Objectives We conducted a systematic review and meta-analysis to determine the magnitude of infection risk in patients with SLE and evaluate the effect of general and SLE-related factors on infection risk. Methods We searched MEDLINE and Embase from inception to July 2018, screening for observational studies that evaluated infection risk in patients with SLE compared with the general population/healthy controls. Outcomes of interest included overall severe infection, herpes zoster infection/reactivation, opportunistic infections, pneumonia and tuberculosis. Random-effects models were used to calculate pooled risk ratios (RRs) for each type of infection. Sensitivity analysis assessed the impact of removing studies with high risk of bias. Results Eleven retrospective or prospective cohort studies were included in the meta-analysis: overall severe infection (n = 4), pneumonia (n = 6), tuberculosis (n = 3) and herpes zoster (n = 2). Pooled RRs for overall severe infection significantly increased for patients with SLE compared with the general population/healthy controls [RR 2.96 (95% CI 1.28, 6.83)]. Pooled RRs for pneumonia, herpes zoster and tuberculosis showed significantly increased risk compared with the general population/healthy controls [RR 2.58 (1.80, 3.70), 2.50 (2.36, 2.65) and 6.11 (3.61, 10.33), respectively]. Heterogeneity and evidence of publication bias were present for all analyses, except herpes zoster. Sensitivity analyses confirmed robustness of the results. Conclusion Patients with SLE have significantly higher risk of infection compared with the general population/healthy controls. Efforts to strengthen strategies aimed at preventing infections in SLE are needed. Protocol registration PROSPERO number: CRD42018109425.

ObjectiveTo evaluate the risk of stroke and myocardial infarction (MI) in adult patients with systemic lupus erythematosus (SLE) through a systematic review and meta-analysis.MethodsWe searched MEDLINE and EMBASE from inception to May 2020 to identify observational studies (cohort and cross-sectional) that evaluated risk of stroke and MI in adult patients with SLE compared with the general population or healthy controls. Studies were included if they reported effect-size estimates that could be used for calculating pooled-effect estimates. Random-effects models were used to calculate pooled risk ratios (RRs) and 95% CIs for stroke and MI. Heterogeneity quantified by the I2 test and sensitivity analyses assessed bias.ResultsIn total, 26 studies were included in this meta-analysis: 14, 5 and 7 studies on stroke, MI and both stroke and MI, respectively. The pooled RR for ischaemic stroke was 2.18 (95% CI 1.78 to 2.67; I2 75%), intracerebral haemorrhage 1.84 (95% CI 1.16 to 2.90; I2 67%), subarachnoid haemorrhage 1.95 (95% CI 0.69 to 5.52; I2 94%), composite stroke 2.13 (95% CI 1.73 to 2.61; I2 88%) and MI 2.99 (95% CI 2.34 to 3.82; I2 85%). There was no evidence for publication bias, and sensitivity analyses confirmed the robustness of the results.ConclusionsOverall, patients with SLE were identified to have a twofold to threefold higher risk of stroke and MI. Future research on the interaction between known SLE-specific modifiable risk factors and risk of stroke and MI to support development of prevention and treatment strategies are needed.PROSPERO registration numberCRD42018098690.

No abstract

Vaccines developed against SARS-CoV-2 have proven to be highly effective in preventing symptomatic infection. Similarly, prior infection with SARS-CoV-2 has been shown to provide substantial protection against reinfection. However, it has become apparent that the protection provided to an individual after either vaccination or infection wanes over time. Waning protection is driven by both waning immunity over time since vaccination or initial infection, and the evolution of new variants of SARS-CoV-2. Both antibody and T/B-cells levels have been investigated as potential correlates of protection post-vaccination or post-infection. The activity of antibodies and T/B-cells provide some potential insight into the underlying causes of waning protection. This review seeks to summarise what is currently known about the waning of protection provided by both vaccination and/or prior infection, as well as the current information on the respective antibody and T/B-cell responses.

Background: The majority of patients with chronic obstructive pulmonary disease (COPD) suffer from comorbid cardiovascular (CV) disease. Accumulating evidence suggests a temporal association between COPD exacerbations and acute CV events, possibly due to lung hyperinflation, increased hypoxemia and systemic inflammation. The aims of the study were to estimate the risk of (1) acute CV events [acute myocardial infarction (AMI), CV-related death] or stroke in the months following a COPD exacerbation and (2) COPD exacerbation in the months following an acute CV event. Methods: A systematic literature review of observational studies published since 2000 was conducted by searching literature databases (Medline and Embase). Studies were eligible if conducted in adults with COPD, exposed to either COPD exacerbation or acute CV events, with outcomes of acute CV events or COPD exacerbation reported. Studies were appraised for relevance, bias and quality. Meta-analyses, using random-effect models, were performed for each outcome of interest, thus providing a pooled relative risk (RR) and its 95% confidence interval. Results: Eight studies were identified, of which seven were used for the meta-analyses examining the risk of CV events 1–3 months after an exacerbation compared with none. For stroke (six studies), RR was 1.68 (95% CI = 1.19–2.38). For AMI (six studies), RR was 2.43 (95% CI = 1.40–4.20). No studies exploring risk of exacerbation following an acute CV event were identified. Conclusion: This meta-analysis identified a markedly increased risk of stroke or AMI within a relatively short period of time following a COPD exacerbation. Although the underlying mechanisms are not fully elucidated, patients with COPD should be monitored for risk of CV outcomes after exacerbations. In addition, preventing exacerbations may decrease the risk of subsequent acute CV events. Registration: The study protocol was published via PROSPERO: International Prospective Register of Systematic Reviews (#CRD42020211055).

Background: Guidelines recommend that treatment with a long-acting β 2 agonist (LABA), a long-acting muscarinic antagonist (LAMA), and inhaled corticosteroids (ICS), i.e. triple therapy, is reserved for a select group of symptomatic patients with chronic obstructive pulmonary disease (COPD) who continue to exacerbate despite treatment with dual therapy (LABA/LAMA). A number of single-inhaler triple therapies are now available and important clinical questions remain over their role in the patient pathway. We compared the efficacy and safety of single-inhaler triple therapy to assess the magnitude of benefit and to identify patients with the best risk-benefit profile for treatment. We also evaluated and compared study designs and population characteristics to assess the strength of the evidence base. Methods: We conducted a systematic search, from inception to December 2018, of randomised controlled trials (RCTs) of single-inhaler triple therapy in patients with COPD. The primary outcome was the annual rate of moderate and severe exacerbations. Results: We identified 523 records, of which 15 reports/abstracts from six RCTs were included. Triple therapy resulted in the reduction of the annual rate of moderate or severe exacerbations in the range of 15-52% compared with LAMA/LABA, 15-35% compared to LABA/ICS and 20% compared to LAMA. The patient-based number needed to treat for the moderate or severe exacerbation outcome ranged between approximately 25-50 (preventing one patient from having an event) and the event-based number needed to treat of around 3-11 (preventing one event). The absolute benefit appeared to be greater in patients with higher eosinophil counts or historical frequency of exacerbations and ex-smokers. In the largest study, there was a significantly higher incidence of pneumonia in the triple therapy arm. There were important differences in study designs and populations impacting the interpretation of the results and indicating there would be significant heterogeneity in cross-trial comparisons. Conclusion: The decision to prescribe triple therapy should consider patient phenotype, magnitude of benefit and increased risk of adverse events. Future research on specific patient phenotype thresholds that can support treatment and funding decisions is now required from well-designed, robust, clinical trials. Trial registration: PROSPERO #CRD42018102125.

No abstract

No abstract