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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

Aims: This review aims to evaluate prospective controlled trials of primary prevention of anthracycline cardiotoxicity in paediatric cancer patients. Methods and Results: Prospective controlled trials in which any cardioprotective agent was compared to no additional therapy or placebo in paediatric cancer patients receiving anthracyclines (PROSPERO: CRD42022367791). Outcomes were assessed using random and fixed-effects meta-analysis models as well as a synthesis without meta-analysis approach. A total of 24 reports of 19 trials were included in our review, 11 trials administered dexrazoxane, two trials administered the angiotensin converting enzyme inhibitor enalapril, one trial administered the beta-blocker carvedilol, one omega-3 fatty acids, one coenzyme Q10, one amifostine, one silymarin and one black seed oil. A total of 1333 paediatric patients receiving anthracyclines were included in meta-analysis of the cardio-protective effect of dexrazoxane in reducing the risk of developing significant systolic dysfunction. A risk ratio of 0.44 (95% CI: 0.33 to 0.61; I2 = 0%) was found, showing that the administration of dexrazoxane was highly effective. Overall, enalapril, carvedilol and dexrazoxane resulted in less left ventricular dysfunction and fewer cardiac biomarker abnormalities compared to placebo. Omega-3 fatty acids, silymarin and black seed oil each demonstrated benefit through less reduction of systolic function and fewer cardiac biomarker abnormalities. Conclusion: Enalapril and dexrazoxane are highly effective in preventing the anthracycline-induced cardiotoxicity in paediatric cancer patients with a highly acceptable safety profile. More randomised-controlled trials are required to reach a conclusion on the efficacy of omega-3 fatty acids, co-enzyme Q10 and amifostine.

Diabetes is a leading chronic illness in the modern world and 19-34% develop chronic diabetic foot ulcers (DFUs) in their lifetime, often necessitating amputation. The reduction in tissue growth factors and resulting imbalance between proteolytic enzymes and their inhibitors, along with systemic factors impairing healing appear particularly important in chronic wounds. Growth factors applied topically have thus been suggested to be a non-invasive, safe, and cost-effective adjunct to improve wound healing and prevent complications. Comprehensive database searches of MEDLINE via PubMed, EMBASE, Cochrane, and ClinicalTrials.gov were performed to identify clinical evidence and ongoing trials. The risk of bias analysis included randomized controlled trials (RCTs) was performed using the Cochrane Risk of Bias 2.0 tool. We included randomized controlled trials that compared the use of a topical biologic growth factor-containing regimen to any other regimen. Primary outcomes of interest were time to wound closure, healing rate, and time. Secondary outcomes included the incidence of adverse events such as infection. A total of 41 trials from 1992-2020 were included in this review, with a total recorded 3,112 patients. Platelet-derived growth factors (PDGF) in the form of becaplermin gel are likely to reduce the time of closure, increase the incidence of wound closure, and complete wound healing. Human umbilical cord-related treatments, dehydrated human amnion and chorion allograft (dHACA), and hypothermically stored amniotic membrane (HSAM), consistently increased the rates and incidence of complete ulcer healing while reducing ulcer size and time to complete ulcer healing. Fibroblast growth factor-1 (FGF1) showed only a slight benefit in multiple studies regarding increasing complete ulcer healing rates and incidence while reducing ulcer size and time to complete ulcer healing, with a few studies showing no statistical difference from placebo. Platelet-rich fibrin (PRF) is consistent in reducing the time to complete ulcer healing and increasing wound healing rate but may not reduce ulcer size or increase the incidence of complete ulcer healing. Targeting the wound healing pathway via the extrinsic administration of growth factors is a promising option to augment wound healing in diabetic patients. Growth factors have also shown promise in specific subgroups of patients who are at risk of significantly impaired wound healing such as those with a history of secondary infection and vasculopathy. As diabetes impairs multiple stages of wound healing, combining growth factors in diabetic wound care may prove to be an area of interest. Evidence from this systematic literature review suggests that topical adjuncts probably reduce time to wound closure, reduce healing time, and increase the healing rate in patients with chronic DFUs.

