developmental biology.

Effects of home-based specialized palliative care and dyadic psychological intervention on caregiver burden: results from a randomized controlled trial.

Background The Domus study, a randomized controlled trial (RCT), evaluated the effect of home-based specialized palliative care (SPC) reinforced with a psychological intervention for the patient-caregiver dyad on increasing advanced cancer patients' time spent at home, as opposed to hospitalized, and the number of home deaths. As palliative care extends to include support for patients' families and may thus assist caregivers and decrease demands on them, in this study we evaluated a secondary outcome, caregiver burden.Material and Methods Patients with incurable cancer and their caregivers were randomized (1:1) to care as usual or home-based SPC. Caregiver burden was assessed using the Zarit Burden Interview (ZBI) at baseline and 2, 4, 8 weeks and 6 months after randomization. Intervention effects were assessed in mixed effects models.Results A total of 258 caregivers were enrolled. Eleven per cent of informal caregivers experienced severe caregiver burden at baseline. Caregiver burden increased significantly over time in both groups (p = 0.0003), but no significant effect of the intervention was seen on overall caregiver burden (p = 0.5046) or burden subscales measuring role and personal strain.Conclusion In line with the majority of previous RCTs, the Domus intervention was not able to significantly reduce caregiver burden. Future interventions should consider targeting only caregivers reporting the greatest caregiver burden.

Impacts of Austerity on Urogenital Infection Rates in Active Duty Servicewomen.

INTRODUCTION: Female warfighters are at increased risk of urogenital infections (UGIs) when serving in austere environments with varying levels of access to water, sanitation, and hygiene resources. Urogenital infections among servicewomen were among the top five reported medical encounters and one of the top seven reasons for medical evacuation from deployed locations between 2008 and 2013. In this study, we examine the use of water and sanitation resources across three environments (home duty station, field training, and deployment) and analyze associations between water, sanitation, and hygiene resource access and UGIs during training or deployment. The analyses are based on answers from 751 diverse active duty servicewomen (ADSW) at a large military installation in the southeastern USA. MATERIALS AND METHODS: Data for this population-based, prospective, cross-sectional survey design were collected during the administration of the Military Women's Readiness Urogenital Health Questionnaire. This research study was guided by two specific research questions derived from self-reported data in sections 2 and 3 of the questionnaire. RESULTS: The sample consisted of an extremely diverse pool of U.S. Army ADSW attached to highly operational units with robust field training and deployment tempos. Over one-half of the participants reported being diagnosed with one or more UGIs before military service. Of that participant group, more than 76.0% experienced one or more infections since joining the military. We found that the majority of UGIs occurred while U.S. Army ADSW were at their home duty stations rather than during field training or deployment. Of the three types of UGIs, bacterial vaginosis is more often associated with water and sanitation constraints. None of the water factors were significantly associated with UGIs during deployment. Intentional dehydration was not associated with UGIs in either field training or deployment, but intentionally delaying urination was associated with a significant increase in the odds of developing urinary tract infection during deployment. We identified trends in hygiene practices that may put ADSW at a higher risk for UGIs. CONCLUSIONS: Austere conditions, which may exist in any service environment, pose risks to the urogenital health and wellness of a female warfighter. Access to clean water and sanitation resources in military settings is essential for optimal health and operational readiness. It is necessary to identify and investigate critical research and policy gaps in need of investment and support for successful, evidence-based integration of female warfighters into military combat roles and to optimize their performance.

Patterns in Urogenital Health in Active Duty Servicewomen: A Prospective Cross-Sectional Survey Evaluating Impacts of Water, Sanitation, and Hygiene Resources Across Three Military Environments.

