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BACKGROUND: SARS-CoV-2 remains rapidly evolving, and many biologically important genomic substitutions/indels have characterised novel SARS-CoV-2 lineages, which have emerged during successive global waves of the pandemic. Worldwide genomic sequencing has been able to monitor these waves, track transmission clusters, and examine viral evolution in real time to help inform healthcare policy. One school of thought is that an apparent greater than average divergence in an emerging lineage from contemporary variants may require persistent infection, for example in an immunocompromised host. Due to the nature of the COVID-19 pandemic and sampling, there were few studies that examined the evolutionary trajectory of SARS-CoV-2 in healthy individuals. METHODS: We investigated viral evolutionary trends and participant symptomatology within a cluster of 16 SARS-CoV-2 infected, immunocompetent individuals with no co-morbidities in a closed transmission chain. Longitudinal nasopharyngeal swab sampling allowed characterisation of SARS-CoV-2 intra-host variation over time at both the dominant and minor genomic variant levels through Nimagen-Illumina sequencing. RESULTS: A change in viral lineage assignment was observed in individual infections; however, there was only one indel and no evidence of recombination over the period of an acute infection. Minor and dominant genomic modifications varied between participants, with some minor genomic modifications increasing in abundance to become the dominant viral sequence during infection. CONCLUSIONS: Data from this cohort of SARS-CoV-2-infected participants demonstrated that long-term persistent infection in an immunocompromised host was not necessarily a prerequisite for generating a greater than average frequency of amino acid substitutions. Amino acid substitutions at both the dominant and minor genomic sequence level were observed in immunocompetent individuals during infection showing that viral lineage changes can occur generating viral diversity.
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COVID-19 , Genoma Viral , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/transmissão , COVID-19/virologia , COVID-19/genética , Masculino , Adulto , Feminino , Pessoa de Meia-Idade , Variação Genética , Imunocompetência , Evolução Molecular , Filogenia , IdosoRESUMO
The UK observed a marked increase in scarlet fever and invasive group A streptococcal infection in 2022 with severe outcomes in children and similar trends worldwide. Here we report lineage M1UK to be the dominant source of invasive infections in this upsurge. Compared with ancestral M1global strains, invasive M1UK strains exhibit reduced genomic diversity and fewer mutations in two-component regulator genes covRS. The emergence of M1UK is dated to 2008. Following a bottleneck coinciding with the COVID-19 pandemic, three emergent M1UK clades underwent rapid nationwide expansion, despite lack of detection in previous years. All M1UK isolates thus-far sequenced globally have a phylogenetic origin in the UK, with dispersal of the new clades in Europe. While waning immunity may promote streptococcal epidemics, the genetic features of M1UK point to a fitness advantage in pathogenicity, and a striking ability to persist through population bottlenecks.
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COVID-19 , Filogenia , Infecções Estreptocócicas , Streptococcus pyogenes , Streptococcus pyogenes/genética , Streptococcus pyogenes/patogenicidade , Streptococcus pyogenes/isolamento & purificação , Reino Unido/epidemiologia , Humanos , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/microbiologia , COVID-19/epidemiologia , Pandemias , Escarlatina/epidemiologia , Escarlatina/microbiologia , Mutação , Proteínas Repressoras/genética , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Genoma Bacteriano , Europa (Continente)/epidemiologia , Proteínas de BactériasRESUMO
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.