Recent trials suggest glucagon-like peptide-1 receptor agonists (GLP-1RAs) may have a cardioprotective role by reducing major adverse cardiac events, stroke mortality and heart failure-related hospitalisations. We examined whether and how GLP-1RAs affect cardiac function in cardiovascular and metabolic diseases including type 2 diabetes, heart failure and post-myocardial infarction.In this PRISMA-adherent systematic review and meta-analysis, three databases were searched from inception to July 2021 and registered on PROSPERO (CRD42021259661).20 reports of 19 randomized placebo-controlled trials including 2062 participants were meta-analyzed. Among type 2 diabetes patients, GLP-1RA resulted in improved systolic function measured by circumferential strain (mean difference [MD]= -5.48; 95% CI: -10.47 to -0.49; P= 0.03; IGLP-1RA drugs may improve systolic and diastolic function in type 2 diabetes and reduce infarct size post-acute myocardial infarction with no demonstrable effect on cardiac function in heart failure. Tailored recommendations for the use of GLP-1RAs for cardioprotection should be considered for each patient's condition.

Patients with cancer have an increased risk of severe disease and mortality from COVID-19, as the disease and antineoplastic therapy cause reduced vaccine immunogenicity. Booster doses have been proposed to enhance protection, and efficacy data are emerging from several studies.To evaluate the proportion of COVID-19 primary vaccination non-responders with cancer who seroconvert after a booster dose.PubMed, EMBASE, CENTRAL and medRxiv were searched from 1st January 2021 to 10th March 2022. Quality was assessed using the Joanna Briggs Institute Critical Appraisal checklist.After the eligibility assessment, 22 studies were included in this systematic review and 17 for meta-analysis of seroconversion in non-responders, pooling a total of 849 patients with haematological cancer and 82 patients with solid cancer. Haematological cancer non-responders exhibited lower seroconversion at 44% (95% CI 36-53%) than solid cancer at 80% (95% CI 69-87%). Individual patient data meta-analysis found the odds of having a meaningful rise in antibody titres to be significantly associated with increased duration between the second and third dose (OR 1.02, 95% CI 1.00-1.03, P ≤ 0.05), age of patient (OR 0.960, 95% CI 0.934-0.987, P ≤ 0.05) and cancer type. With patients with haematological cancer as a reference, patients with lung cancer had 16.8 times the odds of achieving a meaningful increase in antibody titres (OR 16.8, 95% CI 2.95-318, P ≤ 0.05) and gastrointestinal cancer patients had 25.4 times the odds of achieving a meaningful increase in antibody titres (OR 25.4, 95% CI 5.26-492.21, P ≤ 0.05).administration of a COVID-19 vaccine booster dose is effective in improving seroconversion and antibody levels. Patients with haematological cancer consistently demonstrate poorer response to booster vaccines than patients with solid cancer.

IntroductionColorectal cancer screening when done early can significantly reduce mortality. However, screening compliance is still lower than expected even in countries with established screening programs. Motivational interviewing is an approach that has been explored to promote behavioral change including screening compliance. This review synthesizes the efficacy of motivational interviewing in promoting uptake of colorectal screening modalities and is the only review so far that examines motivational interviewing for colorectal cancer screening alone.MethodsA systematic review and meta-analysis was conducted to examine the effects of motivational interviewing for colorectal cancer screening. PubMed, EMBASE, CENTRAL, PsycINFO, and CINAHL were searched to identify eligible studies from inception to June 2021 and selection criteria was defined. Risk of bias was assessed using the Cochrane Risk of Bias 2.0 tool. The DerSimonian and Laird random effects model was used in the statistical analysis for studies included in the meta-analysis.ResultsFourteen studies from 14 randomized-controlled trials with a low to moderate risk of bias were analyzed. 8 studies in the systematic review showed that motivational interviewing is superior to a control group. Meta-analysis was conducted on 11 studies and showed that motivational interviewing is statistically significant in increasing colorectal cancer screening rates in both intention-to-treat and per-protocol analysis. Timing of data collection of colorectal cancer screening rates did not make a significant difference to the efficacy of motivational interviewing. Studies that offered and accepted a mixture of colorectal screening modalities such as colonoscopy and fecal immunochemical tests were significantly more likely to have favorable colorectal screening outcomes. Heterogeneity in intervention was noted between studies, specifically differences in the training of interventionists, intervention delivery and comparator components.ConclusionMotivational interviewing is a tailored intervention demonstrating mixed evidence in improving colorectal cancer screening attendance amongst individuals. More research is needed to rigorously compare the effect of motivational interviewing alone vs. in combination with other screening promotion strategies to enhance colorectal cancer screening compliance.

