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.

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 adult's 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 increase depression, anxiety, mood, and loneliness. Nevertheless, a third (33.0%) also reported positive impacts, where positive and purposeful use of social media would contribute 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 would affect adults and identified areas of research that merit investigations 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.

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.

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.

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.

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.

Trends in Pseudomonas aeruginosa (P. aeruginosa) Bacteremia during the COVID-19 Pandemic: A Systematic Review.

Pseudomonas aeruginosa (P. aeruginosa) is among the most common pathogens associated with healthcare-acquired infections, and is often antibiotic resistant, causing significant morbidity and mortality in cases of P. aeruginosa bacteremia. It remains unclear how the incidence of P. aeruginosa bacteremia changed during the Coronavirus Disease 2019 (COVID-19) pandemic, with studies showing almost contradictory conclusions despite enhanced infection control practices during the pandemic. This systematic review sought to examine published reports with incidence rates for P. aeruginosa bacteremia during (defined as from March 2020 onwards) and prior to the COVID-19 pandemic. A systematic literature search was conducted in accordance with PRISMA guidelines and performed in Cochrane, Embase, and Medline with combinations of the key words (pseudomonas aeruginosa OR PAE) AND (incidence OR surveillance), from database inception until 1 December 2022. Based on the pre-defined inclusion criteria, a total of eight studies were eligible for review. Prior to the pandemic, the prevalence of P. aeruginosa was on an uptrend. Several international reports found a slight increase in the incidence of P. aeruginosa bacteremia during the COVID-19 pandemic. These findings collectively highlight the continued importance of good infection prevention and control and antimicrobial stewardship during both pandemic and non-pandemic periods. It is important to implement effective infection prevention and control measures, including ensuring hand hygiene, stepping up environmental cleaning and disinfection efforts, and developing timely guidelines on the appropriate prescription of antibiotics.

Linking autism spectrum disorders and parkinsonism: clinical and genetic association.

BACKGROUND: Autism spectrum disorders (ASD) comprise many complex and clinically distinct neurodevelopmental conditions, with increasing evidence linking them to parkinsonism. METHODS: We searched Medline and Embase from inception to 21 March 2022 and reviewed the bibliographies of relevant articles. Studies were screened and reviewed comprehensively by two independent authors. RESULTS: Of 863 references from our search, we included eight clinical studies, nine genetic studies, and five case reports. Regardless of age group, Parkinson's disease (PD) and parkinsonian syndromes were more frequently observed in patients with ASD, though the evidence for increased rates of parkinsonism is less clear for children and adolescents. Parkinsonian features and hypokinetic behavior were common in Rett syndrome, with prevalence estimates ranging from 40% to 80%. Frequently observed parkinsonian features include bradykinesia, rigidity, hypomimia, and gait freezing. PD gene PARK2 copy number variations appear more frequently in ASD cases than controls. Evidence suggests that RIT2 and CD157/BST1 are implicated in ASD and PD, while the evidence for other PD-related genes (DRD2, GPCR37, the SLC gene family, and SMPD1) is less clear. Rare mutations, such as ATP13A2, CLN3, and WDR45, could result in autistic behavior and concomitant parkinsonism. CONCLUSION: The prevalence of parkinsonism in ASD is substantially greater than in the general population or matched controls. Various PD-associated gene loci, especially PARK2, could confer susceptibility to ASD as well. Important future directions include conducting prospective cohort studies to understand how parkinsonian symptoms may progress, genetic studies to reveal relevant gene loci, and pathophysiologic studies to identify potential therapeutic targets.

Performance of the paracetamol-aminotransferase multiplication product in risk stratification after paracetamol (acetaminophen) poisoning: a systematic review and meta-analysis.

