OBJECTIVES: To evaluate the benefits and harms of tamoxifen or tamoxifen plus any other anticancer drugs compared with no intervention, placebo, any type of standard care, or alternative treatment in adults with hepatocellular carcinoma, irrespective of sex, administered dose, type of formulation, and duration of treatment.

SEARCH METHODS: We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, three other databases, and major trials registries, and handsearched reference lists up to 26 March 2024.

ELIGIBILITY CRITERIA: Parallel-group randomised clinical trials including adults (aged 18 years and above) diagnosed with advanced or unresectable hepatocellular carcinoma. Had we found cross-over trials, we would have included only the first trial phase. We did not consider data from quasi-randomised trials for analysis.

OUTCOMES: Our critical outcomes were all-cause mortality, serious adverse events, and health-related quality of life. Our important outcomes were disease progression, and adverse events considered non-serious.

RISK OF BIAS: We assessed risk of bias using the RoB 2 tool.

SYNTHESIS METHODS: We used standard Cochrane methods and Review Manager. We meta-analysed the outcome data at the longest follow-up. We presented the results of dichotomous outcomes as risk ratios (RR) and continuous data as mean difference (MD), with 95% confidence intervals (CI) using the random-effects model. We summarised the certainty of evidence using GRADE.

INCLUDED STUDIES: We included 10 trials that randomised 1715 participants with advanced, unresectable, or terminal stage hepatocellular carcinoma. Six were single-centre trials conducted in Hong Kong, Italy, and Spain, while three were conducted as multicentre trials in single countries (France, Italy, and Spain), and one trial was conducted in nine countries in the Asia-Pacific region (Australia, Hong Kong, Indonesia, Malaysia, Myanmar, New Zealand, Singapore, South Korea, and Thailand). The experimental intervention was tamoxifen in all trials. The control interventions were no intervention (three trials), placebo (six trials), and symptomatic treatment (one trial). Co-interventions were best supportive care (three trials) and standard care (one trial). The remaining six trials did not provide this information. The number of participants in the trials ranged from 22 to 496 (median 99), mean age was 63.7 (standard deviation 4.18) years, and mean proportion of men was 74.7% (standard deviation 42%). Follow-up was three months to five years.

SYNTHESIS OF RESULTS: Ten trials evaluated oral tamoxifen at five different dosages (ranging from 20 mg per day to 120 mg per day). All trials investigated one or more of our outcomes. We performed meta-analyses when at least two trials assessed similar types of tamoxifen versus similar control interventions. Eight trials evaluated all-cause mortality at varied follow-up points. Tamoxifen versus the control interventions (i.e. no treatment, placebo, and symptomatic treatment) results in little to no difference in mortality between one and five years (RR 0.99, 95% CI 0.92 to 1.06; 8 trials, 1364 participants; low-certainty evidence). In total, 488/682 (71.5%) participants died in the tamoxifen groups versus 487/682 (71.4%) in the control groups. The separate analysis results for one, between two and three, and five years were comparable to the analysis result for all follow-up periods taken together. The evidence is very uncertain about the effect of tamoxifen versus no treatment on serious adverse events at one-year follow-up (RR 0.44, 95% CI 0.19 to 1.06; 1 trial, 36 participants; very low-certainty evidence). A total of 5/20 (25.0%) participants in the tamoxifen group versus 9/16 (56.3%) participants in the control group experienced serious adverse events. One trial measured health-related quality of life at baseline and at nine months' follow-up, using the Spitzer Quality of Life Index. The evidence is very uncertain about the effect of tamoxifen versus no treatment on health-related quality of life (MD 0.03, 95% CI -0.45 to 0.51; 1 trial, 420 participants; very low-certainty evidence). A second trial found no appreciable difference in global health-related quality of life scores. No further data were provided. Tamoxifen versus control interventions (i.e. no treatment, placebo, or symptomatic treatment) results in little to no difference in disease progression between one and five years' follow-up (RR 1.02, 95% CI 0.91 to 1.14; 4 trials, 720 participants; low-certainty evidence). A total of 191/358 (53.3%) participants in the tamoxifen group versus 198/362 (54.7%) participants in the control group had progression of hepatocellular carcinoma. Tamoxifen versus control interventions (i.e. no treatment or placebo) may have little to no effect on adverse events considered non-serious during treatment, but the evidence is very uncertain (RR 1.17, 95% CI 0.45 to 3.06; 4 trials, 462 participants; very low-certainty evidence). A total of 10/265 (3.8%) participants in the tamoxifen group versus 6/197 (3.0%) participants in the control group had adverse events considered non-serious. We identified no trials with participants diagnosed with early stages of hepatocellular carcinoma. We identified no ongoing trials.