Background: Seroconversion and longevity of vaccine-induced immune response is blunted in immune-mediated inflammatory disease (IMID) patients owing to immunosuppressive regimens. COVID-19 booster vaccines after a primary series have been proposed with inconclusive evidence on efficacy to date. Methods: This PROSPERO-registered systematic review (CRD42022302534) was conducted according to PRISMA guidelines. PubMed, EMBASE, CENTRAL, Web of Science, CORD-19, WHO ICTRP, and medRxiv were searched up to 28 February 2022 for eligible studies. Risk of bias was assessed using the Joanna Briggs Institute critical appraisal tools. Results: From 6647 records, 17 prospective studies were included for systematic review and 12 in meta-analysis of primary series non-responders. The risk of bias was low. Pooling 340 non-responders, a booster dose proved effective with 0.47 seroconverting (95% CI: 0.32–0.63, I2 = 82%). Rituximab therapy was associated with significant impairment, with risks of 0.25 (95% CI: 0.17–0.36, I2 = 50.7%) versus 0.81 (95% CI: 0.72–0.87, I2 = 0.0%) for those without rituximab therapy. A systematic review of antibody levels against COVID-19 showed several-fold increases across studies. Incidence of local and systemic adverse events, including disease flares, were either comparable or slightly increased after the booster dose compared to primary series. No major events such as myocarditis or death were reported. Conclusion: Our results show that booster doses are effective in eliciting seroconversion in non-responders, bolstering immunity to COVID-19. It has also not been associated with major adverse events.

Objective: Identify, design and develop selective strategies to guide the management of ageing surgeons. Materials and Methods: A semi-structured interview with preset open-ended questions was empl...

Chronic heart failure (CHF) is a debilitating condition that affects millions worldwide. It is accompanied by a myriad of adverse consequences, such asdiminishing of quality of life and deterioration of mental health. Caregivers play a pivotal role in helping CHF patients manage their conditions and symptoms, as a result the physical, mental and emotional state of caregivers have a direct impact on CHF patients and the management of this condition.This systematic review aims to synthesize data about the effectiveness of behavioral interventions targeted at patients with chronic heart failure (CHF) and/or informal caregivers of CHF patients to improve overall management and treatment of CHF in the population.Three databases were searched for published studies and studies that included evaluated outcomes of interventions that targeted CHF patients or informal caregivers. All randomized controlled trials, trials of either experimental or quasi-experimental design were included. Studies that only involved formal caregivers, patient populations of adolescents/young adults and patients with non-chronic conditions were excluded.Across the 21 included studies, no study reported a significant improvement in all three domains of quality of life (QoL), depression and loneliness of caregivers while only three studies reported a significant improvement in two outcomes. Within each domain, heterogeneity in measures limited quantitative pooling.This review provides data on the efficacy of interventions targeted at CHF patients and/or informal caregivers. It also highlights successful interventions and its features. Following this, additional resources need to be invested and directed towards implementing these interventions.