BACKGROUND: Risk stratification in paracetamol (acetaminophen) poisoning is crucial because hepatotoxicity is common and can be mitigated with treatment. However, current risk stratification tools have limitations. AIMS: We evaluated the diagnostic performance of the paracetamol concentration × aminotransferase multiplication product, for predicting hepatotoxicity after paracetamol overdose. METHODS: Medline, Cochrane Library and Embase were searched for eligible papers. We used random effects models to obtain pooled estimates of the likelihood ratios and diagnostic odds ratios, from which sensitivity and specificity were computed. We assessed two commonly used cut-off values of paracetamol × aminotransferase, 1500 mg/L × IU/L and 10,000 mg/L × IU/L. Using the confusion matrices of these two cut-offs, area under the summary receiver operator characteristic curve and optimal cut-off values in different clinical scenarios were established. RESULTS: Six studies comprising 5036 participants were included. In 4051 patients, using the cut-off of 1500 mg/L × IU/L, a diagnostic odds ratio of 31.90 (95%CI: 9.52-106.90), sensitivity of 0.98 (95%CI: 0.94-1.00) and specificity of 0.66 (95%CI: 0.49-0.89) were obtained. In 3983 patients, using the cut-off of 10,000 mg/L × IU/L, a diagnostic odds ratio of 99.34 (95%CI: 12.26-804.87), sensitivity of 0.65 (95%CI: 0.51-0.82) and specificity of 0.97 (95%CI: 0.95-1.00) were obtained. For staggered ingestions, the 1500 mg/L × IU/L cut-off yielded a diagnostic odds ratio of 69.53 (95%CI: 4.03-1199.75), sensitivity of 1.00 (95%CI: 0.87-1.00) and specificity of 0.74 (95%CI: 0.43-1.00). Next, using the 10,000 mg/L × IU/L cut-off in this scenario yielded a diagnostic odds ratio of 254.58 (95%CI: 11.12-5827.60), sensitivity of 0.79 (95%CI: 0.59-1.00) and specificity of 0.98 (95%CI: 0.94-1.00). The overall summary receiver operator characteristic curve was 0.91 (95%CI: 0.75-0.97), and the optimal cut-off value was 3840 mg/L × IU/L. The summary receiver operator characteristic curve in patients with staggered ingestions was 0.96 (95%CI: 0.85-0.99). The summary receiver operator characteristic curve in patients with staggered ingestions and whose paracetamol concentration was below the detectable limit of 10 mg/L at presentation was 0.97 (95%CI: 0.94-0.99). CONCLUSION: In this first meta-analysis, paracetamol × aminotransferase demonstrates its use in prognosticating hepatotoxicity in patients with paracetamol poisoning. It complements the Rumack-Matthew nomogram as it has shown promise in addressing two key limitations of the nomogram: it is usable after more than 24 h between overdose and acetylcysteine treatment, and it is applicable in staggered ingestions.

Examining the Public Messaging on 'Loneliness' over Social Media: An Unsupervised Machine Learning Analysis of Twitter Posts over the Past Decade.

Loneliness is an issue of public health significance. Longitudinal studies indicate that feelings of loneliness are prevalent and were exacerbated by the Coronavirus Disease 2019 (COVID-19) pandemic. With the advent of new media, more people are turning to social media platforms such as Twitter and Reddit as well as online forums, e.g., loneliness forums, to seek advice and solace regarding their health and well-being. The present study therefore aimed to investigate the public messaging on loneliness via an unsupervised machine learning analysis of posts made by organisations on Twitter. We specifically examined tweets put out by organisations (companies, agencies or common interest groups) as the public may view them as more credible information as opposed to individual opinions. A total of 68,345 unique tweets in English were posted by organisations on Twitter from 1 January 2012 to 1 September 2022. These tweets were extracted and analysed using unsupervised machine learning approaches. BERTopic, a topic modelling technique that leverages state-of-the-art natural language processing, was applied to generate interpretable topics around the public messaging of loneliness and highlight the key words in the topic descriptions. The topics and topic labels were then reviewed independently by all study investigators for thematic analysis. Four key themes were uncovered, namely, the experience of loneliness, people who experience loneliness, what exacerbates loneliness and what could alleviate loneliness. Notably, a significant proportion of the tweets centred on the impact of the COVID-19 pandemic on loneliness. While current online interactions are largely descriptive of the complex and multifaceted problem of loneliness, more targeted prosocial messaging appears to be lacking to combat the causes of loneliness brought up in public messaging.

