Longitudinal and transcultural assessment of the relationship between hallucinogens, well-being, and post-traumatic growth during the COVID-19 pandemic.

The COVID-19 pandemic has had a devastating impact on the health and wellbeing of the global population. This paper presents the results of a longitudinal transcultural study that was begun at the peak of the pandemic (in April, 2020). An online survey was used to collect data from English-, Spanish-, and Portuguese-speaking participants. The survey collected information about sociodemographics, lifestyle activities, COVID-19-related circumstances, and drug use (with an emphasis on hallucinogenic drugs), as well as involving psychometric questionnaires. Users of hallucinogenic drugs had higher psychological well-being and lower scores on psychopathology scales, both at baseline and during follow-ups. This difference was larger when users were distinguished by frequency of use, as regular users scored higher on psychological well-being and lower on psychopathology scales. Subjects with more psychological distress had lower scores for all scales of post-traumatic growth, but if they were regular hallucinogens users, they had higher scores for post-traumatic growth. When comparing the results between cultural contexts, heterogeneous results were obtained. There were more English-speaking regular users of hallucinogenic drugs. Further research should analyse the potential role of hallucinogens in large-scale catastrophes, with a special focus on post-traumatic growth.

Antidepressants or running therapy: Comparing effects on mental and physical health in patients with depression and anxiety disorders.

BACKGROUND: Antidepressant medication and running therapy are both effective treatments for patients with depressive and anxiety disorders. However, they may work through different pathophysiological mechanisms and could differ in their impact on physical health. This study examined effects of antidepressants versus running therapy on both mental and physical health. METHODS: According to a partially randomized patient preference design, 141 patients with depression and/or anxiety disorder were randomized or offered preferred 16-week treatment: antidepressant medication (escitalopram or sertraline) or group-based running therapy ≥2 per week. Baseline (T0) and post-treatment assessment at week 16 (T16) included mental (diagnosis status and symptom severity) and physical health indicators (metabolic and immune indicators, heart rate (variability), weight, lung function, hand grip strength, fitness). RESULTS: Of the 141 participants (mean age 38.2 years; 58.2 % female), 45 participants received antidepressant medication and 96 underwent running therapy. Intention-to-treat analyses showed that remission rates at T16 were comparable (antidepressants: 44.8 %; running: 43.3 %; p = .881). However, the groups differed significantly on various changes in physical health: weight (d = 0.57; p = .001), waist circumference (d = 0.44; p = .011), systolic (d = 0.45; p = .011) and diastolic (d = 0.53; p = .002) blood pressure, heart rate (d = 0.36; p = .033) and heart rate variability (d = 0.48; p = .006). LIMITATIONS: A minority of the participants was willing to be randomized; the running therapy was larger due to greater preference for this intervention. CONCLUSIONS: While the interventions had comparable effects on mental health, running therapy outperformed antidepressants on physical health, due to both larger improvements in the running therapy group as well as larger deterioration in the antidepressant group. TRIAL REGISTRATION: Trialregister.nl Number of identification: NTR3460.

External validation and updating of prediction models for estimating the 1-year risk of low health-related quality of life in colorectal cancer survivors.

OBJECTIVES: Timely identification of colorectal cancer (CRC) survivors at risk of experiencing low health-related quality of life (HRQoL) in the near future is important for enabling appropriately tailored preventive actions. We previously developed and internally validated risk prediction models to estimate the 1-year risk of low HRQoL in long-term CRC survivors. In this article, we aim to externally validate and update these models in a population of short-term CRC survivors. STUDY DESIGN AND SETTING: In a pooled cohort of 1,596 CRC survivors, seven HRQoL domains (global QoL, cognitive/emotional/physical/role/social functioning, and fatigue) were measured prospectively at approximately 5 months postdiagnosis (baseline for prediction) and approximately 1 year later by a validated patient-reported outcome measure (European Organization for Research and Treatment of Cancer Quality of life Questionnaire-Core 30). For each HRQoL domain, 1-year scores were dichotomized into low vs. normal/high HRQoL. Performance of the previously developed multivariable logistic prediction models was evaluated (calibration and discrimination). Models were updated to create a more parsimonious predictor set for all HRQoL domains. RESULTS: Updated models showed good calibration and discrimination (AUC ≥0.75), containing a single set of 15 predictors, including nonmodifiable (age, sex, education, time since diagnosis, chemotherapy, radiotherapy, stoma, and comorbidities) and modifiable predictors (body mass index, physical activity, smoking, anxiety/depression, and baseline fatigue and HRQoL domain scores). CONCLUSION: Externally validated and updated prediction models performed well for estimating the 1-year risk of low HRQoL in CRC survivors within 6 months postdiagnosis. The impact of implementing the models in oncology practice to improve HRQoL outcomes in CRC survivors needs to be evaluated.

