Educational interventions to reduce depression and anxiety in older adults with cancer in the community: a systematic review, meta-analysis and meta-regression of randomised controlled trials.

BACKGROUND: Older adults make up half of those with cancer and are prone to mood disorders, such as depression and severe anxiety, resulting in negative repercussions on their health-related quality-of-life (HRQOL). Educational interventions have been shown to reduce adverse psychological outcomes. We examined the effect of educational interventions on the severity of psychological outcomes in older adults with cancer (OAC) in the community. METHOD: This PRISMA-adherent systematic review involved a search of PubMed, MedLine, Embase and PsycINFO for randomised controlled trials (RCTs) that evaluated educational interventions impacting the severity of depression, anxiety and HRQOL in OAC. Random effects meta-analyses and meta-regressions were used for the primary analysis. RESULTS: Fifteen RCTs were included. Meta-analyses showed a statistically insignificant decrease in the severity of depression (SMD = -0.30, 95%CI: -0.69; 0.09), anxiety (SMD = -0.30, 95%CI: -0.73; 0.13) and improvement in overall HRQOL scores (SMD = 0.44, 95%CI: -0.16; 1.04). However, subgroup analyses revealed that these interventions were particularly effective in reducing the severity of depression and anxiety in specific groups, such as OAC aged 60-65, those with early-stage cancer, those with lung cancer and those treated with chemotherapy. A systematic review found that having attained a higher education and income level increased the efficacy of interventions in decreasing the severity of adverse psychological outcomes. CONCLUSION: Although overall meta-analyses were statistically insignificant, subgroup meta-analyses highlighted a few specific subgroups that the educational interventions were effective for. Future interventions can be implemented to target these vulnerable groups.

A cross-sectional study on advance care planning documentation attitudes during national advance care planning week in a South-East Asian country.

BACKGROUND: Through advocacy initiatives such as roadshows during "National ACP Week", the Agency for Integrated Care (AIC) had increased advance care planning (ACP) engagement since 2011. Project Happy Apples (PHA), a community initiative project led by medical students from the National University of Singapore, also conducted a public exhibition to raise ACP awareness during this period. This study aimed to investigate and identify predictors of attitudes towards ACP documentation among 'ACP Week' respondents which may be used to formulate strategies to increase ACP documentation in Singapore. METHODS: A cross-sectional study on ACP documentation attitudes of 262 respondents during local roadshows were conducted. Multiple logistic regression models were built to investigate the associations between demographic variables and attitudes toward ACP documentation. RESULTS: The mean age was 43.5 years (SD = 17.4), 79 (30.15%) were males and 49 (18.7%) were healthcare professionals (HCP). 117 (44.66%) respondents had prior experience with serious illness and 116 (44.27%) had heard of ACP. Age was a significant predictor of readiness to sign official papers naming nominated healthcare spokesperson (NHS) (OR = 1.04, 95%CI: 1.02-1.07). Experience with serious illness was a significant predictor of readiness to discuss end-of-life (EOL) care with healthcare professionals (HCP) (OR = 3.65, 95%CI: 1.36-11.61). Being female was a significant predictor for readiness to speak to their nominated healthcare spokesperson about EOL care (OR = 7.33, 95%CI: 2.06-46.73). Subgroup analyses revealed that those aged 20-39 were less likely to speak to their healthcare professional about or sign official papers regarding EOL care. We also found that being a healthcare professional does not necessitate better or worse attitudes. CONCLUSION: Advocacy programs tailored to targeting respondents of different age groups and prior experience with serious illness may improve the efficacy of advocacy efforts.

On Orthorexia Nervosa: A Systematic Review of Reviews.

INTRODUCTION: Orthorexia nervosa (ON), characterized by a pathological preoccupation with "extreme dietary purity," is increasingly observed as a mental health condition among young adults and the general population. However, its diagnosis is not formally recognized and has remained contentious. OBJECTIVE: In this systematic review, we attempt to overview previous reviews on ON, focusing on the methodological and conceptual issues with ON. This would serve both as a summary and a way to highlight gaps in earlier research. METHODS: This systematic review took reference from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines, and using combinations of the search terms ("orthorexia" OR "orthorexia nervosa" OR "ON") AND ("review" OR "systematic review" OR "meta-analysis"), a literature search was performed on EMBASE, Medline and PsycINFO databases from inception up to October 31, 2023. Articles were included if (1) they were written or translated into English and (2) contained information pertaining to the diagnostic stability or validity of ON, or instruments used to measure ON symptoms and behaviors. Only review articles with a systematic literature search approach were included. RESULTS: A total of 22 reviews were qualitatively reviewed. Several studies have reported variable prevalence of ON and highlighted the lack of thoroughly evaluated measures of ON with clear psychometric properties, with no reliable estimates. ORTO-15 and its variations such as ORTO-11, ORTO-12 are popularly used, although their use is discouraged. Existing instruments lack specificity for pathology and several disagreements on the conceptualization and hence diagnostic criteria of ON exist. DISCUSSION: Previous reviews have consistently highlighted the highly variable (and contradictory) prevalence rates with different instruments to measure ON, lack of stable factor structure and psychometrics across ON measures, paucity of data on ON in clinical samples, and a need for a modern re-conceptualization of ON. The diagnosis of ON is challenging as it likely spans a spectrum from "normal" to "abnormal," and "functional" to "dysfunctional." "Non-pathological" orthorexia is not related to psychopathological constructs in the same way that ON is.

