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BackgroundExisting evidence suggests that proinflammatory cytokines play an intermediary role in postchemotherapy cognitive impairment. This is one of the largest multicentered, cohort studies conducted in Singapore to evaluate the prevalence and proinflammatory biomarkers associated with cognitive impairment in breast cancer patients.Patients and methodsChemotherapy-receiving breast cancer patients (stages I-III) were recruited. Proinflammatory plasma cytokines concentrations [interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, granulocyte-macrophage colony-stimulating factor, interferon-γ and tumor necrosis factor-α] were evaluated at 3 time points (before chemotherapy, 6 and 12 weeks after chemotherapy initiation). The FACT-Cog (version 3) was utilized to evaluate patients' self-perceived cognitive disturbances and a computerized neuropsychological assessment (Headminder) was administered to evaluate patients' memory, attention, response speed and processing speed. Changes of cognition throughout chemotherapy treatment were compared against the baseline. Linear mixed-effects models were applied to test the relationships of clinical variables and cytokine concentrations on self-perceived cognitive disturbances and each objective cognitive domain.ResultsNinety-nine patients were included (age 50.5 ± 8.4 years; 81.8% Chinese; mean duration of education = 10.8 ± 3.3 years). Higher plasma IL-1β was associated with poorer response speed performance (estimate: -0.78; 95% confidence interval (CI) -1.34 to -0.03; P = 0.023), and a higher concentration of IL-4 was associated with better response speed performance (P = 0.022). Higher concentrations of IL-1β and IL-6 were associated with more severe self-perceived cognitive disturbances (P = 0.018 and 0.001, respectively). Patients with higher concentrations of IL-4 also reported less severe cognitive disturbances (P = 0.022).ConclusionsWhile elevated concentrations of IL-6 and IL-1β were observed in patients with poorer response speed performance and perceived cognitive disturbances, IL-4 may be protective against chemotherapy-associated cognitive impairment. This study is important because cytokines would potentially be mechanistic mediators of chemotherapy-associated cognitive changes.

Angie Ho Yan Lam,1 Yee Tak Derek Cheung,1 Kwan Ho Wong,2 Sau Fong Leung,3 Wai Tong Chien4 1School of Nursing, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region; 2Department of Psychiatry, The Chinese University of Hong Kong, Hong Kong Special Administrative Region; 3School of Nursing, The Hong Kong Polytechnic University, Hong Kong Special Administrative Region; 4The Nethersole School of Nursing, The Chinese University of Hong Kong, Hong Kong Special Administrative RegionCorrespondence: Angie Ho Yan LamSchool of Nursing, LKS Faculty of Medicine, The University of Hong Kong, 4/F, William M.W. Mong Block, 21 Sassoon Road, Pokfulam, Hong Kong Special Administrative RegionEmail angielam@hku.hkIntroduction: Studies have shown that rumination plays a significant mediating role between dispositional mindfulness (DM) and psychopathological symptoms in both clinical and non-clinical populations. However, no studies have examined this pathway in people with schizophrenia spectrum disorders (SSDs).Methods: A cross-sectional, clinician-administered survey was conducted among people with SSDs (n = 52) in a community setting. Participants completed the Chinese versions of the Depression Anxiety Stress Scale, Five Facet Mindfulness Questionnaire-Short Form, Psychotic Symptom Rating Scale and Scale for the Assessment of Negative Symptoms. Structural equation modelling was performed to examine the pathways of mindfulness facets, rumination, negative emotions and psychotic symptoms.Results: Two facets of mindfulness (nonjudging and acting with awareness) reduced rumination and negative emotional status. Rumination fully mediated the relationship between nonjudging and negative emotions and partially mediated the relationship between acting with awareness and negative emotions. Furthermore, rumination and negative emotions sequentially mediated the relationship between acting with awareness and hallucination (B = − 0.44, 95% confidence interval [CI] = − 0.338 to − 0.045, p = 0.01) and between nonjudging and hallucination (B = − 0.356, 95% CI = − 0.255 to − 0.008, p = 0.034). The model fit the data well (χ2(2) = 1.318, p = 0.517, Tucker–Lewis index = 1.075, comparative fit index = 1, standardised root mean residual = 0.0251, root mean square error of approximation = 0.0001).Conclusion: Rumination and negative emotions serially mediated the relationship between DM and hallucination. The findings support the contribution of changes across transdiagnostic mediators underlying the therapeutic effects of mindfulness training. Further research examining the transdiagnostic processes of DM in influencing clinical outcomes in SSDs is warranted.Keywords: schizophrenia spectrum disorders, psychosis, negative emotions, depression, anxiety, stress, rumination, psychotic symptoms, mindfulness

Background: Till date, no studies have investigated the effects of cardiovascular health on the cardioprotective benefits of fish oil supplementation in people with type 2 diabetes (T2D). The utility of fish oil in reducing the risk of cardiovascular disease (CVD) mortality in people with diabetes remains unclear and inconsistent., Objective: To investigate the potential modifying effect of cardiovascular health (CVH) level, as assessed using the Life's Essential 8 (LE8) score, on the association between regular fish oil supplement use and CVD mortality in middle-aged and older people with T2D., Methods: Participants with T2D in the UK Biobank were included. CVH level was categorized by the mean LE8 score (55 points). Multivariable-adjusted Cox models were used to evaluate the longitudinal association between regular use of fish oil supplements and CVD mortality. We performed stratified analysis across different CVH levels, and tested for potential interaction between fish oil supplement use and CVH level., Results: The analysis included 19,003 participants (mean age 59.9±6.9 years, 36.1% women), of whom 39.6% were regular users of fish oil supplements. During a median follow-up of 13.7 years, regular use of fish oil supplements was significantly associated with a lower risk of CVD mortality among participants with better CVH (i.e., LE8 score ≥55 points; hazard ratio [HR]=0.65, 95% confidence interval [CI] 0.51-0.84, P = 0.001), but not among those with poorer CVH (i.e., LE8 score <55 points; HR=1.02, 95% CI 0.83-1.25, P=0.867). The interaction between the use of fish oil supplements and CVH level on CVD mortality was significant (P=0.018)., Conclusions: Middle-aged and older T2D individuals with a relatively low baseline CVH level may not obtain cardiovascular benefits from fish oil supplements. Our findings highlight the importance of promoting multimodal lifestyle interventions to improve survival outcomes of people with T2D., Competing Interests: Declaration of Competing Interest ☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background: The effect of supplements on mortality risk in patients with cancer remains uncertain and has scarcely been investigated in subgroups of patients with varying characteristics. This study aimed to investigate the association between two popular supplements, fish oil and glucosamine, and mortality risk in a large population-based cohort and determine whether cardiovascular health and clinical prognosis influence these associations., Methods: This prospective cohort study analyzed the data of UK Biobank participants who were diagnosed with cancer. The associations of fish oil and glucosamine consumption with mortality were analyzed using Cox proportional hazards models. Subgroup analyses were performed to assess the effects of Life Essential 8 [LE8] scores (a measure of cardiovascular health) and cancer prognosis (grouped according to the survival rates of specific cancer types) on the associations between supplement use and mortality., Results: This analysis included 14,920 participants (mean age = 59.9 years; 60.2% female). One third (34.1%) of the participants reported using fish oil, and one fifth (20.5%) reported using glucosamine. Over a median follow-up of 12.0 years, 2,708 all-cause deaths were registered. The use of fish oil was associated with reduced risks of all-cause mortality (adjusted hazard ratio [aHR] = 0.89, 95% Confidence Interval [CI] = 0.81-0.97) and cancer mortality (aHR = 0.89, 95% CI = 0.81-0.98). Similarly, glucosamine use was associated with reduced risks of all-cause mortality (aHR = 0.83, 95% CI = 0.74-0.92) and cancer mortality (aHR = 0.83, 95% CI = 0.74-0.93) in the fully adjusted model. Subgroup analyses revealed that the protective effects of fish oil and glucosamine against mortality risk were only observed in patients with LE8 scores lower than the mean score or a poor cancer prognosis. Additionally, the association between glucosamine use and a reduced risk of CVD-related mortality was only observed in patients with lower LE8 scores., Conclusions: This large cohort study identified the potential differential impact of LE8 scores and cancer prognosis on the associations of fish oil and glucosamine supplementation with survival in patients with cancer. This suggests the importance of considering these factors in future research on supplements and in the provision of personalized integrative cancer care., (© 2024. The Author(s).)