Psychosocial and Drug Use Assessment of Regular vs. Non-Regular Ayahuasca Users in a Brazilian Sample: a Web-Based Survey.

Background: Preliminary evidence suggests that long-term ayahuasca use is associated with better psychosocial outcomes and less drug use; however, available data on the association between ayahuasca intake frequency and psychosocial outcomes is limited. Objectives: We sought to characterize and investigate the association of regular ayahuasca use, as compared to non-regular use, on licit (alcohol and tobacco) and illicit (cannabis, psychostimulants, psychedelics, and non-medical opioids) drug use and psychosocial outcomes. Methods: An online-based cross-sectional survey was taken among people who use ayahuasca in Brazil assessing sociodemographic, drug and ayahuasca use, anxiety and depression (HAD-S), intrinsic religiosity (IRI), negative and positive affects (PANAS), satisfaction with life (SWLS), and five quality of life domains (WHOQOL-Brief). Multivariate regressions for each psychosocial outcome and drug use were performed comparing regular to non-regular ayahuasca users while correcting for sociodemographic variables. Results: A total of 286 valid answers were retrieved, divided into people with regular (n = 101) and non-regular (n = 185) ayahuasca use. Groups had similar sociodemographic profiles and lifetime use of drugs. In the multivariate analysis, regular use of ayahuasca was associated with lower anxiety (B: -0.97), negative affect (B: -2.62), general (B: 0.22) and physical (B: 0.17) quality of life, higher intrinsic religiosity scores (B: 4.16), and less past-month licit (OR = 0.30) and illicit (OR = 0.49) use of substances. Conclusions: Our results show that ceremonial regular ayahuasca compared to non-regular use is associated with better psychosocial and mental health outcomes and less drug use. Studies with repeated ayahuasca administration and extended follow-ups are essential to clarify the nature of ayahuasca's therapeutic effects and to guide future clinical research.

Sociodemographic, Clinical, Lifestyle, and Psychological Correlates of Peripheral Neuropathy among 2- to 12-Year Colorectal Cancer Survivors.

BACKGROUND: Peripheral neuropathy (PN) is a debilitating complication among colorectal cancer (CRC) survivors that can become chronic. No large-scale study has yet analyzed correlates in multivariable models. We did multivariable analyses to find correlates of PN. METHODS: In 1,516 all-stage Dutch CRC survivors, cross-sectional data were collected on sensory, motor, autonomic, and total PN, sociodemographic (age, sex, education, employment, partner), clinical (time since diagnosis, tumor location, stage, chemotherapy, radiotherapy, comorbidities), lifestyle (alcohol, smoking, physical activity, body mass index), psychological factors (anxiety, depression, personality), and health-related quality of life (HRQoL). After multiple imputations, correlates were analyzed with linear regressions and eliminated with backward selection. RESULTS: CRC survivors (69 years; 42% female) were on average 5 years post-diagnosis, and 28%-65% reported PN. PN was associated with older age, being male (sensory) or female (motor), shorter time since diagnosis, chemotherapy, comorbidities, anxiety, depression, and worse scores on HRQoL domains, and pain, nausea, vomiting, insomnia, constipation, and financial problems. CONCLUSIONS: In multivariable analyses, PN is affected by receiving chemotherapy, aging, sex, comorbidities, stress-related factors, and HRQoL in CRC survivors. Future PN-related studies can include these factors, and they can be examined in longitudinal studies to gain more knowledge about chronicity and severity of PN.

Longitudinal Associations of Former and Current Alcohol Consumption with Psychosocial Outcomes among Colorectal Cancer Survivors 1-15 Years after Diagnosis.