Social media use and its impact on adults' mental health and well-being: A scoping review.

BACKGROUND: Social media use has grown in importance and prevalence, with its estimated number of users at 4.9 billion worldwide. Social media use research has revealed positive and negative impacts on users' mental health and well-being. However, such impacts among adults have not been examined in any reviews. METHODS: A scoping review was conducted based on the framework by Arksey and O'Malley and reported based on the PRISMA-ScR guidelines. Eight databases were searched from 2005 to December 2021. Articles were included after being reviewed by three independent teams, with discrepancies resolved through consensus with the senior author. Publication-related information (i.e., authors, year of publication, aims, study population, methodology, interventions, comparisons, outcome measures and key findings) were extracted from each study. Thematic analysis was conducted to answer the research questions. RESULTS: Among the 114 eligible articles, young adults (69.6%) represented the main age group. Most studies (78.6%) focused on the negative impacts of social media use on mental health and well-being, with nearly a third (32.1%) assessing such impacts on depression. Notably, this scoping review found that more than three-quarters (78.6%) of the included studies revealed that excessive and passive social media use would increases depression, anxiety, mood and loneliness. Nevertheless, a third (33.0%) also reported positive impacts, where positive and purposeful use of social media contributes to improvements in mental health and well-being, such as increased perceived social support and enjoyment. LINKING EVIDENCE TO ACTION: This review has provided an overview of the existing knowledge on how social media use affects adults and identified areas of research that merit investigation in future studies. More attention should be given to maximizing the positive impacts of social media use on mental health and well-being among adults.

Performance of the ROX index in predicting high flow nasal cannula failure in COVID-19 patients: a systematic review and meta-analysis.

COVID-19 patients with acute hypoxemic respiratory failure (AHRF) benefit from high flow nasal cannula (HFNC) oxygen therapy. However, delays in initiating invasive ventilation after HFNC failure are associated with poorer outcomes. The respiratory oxygenation (ROX) index, combining SpO2/FiO2 and respiratory rate, can predict HFNC failure. This meta-analysis evaluated the optimal ROX index cut-offs in predicting HFNC failure among COVID-19 patients at different measurement timings and clinical settings. Three databases were searched for eligible papers. From each study, we reconstructed the confusion matrices at different cut-offs, fitted linear mixed models to estimate the ROX index distribution function, and derived the area under the summary receiver operator characteristic curve (sAUC) and optimal cut-offs to predict HFNC failure. 24 studies containing 4790 patients were included. Overall sAUC was 0.771 (95% CI: 0.666-0.847) (optimal cut-off: 5.23, sensitivity: 0.732, specificity: 0.690). The cut-off values to achieve 80%, 90% sensitivity, 80%, 90% specificity were 5.70, 6.69, 4.45, 3.37, respectively. We stratified the analysis by ROX measurement time and estimated optimal cut-offs and cut-offs to achieve 80% sensitivity and specificity. For 2-6 h and 6-12 h post-HFNC initiation, we propose the use of 80% specific cut-offs to rule in HFNC failure of < 5.33 and < 3.69, respectively. For 12-24 h post-HFNC initiation, we propose the use of the 80% sensitive cut-off of > 6.07 to rule out HFNC failure. Our analysis confirms the overall utility of the ROX index in risk stratification of COVID-19 patients with AHRF receiving HFNC and provides potentially useful cut-offs for different times from HFNC initiation.

Comparing Renin-Angiotensin-Aldosterone Blockade Regimens for Long-Term Chemotherapy-Related Cardiac Dysfunction: A Network Meta-Analysis.