Importance: Childhood cancer survivorship programs and long-term follow-up (LTFU) practices are inadequate in most regions of China., Objective: To understand the clinician and caregiver perceptions of LTFU care and to identify barriers to adherence to LTFU care in mainland China., Design, Setting, and Participants: This survey study had a 2-phase sequential mixed-methods approach, consisting of a cross-sectional survey followed by semistructured interviews. Participants included oncology clinicians recruited through an educational seminar on LTFU and caregivers recruited through convenience sampling. Data were collected from November 2022 to September 2023., Main Outcomes and Measures: The clinician survey and interview focused on the standards and resources for LTFU care at their practicing institution and barriers to the coordination of LTFU care. For caregivers, the survey and interview focused on their awareness of and participation in LTFU care and their opinions on future LTFU care visits., Results: A total of 101 clinicians (28 [27.7%] male; 73 [72.3%] female; 46 [45.6%] aged >40 to 50 years) completed the survey (response rate: 90.2%) representing 32 institutions from 22 provinces. As for the caregivers' survey, 164 eligible participants (36 [22.0%] male; 128 [78.0%] female) were recruited (response rate: 20.2%). The majority of the caregivers had received a high school or greater education (96 [56.7%]) and were parents of CCSs diagnosed with leukemia (67 [40.9%]), lymphoma or solid tumors (47 [28.7%]), or conditions requiring hematopoietic stem cell transplantation (50 [30.5%]). Most clinicians (74 [73.3%]) reported providing late effects care, yet only 10 (13.5%) had a dedicated follow-up clinic for CCSs. Two-thirds (64 [63.4%]) reported that the LTFU plan for each survivor is solely determined by their clinical judgment. In structured interviews, all doctors admitted to deviating from published guidelines due to challenges in implementing screening recommendations in their settings. Barriers to providing LTFU services included patient-related factors (76 [75.2%]), survivor knowledge deficits (61 [60.4%]), and the absence of dedicated LTFU clinics (61 [60.4%]). Among caregivers responding to the survey, 60 (36.6%) had never heard of late effects. Overall, 22 of 26 caregivers (84.6%) who participated in the interviews were not aware of potential late effects, although 17 (68.0%) could articulate existing conditions and symptoms that their children were experiencing., Conclusions: In this mixed-methods study involving clinicians and caregivers, substantial disparities in the uniformity and accessibility of LTFU in China were observed, suggesting the imperative need for a standardized approach to LTFU care for survivors. This includes advocating for establishment of dedicated clinics, alongside an emphasis on enhanced education and training for both clinicians and caregivers.

Objective: Although the relative survival rate of childhood cancer has increased substantially in recent years, the pursuit of successful outcomes is often accompanied by negative impacts on pediatric and adolescent cancer survivors and their parents' physical and psychological well-being. However, little is known about their experiences during the period of cancer survivorship. This study aimed to gain an understanding of the experience of cancer survivorship among pediatric and adolescent cancer survivors and their parents., Methods: This study utilized a descriptive qualitative study employing the photovoice design. From September 2022 to March 2023, 17 pediatric and adolescent cancer survivors (9-18 years), who had completed active treatment at least 6 months before recruitment, participated in this study. A total of 217 photographs submitted by survivors and their parents and the interview data, were thematically analyzed to identify themes and subthemes., Results: The analysis revealed five prominent themes: indelible marks, struggling with late effects, striving to return to normalcy, the strength of support, and living in the moment and hope for the future., Conclusion: The findings shed light on the experiences of pediatric and adolescent cancer survivors and their parents throughout the cancer journey, elucidating the influence on both negative and positive aspects. Additionally, the study highlighted that photovoice facilitated self-reflection, the discovery of values, and the recognition of strengths and can be a therapeutic strategy for pediatric and adolescent cancer survivors and their parents in further research., (© 2024 The Author(s). Psycho‐Oncology published by John Wiley & Sons Ltd.)

Objectives: Childhood cancer survivors may experience complex health issues during transition and long-term follow-up (LTFU); therefore, high-quality healthcare is warranted. Care coordination is one of the essential concepts in advanced healthcare. Care coordination models vary among childhood cancer survivors in transition and LTFU. This study aimed to identify care coordination models for childhood cancer survivors in transition and LTFU and synthesise essential components of the models., Design: This scoping review was guided by the methodological framework from Arksey and O'Malley and was reported with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. A systematic literature search was conducted on six databases using possible combinations of terms relevant to childhood cancer survivors, transition/LTFU and care coordination model. Data were analysed by descriptive and content analysis., Data Sources: The literature search was first conducted in May 2023 and updated in May 2024. Six databases including Medline, PubMed, Embase, Web of Science, CINAHL and Cochrane Library were searched; meanwhile, a hand search was also conducted., Eligibility Criteria for Selecting Studies: Studies relevant to describing any models, interventions or strategies about care coordination of transition or LTFU healthcare services among childhood cancer survivors were included., Data Extraction and Synthesis: Two reviewers independently screened and included studies. Basic information as well as care coordination model-related data in the included studies were extracted. Descriptive summary and content analysis were used for data analysis., Results: In the 20 545 citations generated by the search strategy, seven studies were identified. The critical determinants of the models in the included studies were the collaboration of the multidisciplinary team, integration of the navigator role and the provision of patient-centred, family-involved, needs-oriented clinical services. The main functions of the models included risk screening and management, primary care-based services, psychosocial support, health education and counselling, and financial assistance. Models of care coordination were evaluated at patient and clinical levels. Based on this review, core concepts of successful care coordination models for childhood cancer survivors in transition or LTFU were synthesised and proposed as the '3 I' framework: individualisation, interaction and integration., Conclusion: This scoping review summarised core elements of care coordination models for childhood cancer survivors' transition and LTFU. A proposed conceptual framework to support and guide the development of care coordination strategies for childhood cancer survivors' transition and LTFU care was developed. Future research is needed to test the proposed model and develop appropriate care coordination strategies for providing high-quality healthcare for childhood cancer survivors' transition and LTFU., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Mucositis is a common and highly impactful side effect of conventional and emerging cancer therapy and thus the subject of intense investigation. Although common practice, mucositis assessment is heterogeneously adopted and poorly guided, impacting evidence synthesis and translation. The Multinational Association of Supportive Care in Cancer (MASCC) Mucositis Study Group (MSG) therefore aimed to establish expert recommendations for how existing mucositis assessment tools should be used, in clinical care and trials contexts, to improve the consistency of mucositis assessment., Methods: This study was conducted over two stages (January 2022-July 2023). The first phase involved a survey to MASCC-MSG members (January 2022-May 2022), capturing current practices, challenges and preferences. These then informed the second phase, in which a set of initial recommendations were prepared and refined using the Delphi method (February 2023-May 2023). Consensus was defined as agreement on a parameter by >80% of respondents., Findings: Seventy-two MASCC-MSG members completed the first phase of the study (37 females, 34 males, mainly oral care specialists). High variability was noted in the use of mucositis assessment tools, with a high reliance on clinician assessment compared to patient reported outcome measures (PROMs, 47% vs 3%, 37% used a combination). The World Health Organization (WHO) and Common Terminology Criteria for Adverse Events (CTCAE) scales were most commonly used to assess mucositis across multiple settings. Initial recommendations were reviewed by experienced MSG members and following two rounds of Delphi survey consensus was achieved in 91 of 100 recommendations. For example, in patients receiving chemotherapy, the recommended tool for clinician assessment in clinical practice is WHO for oral mucositis (89.5% consensus), and WHO or CTCAE for gastrointestinal mucositis (85.7% consensus). The recommended PROM in clinical trials is OMD/WQ for oral mucositis (93.3% consensus), and PRO-CTCAE for gastrointestinal mucositis (83.3% consensus)., Interpretation: These new recommendations provide much needed guidance on mucositis assessment and may be applied in both clinical practice and research to streamline comparison and synthesis of global data sets, thus accelerating translation of new knowledge into clinical practice., Funding: No funding was received., Competing Interests: The authors report no potential conflicts of interests to declare., (© 2024 Published by Elsevier Ltd.)

