scholarly journals ‘Be on the TEAM’ Study (Teenagers Against Meningitis): protocol for a controlled clinical trial evaluating the impact of 4CMenB or MenB-fHbp vaccination on the pharyngeal carriage of meningococci in adolescents

BMJ Open ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. e037358
Author(s):  
Jeremy Carr ◽  
Emma Plested ◽  
Parvinder Aley ◽  
Susana Camara ◽  
Kimberly Davis ◽  
...  

IntroductionCapsular group B Neisseria meningitidis (MenB) is the most common cause of invasive meningococcal disease (IMD) in many parts of the world. A MenB vaccine directed against the polysaccharide capsule remains elusive due to poor immunogenicity and safety concerns. The vaccines licensed for the prevention of MenB disease, 4CMenB (Bexsero) and MenB-fHbp (Trumenba), are serogroup B ‘substitute’ vaccines, comprised of subcapsular proteins and are designed to provide protection against most MenB disease-causing strains. In many high-income countries, such as the UK, adolescents are at increased risk of IMD and have the highest rates of meningococcal carriage. Beginning in the late 1990s, immunisation of this age group with the meningococcal group C conjugate vaccine reduced asymptomatic carriage and disrupted transmission of this organism, resulting in lower group C IMD incidence across all age groups. Whether vaccinating teenagers with the novel ‘MenB’ protein-based vaccines will prevent acquisition or reduce duration of carriage and generate herd protection was unknown at the time of vaccine introduction and could not be inferred from the effects of the conjugate vaccines. 4CMenB and MenB-fHbp may also impact on non-MenB disease-causing capsular groups as well as commensal Neisseria spp. This study will evaluate the impact of vaccination with 4CMenB or MenB-fHbp on oropharyngeal carriage of pathogenic meningococci in teenagers, and consequently the potential for these vaccines to provide broad community protection against MenB disease.Methods and analysisThe ‘Be on the TEAM’ (Teenagers Against Meningitis) Study is a pragmatic, partially randomised controlled trial of 24 000 students aged 16–19 years in their penultimate year of secondary school across the UK with regional allocation to a 0+6 month schedule of 4CMenB or MenB-fHbp or to a control group. Culture-confirmed oropharyngeal carriage will be assessed at baseline and at 12 months, following which the control group will be eligible for 4CMenB vaccination. The primary outcome is the carriage prevalence of potentially pathogenic meningococci (defined as those with genogroups B, C, W, Y or X), in each vaccine group compared separately to the control group at 12 months post-enrolment, that is, 12 months after the first vaccine dose and 6 months after the second vaccine dose. Secondary outcomes include impact on carriage of: genogroup B meningococci; hyperinvasive meningococci; all meningococci; those meningococci expressing vaccine antigens and; other Neisseria spp. A sample size of 8000 in each arm will provide 80% power to detect a 30% reduction in meningococcal carriage, assuming genogroup B, C, W, Y or X meningococci carriage of 3.43%, a design effect of 1.5, a retention rate of 80% and a significance level of 0.05. Study results will be available in 2021 and will inform the UK and international immunisation policy and future vaccine development.Ethics and disseminationThis study is approved by the National Health Service South Central Research Ethics Committee (18/SC/0055); the UK Health Research Authority (IRAS ID 239091) and the UK Medicines and Healthcare products Regulatory Agency. Publications arising from this study will be submitted to peer-reviewed journals. Study results will be disseminated in public forums, online, presented at local and international conferences and made available to the participating schools.Trial registration numbersISRCTN75858406; Pre-results, EudraCT 2017-004609-42.

2003 ◽  
Vol 33 (7) ◽  
pp. 1177-1184 ◽  
Author(s):  
L. V. KESSING ◽  
E. AGERBO ◽  
P. B. MORTENSEN

Background. It is unclear whether there is an interaction of ageing on the association between major life events and onset of depression.Method. This was a population-based nested case–control study with linkage of the Danish Psychiatric Central Research Register and the Integrated Database for Longitudinal Labour Market Research. The study includes data on all admissions at psychiatric wards in Denmark from 1981 to 1998 and data on sociodemographic variables and death/suicide of first-degree relatives.Results. A total of 13006 patients who received a diagnosis of depression at the first ever admission at a psychiatric ward and a gender- and age-matched control group of 260108 subjects were identified. A recent divorce and recent unemployment and suicide of a relative (mother, father, sibling, child, spouse) were associated with increased risk of being admitted for the first time ever at a psychiatric ward with a diagnosis of depression whereas death of a relative by causes other than suicide years had no significant effect. In general, no interaction was found with age with any of the variables, totally, or for men or women, separately.Conclusions. The susceptibility to major life stressors does not seem to change throughout life.


Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1427
Author(s):  
Paula Sobral da Silva ◽  
Sophie Eickmann ◽  
Ricardo Ximenes ◽  
Celina Martelli ◽  
Elizabeth Brickley ◽  
...  

The relation of Zika virus (ZIKV) with microcephaly is well established. However, knowledge is lacking on later developmental outcomes in children with evidence of maternal ZIKV infection during pregnancy born without microcephaly. The objective of this analysis is to investigate the impact of prenatal exposure to ZIKV on neuropsychomotor development in children without microcephaly. We evaluated 274 children including 235 ZIKV exposed and 39 controls using the Bayley-III Scales of Infant and Toddler Development (BSIDIII) and neurological examination. We observed a difference in cognition with a borderline p-value (p = 0.052): 9.4% of exposed children and none of the unexposed control group had mild to moderate delays. The prevalence of delays in the language and motor domains did not differ significantly between ZIKV-exposed and unexposed children (language: 12.3% versus 12.8%; motor: 4.7% versus 2.6%). Notably, neurological examination results were predictive of neurodevelopmental delays in the BSIDIII assessments for exposed children: 46.7% of children with abnormalities on clinical neurological examination presented with delay in contrast to 17.8% among exposed children without apparent neurological abnormalities (p = 0.001). Overall, our findings suggest that relative to their unexposed peers, ZIKV-exposed children without microcephaly are not at considerably increased risk of neurodevelopmental impairment in the first 42 months of life, although a small group of children demonstrated higher frequencies of cognitive delay. It is important to highlight that in the group of exposed children, an abnormal neuroclinical examination may be a predictor of developmental delay. The article contributes to practical guidance and advances our knowledge about congenital Zika.


2021 ◽  
Vol 12 ◽  
pp. 204209862098569
Author(s):  
Phyo K. Myint ◽  
Ben Carter ◽  
Fenella Barlow-Pay ◽  
Roxanna Short ◽  
Alice G. Einarsson ◽  
...  

Background: Whilst there is literature on the impact of SARS viruses in the severely immunosuppressed, less is known about the link between routine immunosuppressant use and outcome in COVID-19. Consequently, guidelines on their use vary depending on specific patient populations. Methods: The study population was drawn from the COPE Study (COVID-19 in Older People), a multicentre observational cohort study, across the UK and Italy. Data were collected between 27 February and 28 April 2020 by trained data-collectors and included all unselected consecutive admissions with COVID-19. Load (name/number of medications) and dosage of immunosuppressant were collected along with other covariate data. Primary outcome was time-to-mortality from the date of admission (or) date of diagnosis, if diagnosis was five or more days after admission. Secondary outcomes were Day-14 mortality and time-to-discharge. Data were analysed with mixed-effects, Cox proportional hazards and logistic regression models using non-users of immunosuppressants as the reference group. Results: In total 1184 patients were eligible for inclusion. The median (IQR) age was 74 (62–83), 676 (57%) were male, and 299 (25.3%) died in hospital (total person follow-up 15,540 days). Most patients exhibited at least one comorbidity, and 113 (~10%) were on immunosuppressants. Any immunosuppressant use was associated with increased mortality: aHR 1.87, 95% CI: 1.30, 2.69 (time to mortality) and aOR 1.71, 95% CI: 1.01–2.88 (14-day mortality). There also appeared to be a dose–response relationship. Conclusion: Despite possible indication bias, until further evidence emerges we recommend adhering to public health measures, a low threshold to seek medical advice and close monitoring of symptoms in those who take immunosuppressants routinely regardless of their indication. However, it should be noted that the inability to control for the underlying condition requiring immunosuppressants is a major limitation, and hence caution should be exercised in interpretation of the results. Plain Language Summary Regular Use of Immune Suppressing Drugs is Associated with Increased Risk of Death in Hospitalised Patients with COVID-19 Background: We do not have much information on how the COVID-19 virus affects patients who use immunosuppressants, drugs which inhibit or reduce the activity of the immune system. There are various conflicting views on whether immune-suppressing drugs are beneficial or detrimental in patients with the disease. Methods: This study collected data from 10 hospitals in the UK and one in Italy between February and April 2020 in order to identify any association between the regular use of immunosuppressant medicines and survival in patients who were admitted to hospital with COVID-19. Results: 1184 patients were included in the study, and 10% of them were using immunosuppressants. Any immunosuppressant use was associated with increased risk of death, and the risk appeared to increase if the dose of the medicine was higher. Conclusion: We therefore recommend that patients who take immunosuppressant medicines routinely should carefully adhere to social distancing measures, and seek medical attention early during the COVID-19 pandemic.