PURPOSE: Cancer therapies including trastuzumab and anthracyclines are cardiotoxic and cause cardiac dysfunction. To prevent cardiotoxicity, pharmacological agents used in heart failure have been administered concomitantly with cardiotoxic cancer therapy, but few studies to date have performed a head-to-head comparison of these different agents. This systematic review and network meta-analysis of randomized-controlled trials aims to evaluate the efficacy of renin-angiotensin-aldosterone system (RAAS) blockers, namely angiotensin-converting enzyme inhibitors (ACE-Is), aldosterone receptor blockers (ARBs), and mineralocorticoid receptor antagonists (MRAs), in primary prevention against chemotherapy-related cardiac dysfunction in patients receiving anthracyclines and/or trastuzumab. METHODS: A systematic search was performed in major web databases for studies from inception to 15 September 2022. A Bayesian network meta-analysis model was used to assess the relative effects of competing treatments on the primary outcomes of risk of significant decline in left ventricular ejection fraction (LVEF) and mean LVEF decline. Secondary outcomes included left ventricular diastolic function, global longitudinal strain, and cardiac biomarkers. This study is registered with PROSPERO, CRD42022357980. RESULTS AND CONCLUSION: Nineteen studies reported the effects of 13 interventions (N = 1905 patients). Only enalapril (RR 0.05, 95% CI 0.00-0.20) was associated with reduced risk of patients developing significant decline in LVEF relative to placebo. Subgroup analysis showed that the beneficial effect of enalapril was driven by protection against anthracycline-associated toxicity. In addition, no RAAS-inhibiting agents showed efficacy in protection against treatment with both anthracycline and trastuzumab. The use of RAAS inhibition therapy did not conclusively impact on other markers of cardiac function, including left ventricular diastolic function and cardiac biomarkers.

The effects of anti-TNF-α biologics on insulin resistance and insulin sensitivity in patients with rheumatoid arthritis: An update systematic review and meta-analysis.

BACKGROUND AND AIM: Increasing evidence demonstrates a link between the chronic inflammatory state in patients with rheumatoid arthritis (RA) and the development of insulin resistance. It is thought that anti-TNF-α biologic therapy may improve insulin sensitivity and ameliorate insulin resistance by the downregulation of inflammatory cytokines, however, pre-clinical and clinical studies have yielded conflicting results. A meta-analysis on this topic is necessary to summarize current evidence and generate hypotheses for future research. METHODS: Literature search was performed in four databases, namely PubMed, EMBASE, Scopus, and The Cochrane Library, from inception till April 9, 2023, querying studies reporting peripheral insulin resistance with and without anti-TNF-α use in patients with RA. Peripheral insulin resistance or sensitivity was quantified by the Homeostasis Model Assessment of Insulin Resistance (HOMA) index or the Quantitative Insulin Sensitivity Check Index (QUICKI) respectively. The difference in insulin resistance or sensitivity between the treatment and control group was calculated using standardized mean difference (SMD) for the purposes of the meta-analysis. RESULTS: Twelve articles were reviewed, with 10 longitudinal studies with a total of 297 patients included in the meta-analysis. The pooled standardized mean difference (SMD) from baseline HOMA was -0.82 (95% CI: -1.38 to -0.25) suggesting significant beneficial effects of anti-TNF-α therapy on insulin resistance. CONCLUSION: Current evidence supports the significant clinical efficacy of anti-TNF-α biologics in alleviating insulin resistance and improving insulin sensitivity in patients with active RA.

Effectiveness of mindfulness-based interventions on the well-being of healthcare workers: a systematic review and meta-analysis.

Background: Growing evidence attests to the efficacy of mindfulness-based interventions (MBIs), but their effectiveness for healthcare workers remains uncertain. Aims: To evaluate the evidence for MBIs in improving healthcare workers' psychological well-being. Methods: A systematic literature search was conducted on Medline, Embase, Cumulative Index for Nursing and Allied Health Literature, PsycINFO and Cochrane Central Register of Controlled Trials up to 31 August 2022 using the keywords 'healthcare worker', 'doctor', 'nurse', 'allied health', 'mindfulness', 'wellness', 'workshop' and 'program'. Randomised controlled trials with a defined MBI focusing on healthcare workers and quantitative outcome measures related to subjective or psychological well-being were eligible for inclusion. R V.4.0.3 was used for data analysis, with the standardised mean difference as the primary outcome, employing DerSimonian and Laird's random effects model. Grading of Recommendations, Assessment, Development and Evaluation framework was used to evaluate the quality of evidence. Cochrane's Risk of Bias 2 tool was used to assess the risk of bias in the included studies. Results: A total of 27 studies with 2506 participants were included, mostly from the USA, involving various healthcare professions. MBIs such as stress reduction programmes, apps, meditation and training showed small to large effects on anxiety, burnout, stress, depression, psychological distress and job strain outcomes of the participants. Positive effects were also seen in self-compassion, empathy, mindfulness and well-being. However, long-term outcomes (1 month or longer postintervention) varied, and the effects were not consistently sustained. Conclusions: MBIs offer short-term benefits in reducing stress-related symptoms in healthcare workers. The review also highlights limitations such as intervention heterogeneity, reduced power in specific subgroup analyses and variable study quality. PROSPERO registration number: CRD42022353340.