Purpose: Implementation of patient-reported outcomes (PROs) collection is an important priority in cancer care. We examined perceived barriers toward implementing PRO collection between centers with and without PRO infrastructure and administrators and nonadministrators., Patients and Methods: We performed a multinational survey of oncology practitioners on their perceived barriers to PRO implementations. Multivariable regression models evaluated for differences in perceived barriers to PRO implementation between groups, adjusted for demographic and institutional variables., Results: Among 358 oncology practitioners representing six geographic regions, 31% worked at centers that did not have PRO infrastructure and 26% self-reported as administrators. Administrators were more likely to perceive concerns with liability issues (aOR, 2.00 [95% CI, 1.12 to 3.57]; P = .02) while having nonsignificant trend toward less likely perceiving concerns with disruption of workflow (aOR, 0.58 [95% CI, 0.32 to 1.03]; P = .06) and nonadherence of PRO reporting (aOR, 0.53 [95% CI, 0.26 to 1.08]; P = .08) as barriers. Respondents from centers without PRO infrastructure were more likely to perceive that not having access to a local PRO expert (aOR, 6.59 [95% CI, 3.81 to 11.42]; P < .001), being unsure how to apply PROs in clinical decisions (aOR, 4.20 [95% CI, 2.32 to 7.63]; P < .001), and being unsure about selecting PRO measures (aOR, 3.36 [95% CI, 2.00 to 5.66]; P < .001) as barriers. Heat map analyses identified the largest differences between participants from centers with and without PRO infrastructure in agreed-upon barriers were (1) not having a local PRO expert, (2) being unsure about selecting PRO measures, and (3) not recognizing the role of PROs at the institutional level., Conclusion: Perceived barriers toward PRO implementation differ between administrators and nonadministrators and practitioners at centers with and without PRO infrastructure. PRO implementation teams should consider as part of a comprehensive strategy including frontline clinicians and administrators and members with PRO experience within teams.

Asthma is a common chronic disease amongst children. Epidemiological studies showed that the mortality rate of asthma in children is still high worldwide. Asthma control is therefore essential to minimize asthma exacerbations, which can be fatal if the condition is poorly controlled. Frequent monitoring could help to detect asthma progression and ensure treatment effectiveness. Although subjective asthma monitoring tools are available, the results vary as they rely on patients' self-perception. Emerging evidence suggests several objective tools could have the potential for monitoring purposes. However, there is no consensus to standardise the use of objective monitoring tools. In this review, we start with the prevalence and severity of childhood asthma worldwide. Then, we detail the latest available objective monitoring tools, focusing on their effectiveness in paediatric asthma management. Publications of spirometry, fractional exhaled nitric oxide (FeNO), hyperresponsiveness tests and electronic monitoring devices (EMDs) between 2016 and 2023 were included. The potential advantages and limitations of each tool were also discussed. Overall, this review provides a summary for researchers dedicated to further improving objective paediatric asthma monitoring and provides insights for clinicians to incorporate different objective monitoring tools in clinical practices., (© 2024. The Author(s).)

Aims: To examine the patterns of use of potentially interacting supplement-drug pairs in adults with type 2 diabetes (T2D) in real-world settings, and to explore the impact of potentially interacting supplement-drug pairs on downstream outcomes., Methods: Potentially interacting supplement-drug pairs were identified from four tertiary databases. We categorized the potential pharmacodynamic interactions into different clinical types according to their related outcomes and explored their associations with incident outcomes using Cox models., Results: 26,394 participants with T2D in the UK Biobank were included. Half (48.5 %) were supplement users, of whom 85.0 % were taking potentially interacting supplement-drug pairs. The potential pharmacodynamic interactions were related to various clinical outcomes, including reducing the effects of glucose-lowering drugs (50.7 %), hypotension (49.8 %), bleeding (50.4 %) and hepatotoxicity (34.8 %). Exploratory analyses found that the use of potentially interacting supplement-drug pairs was associated with incident hepatic diseases (hazard ratio = 1.26, 95 % confidence interval 1.10-1.44, P < 0.001)., Conclusions: Real-world data suggests that most adults with T2D who concurrently used supplements and drugs were on potentially interacting supplement-drug combinations, with the potential of causing adverse outcomes such as incident hepatic diseases. Clinicians should communicate with patients and assess the potential risk of supplement-drug interactions in clinical settings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aspidosperma and uleine alkaloids belong to the large family of monoterpene indole alkaloids with diverse biological activities and thus have attracted extensive synthetic interest. Reported is the development of a new synthetic strategy that allows direct C3-C2' linkage of indoles with functionalized 2-hydroxypiperidines to construct the core common to all aspidoserma and uleine alkaloids. Such indole-piperidine linkage is enabled by coupling aza-Achmatowicz rearrangement (AAR) with indoles via an intermolecular aza-Friedel-Crafts (iAFC) reaction. This AAR-iAFC reaction proceeds under mild acidic conditions with wide tolerance of functional groups (33 examples). The synthetic application of the AAR-iAFC method was demonstrated with collective total syntheses of 3 uleine-type and 6 aspidosperma alkaloids: (+)-3- epi-N -nor-dasycarpidone, (+)-3- epi -dasycarpidone, (+)-3- epi -uleine, 1,2-didehydropseudoaspidospermidine, 1,2-dehydroaspidospermidine, vincadifformine, winchinine B, aspidospermidine, and N -acetylaspidospermidine. We expect that this AAR-iAFC strategy is applicable to other monoterpene indole alkaloids with the C3-C2' linkage of indoles and piperidines., Competing Interests: The authors declare no competing interests., (This journal is © The Royal Society of Chemistry.)

Most available data evaluating childhood cancer survivorship care focus on the experiences of high-income Western countries, whereas data from Asian countries are limited. To address this knowledge deficit, we aimed to characterize survivorship care models and barriers to participation in long-term follow-up (LTFU) care among childhood cancer survivors (CCSs) and health care providers in Asian countries. Twenty-four studies were identified. Most institutions in China and Turkey adopt the oncology specialist care model, whereas in Japan, India, Singapore, and South Korea, after completion of therapy LTFU programs are available in some institutions. In terms of survivor barriers, findings highlight the need for comprehensive age-appropriate education and support and personalized approaches in addressing individual preferences and challenges during survivorship. Health care professionals need education about potential late effects of cancer treatment, recommended guidance for health surveillance and follow-up care, and their role in facilitating the transition from pediatric to adult-focused care. To optimize the delivery of cancer survivorship care, efforts are needed to increase patient and family awareness about the purpose and potential benefits of LTFU care, improve provider education and training, and promote policy change to ensure that CCSs have access to essential services and resources to optimize quality of survival.