2004 ◽  
Vol 1 (3) ◽  
pp. 223-232 ◽  
Author(s):  
Michael Irwin ◽  
Jennifer Pike ◽  
Michael Oxman

Both the incidence and severity of herpes zoster (HZ) or shingles increase markedly with increasing age in association with a decline in varicella zoster virus (VZV)-specific immunity. Considerable evidence shows that behavioral stressors, prevalent in older adults, correlate with impairments of cellular immunity. Moreover, the presence of depressive symptoms in older adults is associated with declines in VZV-responder cell frequency (VZV-RCF), an immunological marker of shingles risk. In this review, we discuss recent findings that administration of a relaxation response-based intervention,tai chi chih(TCC), results in improvements in health functioning and immunity to VZV in older adults as compared with a control group. TCC is a slow moving meditation consisting of 20 separate standardized movements which can be readily used in elderly and medically compromised individuals. TCC offers standardized training and practice schedules, lending an important advantage over prior relaxation response-based therapies. Focus on older adults at increased risk for HZ and assay of VZV-specific immunity have implications for understanding the impact of behavioral factors and a behavioral intervention on a clinically relevant end-point and on the response of the immune system to infectious pathogens.


2018 ◽  
Vol 25 (5) ◽  
pp. 104-110
Author(s):  
V. S. Uchaeva ◽  
Yu. A. Vasiliev ◽  
A. S. Gracheva ◽  
O. V. Gulenko ◽  
I. G. Udina

Aim. This research was designed to conduct an associative population genetic study for the consideration of the impact of SNP C677T of the gene MTHFR in the congenital maxillofacial developmental anomalies (CMDA): congenital cleft lip (CCL), congenital cleft palate (CCP), congenital cleft lip and palate (CCLP) in the Krasnodar territory. The aim of the study is to establish the associations between SNP C677T of the gene MTHFR and the development of congenital cleft lip and/ or palate.Materials and methods. In this research, the peculiarities of distribution of SNP C667T of the gene MTHFR in children with congenital cleft lip and/or palate (n=223) and their mothers (n=78) in comparison with the control group (n=124) were studied in the Krasnodar territory. The genetic demographic questionnaires were gathered for children with CMDA, the information about diagnosis was obtained from the medical records. The biological samples, including blood or scrapings of oral mucosa, were collected from children with the pathology and their mothers. The DNA was extracted from the samples by the standard method. The study of the peculiarities of distribution of alleles of SNP C677T of the gene MTHFR was performed by PCR-PFLP with endonuclease Hinf I or by tetra-primer ARMS-PCR method in children with CCL, CCP, CCLP, their mothers and the control group. Statistical processing of the obtained data was performed by the algorithms of the “Statistica” program.Results. While comparing the profiles of frequencies of SNP C677T in children with CCL, CCP and CCLP with the control group, there were identified no significant differences in the frequency of this SNP and no peculiarities of genotypes distribution. There was identified a significant difference in the peculiarities of genotypes distribution with the control group (G=19,5232, d.f.=1, p<0,001) as well as united genotypes (С/C и С/T) in accordance to T/T (G=10,4657, d.f.=1; p<0,001) and united genotypes (C/T и T/T) in accordance to C/C (G=15,1896, d.f.=1, p<0,001) for the mothers of children with CCL, CCP and CCLP.Conclusion. As a result of the study, we established the association of SNP C677T of the MTHFR gene with the development of congenital cleft lip and/or palate: mothers’ T/T genotype is associated with the increased risk of giving birth to a child with CCL, CCP and CCLP (in comparison with mothers with C/C+C/T genotype): odds ratio [OR]=16,63, 95% CI: 3,86-71,71; p=0,0003 and also for mothers with genotypes (C/T+T/T) in comparison with mothers with genotypes C/C: OR=3,22, CI:1,71-6,08; p=0,0002. The amount of risk is not significant in children with CMDA for T/T genotype. So it is possible to make a conclusion about the impact of C677T of the gene MTHFR in the development of CCL, CCP and CCLP only in mother’s genotype. 