We aimed to explore positive and negative associations of consuming alcohol with psychosocial outcomes among colorectal cancer (CRC) survivors. We used data of an observational prospective cohort study, consisting of 2625 Dutch CRC survivors enrolled 1-11 years post-diagnosis that were followed-up in 4 yearly surveys. Generalized estimated equation models were used to examine longitudinal associations between alcohol consumption and anxiety, depression, and health-related quality of life (HRQoL), while correcting for sociodemographic, lifestyle and clinical characteristics. Compared to lifetime abstainers, former alcohol consumption was associated with more depressive symptoms, and worse global quality of life and social functioning, while current drinking was associated with less anxiety, depression and better HRQoL. More drinks per week was associated with less nausea/vomiting. Compared to abstainers, moderate (≤7 drinks/week) and heavy alcohol consumption (>7 drinks/week) were associated with less anxiety and depression and better HRQoL, mostly attributable to wine consumption. Whereas current alcohol consumption was longitudinally associated with less anxiety and depression and better HRQoL, former drinking was associated with worse psychosocial outcomes, although based on a small sample size. It is important to consider that besides the potential negative effects of alcohol on patients' health, alcohol consumption may be positively related with psychosocial outcomes.Supplemental data for this article is available online at https://doi.org/10.1080/01635581.2022.2044063.

Associations between alcohol consumption and anxiety, depression, and health-related quality of life in colorectal cancer survivors.

PURPOSE: Alcohol consumption is a major risk factor for colorectal cancer (CRC). It is currently poorly understood, however, how alcohol and different alcoholic beverage types are related to psychosocial outcomes in CRC survivors. METHODS: We used data of N = 910 CRC survivors from the pooled EnCoRe and PROCORE cohorts and harmonized them into five time points: at diagnosis and 3, 6, 12, and 24 months post-diagnosis. Generalized estimated equation models were used to examine longitudinal associations of alcohol consumption, including consumption of beer, wine, and liquor, with anxiety, depression, and health-related quality of life (HRQoL), while correcting for sociodemographic, lifestyle, and clinical factors. RESULTS: Survivors were on average 67 years and 37% was female. In the first 2 years post-diagnosis, survivors who consumed more alcoholic drinks/week reported lower anxiety and depressive symptoms and better HRQoL on all domains and symptom scales. This was the case for moderate and heavy amounts of alcohol and mostly for consuming beer and wine, but not for liquor. Associations were more often significant for men and for younger persons (< 67 years at baseline). CONCLUSIONS: Generally, alcohol consumption was observed to be longitudinally related to less anxiety and depression and better HRQoL in CRC survivors. IMPLICATIONS FOR CANCER SURVIVORS: Although alcohol consumption is generally unfavorable due to increased risk of carcinogenesis and worse prognosis after CRC, it seems to be associated with better psychosocial outcomes in the first 2 years after diagnosis and treatment. More research is needed to gain knowledge about reasons for drinking and causality.

Cross-Sectional Associations Between Lifetime Use of Psychedelic Drugs and Psychometric Measures During the COVID-19 Confinement: A Transcultural Study.

Background: One of the main public health strategies adopted at the beginning of the COVID-19 pandemic consisted of implementing strict lockdowns to stop the transmission of the virus. Despite being an effective measure, the confinement and the associated social isolation create a stressful, potentially lengthy situations that has been proven to have several psychological consequences. Given the potential benefits that certain psychedelic drugs have shown for the treatment of psychological disorders, this study aimed to assess the impact of lifetime psychedelic drug use on mental health in relation to the first strict lockdown adopted by various countries (April-July 2020). Methods: Subjects completed an online survey that inquired about sociodemographic factors, activities, and lifestyle factors during confinement, as well as health and mental health related factors. Subjects were asked about their lifetime use of psychedelic drugs (MDMA, ayahuasca, psilocybin-containing mushrooms, LSD, peyote, San Pedro, Bufo alvarius or 5-MeO-DMT, and others), being classified as regular users (more than once per 6 months), occasional users, or non-users. The survey included psychometric tests used to assess psychological distress, peritraumatic stress, social support, psychopathological symptoms, and personality. Linear regressions were performed with psychedelic drug users as the independent variable and psychometric factors as the outcomes, while correcting for age, gender, language, religion, spirituality, and use of non-psychedelic drugs. Results: The study included 2,974 English, Portuguese, and Spanish speakers (497 regular users of psychedelic drugs, 606 occasional users, and 1,968 non-users). On average, respondents were 36 years old and 70% were female. Psychedelic drug users, especially regular ones, reported less psychological distress, less peritraumatic stress, and more social support. Regarding personality measures, psychedelic drug users scored higher on the novelty-seeking and self-transcendence scales, and lower on cooperativeness. Conclusion: Our findings showed that regular users of psychedelic drugs had less psychological stress and some personality differences when compared to occasional users and non-users. This suggests that either the use of psychedelics might be a protective factor itself or people with certain previous traits are more prone to frequently using psychedelic drugs. Future prospective longitudinal research should investigate the underlying processes observed in this study to develop consistent hypotheses.