Innovative technology-based interventions in Parkinson's disease: A systematic review and meta-analysis.

OBJECTIVE: Novel technology-based interventions have the potential to improve motor symptoms and gait in Parkinson's disease (PD). Promising treatments include virtual-reality (VR) training, robotic assistance, and biofeedback. Their effectiveness remains unclear, and thus, we conducted a Bayesian network meta-analysis. METHODS: We searched the Medline, Embase, Cochrane CENTRAL, and Clinicaltrials.gov databases until 2 April 2024 and only included randomized controlled trials. Outcomes included changes in UPDRS-III/MDS-UPDRS-III score, stride length, 10-meter walk test (10MWT), timed up-and-go (TUG) test, balance scale scores and quality-of-life (QoL) scores. Results were reported as mean differences (MD) or standardized mean differences (SMD), with 95% credible intervals (95% CrI). RESULTS: Fifty-one randomized controlled trials with 2095 patients were included. For UPDRS (motor outcome), all interventions had similar efficacies. VR intervention was the most effective in improving TUG compared with control (MD: -4.36, 95% CrI: -8.57, -0.35), outperforming robotic, exercise, and proprioceptive interventions. Proprioceptive intervention significantly improved stride length compared to control intervention (MD: 0.11 m, 95% CrI: 0.03, 0.19), outperforming VR, robotic and exercise interventions. Virtual reality improved balance scale scores significantly compared to exercise intervention (SMD: 0.75, 95% CrI: 0.12, 1.39) and control intervention (SMD: 1.42, 95% CrI: 0.06, 2.77). Virtual reality intervention significantly improved QoL scores compared to control intervention (SMD: -0.95, 95% CrI: -1.43, -0.52), outperforming Internet-based interventions. INTERPRETATION: VR-based and proprioceptive interventions were the most promising interventions, consistently ranking as the top treatment choices for most outcomes. Their use in clinical practice could be helpful in managing motor symptoms and QoL in PD.

Association of depression with all-cause and cancer-specific mortality in older adults with cancer: Systematic review, meta-analysis, and meta-regression.

INTRODUCTION: The incidence and mortality of cancer is increasing worldwide with studies reporting that cumulative risk of cancer rises as age increases. Against the backdrop of the increasing prevalence of cancer amongst older patients, we conducted a systematic review and meta-analysis examining the depression-mortality relationship in older adults with cancer (OAC). MATERIALS AND METHODS: This PRISMA-adherent systematic review involved a systematic search of PubMed, Medline, EMBASE, and PsycINFO for prospective and retrospective cohort studies comparing the risk of all-cause and cancer-related mortality among OAC with depression. Random effects meta-analyses and meta-regressions were used for the primary analysis. RESULTS: From 5,280 citations, we included 14 cohort studies. Meta-analyses of hazard ratios (HRs) showed an increased incidence of all-cause mortality in OAC with depression (pooled HR: 1.40; 95% confidence interval [CI]: 1.25, 1.55). Subgroup analyses of other categorical study-level characteristics were insignificant. While risk of cancer-related mortality in OAC with depression was insignificantly increased with a pooled HR of 1.21 (95% CI: 0.98, 1.49), subgroup analysis indicated that risk of cancer-related mortality in OAC with depression significantly differed with cancer type. Our systematic review found that having fewer comorbidities, a higher education level, greater socioeconomic status, and positive social supportive factors lowered risk of all-cause mortality in OAC with depression. DISCUSSION: Depression in OAC significantly increases risk of all-cause mortality and cancer-related mortality among different cancer types. It is imperative for healthcare providers and policy makers to recognize vulnerable subgroups among older adults with cancer to individualize interventions.

Effectiveness of immune checkpoint inhibitors and other treatment modalities in patients with advanced mucosal melanomas: a systematic review and individual patient data meta-analysis.

