Booster vaccines protect hamsters with waning immunity from Delta VOC infection, disease, and transmission

Waning immunity to COVID-19 vaccination is associated with increased risk of breakthrough infection, especially with highly transmissible variants of concern (VOC). Booster vaccination generates rapid immune recall in humans, which real-world observational studies suggest protects against VOC infection and associated disease, and modeling studies suggest could mitigate community spread. We directly tested the impact of booster vaccination on protection against Delta VOC infection, disease, and transmission to naive cohorts in golden Syrian hamsters. Animals with waning immunity to bnt162b2 generated rapid immune recall and strong protection against upper- and lower-respiratory tract infection when boosted with bnt126b2, mRNA-1273 or AZD1222. Boosting with either mRNA vaccine generated moderate protection against lung inflammation and virus transmission to unvaccinated animals. Our data support booster vaccination as a tool to address emerging VOC in the COVID-19 pandemic.

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The impact of selective serotonin reuptake inhibitors on the risk of intracranial haemorrhage: A systematic review and meta-analysis

European Stroke Journal ◽

10.1177/2396987319827211 ◽

2019 ◽

Vol 4 (2) ◽

pp. 144-152 ◽

Cited By ~ 2

Author(s):

Melanie P Jensen ◽

Oliver J Ziff ◽

Gargi Banerjee ◽

Gareth Ambler ◽

David J Werring

Keyword(s):

Serotonin Reuptake ◽

Observational Studies ◽

Intracranial Haemorrhage ◽

Selective Serotonin Reuptake Inhibitors ◽

Meta Analysis ◽

Serotonin Reuptake Inhibitors ◽

Quality Data ◽

Selective Serotonin ◽

Increased Risk ◽

The Impact

Introduction Observational studies have suggested increased risk of intracranial haemorrhage (ICrH) in patients receiving selective serotonin reuptake inhibitors (SSRIs). We sought to clarify the impact of SSRIs on ICrH, accounting for study methodology. Patients and methods A comprehensive search of Medline, Embase and the Cochrane Library from 1960 to December 2017 identified studies comparing SSRIs with control. The outcomes (first-ever and recurrent ICrH) were meta-analysed using a random effects model. Results Twenty-four observational studies and three randomised trials were available for meta-analysis, totalling 4,844,090 patient-years of follow-up. Those receiving SSRIs were more likely to be female ( p = 0.01) and have depression ( p < 0.001). Compared to controls, SSRI users had a significantly increased risk of ICrH (relative risk (RR) 1.26, 95%CI 1.11–1.42). Although SSRI use was associated with increased ICrH risk in those without previous ICrH (RR 1.31, 95%CI 1.15–1.48), this was not the case in those with previous ICrH (RR 0.95, 95%CI 0.83–1.09). Sensitivity analysis according to the bleeding definition reported demonstrated that although ‘haemorrhagic stroke’ was associated with SSRIs (RR 1.40, 95%CI 1.13–1.72), intracerebral haemorrhage was not (RR 1.11, 95%CI 0.86–1.42). Additional sensitivity analyses demonstrated a stronger association between SSRIs and ICrH in studies with a high ( p < 0.001) compared to low risk of bias ( p = 0.09) and with retrospective ( p < 0.001) compared to prospective (p=0.31) study designs. Discussion Although SSRIs are associated with an increased risk of ICrH, the association is partly accounted for by important biases and other methodological limitations in the available observational data. Conclusion Our findings suggest there is insufficient high-quality data to advise restriction of SSRIs because of concern regarding ICrH risk.

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Prevention of perinatal hepatitis B virus transmission in the Netherlands, 2003–2007: Children of Chinese mothers are at increased risk of breakthrough infection

Vaccine ◽

10.1016/j.vaccine.2011.12.071 ◽

2012 ◽

Vol 30 (9) ◽

pp. 1715-1720 ◽

Cited By ~ 4

Author(s):

Susan Hahné ◽

Anneke van den Hoek ◽

Dorothé Baayen ◽

Marianne van der Sande ◽

Hester de Melker ◽

...