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Saúde Mental , Mídias Sociais , Humanos , Mídias Sociais/tendências , Mídias Sociais/estatística & dados numéricos , Mídias Sociais/normas , Saúde Mental/estatística & dados numéricos , Saúde Mental/normas , AdultoRESUMO
CONTEXT: Diabetes mellitus is associated with morbid complications such as diabetic foot ulcers (DFUs) that may lead to amputations or mortality if not managed adequately. OBJECTIVE: New adjunctive interventions to treat diabetic wounds include topical biologics and growth factors. This study aims to evaluate their efficacy in improving wound-healing outcomes and safety. METHODS: Comprehensive database searches of MEDLINE via PubMed, EMBASE, and Cochrane were performed from inception to December 2022. Three independent researchers selected the studies. Randomized controlled trials that compared the use of a topical biologic growth factor-containing regimen to other biologics or standard of care (SOC) were included. This review followed PRISMA guidelines. Risk of bias analysis was performed using the Jadad scale. Network meta-analysis was performed. Treatments were grouped into common nodes based on the type of biologic agent. Primary outcomes of interest were healing rate and time to wound closure. Secondary outcomes included wound infection, serious adverse events (AEs), and amputation rate. RESULTS: Human umbilical cord (HUC) was associated with the highest cure, followed by recombinant human epidermal growth factor (hEGF). A significantly greater reduction in the time to cure DFUs was seen in HUC, hEGF, and fibroblast growth factor (FGF). There was a significantly lower risk of AEs when platelet-rich plasma (PRP) was administered. CONCLUSION: HUC, hEGF, and FGF are promising topical biologics with statistically significant primary outcomes compared to SOC, while PRP is effective in reducing ulcer-related AEs. HUC has been found to be the most effective in terms of cure rate and a reduction in time to cure.
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Administração Tópica , Pé Diabético , Peptídeos e Proteínas de Sinalização Intercelular , Cicatrização , Humanos , Cicatrização/efeitos dos fármacos , Pé Diabético/tratamento farmacológico , Peptídeos e Proteínas de Sinalização Intercelular/administração & dosagem , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto , Fator de Crescimento Epidérmico/administração & dosagem , Fator de Crescimento Epidérmico/uso terapêuticoRESUMO
Background: Panton-Valentine leukocidin (PVL) Staphylococcus aureus (SA) is an emergent public health concern. PVL toxin has been mostly associated with methicillin-sensitive S. aureus (MSSA)-related skin and soft tissue infections occurring in high-risk groups such as people who inject drugs (PWID). The emergence of PVL methicillin-resistant S. aureus (MRSA) infection is causing severe and life-threatening disease in PWID. Clinical cases: We present an outbreak of eight PVL-MRSA bacteraemia cases at a UK teaching hospital between 2018 and 2022. An additional four patients developed bacteraemia with PVL-negative MRSA of the same multilocus sequence type (MLST). All patients were PWID and aged 33-51 years old. Four patients developed MRSA bacterial endocarditis. Three patients died. These cases represent the initial cases detected at Doncaster and Bassetlaw Teaching Hospitals of what is an ongoing and developing outbreak. Management: An outbreak investigation has been undertaken in association with the UK Health Security Agency. Epidemiological factors have been explored, including via direct contact at a local sheltered accommodation and the possibility of a contaminated drug supply. Whole-genome sequencing confirmed that all isolates were closely related and of the same MLST (sequence type 5). A community substance misuse group disseminated health education on the prevention of PVL-MRSA. Preventing infection in PWID presents a major challenge due to the impact of addiction on engagement with services and the significant barriers faced by our patients in observing infection prevention measures. Conclusion: PVL-MRSA is of major public health concern and outbreak investigation and mapping out local epidemiological patterns plays a vital role in preventing further spread throughout the community. Additionally, this work enables targeted and early treatment in patients in high-risk categories for disease. These cases of PVL-MRSA infection in PWID highlights the transmissibility, pathogenic potential and severe clinical disease spectrum within this population. Further work is required to tackle transmission and infection from this pathogenic strain.
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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.
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Depressão , Neoplasias , Humanos , Neoplasias/mortalidade , Neoplasias/psicologia , Idoso , Depressão/epidemiologia , Causas de Morte , Fatores de Risco , Feminino , Masculino , Idoso de 80 Anos ou maisRESUMO
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.