INTRODUCTION: Female warfighters are at risk for sex-specific and frequently unrecognized urogenital health challenges that may impede their ability to serve. The constraints on water, sanitation, and hygiene (WASH) resources by austere environments, whether at home or abroad, require women to practice unhealthy hygiene behaviors that jeopardize their urogenital health. In this manuscript, we examine the use of WASH resources by U.S. Army active duty servicewomen (ADSW) across three settings-home duty, field training, and deployment-to determine how the changing availability of WASH resources alters hygiene and sanitation practices in austere environments. Additionally, we report findings from a previously developed theoretical framework for determining the impacts of austere environments on ADSW's hygiene knowledge, behaviors, and outcomes. MATERIALS AND METHODS: This study used a prospective, cross-sectional survey design with population sampling and generalized ordered logit regression models. We recruited ADSW assigned to a large military installation in the southeastern United States after conducting a structured field hygiene training for female readiness. RESULTS: We surveyed a highly diverse sample of 751 ADSW and found that the use of WASH resources significantly differs between field training and deployment. Clean running water significantly differed among all settings, with nearly 70% reporting clean running water to be rarely or never available during field training. Bathing facility types significantly differed in each setting, with Cadillac bathrooms more often used during deployment than during field training and wipe baths more often used during field training than during deployment. We found that women were significantly less likely to wash their private areas more than 2 days a week during field training, compared to deployment. Women reported changing their underwear ≤2 times per week in field training environments as compared to during deployment. Soap and water were reported as the most common ways of washing in both home duty stations and during deployment, followed by wipes at home duty stations and in deployed settings. Participants reported wipes as their primary bathing method during field training, followed by soap and water. Participants used intentional dehydration or delayed urination more frequently in field training than during deployment. Women reported significant differences in holding their urine between field training and deployment, with principal reasons reported as "dirty facilities" and "distance to the nearest restroom." Significantly, they reported safety concerns when bathing, using the bathroom, or toileting facilities across the three settings. CONCLUSIONS: This is the first study to characterize sex-specific challenges by a large sample of operational ADSW and to explore the use of WASH resources in home duty, field training, and deployment settings. The results show that field training is more austere than deployed settings, indicating that austerity, not deployment, increases the urogenital infection risk for ADSW. With women more integrated into the military strategy than at any time in U.S. history, military leaders can use our results to develop interventions that ameliorate the unique challenges that influence the military readiness and overall health of female warfighters.

Effects on Pediatric Cancer Survivors: The FAMily-Oriented Support (FAMOS) Randomized Controlled Trial.

OBJECTIVE: To examine as secondary analyses the effect the FAMily-Oriented Support (FAMOS) family therapy program on reducing parent-reported medical traumatic stress in the sub-sample of pediatric cancer survivors, age 2-5 years. METHODS: The FAMOS study was a national multicenter randomized controlled trial with all four pediatric oncology departments in Denmark (Clinicaltrials.gov [NCT02200731]). Families were randomized in parallel design (1:1) to intervention or usual care. The FAMOS program includes seven home-based psychotherapeutic sessions and is based on family systems therapy to address the individuals in the family system using cognitive behavioral, problem-solving and goal-setting techniques. Questionnaires were completed by parents at baseline, 6, and 12 months. In linear mixed-effects models, the effect of FAMOS on reducing children's trauma-related behavior after 6 and 12 months was examined in 62 children (31 in the intervention and 29 in the control group, respectively). It was also examined if a trauma-related behavior effect was mediated through reduced symptoms of depression in mothers and fathers, respectively. RESULTS: On average, children in the intervention group experienced significantly larger decreases in trauma-related behaviors at 6 and 12 months than the control group (predicted mean difference -3.89, p = .02 and -6.24, p = .003, respectively). The effect on trauma-related behavior was partly mediated through reduced symptoms of depression in mothers, but not fathers. CONCLUSIONS: Adding to previously reported positive effects of the FAMOS intervention on parents' symptoms of post-traumatic stress and depression, significant improvements were found in young children's trauma related-behavior. Further research is needed to develop therapy for children with cancer.

NAVIGATE: improving survival in vulnerable patients with lung cancer through nurse navigation, symptom monitoring and exercise - study protocol for a multicentre randomised controlled trial.