Background: Mucosal melanomas (MM) are an aggressive subtype of melanoma. Given the rarity of this disease, the conduct of clinical trials is challenging and has been limited. Current treatment options have been extrapolated from the more common cutaneous melanoma even though MM is distinct in pathogenesis, etiology and prognosis. This is the first meta-analysis to comprehensively assess the efficacy of immune checkpoint inhibitors (anti-PD1 and anti-CTLA4) and other treatment modalities (targeted therapy such as KIT inhibitors and VEGF inhibitors, as well as radiotherapy) on survival outcomes in MM to develop clinical guidelines for evidence-based management. Methods: The protocol was prospectively registered on PROSPERO (PROSPERO ID: CRD42023411195). PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science and Google Scholar were searched from inception until 25 July 2024, for all cohort and observational studies. Eligible studies included those with five or more participants with locally advanced or metastatic MM treated with anti-PD1, anti-CTLA4, VEGF inhibitors and/or KIT inhibitors. Titles and abstracts of potential articles were screened and full texts of all potentially eligible studies were retrieved and reviewed by two independent reviewers. Individual patient data (IPD) from published Kaplan-Meier curves were reconstructed using a graphical reconstruction method and pooled as a one-stage meta-analysis. A sensitivity analysis using a two-stage meta-analysis approach was conducted. Extracted outcomes included overall survival (OS) and progression-free survival (PFS). For each treatment arm, median survival time and 12-month survival proportion were estimated. Data from double-arm trials was pooled to estimate hazard ratios (HRs), ratios of restricted mean time lost (RMTL) and restricted mean survival time (RMST). Findings: From a total of 7402 studies, 35 eligible studies comprising a total of 2833 participants were included. Combined anti-PD1 and anti-CTLA4 therapy had the highest 12-month OS and 12-month PFS at 71.8% (95% CI: 67.6%, 76.2%, n = 476) and 35.1% (95% CI: 30.5%, 40.4%, n = 401) respectively, followed by anti-PD1 therapy alone (OS: 64.0% (95% CI: 61.4%, 66.7%, n = 1399); PFS: was 28.3% (95% CI: 25.8%, 31.2%, n = 1142), anti-PD1 and VEGF inhibitor combination therapy (OS: 57.1% (95% CI: 51.0%, 63.9%)), KIT inhibitors (OS: 48.2% (95% CI: 37.6%, 61.8%); PFS: 8.3% (95% CI: 3.7%, 18.7%)) and anti-CTLA4 therapy alone (OS: 33.3% (95% CI: 28.4%, 39.1%); PFS: 9.8% (95% CI: 5.9%, 16.5%)). In the double-arm studies, combination therapy with anti-PD1 and anti-CTLA4 had similar OS and PFS with anti-PD1 alone (OS: HR 0.856 (95% CI: 0.704, 1.04); RMTL ratio 0.932 (95% CI: 0.832, 1.044, P = 0.225); RMST ratio 1.102 (95% CI: 0.948, 1.281, P = 0.204); PFS: HR 0.919 (95% CI: 0.788, 1.07); RMTL ratio 0.936 (95% CI: 0.866, 1.013, P = 0.100); RMST ratio 1.21 (95% CI: 0.979, 1.496, P = 0.078)), however, anti-PD1 therapy alone had significantly better PFS than anti-CTLA4 alone (HR 0.548 (95% CI: 0.376, 0.799); RMTL ratio 0.715 (95% CI: 0.606, 0.844, P < 0.001); RMST ratio 1.659 (95% CI: 1.316, 2.092, P < 0.001)). Anti-PD1 therapy with radiotherapy versus anti-PD1 alone showed no significant difference (OS: HR 0.854 (95% CI: 0.567, 1.29); RMTL ratio 0.855 (95% CI: 0.675, 1.083, P = 0.193); RMST ratio 1.194 (95% CI: 0.928, 1.536, P = 0.168; PFS: HR 0.994 (95% CI: 0.710, 1.39); RMTL ratio 1.006 (95% CI: 0.87, 1.162, P = 0.939); RMST ratio 0.984 (95% CI: 0.658, 1.472, P = 0.939)). Interpretation: For the systemic treatment of MM, anti-PD1 is the best monotherapy. While combining anti-PD1 with other treatment options such as anti-CTLA4, VEGF inhibitors or radiotherapy might achieve better outcomes, these improvements did not reach statistical significance when evaluated by HR, RMTL and RMST ratios. Funding: This work was supported by the National Medical Research Council Transition Award (TA20nov-0020), SingHealth Duke-NUS Oncology Academic Clinical Programme (08/FY2020/EX/67-A143 and 08/FY2021/EX/17-A47), the Khoo Pilot Collaborative Award (Duke-NUS-KP(Coll)/2022/0020A), the National Medical Research Council Clinician Scientist-Individual Research Grant-New Investigator Grant (CNIGnov-0025), the Terry Fox Grant (I1056) and the Khoo Bridge Funding Award (Duke-NUS-KBrFA/2024/0083I).

Socioeconomic disadvantage and long-term survival duration in out-of-hospital cardiac arrest patients: A population-based cohort study.