Introduction: Anxiety, nausea and vomiting are common side effects suffered by paediatric patients receiving chemotherapy. Emerging evidence supports the efficacy of immersive virtual reality (IVR) on improving anxiety and distress symptoms including nausea and vomiting in this vulnerable group. This trial aims to evaluate the effects of IVR intervention on anxiety, chemotherapy-induced nausea and vomiting and anticipatory nausea and vomiting in patients with paediatric cancer receiving first chemotherapy., Method and Analysis: An assessor-blinded, randomised controlled trial with a mixed methods evaluation approach. On the basis of our pilot results, 128 chemotherapy-naive patients with paediatric cancer scheduled to receive their first intravenous chemotherapy will be recruited from a public hospital and randomly allocated to intervention (n=64) or control groups (n=64). The intervention group will receive the IVR intervention for three sessions: 2 hours before the first chemotherapy, 5 min before and during their first chemotherapy and 5 min before and during their second chemotherapy, respectively. The control group will receive standard care only. A subsample of 30 participants in the intervention group will be invited for a qualitative interview. Study instruments are: (1) short form of the Chinese version of the State Anxiety Scale for Children, (2) visual analogue scale for anticipatory nausea and vomiting, (3) Chinese version of the Multinational Association of Supportive Care in Cancer Antiemesis Tool and (4) individual face-to-face semistructured interviews to explore intervention participants' perceptions of the IVR intervention., Ethics and Dissemination: This study has been approved by the Hong Kong Children's Hospital Research Ethics Committee (HKCH-REC-2021-009). The findings will be disseminated in peer-reviewed journals and through local or interventional conference presentations., Trial Registration Number: ChiCTR2100048732., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To evaluate the association between healthy lifestyle behaviours and the incidence of irritable bowel syndrome (IBS)., Design: Population-based prospective cohort study., Setting: The UK Biobank., Participants: 64 268 adults aged 37 to 73 years who had no IBS diagnosis at baseline were enrolled between 2006 and 2010 and followed up to 2022., Main Exposure: The five healthy lifestyle behaviours studied were never smoking, optimal sleep, high level of vigorous physical activity, high dietary quality and moderate alcohol intake., Main Outcome Measure: The incidence of IBS., Results: During a mean follow-up of 12.6 years, 961 (1.5%) incident IBS cases were recorded. Among the 64 268 participants (mean age 55.9 years, 35 342 (55.0%) female, 7604 (11.8%) reported none of the five healthy lifestyle behaviours, 20 662 (32.1%) reported 1 behaviour, 21 901 (34.1%) reported 2 behaviours and 14 101 (21.9%) reported 3 to 5 behaviours at baseline. The multivariable adjusted hazard ratios associated with having 1, 2 and 3 to 5 behaviours for IBS incidence were 0.79 (95% confidence intervals 0.65 to 0.96), 0.64 (0.53 to 0.78) and 0.58 (0.46 to 0.72), respectively (P for trend <0.001). Never smoking (0.86, 0.76 to 0.98, P=0.02), high level of vigorous physical activity (0.83, 0.73 to 0.95, P=0.006) and optimal sleep (0.73, 0.60 to 0.88, P=0.001) demonstrated significant independent inverse associations with IBS incidence. No significant interactions were observed between these associations and age, sex, employment status, geographic location, gastrointestinal infection, endometriosis, family history of IBS or lifestyle behaviours., Conclusions: Adhering to a higher number of healthy lifestyle behaviours is significantly associated with a lower incidence of IBS in the general population. Our findings suggest the potential of lifestyle modifications as a primary prevention strategy for IBS., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

This short report evaluated the accuracy and quality of information provided by ChatGPT regarding the use of complementary and integrative medicine for cancer. Using the QUality Evaluation Scoring Tool, a panel of 12 reviewers assessed ChatGPT's responses to 8 questions. The study found that ChatGPT provided moderate-quality responses that were relatively unbiased and not misleading. However, the chatbot's inability to reference specific scientific studies was a significant limitation. Patients with cancer should not rely on ChatGPT for clinical advice until further systematic validation. Future studies should examine how patients perceive ChatGPT's information and its impact on communication with health care professionals.

Purpose: Patients with cancer may be prescribed psychotropic medications to address their psychiatric symptoms and disorders. This study examined the patterns and factors associated with the prescription of psychotropics after cancer diagnosis using a population-based database in Hong Kong., Methods: Patients who were diagnosed with malignant cancer and had no documented psychiatric diagnosis or psychotropic medications prior to cancer diagnosis, were included. Multivariable log-binomial models were used to explore the associations between predictive factors and psychotropic medications use., Results: Among 9337 patients, 1868 patients (20.0%) were newly prescribed with psychotropic medications after cancer diagnoses, most commonly hypnotics (50.3%) and antidepressants (32.8%). About one-third (31.4%) were prescribed chronic psychotropics (≥90 days). Approximately 48.3% of patients who were prescribed psychotropic medications received their prescriptions within 1 year after diagnosed with cancer. Only 18.6% of those prescribed psychotropic medications had a registered psychiatric diagnosis. Patients with multiple comorbidities (adjusted risk ratio[aRR] = 2.74; CI = 2.46-3.05) and diagnosed with oral (aRR = 1.89; CI = 1.52-2.35) or respiratory cancers (aRR = 1.62; CI = 1.36-1.93) were more likely to be prescribed psychotropics., Conclusions: The use of psychotropic medication is common (20%) among patients with cancer. Our findings highlight the importance of identification and documentation of psychiatric needs among patients with cancer., (© 2024 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Background & Aims: The concurrent use of herbal and dietary supplements and conventional drugs can lead to interactions in patients with cancer, of which hepatotoxicity is one of the most concerning sequelae. This study examined the potential supplement-drug interactions involving the hepatic system, and their associations with documented liver diseases, among patients with cancer in a large population-based cohort in the UK Biobank., Methods: Participants diagnosed with cancer and had completed supplement-use assessment after diagnosis were included. Potentially interacting supplement-drug combinations that involved CYP enzymes or increased the risk of hepatotoxicity were identified from four tertiary databases. Liver diseases were identified using ICD-codes K70-77. Log-binomial regression was used to investigate the associations between potentially-interacting supplement-drug combinations and liver diseases documented (1) at any time, and (2) confined to only after the time of supplement-use assessment, adjusting for age, sex and pre-existing comorbidities., Results: This analysis included 30,239 participants (mean age = 60.0 years; 61.9% female). Over half (n = 17,698, 58.5%) reported the use of supplements after cancer diagnoses. Among supplements users, 36.9% (n = 6537/17,698) were on supplement-drug combinations with interacting potential involving the hepatic system. Patients taking supplements and drugs who had hepatic comorbidities were more likely to take potentially interacting pairs (adjusted risk ratio = 1.14, 95% CI = 1.06-1.23, p < 0.001). However, no significant association was observed between the use of these combinations and subsequent liver diseases (all p > 0.05)., Conclusion: Approximately one-third of the participants who had cancer and were supplement users had a risk of potential supplement-drug interactions that contribute to adverse liver effect. Healthcare professionals should communicate with patients with cancer, especially those with pre-existing liver diseases, about supplement use and proactively assess the clinical significance of potential interactions., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare that are relevant to the content of this article., (Copyright © 2023 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

The optimization of outcomes for pediatric cancer patients relies on the successful advancement of supportive care to ease the treatment burden and mitigate the long-term impacts of cancer therapy. Advancing pediatric supportive care requires research prioritization as well as the development and implementation of innovations. Like the prevailing theme throughout pediatric oncology, there is a clear need for personalized or precision approaches that are consistent, evidence-based, and guided by clinical practice guidelines. By incorporating technology and datasets, we can address questions which may not be feasible to explore in clinical trials. Now is the time to listen to patients' voices by using patient-reported outcomes (PROs) to ensure that their contributions and experiences inform clinical care plans. Furthermore, while the extrapolation of knowledge and approaches from adult populations may suffice in the absence of pediatric-specific evidence, there is a critical need to specifically understand and implement elements of general and developmental pediatrics like growth, nutrition, development, and physical activity into care. Increased research funding for pediatric supportive care is critical to address resource availability, equity, and disparities across the globe. Our patients deserve to enjoy healthy, productive lives with optimized and enriched supportive care that spans the spectrum from diagnosis to survivorship.

An intramolecular aza-Prins cyclization of aza-Achmatowicz rearrangement products was developed in which bismuth tribromide (BiBr 3 ) plays a dual role as an efficient Lewis acid and source of the bromide nucleophile. This approach enables the facile construction of highly functionalized 9-azabicyclo[3.3.1]nonanes (9-ABNs), which are valuable synthetic building blocks and a powerful platform for the synthesis of a variety of alkaloid natural products and drug molecules. Suitable substrates for the aza-Prins cyclization include 1,1-disubstituted alkenes, 1,2-disubstituted alkenes, alkynes, and allenes, with good to excellent yields observed. Finally, we showcase the application of this new approach to the enantioselective total synthesis of six indole alkaloids: (-)-suaveoline (1), (-)-norsuaveoline (2), (-)-macrophylline (3), (+)-normacusine B (4), (+)-N a -methyl-16-epipericyclivine (5) and (+)-affinisine (6) in a total of 9-14 steps. This study significantly expands the synthetic utility of the aza-Achmatowicz rearrangement, and the strategy (aza-Achmatowicz/aza-Prins) is expected to be applicable to the total synthesis of other members of the big family of macroline and sarpagine indole alkaloids., (© 2023 Wiley-VCH GmbH.)