Longitudinal associations of sociodemographic, lifestyle, and clinical factors with alcohol consumption in colorectal cancer survivors up to 2 years post-diagnosis.

PURPOSE: Alcohol consumption can lead to worse prognosis and mortality among colorectal cancer (CRC) patients. We investigated alcohol consumption of CRC survivors up to 2 years post-diagnosis, and how sociodemographic, lifestyle, and clinical factors were associated longitudinally with these habits. METHODS: We pooled longitudinal data of 910 CRC survivors from the ongoing PROCORE and EnCoRe studies with data collected at diagnosis (baseline) and 3, 6, 12, and 24 months post-diagnosis. Both studies assessed alcohol consumption, including beer, wine, and liquor. Generalized estimated equation models were used to examine changes over time in alcohol consumption and multivariable longitudinal associations of sociodemographic, lifestyle, and clinical factors with alcohol consumption. RESULTS: At baseline, participants were on average 67 years old, 332 (37%) were female, and alcohol was consumed by 79%. Most survivors (68-71%) drank less at all follow-ups. Beer, wine, and liquor were consumed by 51%, 58%, and 25% at baseline, respectively, and these declined over time. Males consumed more alcohol, and higher education, more physical activity, and not having a (permanent) stoma were associated with consuming more alcohol. CONCLUSION: CRC survivors decreased their alcohol consumption in the 2 years post-diagnosis. Future studies should take the significant factors that were associated with alcohol post-diagnosis consumption into account, when they investigate CRC health outcomes or for identifying subgroups for interventions. Males with higher education, more physical activity, and no stoma should be reminded after diagnosis for reducing their alcohol consumption.

Development and internal validation of prediction models for colorectal cancer survivors to estimate the 1-year risk of low health-related quality of life in multiple domains.

BACKGROUND: Many colorectal cancer (CRC) survivors experience persisting health problems post-treatment that compromise their health-related quality of life (HRQoL). Prediction models are useful tools for identifying survivors at risk of low HRQoL in the future and for taking preventive action. Therefore, we developed prediction models for CRC survivors to estimate the 1-year risk of low HRQoL in multiple domains. METHODS: In 1458 CRC survivors, seven HRQoL domains (EORTC QLQ-C30: global QoL; cognitive, emotional, physical, role, social functioning; fatigue) were measured prospectively at study baseline and 1 year later. For each HRQoL domain, scores at 1-year follow-up were dichotomized into low versus normal/high. Separate multivariable logistic prediction models including biopsychosocial predictors measured at baseline were developed for the seven HRQoL domains, and internally validated using bootstrapping. RESULTS: Average time since diagnosis was 5 years at study baseline. Prediction models included both non-modifiable predictors (age, sex, socio-economic status, time since diagnosis, tumor stage, chemotherapy, radiotherapy, stoma, micturition, chemotherapy-related, stoma-related and gastrointestinal complaints, comorbidities, social inhibition/negative affectivity, and working status) and modifiable predictors (body mass index, physical activity, smoking, meat consumption, anxiety/depression, pain, and baseline fatigue and HRQoL scores). Internally validated models showed good calibration and discrimination (AUCs: 0.83-0.93). CONCLUSIONS: The prediction models performed well for estimating 1-year risk of low HRQoL in seven domains. External validation is needed before models can be applied in practice.