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Aterosclerose , Lúpus Eritematoso Sistêmico , Adulto , Humanos , Lipoproteínas HDL2 , LDL-Colesterol , Espessura Intima-Media Carotídea , Estudos Transversais , Colesterol , Lipoproteínas HDLRESUMO
Importance: Suicide risk may be increased in patients with Parkinson disease (PD), a common neurodegenerative condition. Mood disorders, especially depression, are prevalent in patients with PD who report suicidality. Objective: To address inconsistent results from studies of suicidal ideation and behavior in patients with PD. Data Sources: The study team searched MEDLINE and Embase from inception to June 14, 2023, and further screened the bibliographies of relevant studies to ensure a comprehensive search. Study Selection: Original studies, published in English, discussing either suicidal ideation, behavior, or both in adults with PD were included. Accepted study designs included cross-sectional, case-control, and cohort studies. Studies that only included patients with PD after deep brain stimulation were excluded. Data Extraction and Synthesis: This meta-analysis was conducted in line with the PRISMA guidelines. Two authors reviewed each study and extracted the data independently, with discrepancies referred to a third independent author. Main Outcomes and Measures: Outcomes included the prevalence of suicidal ideation and behavior, measured as proportions, and the risk of suicidal behavior in patients with PD relative to controls, measured in both odds ratio (OR) and hazards ratio (HR). Results: A total of 28 studies comprising 505â¯950 PD patients were included in the final analysis. The prevalence of suicidal ideation was evaluated in 14 studies (22.2%; 95% CI, 14.6-32.3) and suicidal behavior in 21 studies (1.25%; 95% CI, 0.64-2.41). Excluding 4 outliers, prevalence of suicidal behavior was significantly higher in prospective studies (1.75%; 95% CI, 1.03-2.95) than retrospective studies (0.50%; 95% CI, 0.24-1.01). Excluding 1 outlier, OR of suicidal behavior was pooled across 10 studies and significant (OR, 2.15; 95% CI, 1.22-3.78; P = .01). HR of suicidal behavior was assessed in 9 studies (HR, 1.73; 95% CI, 1.40-2.14; P < .001). Conclusions and Relevance: This meta-analysis involving more than 500â¯000 patients with PD found 22.2% and 1.25% of patients with PD to have suicidal ideation and behavior, respectively. Patients with PD had 2 times the risk of suicidal behavior than controls. Early recognition and management of suicidality in PD can help reduce mortality.
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Doença de Parkinson , Ideação Suicida , Adulto , Humanos , Tentativa de Suicídio , Estudos Retrospectivos , Doença de Parkinson/epidemiologia , Estudos Prospectivos , Estudos TransversaisRESUMO
Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in cancer patients. Low molecular weight heparin (LMWH) has been the standard of care but new guidelines have approved the use of non-vitamin K antagonist oral anticoagulants (NOAC). By conducting an individual patient data (IPD) meta-analysis of randomised controlled trials (RCTs) comparing the outcomes of NOAC versus LMWH in cancer patients, we aim to determine an ideal strategy for the prophylaxis of VTE and prevention of VTE recurrence. Three databases were searched from inception until 19 October 2022. IPD was reconstructed from Kaplan-Meier curves. Shared frailty, stratified Cox and Royston-Parmar models were fit to compare the outcomes of venous thromboembolism recurrence and major bleeding. For studies without Kaplan-Meier curves, aggregate data meta-analysis was conducted using random-effects models. Eleven RCTs involving 4844 patients were included. Aggregate data meta-analysis showed that administering NOACs led to a significantly lower risk of recurrent VTE (RR = 0.65; 95%CI: 0.50-0.84) and deep vein thrombosis (DVT) (RR = 0.60; 95%CI: 0.40-0.90). In the IPD meta-analysis, NOAC when compared with LMWH has an HR of 0.65 (95%CI: 0.49-0.86) for VTE recurrence. Stratified Cox and Royston-Parmar models demonstrated similar results. In reducing risks of recurrent VTE and DVT among cancer patients, NOACs are superior to LMWHs without increased major bleeding.