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

The Netherlands ◽

Virus Transmission ◽

Breakthrough Infection ◽

Increased Risk ◽

B Virus ◽

Chinese Mothers

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Association between progestin-only contraceptive use and cardiometabolic outcomes: A systematic review and meta-analysis

European Journal of Preventive Cardiology ◽

10.1177/2047487318774847 ◽

2018 ◽

Vol 25 (10) ◽

pp. 1042-1052 ◽

Cited By ~ 21

Author(s):

Marija Glisic ◽

Sara Shahzad ◽

Stergiani Tsoli ◽

Mahmuda Chadni ◽

Eralda Asllanaj ◽

...

Keyword(s):

Myocardial Infarction ◽

Systematic Review ◽

Venous Thromboembolism ◽

Observational Studies ◽

Contraceptive Use ◽

Meta Analysis ◽

Relative Risks ◽

Increased Risk ◽

Stratified Analysis ◽

The Impact

Aims The association between progestin-only contraceptive (POC) use and the risk of various cardiometabolic outcomes has rarely been studied. We performed a systematic review and meta-analysis to determine the impact of POC use on cardiometabolic outcomes including venous thromboembolism, myocardial infarction, stroke, hypertension and diabetes. Methods and results Nineteen observational studies (seven cohort and 12 case–control) were included in this systematic review. Of those, nine studies reported the risk of venous thromboembolism, six reported the risk of myocardial infarction, six reported the risk of stroke, three reported the risk of hypertension and two studies reported the risk of developing diabetes with POC use. The pooled adjusted relative risks (RRs) for venous thromboembolism, myocardial infarction and stroke for oral POC users versus non-users based on the random effects model were 1.06 (95% confidence interval (CI) 0.70–1.62), 0.98 (95% CI 0.66–1.47) and 1.02 (95% CI 0.72–1.44), respectively. Stratified analysis by route of administration showed that injectable POC with a RR of 2.62 (95% CI 1.74–3.94), but not oral POCs (RR 1.06, 95% CI 0.7–1.62), was associated with an increased risk of venous thromboembolism. A decreased risk of venous thromboembolism in a subgroup of women using an intrauterine levonorgestrel device was observed with a RR of 0.53 (95% CI 0.32–0.89). No effect of POC use on blood pressure was found, but there was an indication for an increased risk of diabetes with injectable POCs, albeit non-significant. Conclusions This systematic review and meta-analysis suggests that oral POC use is not associated with an increased risk of developing various cardiometabolic outcomes, whereas injectable POC use might increase the risk of venous thromboembolism.

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WED 255 SSRIS and risk of intracranial haemorrhage

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2018-abn.126 ◽

2018 ◽

Vol 89 (10) ◽

pp. A36.3-A36

Author(s):

Melanie P Jensen ◽

Oliver J Ziff ◽

Gargi Banerjee ◽

Gareth Ambler ◽

David J Werring

Keyword(s):

Observational Studies ◽

Intracranial Haemorrhage ◽

Selective Serotonin Reuptake Inhibitors ◽

Meta Analysis ◽

Risk Of Bias ◽

Sensitivity Analyses ◽

Randomised Trials ◽

Increased Risk ◽

Comprehensive Search ◽

The Impact

The abstract has also been presented as an oral presentation at the ESOC conference.Background and aimsObservational studies have suggested increased risk of intracranial haemorrhage (ICrH) in patients receiving selective serotonin reuptake inhibitors (SSRI). We sought to clarify the impact of SSRI on ICrH, accounting for study methodology.MethodA comprehensive search of Medline, Embase and Cochrane from 1960 to December 2017 comparing SSRI with control. ICrH was meta-analysed using a random-effects model and the review was prospectively registered (PROSPERO:CRD42017084513).Results25 observational studies, but no randomised trials, were available for meta-analysis, with a combined total of 4,843,857 patient-years follow-up. Those treated with SSRI were more likely to have depression (p<0.001) and be female (p=0.04). Compared to control, SSRI were significantly associated with first-ever ICrH (RR: 1.31; 95% CI: 1.15 to 1.49); however, in survivors of ICrH there was no association between SSRI and recurrence (0.95, 0.83–1.09). Sensitivity analyses revealed a greater association between SSRI and ICrH in studies with a high risk of bias (p<0.001) than those with a lower risk of bias (p=0.10).ConclusionSSRI are associated with increased risk of first-ever ICrH, but not with recurrence. These findings, based solely on observational data, should be taken with caution due to fundamental differences in patients receiving treatment, highlighting the need for randomised trials.

