Comprehensive Assessment of Incidence, Risk Factors, and Mechanisms of Impaired Medical and Psychosocial Health Outcomes among Adolescents and Young Adults with Cancer:Protocol of the Prospective Observational COMPRAYA Cohort Study

Simple Summary Adolescents and young adults (AYA), aged 18-39 years at first cancer diagnosis, are recognized as a distinct population within the oncology community due to the unique challenges they encounter including recognition, diagnosis, treatment, and monitoring of their disease. It is imperative for advances in the field of AYA oncology to pool data sources (patient-reported outcomes, clinical, treatment, genetic, and biological data) across institutions and countries and create large cohorts that include the full range of AYA ages and diagnoses to be able to address the many pressing questions that remain unanswered in this vulnerable population. The Dutch COMPRAYA study aims to examine the incidence, risk factors, and mechanisms of impaired health outcomes (short- and long-term medical and psychosocial effects) over time among AYA cancer patients. The overarching aim is to provide a research infrastructure for (future) data analyses and observational retrospective/prospective ancillary studies and to expand data collection to other countries. Adolescent and young adult (AYA) cancer patients suffer from delay in diagnosis, and lack of centralized cancer care, age-adjusted expertise, and follow-up care. This group presents with a unique spectrum of cancers, distinct tumor biology, cancer risk factors, developmental challenges, and treatment regimens that differ from children and older adults. It is imperative for advances in the field of AYA oncology to pool data sources across institutions and create large cohorts to address the many pressing questions that remain unanswered in this vulnerable population. We will create a nationwide infrastructure (COMPRAYA) for research into the incidence, predictive/prognostic markers, and underlying mechanisms of medical and psychosocial outcomes for AYA between 18-39 years diagnosed with cancer. A prospective, observational cohort of (n = 4000), will be established. Patients will be asked to (1) complete patient-reported outcome measures; (2) donate a blood, hair, and stool samples (to obtain biochemical, hormonal, and inflammation parameters, and germline DNA); (3) give consent for use of routinely archived tumor tissue and clinical data extraction from medical records and registries; (4) have a clinic visit to assess vital parameters. Systematic and comprehensive collection of patient and tumor characteristics of AYA will support the development of evidence-based AYA care programs and guidelines

Psychological Problems among Head and Neck Cancer Patients in Relation to Utilization of Healthcare and Informal Care and Costs in the First Two Years after Diagnosis

BACKGROUND: To investigate associations between psychological problems and the use of healthcare and informal care and total costs among head and neck cancer (HNC) patients. METHOD: Data were used of the NETherlands QUality of Life and Biomedical Cohort study. Anxiety and depression disorder (diagnostic interview), distress, symptoms of anxiety and depression (HADS), and fear of cancer recurrence (FCR) and cancer worry scale (CWS) were measured at baseline and at 12-month follow-up. Care use and costs (questionnaire) were measured at baseline, 3-, 6-, 12-, and 24-month follow-up. Associations between psychological problems and care use/costs were investigated using logistic and multiple regression analyses. RESULTS: Data of 558 patients were used. Distress, symptoms of anxiety or depression, FCR, and/or anxiety disorder at baseline were significantly associated with higher use of primary care, supportive care, and/or informal care (odds ratios (ORs) between 1.55 and 4.76). Symptoms of anxiety, FCR, and/or depression disorder at 12-month follow-up were significantly associated with use of primary care, supportive care, and/or informal care (ORs between 1.74 and 6.42). Distress, symptoms of anxiety, and FCR at baseline were associated with higher total costs. DISCUSSION: HNC patients with psychological problems make more use of healthcare and informal care and have higher costs. This is not the result of worse clinical outcomes

Prospective longitudinal study on fear of cancer recurrence in patients newly diagnosed with head and neck cancer:Course, trajectories, and associated factors

Background: This study assessed the course of fear of cancer recurrence (FCR) in patients newly diagnosed with head and neck cancer (HNC), identified FCR trajectories and factors associated with FCR trajectories. Methods: Six hundred and seventeen HNC patients from the NET-QUBIC cohort study completed the Cancer Worry Scale-6 at diagnosis, 3 and 6 months post-treatment. FCR trajectories were identified using Latent Class Growth Analysis. Associations were explored between FCR trajectories and baseline demographic and medical variables, coping and self-efficacy. Results: Overall, FCR decreased slightly between baseline and 3 months post-treatment and remained stable up to 6 months. Two FCR trajectories were identified: “high stable” (n = 125) and “low declining” (n = 492). Patients with high stable FCR were younger, reported more negative adjustment, passive coping, and reassuring thoughts, and less avoidance. Conclusions: The majority of HNC patients have low declining FCR after diagnosis, but one in five patients experience persistent high FCR up to 6 months post-treatment