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Background and Aims: Nonsmall cell lung cancer accounts for over 85% of lung cancer incidences worldwide, and often has a poor prognosis. Proteasome inhibitors, such as bortezomib, have previously demonstrated evidence in preclinical and clinical models in the treatment of NSCLC both alone and as part of chemotherapeutic regimens. Methods: Five databases were searched from inception to February 2023 to identify published clinical trial data and ongoing clinical trials on the use of proteasome inhibitors in treatment of NSCLC with a comprehensive search strategy. Results: This review examines the clinical evidence from 21 completed and published phase I and II trials studying the use of bortezomib monotherapy and combination therapy in the treatment of NSCLC. Bortezomib/docetaxel combination resulted in longer median time-to-progression (TTP), median duration of response, median duration of disease control and median progression-free survival (PFS) than bortezomib monotherapy, with concurrent administration having greater 6-month PFS and median overall survival (OS) than sequential administration. Bortezomib/vorinostat with chemotherapy was well tolerated and effective. Bortezomib/gemcitabine/carboplatin, bortezomib/bevacizumab/carboplatin and bortezomib/paclitaxel/carboplatin combinations showed promising results and were of further investigational value. Conclusion: Bortezomib showed some clinical promise in combination therapy but not monotherapy. It also demonstrated a manageable side effect profile. Combination regimens are of further investigation value in Phase II trials.
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Importance: Despite patients with cancer being at risk of poor outcomes from COVID-19, there are few published studies for vaccine efficacy in this group, with suboptimal immunogenicity and waning vaccine efficacy described in small studies being a concern. Objective: To assess the incidence rate of severe COVID-19 disease outcomes associated with the number of vaccine doses received and the waning of protection over time. Design, Setting, and Participants: A prospective multicenter observational cohort study was carried out over 2 time periods (September 15, 2021, to December 20, 2021 [delta wave], and January 20, 2022, to November 11, 2022 [omicron wave]) predominated by SARS-CoV-2 delta and omicron variants, respectively. Overall, 73â¯608 patients with cancer (23â¯217 active treatment, 50â¯391 cancer survivors) and 621â¯475 controls matched by age, sex, race and ethnicity, and socioeconomic status were included. Exposure: Vaccine doses received, from zero to 4 doses, and time elapsed since last vaccine dose. Outcomes: Competing-risk regression analyses were employed to account for competing risks of death in patients with cancer. Main outcomes were incidence rate ratios (IRRs) of COVID-19 infection, hospitalization, and severe disease (defined as requirement for supplemental oxygen, intensive care, or death). The IRRs stratified by time from last vaccine dose served as indicators of waning of vaccine effectiveness over time. Results: The mean (SD) age of actively treated patients with cancer, cancer survivors, and controls were 62.7 (14.7), 62.9 (12.6), and 61.8 (14.7) years, respectively. Of 73â¯608 patients with cancer, 27â¯170 (36.9%) were men; 60â¯100 (81.6%) were Chinese, 7432 (10.1%) Malay, 4597 (6.2%) Indian, and 1479 (2.0%) were of other races and ethnicities. The IRRs for the 3-dose and 4-dose vs the 2-dose group (reference) for COVID-19 hospitalization and severe disease were significantly lower during both the delta and omicron waves in cancer and control populations. The IRRs for severe disease in the 3-dose group for active treatment, cancer survivors, and controls were 0.14, 0.13, and 0.07 during the delta wave and 0.29, 0.19, and 0.21 during omicron wave, respectively. The IRRs for severe disease in the 4-dose group during the omicron wave were even lower at 0.13, 0.10 and 0.10, respectively. No waning of vaccine effectiveness against hospitalization and severe disease was seen beyond 5 months after a third dose, nor up to 5 months (the end of this study's follow-up) after a fourth dose. Conclusion: This cohort study provides evidence of the clinical effectiveness of mRNA-based vaccines against COVID-19 in patients with cancer. Longevity of immunity in preventing severe COVID-19 outcomes in actively treated patients with cancer, cancer survivors, and matched controls was observed at least 5 months after the third or fourth dose.