INTRODUCTION AND AIM: Low socioeconomic position (SEP) has been shown to be strongly associated with impaired lung cancer survival. Barriers related to receiving recommended treatment among patients with lung cancer with low SEP may include adverse health behaviour and limited physical and psychosocial resources influencing the ability to react on high-risk symptoms and to navigate the healthcare system. To address the underlying factors that drive both decisions of treatment, adherence to treatment and follow-up in vulnerable patients with lung cancer, we developed the Navigate intervention. The aim of this randomised controlled trial is to investigate the effect of the intervention on survival (primary outcome), lung cancer treatment adherence, health-related quality of life and other psychosocial outcomes as well as health costs and process evaluation (secondary outcomes) in a study population of vulnerable patients with lung cancer. METHODS AND ANALYSIS: This two-armed multicentre randomised trial will recruit patients from five lung cancer clinics in Denmark identified as vulnerable according to a screening instrument with nine clinical and patient-reported vulnerability criteria developed for the study. We will enrol 518 vulnerable patients >18 years old diagnosed with non-small cell lung cancer at all stages with a performance status <2. Participants will be randomly allocated to either standard treatment and intervention or standard treatment alone. The Navigate intervention is based on principles from motivational interviewing and includes three components of nurse navigation, systematic monitoring of patient-reported outcomes (PROs) and physical exercise in a person-centred delivery model. Data will be collected at baseline and 3, 6, 12 months after randomisation using questionnaires, clinical data and physical function tests. ETHICS AND DISSEMINATION: Ethics Committee, Region Zealand (SJ-884/EMN-2020-37380) and the Data Protection Agency in Region Zealand (REG-080-2021) approved the trial. Participants will provide written informed consent. Results will be reported in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05053997.

Use of hypnotics among women diagnosed with cervical cancer - A population-based cohort study.

OBJECTIVE: Previous studies suggest that sleeping problems are frequent after cervical cancer. However, the evidence on the use of hypnotics is sparse. We investigated if women diagnosed with cervical cancer have an increased risk of using hypnotics and identified risk factors for prolonged use. METHODS: In this nationwide register-based cohort study, 4264 women diagnosed with cervical cancer from 1997 to 2013 and 36,632 cancer-free women were followed in registers until 2016. Prolonged use of hypnotics was defined as more than three prescriptions with no more than three months in between. Data were analysed using Cox proportional hazards regression models and multistate Markov models separately for women with localized and advanced cervical cancer. RESULTS: The rate of first use of hypnotics was substantially increased during the first year after cervical cancer diagnosis compared to cancer-free women (HRlocalized 4.4, 95% CI 3.9-5.1; HRadvanced 8.9, 95% CI 7.5-10.6) and remained markedly increased for up to five years after diagnosis. Dependent on stage of disease and age, 1.4 to 4.7 excess women per 100 with cervical cancer were prolonged users of hypnotics compared to cancer-free women one year after diagnosis. Risk factors for prolonged use of hypnotics were higher age, short education, previous use of antidepressants or anxiolytics, and advanced disease. CONCLUSIONS: Women diagnosed with cervical cancer are at increased risk of prolonged use of hypnotics. For the majority, treatment with hypnotics is initiated within the first year after cancer diagnosis, but the rate of first use is increased for up to five years.

Electrocardiographic characteristics of trained and untrained standardbred racehorses.

BACKGROUND: Long-term exercise induces cardiac remodeling that potentially influences the electrical properties of the heart. HYPOTHESIS/OBJECTIVES: We assessed whether training alters cardiac conduction in Standardbred racehorses. ANIMALS: Two hundred one trained and 52 untrained Standardbred horses. METHODS: Cross-sectional study. Resting ECG recordings were analyzed to assess heart rate (HR) along with standard ECG parameters and for identification of atrial and ventricular arrhythmias. An electrophysiological study was performed in 13 horses assessing the effect of training on sinoatrial (SA) and atrioventricular (AV) nodal function by sinus node recovery time (SNRT) and His signal recordings. Age and sex adjustments were implemented in multiple and logistic regression models for comparison. RESULTS: Resting HR in beats per minute (bpm) was lower in trained vs untrained horses (mean, 30.8 ± 2.6 bpm vs 32.9 ± 4.2 bpm; P = .001). Trained horses more often displayed second-degree atrioventricular block (2AVB; odds ratio, 2.59; P = .04). No difference in SNRT was found between groups (n = 13). Mean P-A, A-H, and H-V intervals were 71 ± 20, 209 ± 41, and 134 ± 41 ms, respectively (n = 7). We did not detect a training effect on AV-nodal conduction intervals. His signals were present in 1 horse during 2AVB with varying H-V interval preceding a blocked beat. CONCLUSIONS AND CLINICAL IMPORTANCE: We identified decreased HR and increased frequency of 2AVB in trained horses. In 5 of 7 horses, His signal recordings had variable H-V intervals within each individual horse, providing novel insight into AV conduction in horses.