2021 ◽  
Vol 67 (4) ◽  
pp. 409-415
Author(s):  
Köksal Sarıhan ◽  
Hülya Uzkeser ◽  
Akın Erdal

Objectives: In this study, we aimed to evaluate whether fibromyalgia patients had a higher fall risk compared to healthy individuals and to identify its relationship, if there was an increase, with clinical features. Patients and methods: Between March 2018 and September 2018, a total of 50 consecutive female patients with fibromyalgia (median age: 35 years; interquantile range [IQR], 27 to 40 years) and 50 healthy female volunteers (median age: 30 years; IQR, 23 to 40 years) were included in the study. Pain was evaluated with the Visual Analog Scale (VAS), life quality with the Nottingham Health Profile (NHP), balance functions with the Berg Balance Test (BBT), and the risk of falls with a posturography device. Disease activity of fibromyalgia patients was evaluated with the Fibromyalgia Impact Questionnaire (FIQ). Results: The mean fall risk index of the fibromyalgia patients was 45%. The fall risk index was significantly higher (p=0.010) and the BBT scores were significantly lower in the patient group (p<0.001). There was a significant difference in terms of fall risk between the control group and drug-free fibromyalgia patients; however, no significant difference was found between the balance scores of the two groups. In the fibromyalgia group, a weak positive relationship was determined between the fall risk index and the social isolation subscale of the NHP. Conclusion: Our study results showed an increased risk of loss of balance and falls in fibromyalgia patients, compared to healthy individuals. This fall risk increase was also detected in fibromyalgia patients who did not use drugs. These findings suggest a possible relationship between social isolation and an increased risk of falls.


Doctor Ru ◽  
2021 ◽  
Vol 20 (6) ◽  
pp. 6-11
Author(s):  
A.O. Godzoeva ◽  
◽  
I.E. Zazerskaya ◽  
V.S. Vlasov ◽  
T.V. Vavilova ◽  
...  

Study Objective: To evaluate the impact of multifollicular ovarian stimulation in in vitro fertilisation (IVF) programmes on hemostasis. Study Design: perspective comparative study. Materials and Methods. The study included 68 patients divided into two groups: study group (n = 36) — infertile patients; control group (n = 32) — healthy non-pregnant women of reproductive age. The protocol with gonadotrophin releasing hormone antagonists was used for ovulation stimulation. Hemostasis system in study patients was evaluated in 2 weeks after embryos were transferred to uterus; in control group — on day 20–22 of menstrual period. For the study group, we evaluated clotting test parameters of hemostasis system, D-dimers (D-d) and fibrin monomer (FM). Study Results. We have not found statistically significant differences between hemostasis screening results of study groups. We have identified increase in pro-coagulatory properties of blood in the study group patients: increase in FM and D-d (р < 0.0001 in both cases). There is an association between study parameters and pregnancy (p < 0.001) and no association with obesity, age and infertility. Conclusion. In IVF programme, FM and D-d levels rise, evidencing hypercoagulation development. An increase in FM levels was even more significant and can be used as an early and specific fibrogenesis marker. Keywords: assisted reproductive technologies, fibrin monomer, D-dimer, hypercoagulation, venous thromboembolic events.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Esther Wong ◽  
Dorothea Nitsch