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COVID-19 , Neoplasias , Masculino , Humanos , Feminino , COVID-19/epidemiologia , COVID-19/prevenção & controle , Singapura/epidemiologia , Vacinas contra COVID-19 , Estudos de Coortes , Estudos Prospectivos , SARS-CoV-2 , Neoplasias/terapiaRESUMO
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.
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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.
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Sobreviventes de Câncer , Neoplasias , Suicídio , Criança , Humanos , Adolescente , Adulto Jovem , Saúde Mental , Estudos Prospectivos , Fatores de RiscoRESUMO
INTRODUCTION: Beta-2-microglobulin (B2M), cystatin C and lipocalin-2 (LCN-2) are established renal biomarkers, yet their roles in stroke have not been fully evaluated. We aimed to investigate the relationship of B2M, cystatin C, and LCN-2 with stroke risk in a general Chinese population. METHODS: We used ordinal regression to study the relationship between serum B2M, cystatin C, and LCN-2 with stroke risk in 1060 participants (mean age 45.4 ± 10.8 years, 46% male) from the Shenzhen-Hong Kong United Network on Cardiovascular Disease (SHUN-CVD) study. Stroke risk was classified into low-risk, middle-risk and high-risk groups according to the China National Stroke Screening Survey criteria. Serum biomarker levels were measured using immunoturbidimetric assays. Participants with valid data on serum biomarker levels and stroke risk were included in the analysis. RESULTS: The number of participants in the low-risk, middle-risk and high-risk stroke risk groups were 663, 143 and 254 respectively. Elevated serum B2M, cystatin C, and LCN-2 levels were associated with being male, overweight/obesity, hypertension, alcohol consumption and smoking. Serum B2M, cystatin C and LCN-2 levels were significantly associated with stroke risk in the overall population (B2M: ß = 0.595, p < .001; cystatin C: ß = 3.718, p < .001; LCN-2: ß = 0.564, p < .001) after adjustment for age. CONCLUSION: Elevated serum B2M, cystatin C and LCN-2 levels are associated with stroke risk. They may be novel biomarkers for clinicians to assess stroke risk.Key messagesSerum beta-2-microglobulin, cystatin C and lipocalin-2 levels are significantly associated with stroke risk.Beta-2-microglobulin, cystatin C and lipocalin-2 may serve as useful biomarkers for stroke risk stratification in the general population.
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Cistatina C , Acidente Vascular Cerebral , Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Feminino , Lipocalina-2 , População do Leste Asiático , Biomarcadores , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , CreatininaRESUMO
BACKGROUND: A diagnosis of cancer and treatment may constitute a highly traumatic period for paediatric cancer patients (PYACPs). However, no review has comprehensively analysed how the mental health of PYACPs is acutely affected and the longitudinal course. METHODS: This systematic review followed PRISMA guidelines. Comprehensive searches of databases were conducted to identify studies of depression, anxiety and post-traumatic stress symptoms in PYACPs. Random effects meta-analyses were used for the primary analysis. RESULTS: From 4898 records, 13 studies were included. Acutely after diagnosis, depressive and anxiety symptoms were significantly elevated in PYACPs. Depressive symptoms only significantly decreased after 12 months (standardised mean difference, SMD = -0.88; 95% CI: -0.92, -0.84). This downward trajectory persisted to 18 months (SMD = -1.862; 95% CI: -1.29, -1.09). Anxiety symptoms similarly only decreased after 12 (SMD = -0.34; 95% CI: -0.42, -0.27) up to 18 months (SMD = -0.49; 95% CI: -0.60, -0.39) after the cancer diagnosis. Post-traumatic stress symptoms showed protracted elevations throughout follow-up. Overall, significant predictors of poorer psychological outcomes included unhealthy family functioning, concomitant depression or anxiety, poor cancer prognosis or experiencing cancer and treatment-related side effects. CONCLUSIONS: While depression and anxiety may improve over time with a favourable environment, post-traumatic stress may have a protracted course. Timely identification and psycho-oncological intervention are critical.