Purpose: Adolescent and young adult (AYA) patients with cancer often experience unique physical and psychosocial complications. They may turn to traditional, complementary and integrative medicines (TCIM) to address these concerns. To examine the pattern of TCIM use among AYA patients with cancer and explored their preferences regarding TCIM education., Methods: Between August 2021 and December 2022, 246 patients diagnosed with cancer between 15 and 39 years old were recruited from hospitals in Hong Kong. They completed a structured questionnaire on TCIM use, symptom burden, psychological status and preference on education content. Multivariable logistic regression was used to identify predictors of TCIM use, adjusting for age and sex., Results: Overall, 60.2% reported TCIM use, most commonly vitamins (24.0%) and Chinese herbal medicine (22.0%). The most common reasons for using TCIM were to improve general health (70.9%) and manage chronic symptoms (33.1%). Among patients on active treatment, TCIM users tend to report higher anxiety symptoms (aOR = 1.13, 95% CI = 1.02-1.27). TCIM users who were post-treatment were more likely to have chronic comorbidities (aOR = 3.54, 95% CI = 1.29-11.5). AYA patients indicated that they would like TCIM information to address specific needs, particularly fatigue (53.7%) and psychological problems (54.1%)., Conclusions: The use of TCIM is common among AYA patients with cancer, especially among patients with high symptom burdens. A tailored education programme should be provided based on patients' preferences and needs. Healthcare professionals including oncologists and oncology nurses should communicate with AYA patients about TCIM use and address their needs by making evidence-based referrals/recommendations based on treatment status and symptom burden., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: To develop and validate an oral anticoagulant knowledge tool for Chinese-speaking patients treated with warfarin or direct oral anticoagulants (DOACs) in Hong Kong., Method: This pilot validation study consisted of the following three phases: (1) the development of a knowledge tool and content validity assessment; (2) a pilot study of 200 participants, consisting of 100 patients taking warfarin or DOACs, 50 pharmacists, and 50 members of the general public; and (3) known-group validity and reliability assessments., Results: A 19-item "Chinese Oral Anticoagulants Knowledge Tool (C-OAKT)" was developed with a scale content validity index of 0.95. The mean score for known-group validity was significantly higher in the pharmacist group than the patient groups, and the patient groups scored significantly higher than the general public (mean ± standard deviation [SD] = 90.00 ± 7.11 vs. 51.55 ± 17.49 vs. 19.0 ± 15.42, respectively; p  < 0.001). The mean score was higher for patients who attended a pharmacist-managed anticoagulant therapy management clinic (PAC) than for non-PAC patients (mean ± SD = 56.80 ± 13.60 vs. 46.30 ± 9.43; p  = 0.004). An analysis of internal consistency showed a Cronbach's alpha value of 0.86., Conclusion: The results of the pilot validation study suggested that the C-OAKT is a valid and reliable instrument for assessing patients' knowledge of oral anticoagulants in ambulatory care settings., Innovations: This is the first validated Chinese version of an anticoagulant knowledge assessment tool. This tool will be utilized in public hospitals in Hong Kong, and will facilitate future research exploring the relationship between anticoagulant knowledge and patient-related outcomes., Competing Interests: All authors do not have any conflict of interest to declare., (© 2023 The Authors.)

Induction of ferroptosis emerges as an effective method for cancer treatment. With massive efforts to elucidate the ferroptosis mechanism, the development of new ferroptosis inducers proceeds rather slowly, with only a few small molecules identified. Herein, we report our discovery of marine alkaloid lepadins E and H as a new class of ferroptosis inducers. Our in vitro studies show that lepadins E and H exhibit significant cytotoxicity, promote p53 expression, increase ROS production and lipid peroxides, reduce SLC7A11 and GPX4 levels, and upregulate ACSL4 expression, all of which consistently support induction of ferroptosis through the classical p53-SLC7A11-GPX4 pathway. Our animal model study of lepadin H confirms its in vivo antitumor efficacy with negligible toxicity to normal organs. This work elucidates the mode of action of lepadins (E and H) and verifies their in vivo efficacy as a new class of ferroptosis inducers for anticancer therapy with translational potential.

Background: Despite the popularity of dietary supplements, their effectiveness and safety in patients with diabetes remain controversial. Furthermore, evidence from clinical trials may not be generalizable to real-world settings. This study examined the association between dietary supplement use and mortality outcomes among patients with diabetes based on a nationally representative sample of US adults., Methods: This study analyzed data from National Health and Nutrition Examination Survey (NHANES) 1999-2018. Supplement users referred to adults with diabetes who reported the use of any dietary supplements in the last 30 days, and with a cumulative duration of ≥ 90 days. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between supplement use and all-cause mortality, and mortality from cardiovascular diseases (CVD), diabetes, and cancer. Subgroup analysis of different supplement classes (vitamins, minerals, botanicals, amino acids, fatty acids, probiotics and glucosamine) were also conducted., Results: We included 8,122 adults with diabetes (mean age: 59.4 years; 48.7% female), of whom 3,997 (54.0%) reported using supplements regularly. Vitamins (87.3%), minerals (75.3%) and botanicals (51.8%) were the most popular supplements. At a median follow-up of 6.9 years, 2447 all-cause deaths had occurred. Overall supplement use was not associated with risk of all-cause mortality among patients with diabetes (HR = 0.97, 95% CI: 0.87 to 1.08, P = 0.56). Subgroup analyses suggested that amino acid use was associated with a lower all-cause mortality (HR = 0.66, 95% CI: 0.46 to 0.96, P = 0.028), while the use of fatty acids (HR = 0.62, 95% CI: 0.42 to 0.92, P = 0.018) and glucosamine (HR = 0.69, 95% CI: 0.51 to 0.95, P = 0.022) supplements were significantly associated with lower CVD mortality., Conclusions: Our results derived from real-world data suggested that overall supplement use was not associated with any mortality benefit in patients with diabetes. However, there is preliminary evidence that suggests a protective effect of amino acid use on all-cause mortality, and a benefit of fatty acids and glucosamine supplement use on CVD mortality. Future large-scale longitudinal studies are needed to investigate the association between dietary supplement use and other intermediate diabetes-related outcomes, such as glucose control and reducing diabetes-related complications., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Few studies have evaluated the impact of subclinical microstructural changes and psychosocial factors on cognitive function in patients with haemophilia., Objectives: To determine the prevalence and characteristics of cognitive impairment in patients with haemophilia, and identify associated risk factors., Methods: We recruited haemophilia A or B patients who were aged ≥10 years old from three public hospitals in Hong Kong. A neurocognitive battery was administered to evaluate their attention, memory, processing speed and cognitive flexibility performances. They also underwent magnetic resonance imaging to identify cerebral microbleeds. Validated self-reported questionnaires were administered to assess their mental health status and adherence to prophylactic treatment. General linear modelling was used to investigate the association of neurocognitive outcomes with risks factors, adjusting for age and education attainment., Results: Forty-two patients were recruited (median age 32.0 years; 78.6% haemophilia A; 80.9% moderate-to-severe disease). Six patients (14.3%) had developed cerebral microbleeds. A subgroup of patients demonstrated impairments in cognitive flexibility (30.9%) and motor processing speed (26.2%). Hemarthrosis in the previous year was associated with worse attention (Estimate = 7.62, 95% CI: 1.92-15.33; p = .049) and cognitive flexibility (Estimate = 8.64, 95% CI: 2.52-13.29; p = .043). Depressive (Estimate = 0.22, 95% CI: 0.10-0.55; p = .023) and anxiety (Estimate = 0.26, 95% CI: 0.19-0.41; p = .0069) symptoms were associated with inattentiveness. Among patients receiving prophylactic treatment (71.4%), medication adherence was positively correlated with cognitive flexibility (p = .037)., Conclusion: A substantial proportion of patients with haemophilia demonstrated cognitive impairment, particularly higher-order thinking skills. Screening for cognitive deficits should be incorporated into routine care. Future studies should evaluate the association of neurocognitive outcomes with occupational/vocational outcomes., (© 2023 The Authors. Haemophilia published by John Wiley & Sons Ltd.)