Background: Socioeconomic status (SES) is a well-established determinant of cardiovascular health. However, the relationship between SES and clinical outcomes in long-term out-of-hospital cardiac arrest (OHCA) is less well-understood. The Singapore Housing Index (SHI) is a validated building-level SES indicator. We investigated whether SES as measured by SHI is associated with long-term OHCA survival in Singapore. Methods: We conducted an open cohort study with linked data from the Singapore Pan-Asian Resuscitation Outcomes Study (PAROS), and the Singapore Registry of Births and Deaths (SRBD) from 2010 to 2020. We fitted generalized structural equation models, calculating hazard ratios (HRs) using a Weibull model. We constructed Kaplan-Meier survival curves and calculated the predicted marginal probability for each SHI category. Results: We included 659 cases. In both univariable and multivariable analyses, SHI did not have a significant association with survival. Indirect pathways of SHI mediated through covariates such as Emergency Medical Services (EMS) response time (HR of low-medium, high-medium and high SHI when compared to low SHI: 0.98 (0.88-1.10), 1.01 (0.93-1.11), 1.02 (0.93-1.12) respectively), and age of arrest (HR of low-medium, high-medium and high SHI when compared to low SHI: 1.02 (0.75-1.38), 1.08 (0.84-1.38), 1.18 (0.91-1.54) respectively) had no significant association with OHCA survival. There was no clear trend in the predicted marginal probability of survival among the different SHI categories. Conclusions: We did not find a significant association between SES and OHCA survival outcomes in residential areas in Singapore. Among other reasons, this could be due to affordable healthcare across different socioeconomic classes.

Comparing the Impact of Stenting vs. Medical Therapy for Intracranial Arterial Stenosis : A Systematic Review and One-stage and Two-stage Meta-Analysis of Randomized Clinical Trials.

PURPOSE: In the treatment of intracranial arterial stenosis (ICAS), controversies remain regarding the optimal treatment strategy. Our study aims to conduct an individual patient-level data meta-analysis of existing RCTs comparing PTAS versus best medical therapy and to identify differences in outcomes such as incidence of ischemic stroke or death. METHODS: Randomised controlled trials comparing the outcomes of stenting versus best medical therapy for patients who had symptomatic ICAS of >50%. Excluded studies included case reports, case series, reviews, observational studies,  letters or studies evaluating isolated angioplasty techniques without stenting. Data was extracted in accordance with PRISMA guidelines. RESULTS: 7 studies involving 1425 participants were included. There was an increased risk in the incidence of stroke and death within the first 30 days post-procedure for patients treated with PTAS over best medical therapy (RR = 2.22 [1.28-3.86], I²â€¯= 0%). Patients who underwent stenting also had a significantly higher risk of intracranial haemorrhage (RR = 12.66 [2.41-66.45], I²â€¯= 0%) and death (RR = 5.41 [1.20-24.28], I²â€¯= 0%).Under the shared frailty model, stenting when compared to medical therapy has a HR of 1.81 (95% CI:1.25-2.6) of stroke or death across 1 year. Under the parametric Royston-Parmar model, stenting has a significant decrease in the RMST(-0.83 months; 95% CI: -1.30-0.37). Stenting continued to show worse outcomes up to the 3 year mark with a HR of 1.60 (95% CI: 1.11-2.32). CONCLUSIONS AND RELEVANCE: There is an increased risk of peri- and post-procedural stroke and death over best medical therapy in patients with symptomatic ICAS who undergo PTAS. Further work is required to refine patient selection and mitigate peri-procedural risks.

Predictors of major adverse cardiac events among patients with chest pain and low HEART score in the emergency department.

AIM: For patients who present to the emergency departments (ED) with undifferentiated chest pain, the risk of major adverse cardiac events (MACE) may be underestimated in low-HEART score patients. We aimed to identify characteristics of patients who were classified as low risk by HEART score but subsequently developed MACE at 6 weeks. METHODS: We studied a multiethnic cohort of patients who presented with chest pain arousing suspicion of acute coronary syndrome to EDs in the Netherlands and Singapore. Patients were risk-stratified using HEART score and followed up for MACE at 6 weeks. Risk factors of developing MACE despite low HEART scores (scores 0-3) were identified using logistic and Cox regression models. RESULTS: Among 1376 (39.8%) patients with low HEART scores, 63 (4.6%) developed MACE at 6 weeks. More males (53/806, 6.6%) than females (10/570, 2.8%) with low HEART score developed MACE. There was no difference in outcomes between ethnic groups. Among low-HEART score patients with 2 points for history, 21% developed MACE. Among low-HEART score patients with 1 point for troponin, 50% developed MACE, while 100% of those with 2 points for troponin developed MACE. After adjusting for HEART score and potential confounders, male sex was independently associated with increased odds (OR 4.12, 95%CI 2.14-8.78) and hazards (HR 3.93, 95%CI 1.98-7.79) of developing MACE despite low HEART score. CONCLUSION: Male sex, highly suspicious history and elevated troponin were disproportionately associated with MACE. These characteristics should prompt clinicians to consider further investigation before discharge.