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OBJECTIVE: To systematically evaluate the risk factors of depression and anxiety in older adults with cancer. METHOD: This PRISMA-adherent systematic review (PROSPERO CRD42022372747) involved a systematic database search for prospective and retrospective cohort studies. RESULTS: We included 33 cohort studies with 31 evaluating depression and seven evaluating anxiety. Systematic synthesis yielded various protective and exacerbating factors for depression and anxiety amongst older adults with cancer. These factors span a range of domains: (1) Cancer and associated treatment-related factors; (2) Medical, physical and functional factors; (3) Demographic factors and; (4) Social and lifestyle factors. At the individual-level, the most significant factors were the presence of chronic medical comorbidities, having pre-existing psychological symptoms, and poor baseline physical and functional status. Within the social unit, the degree of social support and presence of a partner were most significant. CONCLUSION: The deleterious impact comorbid psychological symptoms can have on older adults with cancer can be profound. In this review, we highlight a range of protective and exacerbating factors identified from cohort studies that may enable policymakers to tailor and individualise interventions to manage depression, anxiety and associated burden in this vulnerable population. The relative paucity of studies evaluating anxiety highlights an important research gap.
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Depressão , Neoplasias , Idoso , Humanos , Ansiedade/epidemiologia , Ansiedade/etiologia , Depressão/epidemiologia , Neoplasias/epidemiologia , Neoplasias/psicologia , Estudos Prospectivos , Estudos RetrospectivosRESUMO
INTRODUCTION: Three doses of SARS-CoV-2 mRNA vaccines have been recommended for cancer patients to reduce the risk of severe disease. Anti-neoplastic treatment, such as chemotherapy, may affect long-term vaccine immunogenicity. METHOD: Patients with solid or haematological cancer were recruited from 2 hospitals between July 2021 and March 2022. Humoral response was evaluated using GenScript cPASS surrogate virus neutralisation assays. Clinical outcomes were obtained from medical records and national mandatory-reporting databases. RESULTS: A total of 273 patients were recruited, with 40 having haematological malignancies and the rest solid tumours. Among the participants, 204 (74.7%) were receiving active cancer therapy, including 98 (35.9%) undergoing systemic chemotherapy and the rest targeted therapy or immunotherapy. All patients were seronegative at baseline. Seroconversion rates after receiving 1, 2 and 3 doses of SARS-CoV-2 mRNA vaccination were 35.2%, 79.4% and 92.4%, respectively. After 3 doses, patients on active treatment for haematological malignancies had lower antibodies (57.3%±46.2) when compared to patients on immunotherapy (94.1%±9.56, P<0.05) and chemotherapy (92.8%±18.1, P<0.05). SARS-CoV-2 infection was reported in 77 (28.2%) patients, of which 18 were severe. No patient receiving a third dose within 90 days of the second dose experienced severe infection. CONCLUSION: This study demonstrates the benefit of early administration of the third dose among cancer patients.