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Safety of psychotropic medicines: contribution from observational evidence

Epidemiology and Psychiatric Sciences ◽

10.1017/s2045796018000276 ◽

2018 ◽

Vol 27 (6) ◽

pp. 531-536

Author(s):

H. Verdoux

Keyword(s):

Drug Safety ◽

Observational Studies ◽

Drug Exposure ◽

Heart Diseases ◽

Real Life ◽

Population Level ◽

Metabolic Effects ◽

Random Allocation ◽

Increased Risk ◽

The Impact

The risks associated with psychotropic drugs use should be accurately documented at the population level in view of the growing number of persons exposed to these drugs. The strengths of observational studies regarding the identification of drug-related harms mirror the limitations of randomised controlled trials and vice-versa. Observational studies can be carried out in large samples of unselected participants treated in real-life conditions and who may be followed up over long periods. Serious adverse effects undetected during pre-marketing clinical trials may be observed only in post-marketing use, such as metabolic effects of second-generation antipsychotics. Observational studies play a key role in the identification of teratogenic risks, such as those induced by prenatal exposure to anticonvulsants. These studies are the main source of information to investigate the long-term effects of drugs, such as the possible increased risk of dementia in benzodiazepine users. They may also contribute to the accurate assessment at population level of risks overestimated by studies carried out in non-representative samples, such as the risk of congenital heart diseases in babies prenatally exposed to lithium. Owing to the lack of random allocation of drugs, confounding by indication or by disease severity are the major sources of biases in observational studies exploring drug safety. An adverse outcome may be wrongly imputed to drug exposure while it is a symptom/outcome of the disease motivating the decision to prescribe. Such a bias may occur in studies investigating the link between exposure to antidepressants and suicidality. As several methods have been developed to lessen the impact of such biases, pharmaco-epidemiological studies based upon stringent methodological designs should be regarded as a valid approach for assessing psychotropic drug safety.

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Morphine in acute coronary syndrome: systematic review and meta-analysis

BMJ Open ◽

10.1136/bmjopen-2018-025232 ◽

2019 ◽

Vol 9 (3) ◽

pp. e025232 ◽

Cited By ~ 6

Author(s):

Gonçalo Silva Duarte ◽

Afonso Nunes-Ferreira ◽

Filipe Brogueira Rodrigues ◽

Fausto J Pinto ◽

Joaquim J Ferreira ◽

...

Keyword(s):

Systematic Review ◽

Acute Coronary Syndrome ◽

Hospital Mortality ◽

Observational Studies ◽

Platelet Reactivity ◽

Meta Analysis ◽

Low Grade ◽

Coronary Syndrome ◽

Increased Risk ◽

The Impact

ObjectiveMorphine is frequently used in acute coronary syndrome (ACS) due to its analgesic effect, it being recommended in the main cardiology guidelines in Europe and the USA. However, controversy exists regarding its routine use due to potential safety concerns. We conducted a systematic review of randomised-controlled trials (RCTs) and observational studies to synthesise the available evidence.DesignSystematic review and meta-analysis.Data sourcesCENTRAL, MEDLINE, EMBASE and trial registries.Eligibility criteria for selecting studiesWe included RCTs and observational studies evaluating the impact of morphine in cardiovascular outcomes or platelet reactivity measures.Data extraction and synthesisData were screened, extracted and appraised by two independent reviewers. The data were pooled results using a random-effects model. Outcomes included in-hospital mortality, major adverse cardiovascular events (MACE), platelet reactivity (using VerifyNow) and bleeding, reported as relative risk (RR) with 95% CI. We assessed the confidence in the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. We followed the Meta-analysis Of Observational Studies in Epidemiology and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.ResultsFive RCTs and 12 observational studies were included, enrolling 69 993 participants. Pooled results showed an increased risk of in-hospital mortality (RR 1.45 [95% CI 1.10 to 1.91], low GRADE confidence), MACE (RR 1.21, 95% CI 1.02 to 1.45) and an increased platelet reactivity at 1 and 2 hours (59.37 platelet reactivity units [PRU], 95% CI 36.04 to 82.71; 68.28 PRU, 95% CI 37.01 to 99.55, high GRADE confidence) associated with morphine. We found no significant difference in the risk of bleeding. We found no differences in subgroup analyses based on study design and ACS subtype.ConclusionsMorphine was associated with an increased risk of in-hospital mortality and MACE but the high risk of bias leads to low result confidence. There is high confidence that morphine decreases the antiplatelet effect of P2Y12 inhibitors.PROSPERO registration numberCRD42016036357.