Risk of somatic hospitalization in parents after cancer in a child, a nationwide cohort study.

OBJECTIVE: The diagnosis of cancer in a child is a profoundly stressful experience. The impact on parents' somatic health, including lifestyle-related diseases, however, is unresolved. This paper assesses parents' risk of hospitalization with somatic disease after a child's cancer diagnosis. METHODS: We conducted a nationwide population- and register-based study with parents of all children under age 20 diagnosed with cancer in Denmark between 1998 and 2013 and parents of cancer-free children, matched (1:10) on child's age and family type. We estimated HR with 95% CI in Cox proportional hazard models for 13 major International Classification of Diseases-10 disease groups, selected stress- and lifestyle-related disease-groups, and investigated moderation by time since diagnosis, parental sex, and cancer type. RESULTS: Among n = 7797 parents of children with cancer compared with n = 74,388 parents of cancer-free children (51% mothers, mean age 42), we found no overall pattern of increased risk for 13 broad disease groups. We found increases in digestive system diseases (HR 1.06, 95% CI 1.01-1.12), genitourinary system diseases (HR 1.08, 95% CI 1.02-1.14), and neoplasms (HR 1.20, 95% CI 1.13-1.27), the latter attributable mostly to increased rates of tobacco-related cancers and mothers' diet-related cancers. CONCLUSIONS: This is the first attempt to document the impact of childhood cancer on parents' somatic health. With the exception of increased risk for neoplasms, likely due to shared genetic or lifestyle factors, our findings offer the reassuring message, that the burden of caring for a child with cancer does not in general increase parents' risk for somatic diseases.

Postoperative epilepsy and survival in glioma patients: a nationwide population-based cohort study from 2009 to 2018.

PURPOSE: Postoperative epilepsy is common in glioma patients and has been suggested to indicate disease progression, yet knowledge of its role as a prognostic factor is limited. This study investigates the association between postoperative epilepsy and survival amongst patients with gliomas. METHODS: We included 3763 patients with histopathologically diagnosed grade II, III, and IV gliomas from 2009 to 2018 according to the Danish Neuro-Oncology Registry. Information on epilepsy diagnosis was redeemed from the Danish National Patient Registry, the National Prescription Registry and the Danish Neuro-Oncology Registry. We used Cox proportional hazards models with 95% confidence intervals (CIs) to examine hazard ratios (HRs) for the association between postoperative epilepsy and risk of death. We examined the role of the timing of epilepsy in three different samples: Firstly, in all glioma patients with postoperative epilepsy; secondly, in patients with postoperative de novo epilepsy; thirdly, exclusively in a homogeneous sub-group of grade IV patients with postoperative de novo epilepsy. RESULTS: Glioma patients with postoperative epilepsy had an increased risk of death, regardless of prior epilepsy status (HR = 4.03; CI 2.69-6.03). A similar increase in the risk of death was also seen in patients with postoperative de novo epilepsy (HR = 2.08; CI 1.26-3.44) and in the sub-group of grade IV patients with postoperative de novo epilepsy (HR = 1.83; CI 1.05-3.21). CONCLUSIONS: Postoperative epilepsy may negatively impact survival after glioma diagnosis, regardless of preoperative epilepsy status. Postoperative epilepsy may be an expression of a more invasive growth pattern of the gliomas following primary tumor treatment.