The \u2018COmorBidity in Relation to AIDS\u2019 (COBRA) cohort: Design, methods and participant characteristics

Background Persons living with HIV on combination antiretroviral therapy (cART) may be at increased risk of the development of age-associated non-communicable comorbidities (AANCC) at relatively young age. It has therefore been hypothesised that such individuals, despite effective cART, may be prone to accelerated aging. Objective The COmorBidity in Relation to AIDS (COBRA) cohort study was designed to investigate the potential causal link between HIV and AANCC, amongst others, in a cohort of middle-aged individuals with HIV with sustained viral suppression on cART and otherwise comparable HIV-negative controls. Methods Longitudinal cohort study of HIV-positive subjects 45 years of age, with sustained HIV suppression on cART recruited from two large European HIV treatment centres and similarly-aged HIV-negative controls recruited from sexual health centres and targeted community groups. Both HIV-positive and HIV-negative subjects were assessed at study entry and again at follow-up after 2 years. Results Of the 134 HIV-positive individuals with a median (IQR) age of 56 (51, 62) years recruited, 93% were male, 88% of white ethnicity and 86% were men who have sex with men (MSM). Similarly, the 79 HIV-negative subjects had a median (IQR) age of 57 (52, 64) and 92% were male, 97% of white ethnicity and 80% were MSM. Conclusions The results from the COBRA study will be a significant resource to understand the link between HIV and AANCC and the pathogenic mechanisms underlying this link. COBRA will inform future development of novel prognostic tools for earlier diagnosis of AANCC and of novel interventions which, as an adjunct to cART, may prevent AANCC

Effects and moderators of psychosocial interventions on quality of life, and emotional and social function in patients with cancer : an individual patient data meta-analysis of 21 RCTs

Objective: This individual patient data (IPD) meta‐analysis aimed to evaluate the effects of psychosocial interventions (PSI) on quality of life (QoL), emotional function (EF), and social function (SF) in patients with cancer, and to study moderator effects of demographic, clinical, personal, and intervention‐related characteristics. Methods: Relevant studies were identified via literature searches in 4 databases. We pooled IPD from 22 (n = 4217) of 61 eligible randomized controlled trials. Linear mixed‐effect model analyses were used to study intervention effects on the post‐intervention values of QoL, EF, and SF (z‐scores), adjusting for baseline values, age, and cancer type. We studied moderator effects by testing interactions with the intervention for demographic, clinical, personal, and intervention‐related characteristics, and conducted subsequent stratified analyses for significant moderator variables.Results: PSI significantly improved QoL (β = 0.14,95%CI = 0.06;0.21), EF (β = 0.13,95%CI = 0.05;0.20), and SF (β = 0.10,95%CI = 0.03;0.18). Significant differences in effects of different types of PSI were found, with largest effects of psychotherapy. The effects of coping skills training were moderated by age, treatment type, and targeted interventions. Effects of psychotherapy on EF may be moderated by cancer type, but these analyses were based on 2 randomized controlled trials with small sample sizes of some cancer types. Conclusions: PSI significantly improved QoL, EF, and SF, with small overall effects. However, the effects differed by several demographic, clinical, personal, and intervention‐related characteristics. Our study highlights the beneficial effects of coping skills training in patients treated with chemotherapy, the importance of targeted interventions, and the need of developing interventions tailored to the specific needs of elderly patients

Moderators of the effect of psychosocial interventions on fatigue in women with breast cancer and men with prostate cancer:Individual patient data meta-analyses

Objective Psychosocial interventions can reduce cancer-related fatigue effectively. However, it is still unclear if intervention effects differ across subgroups of patients. These meta-analyses aimed at evaluating moderator effects of (a) sociodemographic characteristics, (b) clinical characteristics, (c) baseline levels of fatigue and other symptoms, and (d) intervention-related characteristics on the effect of psychosocial interventions on cancer-related fatigue in patients with non-metastatic breast and prostate cancer. Methods Data were retrieved from the Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS) consortium. Potential moderators were studied with meta-analyses of pooled individual patient data from 14 randomized controlled trials through linear mixed-effects models with interaction tests. The analyses were conducted separately in patients with breast (n = 1091) and prostate cancer (n = 1008). Results Statistically significant, small overall effects of psychosocial interventions on fatigue were found (breast cancer: beta = -0.19 [95% confidence interval (95%CI) = -0.30; -0.08]; prostate cancer: beta = -0.11 [95%CI = -0.21; -0.00]). In both patient groups, intervention effects did not differ significantly by sociodemographic or clinical characteristics, nor by baseline levels of fatigue or pain. For intervention-related moderators (only tested among women with breast cancer), statistically significant larger effects were found for cognitive behavioral therapy as intervention strategy (beta = -0.27 [95%CI = -0.40; -0.15]), fatigue-specific interventions (beta = -0.48 [95%CI = -0.79; -0.18]), and interventions that only targeted patients with clinically relevant fatigue (beta = -0.85 [95%CI = -1.40; -0.30]). Conclusions Our findings did not provide evidence that any selected demographic or clinical characteristic, or baseline levels of fatigue or pain, moderated effects of psychosocial interventions on fatigue. A specific focus on decreasing fatigue seems beneficial for patients with breast cancer with clinically relevant fatigue