Needs with Regard to Decision Support Systems for Treating Patients with Incurable Non-small Cell Lung Cancer.

Treatment decision-making for patients with incurable non-small cell lung cancer (NSCLC) is complex due to the rapidly increasing number of treatments and discovery of new biomarkers. Decision support systems (DSS) could assist thoracic oncologists (TO) weighing of the pros and cons of treatments in order to arrive at an evidence-based and personalized treatment advice. Our aim is to inventory (1) TO's needs with regard to DSS in the treatment of incurable (stage IIIB/IV) NSCLC patients, and (2) preferences regarding the development of future tools in this field. We disseminated an online inventory questionnaire among all members of the Section of Oncology within the Society of Physicians in Chest Medicine and Tuberculosis. Telephone interviews were conducted to better contextualize the findings from the questionnaire. In total, 58 TO completed the questionnaire and expressed a need for new DSS. They reported that it is important for tools to include genetic and immune markers, to be sufficiently validated, regularly updated, and time-efficient. Also, future DSS should incorporate multiple treatment options, integrate estimates of toxicity, quality of life and cost-effectiveness of treatments, enhance communication between caregivers and patients, and use IT solutions for a clear interface and continuous updating of tools. With this inventory among Dutch TO, we summarized the need for new DSS to aid treatment decision-making for patients with incurable NSCLC. To meet the expressed needs, substantial additional efforts will be required by DSS developers, above already existing tools.

Anxiety and depression mediate the association between chemotherapy-induced peripheral neuropathy and fatigue: Results from the population-based PROFILES registry.

OBJECTIVE: Chemotherapy-induced sensory peripheral neuropathy (CIPN) is common among colorectal cancer (CRC) survivors. The aim of this study was to examine whether CIPN is associated with both psychological distress (ie, anxiety and depression) and fatigue and whether the relationship between CIPN and fatigue can (partly) be explained by psychological distress. METHODS: All CRC survivors diagnosed between 2000 and 2009 as registered by the population-based Netherlands Cancer Registry (Eindhoven region) were eligible for participation. Chemotherapy-treated survivors completed questions on CIPN (EORTC QLQ-CIPN20), psychological distress (HADS), and fatigue (FAS) on average 5.6 years after diagnosis. Simple and multiple mediation analyses were performed to examine anxiety and depression as possible mediators in the association between CIPN and fatigue. RESULTS: Survivors with high (ie, upper 30% of scores) CIPN (n = 172) reported more anxiety and depressive symptoms and more fatigue compared with those with low CIPN (n = 299). Furthermore, among survivors with high CIPN, those who were anxious, depressed, or both reported more fatigue compared with those without psychological distress. These differences were clinically relevant. Finally, mediation analyses showed that while CIPN was directly associated with fatigue, the relationship between CIPN and fatigue was also significantly mediated by both anxiety and depression. CONCLUSIONS: CRC survivors with high CIPN report more fatigue, especially those who are also anxious and/or depressed. More research is needed on the direction of the relationship between CIPN, psychological distress, and fatigue. For now, the treatment of fatigue should also focus on addressing psychological distress, as treating fatigue alone might not be sufficient.

Smoking does not accelerate leucocyte telomere attrition: a meta-analysis of 18 longitudinal cohorts.

Smoking is associated with shorter leucocyte telomere length (LTL), a biomarker of increased morbidity and reduced longevity. This association is widely interpreted as evidence that smoking causes accelerated LTL attrition in adulthood, but the evidence for this is inconsistent. We analysed the association between smoking and LTL dynamics in 18 longitudinal cohorts. The dataset included data from 12 579 adults (4678 current smokers and 7901 non-smokers) over a mean follow-up interval of 8.6 years. Meta-analysis confirmed a cross-sectional difference in LTL between smokers and non-smokers, with mean LTL 84.61 bp shorter in smokers (95% CI: 22.62 to 146.61). However, LTL attrition was only 0.51 bp yr-1 faster in smokers than in non-smokers (95% CI: -2.09 to 1.08), a difference that equates to only 1.32% of the estimated age-related loss of 38.33 bp yr-1. Assuming a linear effect of smoking, 167 years of smoking would be required to generate the observed cross-sectional difference in LTL. Therefore, the difference in LTL between smokers and non-smokers is extremely unlikely to be explained by a linear, causal effect of smoking. Selective adoption, whereby individuals with short telomeres are more likely to start smoking, needs to be considered as a more plausible explanation for the observed pattern of telomere dynamics.