Prediagnosis epilepsy and survival in patients with glioma: a nationwide population-based cohort study from 2009 to 2018.

OBJECTIVE: Considering that epilepsy is common, and knowledge is lacking on its role especially for the prognosis of high-grade gliomas, the objective of this study was to investigate the association between epilepsy prior to glioma diagnosis and survival among glioma patients. METHODS: In a nationwide population-based cohort study, we included 3763 adult glioma patients diagnosed between 2009 and 2018 according to the Danish Neuro-Oncology Registry. Information on epilepsy was redeemed through Danish Neuro-Oncology Registry, National Patient Registry, and National Prescription Registry. Cox proportional hazard models with 95% confidence intervals (CIs) were applied to examine hazard ratios (HRs) for the association between epilepsy (< 1 year prior to glioma including epilepsy at onset; 1-10 years prior to glioma; no prior epilepsy) and risk of death, and whether it differed according to tumor grade and size, performance status, and treatment modalities. RESULTS: A 32% decreased risk of death in patients with epilepsy within 1 year prior to glioma compared to no prior epilepsy was found (HR = 0.68; CI 0.63-0.75). A favorable prognosis was seen for epilepsy in all glioma grades: II (HR = 0.55; CI 0.39-0.77), III (HR = 0.59; CI 0.48-0.73), and IV (HR = 0.85; CI 0.77-0.94). CONCLUSIONS: Patients with epilepsy within 1 year prior to glioma diagnosis had significant survival benefits compared to patients with no prior epilepsy. This association was significant for both low-grade gliomas (grade II) and high-grade gliomas (grade III and IV). Survival benefits in glioma patients with epilepsy at onset are possibly primarily attributable to tumor-specific histopathology, molecular biomarkers, and early diagnosis.

Psychiatric disorders in childhood cancer survivors in Denmark, Finland, and Sweden: a register-based cohort study from the SALiCCS research programme.

BACKGROUND: A childhood cancer diagnosis and treatment-induced somatic late effects can affect the long-term mental health of survivors. We aimed to explore whether childhood cancer survivors are at higher risk of psychiatric disorders later in life than their siblings and the general population. METHODS: In this register-based cohort study (part of the Socioeconomic Consequences in Adult Life after Childhood Cancer [SALiCCS] research programme), we included 5-year survivors of childhood cancer diagnosed before 20 years of age between Jan 1, 1974 and Dec 31, 2011, in Denmark, Finland, and Sweden. In Denmark and Sweden, 94·7% of individuals were born in a Nordic country (ie, Denmark, Finland, Iceland, Norway, or Sweden); similar information was not available in Finland. Data on ethnicity were not collected. Survivors were compared with their siblings and randomly selected individuals from the general population who were matched to the survivors by year of birth, sex, and geographical region. We followed up our study population from 5 years after the childhood cancer diagnosis or corresponding calendar date for matched individuals (the index date) until Aug 11, 2017, and assessed information on hospital contacts for any and specific psychiatric disorders. For siblings, the index date was defined as 5 years from the date on which they were of the same age as their sibling survivor when diagnosed with cancer. FINDINGS: The study population included 18 621 childhood cancer survivors (9934 [53·3%] males and 8687 [46·7%] females), 24 775 siblings (12 594 [50·8%] males and 12 181 [49·2%] females), and 88 630 matched individuals (47 300 [53·4%] males and 41 330 [46·6%] females). The cumulative incidence proportion of having had a psychiatric hospital contact by 30 years of age between Jan 1, 1979, and Aug 11, 2017, was 15·9% (95% CI 15·3-16·5) for childhood cancer survivors, 14·0% (13·5-14·5) for siblings, and 12·7% (12·4-12·9) for matched individuals. Despite a small absolute difference, survivors were at higher relative risk of any psychiatric hospital contact than their siblings (1·39, 1·31-1·48) and matched individuals (hazard ratio 1·34, 95% CI 1·28-1·39). The higher risk persisted at the age of 50 years. Survivors had a higher burden of recurrent psychiatric hospital contacts and had more hospital contacts for different psychiatric disorders than their siblings and the matched individuals. INTERPRETATION: Childhood cancer survivors are at higher long-term risk of psychiatric disorders than their siblings and matched individuals from the general population. To improve mental health and the overall quality of life after childhood cancer, survivorship care should include a focus on early signs of mental health problems, especially among high-risk groups of survivors. FUNDING: NordForsk, Aarhus University, Swedish Childhood Cancer Foundation, Danish Health Foundation, and Swiss National Science Foundation.