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COVID-19 , Neoplasias Hematológicas , Neoplasias , Humanos , SARS-CoV-2 , COVID-19/prevenção & controle , Resultado do Tratamento , Neoplasias/tratamento farmacológico , Vacinação , RNA Mensageiro , Anticorpos Antivirais , Imunogenicidade da VacinaRESUMO
BACKGROUND: Anthracyclines form the backbone of many systemic chemotherapy regimens but are accompanied by dose-limiting cardiotoxicity. We elucidate the progression and severity of cardiac function over time, in the absence of cardioprotection, which less is known about. METHODS: This PRISMA-guideline-adherent review was registered on PROSPERO (CRD42022373496). RESULTS: 26 studies met the eligibility criteria including a total of 910 patients. The overall reduction in post-anthracycline pooled mean left ventricular ejection fraction (LVEF) in placebo arms of the included randomised-controlled trials was 4.5% (95% CI, 2.6 to 6.4). The trend in LVEF showed a progressive decline until approximately 180 days, after which there was no significant change. Those receiving a cumulative anthracycline dose of 300 mg/m2 experienced a more profound reduction. The overall pooled risk of a 10% absolute decline in LVEF from baseline, or a decline to an LVEF below 50%, was 17% (95% CI: 11 to 24; I2 = 71%). Sensitivity analyses of baseline LVEF and trastuzumab treatment status did not yield significant differences. CONCLUSION: While the mean LVEF decline in patients without cardioprotective therapy was clinically small, a vulnerable subset experienced significant impairment. Further research to best identify those who benefit most from cardioprotective therapies when receiving anthracyclines is required.
RESUMO
Chlorine (Cl2) gas is a toxic industrial chemical (TIC) that poses a hazard to human health following accidental and/or intentional (e.g. terrorist) release. By using a murine model of sub-lethal Cl2 exposure we have examined the airway hyper responsiveness, cellular infiltrates, transcriptomic and proteomic responses of the lung. In the "crisis" phase at 2 h and 6 h there is a significant decreases in leukocytes within bronchoalveolar lavage fluid accompanied by an upregulation within the proteome of immune pathways ultimately resulting in neutrophil influx at 24 h. A flip towards "repair" in the transcriptome and proteome occurs at 24 h, neutrophil influx and an associated drop in the lung function persisting until 14 d post-exposure and subsequent "recovery" after 28 days. Collectively, this research provides new insights into the mechanisms of damage, early global responses and processes of repair induced in the lung following the inhalation of Cl2.
Assuntos
Cloro , Proteoma , Camundongos , Humanos , Animais , Cloro/toxicidade , Proteômica , Pulmão , Líquido da Lavagem BroncoalveolarRESUMO
Background: Transcranial alternating current stimulation (TACS) is a non-invasive method of brain stimulation that is hypothesised to alter cortical excitability and brain electrical activity, modulating functional connectivity within the brain. Several trials have demonstrated its potential in treating psychiatric disorders such as depression and schizophrenia. Objectives: To study the efficacy of TACS in ameliorating symptoms of depression and schizophrenia in patients and its effects on cognition in patients and healthy subjects compared to sham stimulation. Design: Systematic review with meta-analysis. Data Sources and Methods: This PROSPERO-registered systematic review (CRD42022331149) is reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, EMBASE, CENTRAL and PsycINFO were searched from inception to March 2022. Only randomised-controlled trials were included. Results: A total of 12 randomised-controlled trials are reviewed for meta-analysis, with three randomised-controlled trials reporting only effects on cognition in psychiatric and cognitively impaired patients, three trials on cognition in healthy subjects, one trial on cognition in both patients and healthy subjects, one trial on only depression, two on both cognition and depression in patients and two on schizophrenia symptoms. No studies were at significant risk of bias. For cognition, TACS showed significant improvement [positive standardised mean differences (SMD) denoting improvement] over sham stimulation in those with psychiatric disorders with an SMD of 0.60 (95% confidence interval [CI]: 0.14, 1.06). Similarly, among patients with depression, an SMD of 1.14 (95% CI: 0.10, 2.18) was found significantly favouring TACS over sham stimulation. Two studies assessed the effect of TACS on schizophrenia symptoms with mixed results. Conclusion: TACS has shown promise in ameliorating symptoms of both schizophrenia and depression in patients. TACS also improves cognition in both patients and healthy subjects. However, these findings are limited by the sample size of included studies, and future studies may be required to better our understanding of the potential of TACS. Registration: PROSPERO (CRD42022331149).