Background: Survivors of childhood acute lymphoblastic leukemia (ALL) are at-risk of developing cognitive impairment and neurobehavioral symptoms. Inflammation induced by a compromised health status during cancer survivorship is proposed as a pathophysiological mechanism underlying cognitive impairment in cancer survivors., Objectives: To evaluate the associations of biomarkers of inflammation with attention and neurobehavioral outcomes in survivors of childhood ALL, and to identify clinical factors associated with biomarkers of inflammation in this cohort., Methods: We recruited patients who were diagnosed with ALL at ≤ 18 years old and were currently ≥5 years post-cancer diagnosis. The study outcomes were attention (Conners Continuous Performance Test) and self-reported behavioral symptoms (Adult Self-Report [ASR] checklist). Using a commercial screening kit, survivors' plasma (5ml) was assayed for 17 cytokines/chemokine cell-signaling molecules that are associated with neurodegenerative diseases. The final panel of the targeted markers included interleukin (IL)-8, IL-13, interferon-gamma (IFN - γ), monocyte chemoattractant protein - 1 ( MCP - 1), macrophage inflammatory protein-1β, and tumor necrosis factor- α . Biomarker levels were rank-ordered into tertiles based on the sample distribution. Multivariable general linear modeling was used to test for associations between biomarkers and study outcomes in the overall cohort and stratified by gender., Results: This study included 102 survivors (55.9% males, mean[SD] age 26.2[5.9] years; 19.3[7.1] years post-diagnosis). Survivors within top tertiles of IFN-γ (Estimate =6.74, SE=2.26; P =0.0037) and IL-13 (Estimate =5.10, SE=2.27; P =0.027) demonstrated more inattentiveness. Adjusting for age, gender and treatment, more self-reported thought (Estimate=3.53, SE=1.78; P =0.050) and internalizing problems (Estimate =6.52, SE=2.91; P =0.027) correlated with higher IL-8. Higher levels of IL-13 (RR = 4.58, 95% CI: 1.01-11.10) and TNF-α (RR = 1.44, 95% CI: 1.03-4.07) were observed in survivors had developed chronic health conditions (n=26, 25.5%). The stratified analysis showed that association of IFN-γ with attention was stronger in male survivors than in female survivors., Conclusion: Inflammation due to cancer-related late effects may potentially be mechanistic mediators of neurobehavioral problems in pediatric ALL survivors. Markers of inflammation can potentially be applied to assess or monitor the effectiveness of interventions, particularly behavioral interventions, in improving cognitive outcomes in survivors. Future work includes understanding the underlying gender-specific pathophysiology behind functional outcomes in the population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cheung, To, Hua, Lee, Chan and Li.)

Insertions are one of the major types of structural variations and are defined as the addition of 50 nucleotides or more into a DNA sequence. Several methods exist to detect insertions from next-generation sequencing short read data, but they generally have low sensitivity. Our contribution is two-fold. First, we introduce INSurVeyor, a fast, sensitive and precise method that detects insertions from next-generation sequencing paired-end data. Using publicly available benchmark datasets (both human and non-human), we show that INSurVeyor is not only more sensitive than any individual caller we tested, but also more sensitive than all of them combined. Furthermore, for most types of insertions, INSurVeyor is almost as sensitive as long reads callers. Second, we provide state-of-the-art catalogues of insertions for 1047 Arabidopsis Thaliana genomes from the 1001 Genomes Project and 3202 human genomes from the 1000 Genomes Project, both generated with INSurVeyor. We show that they are more complete and precise than existing resources, and important insertions are missed by existing methods., (© 2023. The Author(s).)

Background: Avascular necrosis (AVN) of bone is a debilitating complication of pediatric patients with acute lymphoblastic leukemia (ALL). While it is extensively studied and reported in Western population, studies focused on Orientals are limited. This study aims to evaluate the incidence, risk factors, and clinical outcomes of AVN among Chinese children with ALL., Methods: This study is a retrospective, territory-wide population-based cohort study of pediatric patients with ALL enrolled on one of the three consecutive ALL study protocols (ALL-IC-BFM 2002, CCLG-ALL 2008, and CCCG-ALL 2015)., Results: A total of 24 out of 533 pediatric subjects with ALL (4.5%) had symptomatic AVN. Age was the single most important risk factor associated with the development of AVN. Only three patients were below age of 10 at the time of diagnosis of ALL. The incidences of AVN in patients aged above and below 10 years were 18.2% ± 3.6% and 0.8% ± 0.5%, respectively, and were significantly different (p < 0.005). Treatment protocol, immunophenotype, and gender were not predictive of AVN. Among the 24 patients, five required orthopedic interventions in view of progressive and severe disease. For subjects with hip joints involvement, follow-up assessments showed 12 of 22 hip joints had radiological progression over a median duration of 3.63 years. Seventeen of them did not have pain at the latest follow-up and among patients with pain (n = 7), five did not experience any limitation on activities of daily living while two required use of walking aids or wheelchair., Conclusion: The incidence of symptomatic AVN in Chinese ALL patients was comparable to other studies in Western population. Adolescent age more than 10 years old was recognized to be the most important factor for development of AVN. Significant proportion of patients had radiological progression over time with a small percentage of subjects had daily activities affected., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Patients with cancer are increasingly using forums and social media platforms to access health information and share their experiences, particularly in the use of traditional, complementary, and integrative medicine (TCIM). Despite the popularity of TCIM among patients with cancer, few related studies have used data from these web-based sources to explore the use of TCIM among patients with cancer., Objective: This study leveraged multiple forums and social media platforms to explore patients' use, interest, and perception of TCIM for cancer care., Methods: Posts (in English) related to TCIM were collected from Facebook, Twitter, Reddit, and 16 health forums from inception until February 2022. Both manual assessments and natural language processing were performed. Descriptive analyses were performed to explore the most commonly discussed TCIM modalities for each symptom and cancer type. Sentiment analyses were performed to measure the polarity of each post or comment, and themes were identified from posts with positive and negative sentiments. TCIM modalities that are emerging or recommended in the guidelines were identified a priori. Exploratory topic-modeling analyses with latent Dirichlet allocation were conducted to investigate the patients' perceptions of these modalities., Results: Among the 1,620,755 posts available, cancer-related symptoms, such as pain (10/10, 100% cancer types), anxiety and depression (9/10, 90%), and poor sleep (9/10, 90%), were commonly discussed. Cannabis was among the most frequently discussed TCIM modalities for pain in 7 (70%) out of 10 cancer types, as well as nausea and vomiting, loss of appetite, anxiety and depression, and poor sleep. A total of 7 positive and 7 negative themes were also identified. The positive themes included TCIM, making symptoms manageable, and reducing the need for medication and their side effects. The belief that TCIM and conventional treatments were not mutually exclusive and intolerance to conventional treatment may facilitate TCIM use. Conversely, TCIM was viewed as leading to patients' refusal of conventional treatment or delays in diagnosis and treatment. Doctors' ignorance regarding TCIM and the lack of information provided about TCIM may be barriers to its use. Exploratory analyses showed that TCIM recommendations were well discussed among patients; however, these modalities were also used for many other indications. Other notable topics included concerns about the legalization of cannabis, acupressure techniques, and positive experiences of meditation., Conclusions: Using machine learning techniques, social media and health forums provide a valuable resource for patient-generated data regarding the pattern of use and patients' perceptions of TCIM. Such information will help clarify patients' needs and concerns and provide directions for research on integrating TCIM into cancer care. Our results also suggest that effective communication about TCIM should be achieved and that doctors should be more open-minded to actively discuss TCIM use with their patients., (©Chun Sing Lam, Keary Zhou, Herbert Ho-Fung Loong, Vincent Chi-Ho Chung, Chun-Kit Ngan, Yin Ting Cheung. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 21.04.2023.)