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Atrial Fibrillation, Cognitive Decline and Dementia

European Cardiology Review ◽

10.15420/ecr.2016:13:2 ◽

2016 ◽

Vol 11 (1) ◽

pp. 49 ◽

Cited By ~ 25

Author(s):

Alvaro Alonso ◽

Antonio P Arenas de Larriva ◽

◽

Keyword(s):

Atrial Fibrillation ◽

Cognitive Decline ◽

Observational Studies ◽

Cognitive Outcomes ◽

Cerebral Hypoperfusion ◽

Cardiovascular Risk Profile ◽

Cerebral Infarcts ◽

Community Based ◽

Increased Risk ◽

The Impact

Atrial fibrillation (AF) is a common cardiac arrhythmia. There is growing evidence that AF is a risk factor for cognitive decline and dementia. In this review, we summarise epidemiological observations linking AF with cognitive outcomes, describe potential mechanisms and explore the impact of AF treatments on cognitive decline and dementia. Community-based observational studies show a consistently higher rate of cognitive decline and increased risk of dementia in persons with AF. These associations are partly due to the increased risk of clinical stroke in AF, but other mechanisms, including the incidence of silent cerebral infarcts, microbleeds and cerebral hypoperfusion, are likely additional contributors. Adequate oral anticoagulation and improved management of the overall cardiovascular risk profile in individuals with AF offer the promise of reducing the impact of AF on cognitive decline and dementia.

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Zinc Depletion Increases Readmission in Older Patients: An Example of Interactions Between Nutrition and Disease

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000275 ◽

2017 ◽

Vol 87 (1-2) ◽

pp. 10-16 ◽

Cited By ~ 1

Author(s):

Salah Gariballa ◽

Awad Alessa

Keyword(s):

Nutritional Status ◽

Inductively Coupled Plasma ◽

Older Patients ◽

Controlled Trial ◽

Prognostic Indicators ◽

Hospitalised Patients ◽

Increased Risk ◽

Co Morbidity ◽

The Impact ◽

Poor Nutrition

Abstract. Background: ill health may lead to poor nutrition and poor nutrition to ill health, so identifying priorities for management still remains a challenge. The aim of this report is to present data on the impact of plasma zinc (Zn) depletion on important health outcomes after adjusting for other poor prognostic indicators in hospitalised patients. Methods: Hospitalised acutely ill older patients who were part of a large randomised controlled trial had their nutritional status assessed using anthropometric, hematological and biochemical data. Plasma Zn concentrations were measured at baseline, 6 weeks and at 6 months using inductively- coupled plasma spectroscopy method. Other clinical outcome measures of health were also measured. Results: A total of 345 patients assessed at baseline, 133 at 6 weeks and 163 at 6 months. At baseline 254 (74%) patients had a plasma Zn concentration below 10.71 μmol/L indicating biochemical depletion. The figures at 6 weeks and 6 months were 86 (65%) and 114 (70%) patients respectively. After adjusting for age, co-morbidity, nutritional status and tissue inflammation measured using CRP, only muscle mass and serum albumin showed significant and independent effects on plasma Zn concentrations. The risk of non-elective readmission in the 6-months follow up period was significantly lower in patients with normal Zn concentrations compared with those diagnosed with Zn depletion (adjusted hazard ratio 0.62 (95% CI: 0.38 to 0.99), p = 0.047. Conclusions: Zn depletion is common and associated with increased risk of readmission in acutely-ill older patients, however, the influence of underlying comorbidity on these results can not excluded.