Accelerating research on biological aging and mental health: Current challenges and future directions.

Aging is associated with complex biological changes that can be accelerated, slowed, or even temporarily reversed by biological and non-biological factors. This article focuses on the link between biological aging, psychological stressors, and mental illness. Rather than comprehensively reviewing this rapidly expanding field, we highlight challenges in this area of research and propose potential strategies to accelerate progress in this field. This effort requires the interaction of scientists across disciplines - including biology, psychiatry, psychology, and epidemiology; and across levels of analysis that emphasize different outcome measures - functional capacity, physiological, cellular, and molecular. Dialogues across disciplines and levels of analysis naturally lead to new opportunities for discovery but also to stimulating challenges. Some important challenges consist of 1) establishing the best objective and predictive biological age indicators or combinations of indicators, 2) identifying the basis for inter-individual differences in the rate of biological aging, and 3) examining to what extent interventions can delay, halt or temporarily reverse aging trajectories. Discovering how psychological states influence biological aging, and vice versa, has the potential to create novel and exciting opportunities for healthcare and possibly yield insights into the fundamental mechanisms that drive human aging.

The impact of depression and anxiety treatment on biological aging and metabolic stress: study protocol of the MOod treatment with antidepressants or running (MOTAR) study.

BACKGROUND: Depressive and anxiety disorders have shown to be associated to premature or advanced biological aging and consequently to adversely impact somatic health. Treatments with antidepressant medication or running therapy are both found to be effective for many but not all patients with mood and anxiety disorders. These interventions may, however, work through different pathophysiological mechanisms and could differ in their impact on biological aging and somatic health. This study protocol describes the design of an unique intervention study that examines whether both treatments are similarly effective in reducing or reversing biological aging (primary outcome), psychiatric status, metabolic stress and neurobiological indicators (secondary outcomes). METHODS: The MOod Treatment with Antidepressants or Running (MOTAR) study will recruit a total of 160 patients with a current major depressive and/or anxiety disorder in a mental health care setting. Patients will receive a 16-week treatment with either antidepressant medication or running therapy (3 times/week). Patients will undergo the treatment of their preference and a subsample will be randomized (1:1) to overcome preference bias. An additional no-disease-no-treatment group of 60 healthy controls without lifetime psychopathology, will be included as comparison group for primary and secondary outcomes at baseline. Assessments are done at week 0 for patients and controls, and at week 16 and week 52 for patients only, including written questionnaires, a psychiatric and medical examination, blood, urine and saliva collection and a cycle ergometer test, to gather information about biological aging (telomere length and telomerase activity), mental health (depression and anxiety disorder characteristics), general fitness, metabolic stress-related biomarkers (inflammation, metabolic syndrome, cortisol) and genetic determinants. In addition, neurobiological alterations in brain processes will be assessed using structural and functional Magnetic Resonance Imaging (MRI) in a subsample of at least 25 patients per treatment arm and in all controls. DISCUSSION: This intervention study aims to provide a better understanding of the impact of antidepressant medication and running therapy on biological aging, metabolic stress and neurobiological indicators in patients with depressive and anxiety disorders in order to guide a more personalized medicine treatment. TRIAL REGISTRATION: Trialregister.nl Number of identification: NTR3460, May 2012.

Inventory of oncologists' unmet needs for tools to support decision-making about palliative treatment for metastatic colorectal cancer.