AUTHORS' CONCLUSIONS: Based on the low- and very low-certainty evidence, the effects of tamoxifen on all-cause mortality, disease progression, serious adverse events, health-related quality of life, and adverse events considered non-serious in adults with advanced, unresectable, or terminal stage hepatocellular carcinoma when compared with no intervention, placebo, or symptomatic treatment could not be established. Our findings are mostly based on trials at high risk of bias with insufficient power (fewer than 100 participants), and a lack of trial data on clinically important outcomes. Therefore, firm conclusions cannot be drawn. Trials comparing tamoxifen administered with any other anticancer drug versus standard care, usual care, or alternative treatment as control interventions were lacking. Evidence on the benefits and harms of tamoxifen in participants at the early stages of hepatocellular carcinoma was also lacking.

FUNDING: This Cochrane review had no dedicated funding.

OBJECTIVE: The objectives of this study are (1) to evaluate the feasibility of a brief mindfulness-based mobile app (BM-MA) for Indonesian senior high school teachers experiencing anxiety and stress and (2) to examine the effects of using the BM-MA on anxiety, stress, life satisfaction, self-efficacy, trait mindfulness, self-compassion, and physical and social dysfunction among the participants.

METHODS: We followed the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013 statement for this feasibility randomized controlled trial (RCT) protocol. A total of 60 Indonesian senior high school teachers were recruited for this study and randomly assigned to either the intervention group (BM-MA) or a wait-list control group (CG) in a 1:1 ratio. The BM-MA group was required to engage in mindfulness practices using the app for 10-20 minutes per day for 3 weeks. All participants were assessed with a battery of self-report measures at baseline, postintervention, and at 1-month follow-up. Validated scales used to measure the outcome variables of interest included the Satisfaction With Life Scale (SLS), the Teachers' Sense of Efficacy Scale (TSES), the Self-Compassion Scale-Short Form (SCS-SF), Generalized Anxiety Disorder-7 (GAD-7), General Health Questionnaire-12 (GHQ-12), and the Five Facet Mindfulness Questionnaire (FFMQ). The practicality and acceptability of the app will be evaluated using the Client Satisfaction Questionnaire-8 (CSQ-8) and structured qualitative interviews. Data from the interviews will be analyzed with the deductive thematic analysis framework as a process of qualitative inquiry. Repeated measures ANOVA with groups (intervention vs control) as a between-subject factor and time as a within-subject factor (baseline, postintervention, and 1-month follow-up) will be used to examine the effects of the BM-MA on the outcome variables. The data will be analyzed using an intent-to-treat approach and published in accordance with CONSORT (Consolidated Standards of Reporting Trials) recommendations.

RESULTS: Participants were recruited in December 2023, and this pilot RCT was conducted from January through March 2024. Data analysis was conducted from March through May 2024. The results of this study are expected to be published in December 2024. The trial registration of this protocol was submitted to the Chinese Clinical Trial Registry.

CONCLUSIONS: This study aims to determine the feasibility and efficacy of the BM-MA, a digital mental health intervention developed using an existing mindfulness-based app, and assess its potential for widespread use.

TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300068085; https://tinyurl.com/2d2x4bxk.

METHODS: The study was based on data from 7035 fully vaccinated respondents to the online COVAD questionnaire with SLE (N = 852), rAIDs (N = 3098), or nrAIDs (N = 414), and HCs (N = 2671). BI was defined as COVID-19 infection occurring in individuals vaccinated with ≥ 2 doses (or 1 dose of J&J) ≥ 14 days after vaccination and not after 6 months since the last vaccine dose. Data were analysed using linear and logistic regression models.

OBJECTIVES: To explore the experiences and preferences of Malaysian patients with advanced cancer.

DESIGN: Qualitative study of semi-structured interviews with thematic analysis.

SETTING/SUBJECTS: Purposive sampling of 19 patients with Stage 4 cancer recruited from inpatient and outpatient settings in National Cancer Institute Malaysia.

RESULTS: Three major themes emerged in the exploration of patients' experiences and care preferences in facing advanced cancer namely: 1) Dealing with poor prognosis 2) Spirituality as a source of strength and 3) Enablers of advance care planning.

METHODS: A systematic search of PubMed, EMBASE, and Web of Science was conducted up to June 7, 2024, following PRISMA guidelines to identify studies related to COVID-19 vaccines and POTS. Eligible studies included randomized controlled trials, cohort studies, cross-sectional studies, case-control studies, case series, and case reports. Screening, data extraction, and quality assessment were independently performed by two reviewers using the Joanna Briggs Institute Checklists and the Newcastle-Ottawa Scale.

RESULTS: Of the 1,531 articles identified, 10 met the inclusion criteria, encompassing a total of 284,678 participants. These studies included five case reports, two case series, one cross-sectional study, one prospective observational study, and one cohort study. The cohort study reported that the odds of new POTS diagnoses post-vaccination were 1.33 (95% CI: 1.25-1.41) compared to the 90 days prior. In contrast, the post-infection odds were 2.11 (95% CI: 1.70-2.63), and the risk of POTS was 5.35 times higher (95% CI: 5.05-5.68) post-infection compared to post-vaccination. Diagnostic findings across studies included elevated norepinephrine levels and reduced heart rate variability. Reported management strategies involved ivabradine, intravenous therapies, and lifestyle modifications.