ObjectiveTo compare the efficacy of covid-19 vaccines between immunocompromised and immunocompetent people.DesignSystematic review and meta-analysis.Data sourcesPubMed, Embase, Central Register of Controlled Trials, COVID-19 Open Research Dataset Challenge (CORD-19), and WHO covid-19 databases for studies published between 1 December 2020 and 5 November 2021. ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform were searched in November 2021 to identify registered but as yet unpublished or ongoing studies.Study selectionProspective observational studies comparing the efficacy of covid-19 vaccination in immunocompromised and immunocompetent participants.MethodsA frequentist random effects meta-analysis was used to separately pool relative and absolute risks of seroconversion after the first and second doses of a covid-19 vaccine. Systematic review without meta-analysis of SARS-CoV-2 antibody titre levels was performed after first, second, and third vaccine doses and the seroconversion rate after a third dose. Risk of bias and certainty of evidence were assessed.Results82 studies were included in the meta-analysis. Of these studies, 77 (94%) used mRNA vaccines, 16 (20%) viral vector vaccines, and 4 (5%) inactivated whole virus vaccines. 63 studies were assessed to be at low risk of bias and 19 at moderate risk of bias. After one vaccine dose, seroconversion was about half as likely in patients with haematological cancers (risk ratio 0.40, 95% confidence interval 0.32 to 0.50, I2=80%; absolute risk 0.29, 95% confidence interval 0.20 to 0.40, I2=89%), immune mediated inflammatory disorders (0.53, 0.39 to 0.71, I2=89%; 0.29, 0.11 to 0.58, I2=97%), and solid cancers (0.55, 0.46 to 0.65, I2=78%; 0.44, 0.36 to 0.53, I2=84%) compared with immunocompetent controls, whereas organ transplant recipients were 16 times less likely to seroconvert (0.06, 0.04 to 0.09, I2=0%; 0.06, 0.04 to 0.08, I2=0%). After a second dose, seroconversion remained least likely in transplant recipients (0.39, 0.32 to 0.46, I2=92%; 0.35, 0.26 to 0.46), with only a third achieving seroconversion. Seroconversion was increasingly likely in patients with haematological cancers (0.63, 0.57 to 0.69, I2=88%; 0.62, 0.54 to 0.70, I2=90%), immune mediated inflammatory disorders (0.75, 0.69 to 0.82, I2=92%; 0.77, 0.66 to 0.85, I2=93%), and solid cancers (0.90, 0.88 to 0.93, I2=51%; 0.89, 0.86 to 0.91, I2=49%). Seroconversion was similar between people with HIV and immunocompetent controls (1.00, 0.98 to 1.01, I2=0%; 0.97, 0.83 to 1.00, I2=89%). Systematic review of 11 studies showed that a third dose of a covid-19 mRNA vaccine was associated with seroconversion among vaccine non-responders with solid cancers, haematological cancers, and immune mediated inflammatory disorders, although response was variable in transplant recipients and inadequately studied in people with HIV and those receiving non-mRNA vaccines.ConclusionSeroconversion rates after covid-19 vaccination were significantly lower in immunocompromised patients, especially organ transplant recipients. A second dose was associated with consistently improved seroconversion across all patient groups, albeit at a lower magnitude for organ transplant recipients. Targeted interventions for immunocompromised patients, including a third (booster) dose, should be performed.Systematic review registrationPROSPERO CRD42021272088.

Background: Recently, it has been discovered that anti-inflammatory and anti-oxidative pathways play a role in depression and anxiety. Lower serum levels of antioxidants, such as vitamin E, have been implicated in both depression and anxiety. Methods: This PROSPERO-registered systematic review (Reference: CRD42021260058) is reported according to PRISMA guidelines. PubMed, EMBASE, CENTRAL, PsycINFO, and CINAHL were searched from inception to June 2021. Results: Twelve studies were included in this systematic review, and nine in meta-analysis of vitamin E versus placebo. For depression, meta-analysis of 354 participants showed a standardised mean difference of –0.88 (95% CI: –1.54, –0.21; I2 = 87%) favouring vitamin E. For anxiety, meta-analysis of 306 participants showed a standardised mean difference of –0.86 (95% CI: –2.11, 0.40; I2 = 95%) favouring vitamin E. Three of the studies involved a pure comparison of vitamin E against placebo, while others included constituents such as omega-3 fatty acids. Nine of the studies were at low risk of bias, two had some concerns, and one was at high risk of bias. Conclusion: Vitamin E supplementation has shown inconclusive results in ameliorating both depression and anxiety. Containing a reassuring safety profile and low cost, future studies would be of promise, and they would benefit from both larger sample sizes and from excluding other constituents, such as omega-3 fatty acids, from experimental and comparator arms.