Purpose: Despite the increasing popularity of supplement use among the cancer community, the current evidence on its effect on mortality in large studies is inconclusive. This study examined the association of dietary supplement use with mortality risk in a large population-based cohort., Methods: This prospective cohort study analyzed data from the UK Biobank on participants who were diagnosed with cancer before July 31, 2019 and self-reported whether they had regular intake of dietary supplements (vitamins, minerals, or non-vitamin non-mineral [NVNM] supplements) after cancer diagnosis. The associations between the use of supplements with mortality were analyzed using Cox proportional hazards models, adjusting for confounders (sociodemographic factors, lifestyle and comorbidities)., Results: This analysis included 30,239 participants (mean age: 60.0 years; 61.9% female). Over half (57.8%) were supplement users. At a median follow-up of 11.9 years, 5577 all-cause deaths were registered. A marginal protective effect of supplement use on the risk of all-cause (adjusted hazard ratio [aHR] = 0.95, 95% CI = 0.90-0.99) and cancer (aHR = 0.89, 95% CI = 0.83-0.95) mortality were found, but not the risk of mortality due to other causes. In subgroup analyses, only NVNM dietary supplements were significantly associated with a lower risk of all-cause mortality (aHR = 0.88, 95% CI = 0.83-0.93). Both vitamins (aHR = 0.93, 95% CI = 0.87-0.99) and NVNM dietary supplements (aHR = 0.88, 95% CI = 0.82-0.94) were associated with a modest decrease in cancer mortality which were marginally significant., Conclusions: This is one of the largest cohort studies that identified the associations of dietary supplements with survival in the cancer population. However, the associations are small and should be interpreted cautiously due to the variations among different supplements and the small effect size. Future studies should investigate the effect of individual supplements, particularly NVNM supplements, on improving other cancer-related outcomes., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Purpose: Studies of the association between body mass index (BMI) at diagnosis and treatment outcome in children with acute lymphoblastic leukemia (ALL) have yielded inconsistent results. Hence, we conducted a retrospective study in a large cohort of Chinese children with ALL treated with contemporary protocols., Patients and Methods: A total of 1437 children (62.1% male; median age at diagnosis 5.7 years, range: 2.3-16.3 years) were enrolled in two consecutive clinical trials at the Shanghai Children's Medical Center. The rates of overall survival, event-free survival, relapse, treatment-related mortality, and adverse events were compared among patients who were underweight (BMI < 5th percentile), at a healthy weight (5th to 85th percentile), overweight (>85th to <95th percentile), and obese (≥95th percentile)., Results: At diagnosis, 91 (6.3%) patients were underweight, 1070 (74.5%) were at a healthy weight, 91 (6.3%) were overweight, and 185 (12.9%) were obese. No significant association was found between weight status and 5-year overall survival, event-free survival, or relapse in the overall cohort. When analyzed as a continuous variable, a higher BMI Z-score was associated with treatment-related mortality (hazard ratio 1.33 (95% confidence interval [CI], 1.05-1.68%), p = 0.02). The treatment-related mortality rate was higher in the overweight (5.5%, 95% CI 0.8-10.2%) and obese (3.2%, 95% CI 0.6-5.8%) groups compared with the underweight (0.0%) and healthy-weight groups (1.9%, 95% CI 1.1-2.7%; p = 0.04). Multivariable analysis showed that children who were overweight had a higher risk of treatment-related mortality (hazard ratio 3.8, 95% CI 1.3-11.4)., Conclusion: While body weight status was not associated with event-free survival or overall survival, overweight patients were at higher risk of treatment-related mortality., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: To evaluate the short-term effectiveness of a personalized survivorship care plan (SCP) in improving cancer-related literacy among childhood cancer survivors, and to identify characteristics of survivors who demonstrated minimal gain from the intervention., Methods: We recruited survivors diagnosed with cancer at ≤18 years old and were >2 years post treatment. The intervention included a personalized SCP and 30-minute health risk counseling. The participants' knowledge of their cancer diagnosis and potential treatment-related late effects (LEs) was assessed at baseline, immediately post intervention, and 1-3 months post intervention. Generalized estimating equation was used to test for changes in the awareness scores, with interacting terms (time*factor) added to identify differences in the score trajectory across clinically relevant subgroups., Results: In total, 248 survivors completed the intervention (mean age: 19.4 [SD = 6.7] years; 54.1% male; 66.1% hematological malignancies), of whom 162 completed all assessments. There was significant increase in survivors' awareness of their cancer diagnoses (mean adjusted score: baseline 66.9, post intervention 86.3; p < .001) and potential LEs (baseline 30.9, post intervention 66.3; p < .001). The proportion of survivors who demonstrated awareness of their potential LEs increased from 9.7% to 54.3%. The interaction analysis showed that there was significantly less improvement in awareness among survivors of non-central nervous system (non-CNS) solid tumors (p = .032), lower socioeconomic status (p = .014), and parents of pediatric survivors (vs. adult survivors; p = .013)., Conclusions: The provision of a personalized SCP showed preliminary effectiveness in improving survivors' understanding of their treatment-related LEs. Health counseling with SCP should be reinforced in vulnerable subgroups. Future work includes evaluating its long-term impact on lifestyle and health outcomes., (© 2022 Wiley Periodicals LLC.)

Iron deficiency (ID) is a prevalent nutritional deficiency affecting children/adolescents worldwide. We reported (1) the prevalence of ID and ID with anemia (IDA) among Chinese school-aged adolescents, (2) clinical and dietary predictors of iron status, and (3) its impact on health-related qualities of life (HRQoL). This cross-sectional study recruited 183 boys and 340 girls (mean age = 17.55) from 16 schools in Hong Kong. ID is defined as serum ferritin <15 μg/L. The participants reported their dietary habits, menstrual patterns (girls), and HRQoL using structured questionnaires. The overall prevalence of ID was 11.1%. None of the boys had ID or IDA. Among girls, the rate of ID was 17.1% and IDA was 10.9%. One-third (36.3%) reported a regular habit of skipping ≥1 meal/day. Lower ferritin was found in adolescents who skipped meals (Est = -35.1, p = 0.017). Lower ferritin is correlated with poorer school functioning (Est = 0.81, p = 0.045) and fatigue (Est = 0.92, p = 0.016). Skipping meals is associated with poorer physical ( p = 0.0017) and school functioning ( p = 0.027). To conclude, 1 in 10 school-aged adolescents in Hong Kong are iron-deficient. The ID rate in girls (17.1%) is similar to that in other industrialized countries (5.2-16.6%). Future work should promote awareness on the potential health consequences of poor dietary habits on ID and the well-being of adolescents.

Background: The effect of lifestyle on neurocognitive impairment among cancer survivors remain an understudied area. This study explored the association between lifestyle factors and neurocognitive outcomes (specifically, attention, memory, processing speed and cognitive flexibility) in AYA survivors (aged 15-39 years) of sarcoma., Methods: This study recruited 116 AYA survivors (age 28.2 (SD = 8.2) years), who were diagnosed with osteosarcoma (49%) or soft-tissue sarcoma (51%) at age 13.3 (SD = 7.2) years. The neurocognitive battery included measures of attention, memory, motor-processing speed, and cognitive flexibility. Survivors reported health-damaging practices, which included: physical inactivity, smoking, alcohol intake, inadequate sleep (<7 h of actual sleep/day), sleep-related fatigue (Multidimensional Fatigue Scale) and long working hours (>9 h/day). General linear modeling was conducted to examine the association between lifestyle factors and neurocognitive outcomes, adjusting for age at diagnosis, sex, education attainment and clinical/treatment variables., Results: At 14.9 (SD = 7.6) years post-diagnosis, survivors demonstrated impairment in attentiveness (4.3-13.0%), processing speed (34.5%) and cognitive flexibility (18.1%). Nearly half (45.7%) had developed a chronic health condition (CHC). Low physical activity (estimate = -0.97, p = 0.003) and sleep-related fatigue (estimate = -0.08, p = 0.005) were associated with inattention. Survivors who worked >9 h/day (n = 15) demonstrated worse attention (estimate = 5.42, p = 0.023) and cognitive flexibility (estimate = 5.22, p = 0.005) than survivors who worked ≤9 h/day (n = 66). Interaction analysis (CHCs* physical activity ) showed that survivors who developed CHCs and reported low physical activity had worse attention ( p = 0.032) and cognitive-flexibility ( p = 0.019) scores than other subgroups., Conclusion: Treatment-related CHCs, coupled with continued physical inactivity, may exacerbate inattention and executive dysfunction among survivors. Long working hours and sleep-related fatigue are associated with worse functioning; this finding should be validated with prospective assessment of work-related stressors and objective sleep measures.