Recent updates on central nervous system prophylaxis in patients with high-risk diffuse large B-cell lymphoma.

The use of central nervous system (CNS) prophylaxis for patients with diffuse large B-cell lymphoma (DLBCL) remains controversial. Although uncommon, CNS relapses are invariably fatal in this otherwise curable disease. Accurate identification of patients at risk and the optimal approach to CNS prophylaxis therefore remains an area of unmet need. The existing literature, largely retrospective in nature, provides mixed conclusions regarding the efficacy of CNS prophylaxis. The utility of CNS prophylaxis has itself been challenged. In this review, we dissect the issues which render the value of CNS prophylaxis uncertain. We first compare international clinical guidelines for CNS prophylaxis. We then interrogate the factors that should be used to identify high-risk patients accurately. We also explore how clinical patterns of CNS relapse have changed in the pre-rituximab and rituximab era. We then discuss the efficacy of CNS-directed approaches, intensification of systemic treatment and other novel approaches in CNS prophylaxis. Improved diagnostics for early detection of CNS relapses and newer therapeutics for CNS prophylaxis are areas of active investigation. In an area where prospective, randomized studies are impracticable and lacking, guidance for the use of CNS prophylaxis will depend on rigorous statistical review of retrospective data.

High-density lipoprotein cholesterol subfraction HDL2 is associated with improved endothelial function in systemic lupus erythematosus.

OBJECTIVE: Patients with systemic lupus erythematosus (SLE) have increased risk of premature atherosclerosis but the exact mechanisms remains unclear. Flow-mediated dilatation (FMD) is an established non-invasive assessment of vascular endothelial function. Lipoprotein subfractions may be better predictors of FMD than conventional cholesterol measurements. We tested the hypothesis that lipoprotein subfractions are independently associated with FMD. METHODS: Forty-one consecutive adult patients with SLE without known cardiovascular risk factors or disease were recruited in this cross-sectional study. Endothelial function and early atherosclerosis were assessed by brachial FMD and common carotid artery (CCA) intima-media thickness (IMT). High-density lipoprotein (HDL)/low-density lipoprotein (LDL) subfractions were measured. Machine learning models were also constructed to predict FMD and CCA IMT. RESULTS: Median FMD was 4.48% (IQR 5.00%) while median IMT was 0.54 mm (IQR 0.12 mm). Univariate analysis showed lower LDL1 (r=-0.313, p<0.05) and higher HDL2 subfractions (r=0.313, p<0.05) were significantly associated with higher log-transformed FMD. In a multiple linear regression model, HDL2 (ß=0.024, SE=0.012, p<0.05) remained an independent predictor of higher FMD after adjusting for age, body mass index, LDL1 and systolic blood pressure. The machine learning model included parameters such as HDL2 (positive association), prednisolone dose, LDL cholesterol and LDL1 for prediction of FMD (r=0.433, p<0.01). Age, LDL cholesterol and systolic blood pressure were independently associated with higher CCA IMT after adjusting for body mass index and HDL2. CONCLUSIONS: HDL 2, a large HDL particle, was independently associated with greater FMD and may be a biomarker of vascular health in SLE.

Using Deauville Scoring to Guide Consolidative Radiotherapy in Diffuse Large B-Cell Lymphoma.

BACKGROUND: The most common aggressive lymphoma in adults is diffuse large B-cell lymphoma (DLBCL). Consolidative radiotherapy (RT) is often administered to DLBCL patients but guidelines remain unclear, which could lead to unnecessary RT. We aimed to evaluate the value of end-of-treatment PET-CT scans, interpreted using the Deauville score (DV), to guide the utilization of consolidative RT, which may help spare low-risk DLBCL patients from unnecessary RT. METHODS: We included all DLBCL patients diagnosed between 2010 and 2022 at the National Cancer Centre Singapore with DV measured at the end of the first-line chemoimmunotherapy. The outcome measure was time-to-progression (TTP). The predictive value of DV for RT was assessed based on the interaction effect between the receipt of RT and DV in Cox regression models. RESULTS: The data of 349 patients were analyzed. The median follow-up time was 38.1 months (interquartile range 34.0-42.3 months). RT was associated with a significant improvement in TTP amongst the DV4-5 patients (HR 0.33; 95%CI 0.13-0.88; p = 0.027) but not the DV1-3 patients (HR 0.85; 95%CI 0.40-1.81; p = 0.671) (interaction's p = 0.133). Multivariable analysis reported that RT was again significantly associated with improved TTP among the DV4-5 patients (adjusted HR 0.29; 95%CI 0.10-0.80; p = 0.017) but not the DV1-3 group (HR 0.86; 95%CI 0.40-1.86; p = 0.707) (interaction's p = 0.087). CONCLUSION: Our results suggests that DLBCL patients with end-of-treatment PET-CT DV1-3 may not need consolidative RT. Longer follow-up and prospective randomized trials are still necessary to investigate long-term outcomes.

