To compare the efficacy of covid-19 vaccines between immunocompromised and immunocompetent people.
Systematic review and meta-analysis.
PubMed, 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WHO International Clinical Trials Registry Platform were searched in November 2021 to identify registered but as yet unpublished or ongoing studies.
Prospective observational studies comparing the efficacy of covid-19 vaccination in immunocompromised and immunocompetent participants.
A 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.
82 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, I
=80%; absolute risk 0.29, 95% confidence interval 0.20 to 0.40, I
=89%), immune mediated inflammatory disorders (0.53, 0.39 to 0.71, I
=89%; 0.29, 0.11 to 0.58, I
=97%), and solid cancers (0.55, 0.46 to 0.65, I
=78%; 0.44, 0.36 to 0.53, I
=84%) compared with immunocompetent controls, whereas organ transplant recipients were 16 times less likely to seroconvert (0.06, 0.04 to 0.09, I
=0%; 0.06, 0.04 to 0.08, I
=0%). After a second dose, seroconversion remained least likely in transplant recipients (0.39, 0.32 to 0.46, I
=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, I
=88%; 0.62, 0.54 to 0.70, I
=90%), immune mediated inflammatory disorders (0.75, 0.69 to 0.82, I
=92%; 0.77, 0.66 to 0.85, I
=93%), and solid cancers (0.90, 0.88 to 0.93, I
=51%; 0.89, 0.86 to 0.91, I
=49%). Seroconversion was similar between people with HIV and immunocompetent controls (1.00, 0.98 to 1.01, I
=0%; 0.97, 0.83 to 1.00, I
=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.
Seroconversion 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.
PROSPERO CRD42021272088.
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.
•80% of patients with previously non-seroconverted solid cancer do so after a third dose.•Less than half of patients with haematological cancer seroconvert after a third dose.•After the third dose, antibody titres rose up to 30-fold across studies.•Individual patient data (IPD) revealed that gastrointestinal (GI) and lung cancers performed best among patients with solid cancer.•More days between second and third doses increased the odds of a 2x rise in titres.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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)
Clinical prediction models are commonly utilized in clinical practice to screen high-risk patients. This enables healthcare professionals to initiate interventions aimed at delaying or preventing ...adverse medical events. Nevertheless, the majority of these models focus on calculating probabilities or risk scores for medical events. This information can pose challenges for patients to comprehend, potentially causing delays in their treatment decision-making process. Our paper presents a statistical methodology and protocol for the utilization of a Weibull accelerated failure time (AFT) model in predicting the time until a health-related event occurs. While this prediction technique is widely employed in engineering reliability studies, it is rarely applied to medical predictions, particularly in the context of predicting survival time. Furthermore, we offer a practical demonstration of the implementation of this prediction method using a publicly available dataset.
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.
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.
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.
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.
Molnupiravir is an antiviral, currently approved by the UK Medicines and Healthcare products Regulatory Agency (MHRA) for treating at-risk COVID-19 patients, that induces lethal error catastrophe in ...SARS-CoV-2. How this drug-induced mechanism of action might impact the emergence of resistance mutations is unclear. To investigate this, we used samples from the AGILE Candidate Specific Trial (CST)-2 (clinical trial number NCT04746183). The primary outcomes of AGILE CST-2 were to measure the drug safety and antiviral efficacy of molnupiravir in humans (180 participants randomised 1:1 with placebo). Here, we describe the pre-specified exploratory virological endpoint of CST-2, which was to determine the possible genomic changes in SARS-CoV-2 induced by molnupiravir treatment. We use high-throughput amplicon sequencing and minor variant analysis to characterise viral genomics in each participant whose longitudinal samples (days 1, 3 and 5 post-randomisation) pass the viral genomic quality criteria (n = 59 for molnupiravir and n = 65 for placebo). Over the course of treatment, no specific mutations were associated with molnupiravir treatment. We find that molnupiravir significantly increased the transition:transversion mutation ratio in SARS-CoV-2, consistent with the model of lethal error catastrophe. This study highlights the utility of examining intra-host virus populations to strengthen the prediction, and surveillance, of potential treatment-emergent adaptations.
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.
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.
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: β = 0.595, p < .001; cystatin C: β = 3.718, p < .001; LCN-2: β = 0.564, p < .001) after adjustment for age.
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 messages
Serum 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.
Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases and its prevalence is increasing worldwide. It is reported that NAFLD is associated with colorectal polyps. ...Since identifying NAFLD in its early stages could prevent possible disease progression to cirrhosis and decrease the risk of HCC by early intervention, patients with colorectal polyp may thus be considered a target group for screening NAFLD. This study aimed to investigate the potential of serum microRNAs (miRNAs) in identifying NAFLD for colorectal polyp patients. Serum samples were collected from 141 colorectal polyp patients, of which 38 had NAFLD. The serum level of eight miRNAs was determined by quantitative PCR and delta Ct values of different miRNA pairs which were compared between NAFLD and control groups. A miRNA panel was formulated from candidate miRNA pairs by multiple linear regression model and ROC analysis was performed to evaluate its diagnostic potential for NAFLD. Compared to the control group, the NAFLD group showed significantly lower delta Ct values of miR-18a/miR-16 (6.141 vs. 7.374,
= 0.009), miR-25-3p/miR-16 (2.311 vs. 2.978,
= 0.003), miR-18a/miR-21-5p (4.367 vs. 5.081,
= 0.021) and miR-18a/miR-92a-3p (8.807 vs. 9.582,
= 0.020). A serum miRNA panel composed of these four miRNA pairs significantly identified NAFLD in colorectal polyp patients with an AUC value of 0.6584 (
= 0.004). The performance of the miRNA panel was further improved to an AUC value of 0.8337 (
< 0.0001) when polyp patients with other concurrent metabolic disorders were removed from the analysis. The serum miRNA panel is a potential diagnostic biomarker for screening NAFLD in colorectal polyp patients. This serum miRNA test could be performed for colorectal polyp patients for early diagnosis and for prevention of the disease from progressing into more advanced stages.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Mutations in a synaptic organizing pathway contribute to autism. Autism-associated mutations in MDGA2 (MAM domain containing glycosylphosphatidylinositol anchor 2) are thought to reduce ...excitatory/inhibitory transmission. However, we show that mutation of Mdga2 elevates excitatory transmission, and that MDGA2 blocks neuroligin-1 interaction with neurexins and suppresses excitatory synapse development. Mdga2+/− mice, modeling autism mutations, demonstrated increased asymmetric synapse density, mEPSC frequency and amplitude, and altered LTP, with no change in measures of inhibitory synapses. Behavioral assays revealed an autism-like phenotype including stereotypy, aberrant social interactions, and impaired memory. In vivo voltage-sensitive dye imaging, facilitating comparison with fMRI studies in autism, revealed widespread increases in cortical spontaneous activity and intracortical functional connectivity. These results suggest that mutations in MDGA2 contribute to altered cortical processing through the dual disadvantages of elevated excitation and hyperconnectivity, and indicate that perturbations of the NRXN-NLGN pathway in either direction from the norm increase risk for autism.
•Autism-linked MDGA2 negatively regulates the NLGN-NRXN synaptic pathway•Mdga2+/− mice show increased excitatory synapse number and function and altered LTP•Mdga2+/− mice represent a heterozygous model with an autism-like behavior phenotype•In vivo imaging reveals enhanced activity and hyperconnectivity in Mdga2+/− cortex
MDGA2 is genetically linked to autism spectrum disorders (ASDs) and was thought to regulate inhibitory synapse development. Connor et al. show that haploinsufficiency of MDGA2 alters neuroligin-1 signaling and results in increased excitatory synaptic drive, enhanced cortical network dynamics, and impaired cognitive and social function, paralleling phenotypes observed in ASD.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Recently the role of microRNAs has been explored immensely as novel regulators and potential biomarkers in several cancers. MiR-509-3p is one such miRNA that has been observed to show a mixed ...expression in different cancers, while it's expression and clinical relevance in colorectal cancer (CRC) has not yet been characterized.
We used quantitative PCR to evaluate the expression of miR-509-3p in fresh-frozen CRC tumor tissues and the corresponding tumor-adjacent normal (NAT) tissues from 103 patients. Subsequently, functional studies were performed to further interpret the role of the miRNA in CRC.
MiR-509-3p was found to be overexpressed in CRC tissues in nearly 80% of cases and was associated with an aggressive disease presentation. Notably, a higher expression of the miRNA promoted cell proliferation, migration, and invasion of CRC cells in in vitro and in vivo models. Mechanistically, we confirmed that miR-509-3p directly binds the 3'UTR of the tumor suppressor PHLPP2 and inhibits its expression. Furthermore, within the previous 103 clinical tissue specimens, we observed an overexpression of miR-509-3p within the NAT tissue of patients associated with a poor disease prognosis. Using multivariate analysis, it was observed that the expression of miR-509-3p within the NAT tissue was an independent predictor of prognosis in CRC. At the cellular level, through indirect coculture experiments, miR-509-3p was observed to regulate the proliferative, migratory, and invasive behavior of normal colon cells.
MiR-509-3p strongly contributes to the development and progression of CRC and can potentially function as a prognostic biomarker in the disease.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PDF