Background/objectives: Most of the studies on functional outcomes in pediatric survivors of cancers and bone marrow failure disorders have been conducted in North American, European, and Oceanian populations, with few studies having been performed in China. The objective of this study was to evaluate psychosocial outcomes in a cohort of Chinese pediatric survivors diagnosed with cancer or conditions requiring hematopoietic stem cell transplantation (HSCT), and to identify clinical and behavioral factors associated with adverse psychosocial outcomes., Methods: This was a cross-sectional survey study. We recruited pediatric survivors of cancer or inherited disorder requiring HSCT at ≤18 years old and were ≥6 months post-treatment. Parents completed the St. Jude Children's Research Hospital After Completion of Therapy questionnaire to report their child's emotional functioning, social functioning, attention/concentration and behavior. Multivariable general linear modeling was used to identify clinical, treatment and behavioral factors associated with psychosocial outcomes, adjusting for sex, age and cancer diagnoses., Results: Ninety-five pediatric survivors were recruited (62.1% male; mean [standard deviation] age 9.7 [3.4] years; 4.1 [2.6] years post-diagnosis). They were diagnosed with bone marrow failure disorders (23.2%), hematological malignancies (45.3%) or solid tumors (23.2%). Compared with survivors with no current health problems, those with more than one current health problem performed worse in emotional functioning (Estimate = 2.42, SE = 0.88, P = 0.008) and social functioning (Estimate = 2.90, SE = 1.64, P = 0.03). Higher pain interference was significantly associated with worse emotional functioning (Estimate = 0.19, SE = 0.08, P = 0.03) and attention functioning (Estimate = 0.26, SE = 0.11, P = 0.03). Compared with survivors who reported less sleep problems, those who had more sleep problems demonstrated poorer emotional functioning (Estimate = 0.30, SE = 0.08, P = 0.001). Survivors who had a longer duration of screen usage per day reported more impairment on attention and behavior functioning than those who had a shorter duration of screen usage per day (both P<0.5)., Conclusion: Survivors who were diagnosed at a younger age or had unaddressed/untreated health problems may require additional psychological evaluation. The implementation of psychosocial assessments during routine long-term follow-up care may help to identify high-risk patients during the early phase of survivorship. Rehabilitation interventions should address modifiable behavioral factors (e.g. sleep habits, screen time and chronic pain)., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Cai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Engaging with patients and the public (consumers and community) enhances the relevance of cancer control developments; however, challenges remain to integrate into processes. Medical and other professional societies are well-positioned to foster and endorse best practice., Methods: Between October and December 2021, the Multinational Association of Supportive Care in Cancer (MASCC) conducted a global consultation with those who identified as "people affected by cancer". Recruitment to an online cross-sectional survey was by a combination of purposive and convenience sampling to determine preferred terminologies and experiences with MASCC and other cancer-related societies., Results: The survey was completed by 343 respondents from 29 countries, a majority being female (78.1%) and younger than 60 years of age (62.1%). Respondents preferred to be identified as 'patient' from a set of defined terms; however, this only accounted for 49-67% of selected response across geographical regions. Only 22.2% of respondents had engaged previously with MASCC, of whom 90.8% reported a positive experience through involvement with education and information, networking and collaboration, and practice guidelines. Respondents perceived areas of opportunity as early involvement in decision-making, educational initiatives, open communication, and information sharing. Across all geographical regions, responders chose a preference to contribute to future consumer research (53.0%), policy (31.7%) or consumer engagement activities (56.9%) including participation in a conference session (65.0%) or patient day (47.9%)., Conclusions: This survey provides a first insight into how consumers wish to engage with MASCC. These values will be embedded into a strategy that aims for effective and sustainable partnerships with multinational consumers., (© 2022. The Author(s).)

Purpose: To assess the feasibility and acceptability of immersive virtual reality for managing anxiety, nausea and vomiting amongst paediatric patients with cancer receiving their first chemotherapy., Methods: An exploratory randomised control trial supplemented with qualitative interviews was conducted to enrol Chinese paediatric patients receiving their first intravenous chemotherapy. Participants were randomly assigned to intervention (three immersive virtual reality sessions) or control (standard care) groups. The main outcome measures included (1) feasibility parameters; (2) anxiety, nausea and vomiting; and (3) satisfaction with the chemotherapy procedures. Qualitative data were collected by semi-structured individual interviews with patients, parents and nurses., Results: A total of 19 patients, 19 accompanying parents and 9 nurses were recruited. Results suggested that the intervention was feasible as evidenced by the high consent rate, low withdrawal rate and attrition rate. The intervention group showed significantly better improvement in anxiety at T2 [Hedges' effect size, ES = 1.25, 95% confidence interval (CI): 0.22-2.17)] and T4 [ES = 1.87, 95% CI: 0.72-2.85], as well as greater reduction in acute nausea at T4 [ES = 0.97, 95% CI: 0.02-1.87] than the control group. Qualitative data yielded three categories including positive experiences and perceived benefits of the intervention, and suggested improvements., Conclusions: This study demonstrated the potential effectiveness, feasibility and acceptability of immersive virtual reality for managing anxiety and acute nausea amongst paediatric patients with cancer receiving their first chemotherapy., Competing Interests: Declaration of competing interest No conflict of interest has been declared by all the authors., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: Evidence supports the role of prescribed exercise for cancer survivors, yet few are advised to exercise by a healthcare practitioner (HCP). We sought to investigate the gap between HCPs' knowledge and practice from an international perspective., Methods: An online questionnaire was administered to HCPs working in cancer care between February 2020 and February 2021. The questionnaire assessed knowledge, beliefs, and practices regarding exercise counselling and referral of cancer survivors to exercise programs., Results: The questionnaire was completed by 375 participants classified as medical practitioners (42%), nurses (28%), exercise specialists (14%), and non-exercise allied health practitioners (16%). Between 35 and 50% of participants self-reported poor knowledge of when, how, and which cancer survivors to refer to exercise programs or professionals, and how to counsel based on exercise guidelines. Commonly reported barriers to exercise counselling were safety concerns, time constraints, cancer survivors being told to rest by friends and family, and not knowing how to screen people for suitability to exercise (40-48%). Multivariable logistic regression models including age, gender, practitioner group, leisure-time physical activity, and recall of guidelines found significant effects for providing specific exercise advice (χ 2 (7) = 117.31, p < .001), discussing the role of exercise in symptom management (χ 2 (7) = 65.13, p < .001) and cancer outcomes (χ 2 (7) = 58.69, p < .001), and referring cancer survivors to an exercise program or specialist (χ 2 (7) = 72.76, p < .001)., Conclusion: Additional education and practical support are needed to equip HCPs to provide cancer survivors with exercise guidelines, resources, and referrals to exercise specialists., (© 2022. The Author(s).)

Background: Few studies have evaluated the medication burden borne by survivors of pediatric cancer. This study aimed to describe the drug utilization pattern of chronic medications in a cohort of young pediatric cancer survivors., Methods: This was a population-based study of patients diagnosed with cancer at age 18 years or younger between 2000 and 2013 in Hong Kong and who had survived at least 5 years postdiagnosis. The primary outcome is the use of any chronic medication (medications that were prescribed for ≥30 consecutive days within a 6-month period). Multivariable log-binomial models were used to identify factors associated with chronic medication use. Kaplan-Meier analysis was used to present the cumulative proportion of survivors initiated on a chronic medication across time from cancer diagnosis., Results: Of the 2444 survivors (median age = 22 years, interquartile range = 16-27 years), 669 (27.4%) required at least 1 chronic medication at least 5 years postdiagnosis. Survivors who developed a chronic health condition (CHC) had a 5.48 (95% confidence interval [CI] = 4.49 to 6.71) times higher risk of taking a chronic medication than those without CHC. At 10 years postdiagnosis, the cumulative proportion of survivors being initiated a chronic medication was 33.4% (95% CI = 31.1% to 35.6%) for the overall cohort. Higher cumulative proportions were observed in survivors with endocrine (74.6%, 95% CI = 68.4% to 79.6%), renal (68.8%, 95% CI = 54.2% to 78.7%), neurological (58.6%, 95% CI = 46.1% to 68.1%), and cardiovascular (54.7%, 95% CI = 44.0% to 63.4%) disorders., Conclusion: Survivors with certain CHCs had a higher risk of starting a prescription medication in the early phase of survivorship. Future studies include examining the impact of medication burden on survivors' functional status., (© The Author(s) 2022. Published by Oxford University Press.)