Accuracy of machine learning in predicting outcomes post-percutaneous coronary intervention: a systematic review.

Background: Recent studies have shown potential in introducing machine learning (ML) algorithms to predict outcomes post-percutaneous coronary intervention (PCI). Aims: We aimed to critically appraise current ML models' effectiveness as clinical tools to predict outcomes post-PCI. Methods: Searches of four databases were conducted for articles published from the database inception date to 29 May 2021. Studies using ML to predict outcomes post-PCI were included. For individual post-PCI outcomes, measures of diagnostic accuracy were extracted. An adapted checklist comprising existing frameworks for new risk markers, diagnostic accuracy, prognostic tools and ML was used to critically appraise the included studies along the stages of the translational pathway: development, validation, and impact. Quality of training data and methods of dealing with missing data were evaluated. Results: Twelve cohorts from 11 studies were included with a total of 4,943,425 patients. ML models performed with high diagnostic accuracy. However, there are concerns over the development of the ML models. Methods of dealing with missing data were problematic. Four studies did not discuss how missing data were handled. One study removed patients if any of the predictor variable data points were missing. Moreover, at the validation stage, only three studies externally validated the models presented. There could be concerns over the applicability of these models. None of the studies discussed the cost-effectiveness of implementing the models. Conclusions: ML models show promise as a useful clinical adjunct to traditional risk stratification scores in predicting outcomes post-PCI. However, significant challenges need to be addressed before ML can be integrated into clinical practice.

A circularly permuted CasRx platform for efficient, site-specific RNA editing.

Inactive Cas13 orthologs have been fused to a mutant human ADAR2 deaminase domain at the C terminus to enable programmable adenosine-to-inosine (A-to-I) RNA editing in selected transcripts. Although promising, existing RNA-editing tools generally suffer from a trade-off between efficacy and specificity, and off-target editing remains an unsolved problem. Here we describe the development of an optimized RNA-editing platform by rational protein engineering, CasRx-based Programmable Editing of RNA Technology (xPERT). We demonstrate that the topological rearrangement of a CasRx K940L mutant by circular permutation results in a robust scaffold for the tethering of a deaminase domain. We benchmark our tool against the REPAIR system and show that xPERT exhibits strong on-target activity like REPAIRv1 but low off-target editing like REPAIRv2. Our xPERT platform can be used to alter RNA sequence information without risking genome damage, effect temporary cellular changes and customize protein function.

Public perception on 'healthy ageing' in the past decade: An unsupervised machine learning of 63,809 Twitter posts.

The World Health Organization (WHO) started the initiative on healthy ageing from 2016 to 2020, which has now continued into the United Nations (UN) Decade of Healthy Ageing 2021-2030. Research into healthy ageing and healthy ageing communities have emphasized that the concept of healthy ageing encompasses a plurality of views and has multiple dimensions. Anchored in a transdisciplinary approach, the present report thus aimed to investigate public perceptions of healthy ageing via a deep analysis of social media posts on Twitter. Original tweets, containing the terms "Healthy Ageing" OR "healthy aging" OR "healthyageing" OR "healthyaging", and posted in English between 1 January 2012 and 30 June 2022 were extracted. Bidirectional Encoder Representations from Transformers (BERT) Named Entity Recognition was applied to select for individual users. Topic modelling, specifically BERTopic was used to generate interpretable topics and descriptions pertaining to the concept of healthy ageing. Subsequently, manual thematic analysis was performed by the study investigators, with independent reviews of the topic labels and themes. A total of 63,809 unique tweets were analyzed and clustered semantically into 16 topics. The public perception of healthy ageing could be broadly grouped into three themes: (1) healthy diet and lifestyle, (2) maintaining normal bodily functions and (3) preventive care. While most perceptions dovetail WHO's definition, there are some points regarding skin appearances, beauty and aging that should be closely considered in the design of initiatives in the UN Decade of Healthy Ageing and beyond.