Healthcare Staff Wellbeing, Burnout, and Patient Safety: A Systematic Review

Objective To determine whether there is an association between healthcare professionals’ wellbeing and burnout, with patient safety. Design Systematic research review. Data Sources PsychInfo (1806 to July 2015), Medline (1946 to July 2015), Embase (1947 to July 2015) and Scopus (1823 to July 2015) were searched, along with reference lists of eligible articles. Eligibility Criteria for Selecting Studies Quantitative, empirical studies that included i) either a measure of wellbeing or burnout, and ii) patient safety, in healthcare staff populations. Results Forty-six studies were identified. Sixteen out of the 27 studies that measured wellbeing found a significant correlation between poor wellbeing and worse patient safety, with six additional studies finding an association with some but not all scales used, and one study finding a significant association but in the opposite direction to the majority of studies. Twenty-one out of the 30 studies that measured burnout found a significant association between burnout and patient safety, whilst a further four studies found an association between one or more (but not all) subscales of the burnout measures employed, and patient safety. Conclusions Poor wellbeing and moderate to high levels of burnout are associated, in the majority of studies reviewed, with poor patient safety outcomes such as medical errors, however the lack of prospective studies reduces the ability to determine causality. Further prospective studies, research in primary care, conducted within the UK, and a clearer definition of healthcare staff wellbeing are needed. Implications This review illustrates the need for healthcare organisations to consider improving employees’ mental health as well as creating safer work environments when planning interventions to improve patient safety

3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial

Background: Liraglutide 3·0 mg was shown to reduce bodyweight and improve glucose metabolism after the 56-week period of this trial, one of four trials in the SCALE programme. In the 3-year assessment of the SCALE Obesity and Prediabetes trial we aimed to evaluate the proportion of individuals with prediabetes who were diagnosed with type 2 diabetes. Methods: In this randomised, double-blind, placebo-controlled trial, adults with prediabetes and a body-mass index of at least 30 kg/m2, or at least 27 kg/m2 with comorbidities, were randomised 2:1, using a telephone or web-based system, to once-daily subcutaneous liraglutide 3·0 mg or matched placebo, as an adjunct to a reduced-calorie diet and increased physical activity. Time to diabetes onset by 160 weeks was the primary outcome, evaluated in all randomised treated individuals with at least one post-baseline assessment. The trial was conducted at 191 clinical research sites in 27 countries and is registered with ClinicalTrials.gov, number NCT01272219. Findings: The study ran between June 1, 2011, and March 2, 2015. We randomly assigned 2254 patients to receive liraglutide (n=1505) or placebo (n=749). 1128 (50%) participants completed the study up to week 160, after withdrawal of 714 (47%) participants in the liraglutide group and 412 (55%) participants in the placebo group. By week 160, 26 (2%) of 1472 individuals in the liraglutide group versus 46 (6%) of 738 in the placebo group were diagnosed with diabetes while on treatment. The mean time from randomisation to diagnosis was 99 (SD 47) weeks for the 26 individuals in the liraglutide group versus 87 (47) weeks for the 46 individuals in the placebo group. Taking the different diagnosis frequencies between the treatment groups into account, the time to onset of diabetes over 160 weeks among all randomised individuals was 2·7 times longer with liraglutide than with placebo (95% CI 1·9 to 3·9, p<0·0001), corresponding with a hazard ratio of 0·21 (95% CI 0·13–0·34). Liraglutide induced greater weight loss than placebo at week 160 (–6·1 [SD 7·3] vs −1·9% [6·3]; estimated treatment difference −4·3%, 95% CI −4·9 to −3·7, p<0·0001). Serious adverse events were reported by 227 (15%) of 1501 randomised treated individuals in the liraglutide group versus 96 (13%) of 747 individuals in the placebo group. Interpretation: In this trial, we provide results for 3 years of treatment, with the limitation that withdrawn individuals were not followed up after discontinuation. Liraglutide 3·0 mg might provide health benefits in terms of reduced risk of diabetes in individuals with obesity and prediabetes. Funding: Novo Nordisk, Denmark