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)

Background Maintenance therapy is considered a standard of care in transplant eligible (TE) and non transplant eligible (NTE) patients with newly diagnosed multiple myeloma (NDMM). While immunomodulators (IMID) and proteasome inhibitors (PI) have been proposed as maintenance therapy options, there are no randomised trials (RCTs) directly comparing these agents in the maintenance setting. The IMID lenalidomide (Len) and the PI ixazomib (Ixa) have been compared against placebo as maintenance strategies in NDMM. We present a network meta-analysis (NMA) of RCTs comparing the efficacy and safety of Len and Ixa maintenance therapies in NDMM. Methods We searched various biomedical databases for eligible studies evaluating Len or Ixa against placebo/ observation as maintenance therapy in patients with NDMM from date of inception through November 2020. The primary outcome was progression-free survival (PFS). Secondary outcomes include overall survival (OS) and adverse events (AE). The Cochrane risk of bias tool version 2.0 was used to assess trial quality. A Bayesian NMA model was used to assess the relative effects of competing treatments on PFS and OS outcomes. Adverse events were assessed using the synthesis without meta-analysis (SWIM) approach due to variability in the toxicity scoring criteria. The GRADE approach was used to rate the certainty of the evidence. This study is registered with PROSPERO, CRD42021226157. Results We identified eight studies including 3229 transplant eligible (TE) and 1689 non transplant eligible (NTE) patients. All studies were judged to have low risk of bias. Len but not Ixa was associated with statistically significant improvement in PFS when compared to placebo in TE (Len: Hazard Ratio (HR) 0.46, 95% Credible Interval (CrI) 0.35-0.56, high certainty; Ixa: HR 0.72, 95% CrI 0.46-1.13, moderate certainty) and NTE (Len: HR 0.46, 95% CrI 0.29-0.75, high certainty; Ixa: HR 0.69, 95% CrI 0.43-1.18, moderate certainty). Bayesian modelling demonstrated a 97% and 93% probability that Len resulted in superior PFS compared to Ixa in TE and NTE patients respectively. Both Len and Ixa were not associated with statistically significant improvement in OS compared to placebo in TE and NTE patients. There was no significant effect modification on the effect of Len vs placebo and Ixa vs placebo by cytogenetics status, use of proteasome inhibitors for induction or duration of maintenance therapies for PFS and/or OS outcomes. Len were judged to have a higher incidence of second malignancies and grade 3 or 4 neutropenia than Ixa while Ixa was judged to have a higher incidence of thrombocytopenia than Len. Conclusions Maintenance therapy with Len may provide a larger PFS benefit than Ixa regardless of type of induction therapy and cytogenetic risk in patients with NDDM. The differing toxicity profile of these agents is also an important consideration for treatment decisions. RCTs directly comparing these maintenance strategies are warranted. Figure 1 Figure 1. Disclosures Ooi: Jansen: Honoraria; Teva Pharmaceuticals: Honoraria; GSK: Honoraria; Abbvie: Honoraria; Amgen: Honoraria. Chng: Sanofi: Honoraria; Abbvie: Honoraria; Takeda: Honoraria; Amgen: Honoraria; BMS/Celgene: Honoraria, Research Funding; Johnson and Johnson: Honoraria, Research Funding; Pfizer: Honoraria.