BACKGROUND: Decision-making about palliative care for metastatic colorectal cancer (mCRC) consists of many different treatment-related decisions, and there generally is no best treatment option. Decision support systems (DSS), e.g., prognostic calculators, can aid oncologists' decision-making. DSS that contain features tailored to the needs of oncologists are more likely to be implemented in clinical practice. Therefore, our aim is to inventory colorectal cancer specialists' unmet decision support needs. METHODS: We asked oncologists from the Dutch colorectal cancer group (DCCG), to participate in an online inventory questionnaire on their unmet decision support needs. To get more in-depth insight in required features of the DSS they need, we also conducted semi-structured telephone interviews. RESULTS: Forty-one oncologists started the inventory questionnaire, and 27 of them completed all items. Of all respondents, 18 were surgeons (44%), 22 were medical oncologists (54%), and 28 (68%) had more than 10 years of experience treating mCRC. In both the inventory questionnaire and interviews, respondents expressed a need for an overarching DSS incorporating multiple treatment options, and presenting both the treatment benefits and harms. Respondents found it relevant for other outcomes, such as cost-effectiveness of treatment or quality of life, to be incorporated in DSS. There was also a wish for DSS incorporating an up-to-date "personalized" overview of the ongoing trials for which a specific patient is eligible. CONCLUSIONS: Experienced oncologists indicate that their treatment advice is currently almost solely based on the available clinical guidelines. They experience a lack of good quality DSS to help them personalize their treatment advice. New tools integrating multiple treatment options and providing a broad range of clinically relevant outcomes are urgently needed to stimulate and safeguard more personalized treatment decision-making.

Associations Between Cellular Aging Markers and Metabolic Syndrome: Findings From the CARDIA Study.

Background: Metabolic syndrome (MetS) is thought to promote biological aging, which might lead to cardiovascular and aging-related complications. This large-scale study investigated longitudinal relationships between MetS, its components, and cellular aging markers: leukocyte mitochondrial DNA copy number (mtDNAcn) and telomere length (TL). Methods: We included 989 participants from the Coronary Artery Risk Development in Young Adults Study. MtDNAcn [study year (Y) 15, Y25] and TL (Y15, Y20, Y25) were measured via quantitative polymerase chain reaction. MetS components [waist circumference, triglycerides, high-density lipoprotein (HDL) cholesterol, systolic blood pressure, and fasting glucose] were determined (Y15, Y20, Y25). Generalized estimated equation and linear regression models, adjusting for sociodemographics and lifestyle, were used to examine associations between MetS and cellular aging at all time points, baseline MetS and 10-year changes in cellular aging, baseline cellular aging and 10-year changes in MetS, and 10-year changes in MetS and 10-year changes in cellular aging. Results: MtDNAcn and TL were negatively associated with age [mtDNAcn unstandardized ß (B) = -4.76; P < 0.001; TL B = -51.53; P < 0.001] and positively correlated (r = 0.152; P < 0.001). High triglycerides were associated with low mtDNAcn and low HDL cholesterol with short TL. Greater Y15 waist circumference (B = -7.23; P = 0.05), glucose (B = -13.29; P = 0.001), number of metabolic dysregulations (B = -7.72; P = 0.02), and MetS (B = -28.86; P = 0.006) predicted greater 10-year decrease in mtDNAcn but not TL. The 10-year increase in waist circumference was associated with 10-year telomere attrition (B = -27.61; P = 0.04). Conclusions: Our longitudinal data showed that some metabolic dysregulations were associated with mtDNAcn and TL decreases, possibly contributing to accelerated cellular aging but not the converse.

Clinical Usefulness of Tools to Support Decision-making for Palliative Treatment of Metastatic Colorectal Cancer: A Systematic Review.

BACKGROUND: Decision-making regarding palliative treatment for patients with metastatic colorectal cancer (mCRC) is complex and comprises numerous decisions. Decision-making should be guided by the premise of maintaining and/or improving patients' quality of life, by patient preference, and by the trade-off between treatment benefits and harm. Decision support systems (DSSs) for clinicians (eg, nomograms) can assist in this process. The present systematic review aimed to provide a comprehensive overview of the available DSSs for incurable mCRC and to assess their clinical usefulness. MATERIALS AND METHODS: A systematic literature search was performed in PubMed, Embase, and the Cochrane Library. We extracted information on the DSS characteristics and their discriminatory ability, calibration, and user-friendliness. RESULTS: From 5205 studies, we identified 14 DSSs for decisions regarding palliative resection of the primary tumor (n = 3), radiotherapy for metastases (n = 2), treatment type (invasive vs. symptomatic only; n = 7), and selection of chemotherapy (n = 2). The predictors varied greatly among the DSSs, and only 1 DSS incorporated a genetic marker (ie, UGT1A1). None of the DSSs included > 1 treatment option, nor did any DSS present estimates of treatment benefits and harms. Five tools had not been externally validated, two had only been validated in < 35 patients, and the rest had only been validated in populations similar to the population used for their development. Discriminatory accuracy was generally moderate to poor. Calibration measures were only reported for 2 tools. CONCLUSION: A limited number of DSSs are available to support palliative treatment decisions for patients with mCRC, and the evidence regarding their discriminatory ability and calibration is too limited to recommend their use. New DSSs comparing multiple treatment options and presenting both treatment benefits and harms are needed.