Autophagy modulates cell fate decisions during lineage commitment.

Early events during development leading to exit from a pluripotent state and commitment toward a specific germ layer still need in-depth understanding. Autophagy has been shown to play a crucial role in both development and differentiation. This study employs human embryonic and induced pluripotent stem cells to understand the early events of lineage commitment with respect to the role of autophagy in this process. Our data indicate that a dip in autophagy facilitates exit from pluripotency. Upon exit, we demonstrate that the modulation of autophagy affects SOX2 levels and lineage commitment, with induction of autophagy promoting SOX2 degradation and mesendoderm formation, whereas inhibition of autophagy causes SOX2 accumulation and neuroectoderm formation. Thus, our results indicate that autophagy-mediated SOX2 turnover is a determining factor for lineage commitment. These findings will deepen our understanding of development and lead to improved methods to derive different lineages and cell types.Abbreviations: ACTB: Actin, beta; ATG: Autophagy-related; BafA1: Bafilomycin A1; CAS9: CRISPR-associated protein 9; CQ: Chloroquine; DE: Definitive endoderm; hESCs: Human Embryonic Stem Cells; hiPSCs: Human Induced Pluripotent Stem Cells; LAMP1: Lysosomal Associated Membrane Protein 1; MAP1LC3: Microtubule-Associated Protein 1 Light Chain 3; MTOR: Mechanistic Target Of Rapamycin Kinase; NANOG: Nanog Homeobox; PAX6: Paired Box 6; PE: Phosphatidylethanolamine; POU5F1: POU class 5 Homeobox 1; PRKAA2: Protein Kinase AMP-Activated Catalytic Subunit Alpha 2; SOX2: SRY-box Transcription Factor 2; SQSTM1: Sequestosome 1; ULK1: unc-51 like Autophagy Activating Kinase 1; WDFY3: WD Repeat and FYVE Domain Containing 3.

Protocol for 'Resilient Caregivers': a randomised trial of a resilience-based intervention for psychologically distressed partner caregivers of patients with cancer.

INTRODUCTION: Intimate partners of patients with cancer often experience significant distress, but there is a lack of psychological interventions that specifically target this population. 'Resilient Caregivers' is a novel resilience-based intervention for distressed partner cancer caregivers. The intervention was developed according to a resilience framework focusing on meta-reflective skills, coping strategies and value clarification. The aim of this study is to evaluate the effectiveness of this intervention in a randomised trial. METHODS AND ANALYSIS: Eighty participants will be invited through the Oncology Department at Herlev Hospital, Denmark and randomised to either the intervention or usual care. Participants are eligible if they are partners (married or unmarried) of patients diagnosed with cancer and experience distress (>4 on the distress thermometer). 'Resilient Caregivers' consists of seven manualised group sessions (2.5 hours each), focusing on resilience in relation to being a partner caregiver of a patient with cancer. The primary outcome is symptoms of anxiety, while secondary outcomes include distress, depression, quality of life, sleep quality and resilience. Data will be collected at baseline, 3, 6 and 12 months follow-up using validated scales, and analysed using mixed models for repeated measures. ETHICS AND DISSEMINATION: This study will follow the ethical principles in the Declaration of Helsinki and has been reviewed by the Ethics Committee of the Capital Region of Denmark (Journal no. 18055373). Written informed consent will be obtained from all participants. Results will be reported through scientific peer-reviewed journals and relevant conferences. TRIAL REGISTRATION NUMBER: NCT04610034.