Lifetime Burden of Psychological Symptoms, Disorders, and Suicide Due to Cancer in Childhood, Adolescent, and Young Adult Years: A Systematic Review and Meta-analysis.

Importance: A cancer diagnosis and treatment may result in highly traumatic periods with lasting psychological consequences for children, adolescent, and young adult patients with cancer (CYACs). Early identification and management may prevent long-term psychological morbidity and suicide. Objective: To analyze risk, severity, and risk factors for depression, anxiety, psychotic disorders, and suicide in CYACs and noncancer comparators. Data Sources: Literature search of PubMed, MEDLINE, Embase, PsycINFO, CINAHL, and PubMed Central from January 1, 2000, to November 18, 2022. Study Selection: Full-length articles in peer-reviewed journals that measured and reported risk and/or severity of depression, anxiety, psychotic disorders, and suicide mortality in CYACs and a noncancer comparator group. Data Extraction and Synthesis: Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines were followed with prospective PROSPERO registration. Main Outcomes and Measures: Risk ratios (RRs) were used for dichotomous outcomes, and standardized mean differences (SMDs) were used for continuous outcomes. SMDs were defined as follows: 0.2, small; 0.5, medium; and 0.8, large. Sources of heterogeneity and risk factors were investigated using sensitivity, subgroup, and meta-regression analyses. Results: From 7319 records, 52 studies were included. Meta-analyses revealed that CYACs were at increased lifetime risk of severe symptoms or a disorder of depression (RR, 1.57; 95% CI, 1.29-1.92), anxiety (RR, 1.29; 95% CI, 1.14-1.47), and psychotic disorders (RR, 1.56; 95% CI, 1.36-1.80) relative to both matched controls and their siblings. Overall suicide mortality was not significantly elevated (RR, 1.63; 95% CI, 0.78-3.40). The mean severity of depression was found to be elevated in CYACs receiving treatment (SMD, 0.44; 95% CI, 0.13-0.74) and long-term survivors (SMD, 0.18; 95% CI, 0.02-0.33). The mean severity of anxiety was found to be elevated only during treatment (SMD, 0.16; 95% CI, 0.03-0.20). Conclusions and Relevance: Findings of this systematic review and meta-analysis suggest that CYACs may experience lasting psychological burden long into survivorship. Timely identification, preventive efforts, and psycho-oncological intervention for psychological comorbidity are recommended.

Examining the Negative Sentiments Related to Influenza Vaccination from 2017 to 2022: An Unsupervised Deep Learning Analysis of 261,613 Twitter Posts.

Several countries are witnessing significant increases in influenza cases and severity. Despite the availability, effectiveness and safety of influenza vaccination, vaccination coverage remains suboptimal globally. In this study, we examined the prevailing negative sentiments related to influenza vaccination via a deep learning analysis of public Twitter posts over the past five years. We extracted original tweets containing the terms 'flu jab', '#flujab', 'flu vaccine', '#fluvaccine', 'influenza vaccine', '#influenzavaccine', 'influenza jab', or '#influenzajab', and posted in English from 1 January 2017 to 1 November 2022. We then identified tweets with negative sentiment from individuals, and this was followed by topic modelling using machine learning models and qualitative thematic analysis performed independently by the study investigators. A total of 261,613 tweets were analyzed. Topic modelling and thematic analysis produced five topics grouped under two major themes: (1) criticisms of governmental policies related to influenza vaccination and (2) misinformation related to influenza vaccination. A significant majority of the tweets were centered around perceived influenza vaccine mandates or coercion to vaccinate. Our analysis of temporal trends also showed an increase in the prevalence of negative sentiments related to influenza vaccination from the year 2020 onwards, which possibly coincides with misinformation related to COVID-19 policies and vaccination. There was a typology of misperceptions and misinformation underlying the negative sentiments related to influenza vaccination. Public health communications should be mindful of these findings.