Telomere length is inversely correlated with urinary stress hormone levels in healthy controls but not in un-medicated depressed individuals-preliminary findings.

OBJECTIVE: Leukocyte telomere length (LTL) is a biomarker of cellular aging affected by chronic stress. The relationship of LTL to the stress hormones, cortisol and catecholamines, is unclear, as are possible differences between healthy controls (HC) and individuals with Major Depressive Disorder (MDD). This small pilot study is the first to examine the relationship between cortisol, catecholamines and LTL specifically in un-medicated MDD in comparison with HC. METHODS: Participants included 16 un-medicated MDD subjects and 15 HC for assay of LTL, 12-hour overnight urinary free cortisol and catecholamine levels. RESULTS: LTL, cortisol and catecholamine levels did not significantly differ between groups. In HC, a hierarchical regression analysis indicated that higher levels of cortisol were correlated with shorter LTL (p=0.003) above and beyond age and sex. Higher catecholamine levels were nearly-significant with shorter LTL (p=0.055). Neither hormone was correlated with shorter LTL in MDD (p's>0.28). To assess a possible cumulative effect of stress hormone activation, a summary score was calculated for each subject based on the number of stress hormone levels above the median for that group (HC or MDD). A significant inverse graded relationship was observed between LTL and the number of activated systems in HC (p=0.001), but not in MDD (p=0.96). CONCLUSION: This pilot study provides preliminary evidence that stress hormone levels, especially cortisol, are inversely related to LTL in HC, but not in un-medicated MDD. Clarification of these relationships in larger samples could aid in understanding differential mechanisms underlying stress-related cellular aging in healthy and depressed populations.

The association between three major physiological stress systems and oxidative DNA and lipid damage.

BACKGROUND: Increased activity of the three major physiological stress systems (immune-inflammatory system, hypothalamic-pituitary-adrenal-axis [HPA-axis], and autonomic nervous system [ANS]) is part of the pathophysiology of various somatic and psychiatric diseases. Oxidative damage is a key mechanism in both ageing and disease. Elucidating the relationship between these stress systems and oxidative damage would contribute to the understanding of the role of physiological stress in disease. This study therefore investigates associations between various measures of physiological stress and oxidative DNA (8-hydroxy-2'-deoxyguanosine, 8-OHdG) and lipid (F2-isoprostanes) damage. METHODS: Plasma 8-OHdG and F2-isoprostanes were measured using LC-MS/MS in 2858 subjects (aged 18-65). Plasma inflammation markers, salivary cortisol and ANS markers (three for each stress system) were determined. Linear regression analyses were adjusted for sociodemographics, sampling factors and medication. RESULTS: 8-OHdG was positively associated with all inflammation markers (ß=0.047-0.050, p<0.01), evening cortisol (ß=0.073, p<0.001), and unexpectedly with low respiratory sinus arrhythmia (RSA) reflecting low ANS stress (ß=0.073, p<0.001). F2-isoprostanes were associated with higher C-reactive protein (ß=0.072, p<0.001), high ANS stress reflected in heart rate (ß=0.064, p<0.001) and RSA (ß=-0.076, p=0.001), but not with cortisol. Analyses investigating the cumulative impact of the stress systems demonstrated that the number of systems with ≥1 marker in the high risk quartile showed a positive linear trend with both 8-OHdG (p=0.030) and F2-isoprostanes (p=0.009). CONCLUSION: This large-scale study showed that markers of inflammation, the HPA-axis and ANS are associated with oxidative DNA damage. Oxidative lipid damage is associated with inflammation and the ANS. Increased physiological stress across systems is associated with increasing oxidative damage in a dose-response fashion.