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Thrombophilia and risk of VTE recurrence according to the age at the time of first VTE manifestation

VASA ◽

10.1024/0301-1526/a000447 ◽

2015 ◽

Vol 44 (4) ◽

pp. 313-323 ◽

Cited By ~ 6

Author(s):

Lea Weingarz ◽

Marc Schindewolf ◽

Jan Schwonberg ◽

Carola Hecking ◽

Zsuzsanna Wolf ◽

...

Keyword(s):

Factor V Leiden ◽

Cox Proportional Hazards ◽

First Episode ◽

Factor V ◽

Factor V Leiden Mutation ◽

Younger Patients ◽

Risk Of Recurrence ◽

G20210a Mutation ◽

Increased Risk ◽

The Impact

Abstract. Background: Whether screening for thrombophilia is useful for patients after a first episode of venous thromboembolism (VTE) is a controversial issue. However, the impact of thrombophilia on the risk of recurrence may vary depending on the patient’s age at the time of the first VTE. Patients and methods: Of 1221 VTE patients (42 % males) registered in the MAISTHRO (MAin-ISar-THROmbosis) registry, 261 experienced VTE recurrence during a 5-year follow-up after the discontinuation of anticoagulant therapy. Results: Thrombophilia was more common among patients with VTE recurrence than those without (58.6 % vs. 50.3 %; p = 0.017). Stratifying patients by the age at the time of their initial VTE, Cox proportional hazards analyses adjusted for age, sex and the presence or absence of established risk factors revealed a heterozygous prothrombin (PT) G20210A mutation (hazard ratio (HR) 2.65; 95 %-confidence interval (CI) 1.71 - 4.12; p < 0.001), homozygosity/double heterozygosity for the factor V Leiden and/or PT mutation (HR 2.35; 95 %-CI 1.09 - 5.07, p = 0.030), and an antithrombin deficiency (HR 2.12; 95 %-CI 1.12 - 4.10; p = 0.021) to predict recurrent VTE in patients aged 40 years or older, whereas lupus anticoagulants (HR 3.05; 95%-CI 1.40 - 6.66; p = 0.005) increased the risk of recurrence in younger patients. Subgroup analyses revealed an increased risk of recurrence for a heterozygous factor V Leiden mutation only in young females without hormonal treatment whereas the predictive value of a heterozygous PT mutation was restricted to males over the age of 40 years. Conclusions: Our data do not support a preference of younger patients for thrombophilia testing after a first venous thromboembolic event.

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Percutaneous Coronary Intervention in Patients with Diabetes and Multivessel or Left Main Disease – a Review

Interventional Cardiology Review ◽

10.15420/icr.2012.7.1.37 ◽

2012 ◽

Vol 7 (1) ◽

pp. 37

Author(s):

Donald E Cutlip ◽

Keyword(s):

Percutaneous Coronary Intervention ◽

Coronary Artery ◽

Statistical Significance ◽

Bare Metal Stents ◽

Coronary Intervention ◽

Metal Stents ◽

Increased Risk ◽

Percutaneous Coronary ◽

Patients With Diabetes ◽

The Impact

Coronary artery disease in patients with diabetes is frequently a diffuse process with multivessel involvement and is associated with increased risk for myocardial infarction and death. The role of percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG) in patients with diabetes and multivessel disease who require revascularisation has been debated and remains uncertain. The debate has been continued mainly because of the question to what degree an increased risk for in-stent restenosis among patients with diabetes contributes to other late adverse outcomes. This article reviews outcomes from early trials of balloon angioplasty versus CABG through later trials of bare-metal stents versus CABG and more recent data with drug-eluting stents as the comparator. Although not all studies have been powered to show statistical significance, the results have been generally consistent with a mortality benefit for CABG versus PCI, despite differential risks for restenosis with the various PCI approaches. The review also considers the impact of mammary artery grafting of the left anterior descending artery and individual case selection on these results, and proposes an algorithm for selection of patients in whom PCI remains a reasonable strategy.

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