Abstract Background and Aims Incidence of Acute Kidney Injury (AKI) is known to be seasonal, peaking in winter months among hospitalised patients. Previous studies have suggested that the seasonality of AKI is likely to be influenced by the seasonality of the underlying acute illnesses that are associated with AKI. Mortality of patients with AKI has also been reported as being higher in winter, reflecting well-described excess winter mortality associations. Here we describe the seasonal variations of AKI alerts in England and the associated mortality rate using linked national databases. Method Serum creatinine changes compatible with KDIGO AKI stage 1, 2 and 3 are sent by laboratories in England as AKI alerts to the treating clinicians and the UK Renal Registry (UKRR). We linked the electronic AKI alerts to the Hospital Episode Statistics (HES) data, to identify patients who were hospitalised. We carried out descriptive statistics, and investigate the seasonal effect to the 30-day patient mortality from date of getting AKI alert, using multivariable Cox regression and sequentially adjusting for age, sex, Index of multiple deprivation (IMD) and peak AKI stage Results Winter has the highest number of AKI episodes (N=81,276), which is 6% higher than that in summer (N=76,329) (Table 1). For patients who had an AKI episode and admitted to hospitals, the crude 30-day mortality is higher in the winter season when compared to the summer [HR 1.28 (1.25-1.31), p&lt;0.01] (Figure 1). After adjusting season by age, peak AKI stage, IMD and sex, winter season still has significantly higher 30-day mortality than summer [HR 1.24 (1.21-1.27), p&lt;0.01]. Winter mortality peak is confounded by age and AKI severity, which explained the drop of hazard ratio at winter peaks; whereas season is not confounded by deprivation and sex. The pattern of seasonality varies with age, in age group 18-39, there were 26.1% of AKI episodes in summer and 23.3% in winter, whereas in age group &gt;75, there were 23.7% in summer and 27.1% in winter. Conclusion Analysis of England data confirms seasonal peak in AKI during winter months. Additionally it shows increased risk of mortality for patients with AKI in winter months. Future work will investigate the impact of comorbidities and case-mix on outcomes. By understanding the seasonal variation of AKI, we can potentially plan preventive care and improve clinical practice.


Author(s):  
Valeriya Azorina ◽  
Nicola Morant ◽  
Hedvig Nesse ◽  
Fiona Stevenson ◽  
David Osborn ◽  
...  

People bereaved by suicide have an increased risk of suicide and suicide attempt, yet report receiving less support than people bereaved by other sudden deaths. Reductions in support may contribute to suicide risk, yet their nature is unclear. We explored the impact of suicide bereavement on the interpersonal relationships of young adults in the UK using an online survey to collect qualitative data. We conducted thematic analysis of free-text responses from 499 adults to questions capturing the impact of bereavement on relationships with partners, close friends, close family, extended family, and other contacts. We identified four main themes describing the changes in relationships following the suicide: (1) Social discomfort over the death (stigma and taboo; painfulness for self or others to discuss; socially prescribed grief reactions); (2) social withdrawal (loss of social confidence; withdrawal as a coping mechanism); (3) shared bereavement experience creating closeness and avoidance; (4) attachments influenced by fear of further losses (overprotectiveness towards others; avoiding attachments as protective). These findings contribute to understanding deficits in support and pathways to suicidality after suicide bereavement. Such disrupted attachments add to the burden of grief and could be addressed by public education on how to support those bereaved by suicide.


2020 ◽  
Vol 64 (13-14) ◽  
pp. 1461-1481
Author(s):  
Shaked Kovalsky ◽  
Badi Hasisi ◽  
Noam Haviv ◽  
Ety Elisha

In recent years, yoga practices have been integrated into formal prison rehabilitation programs of the Israel Prison Service (IPS), as part of the informal education system, giving rise to innovative criminological theories such as positive criminology that emphasize the development of offenders’ strengths by facilitating rehabilitation and reintegration processes. The purpose of the present study was to examine the correlation between yoga practice and recidivism among released prisoners who participated in yoga programs during their incarceration in comparison with a matched control group of those who did not participate in yoga programs over a follow-up period of 5 years. To examine the effectiveness of the program, propensity score matching was used to compile the comparison group from among all convicted prisoners who were released from the Israeli prisons. Study results indicate that yoga may affect recidivism, supported by a finding of lower recidivism rates among released prisoners who had practiced yoga during their incarceration, compared with a matched control group. However, further study is needed including randomized controlled trials (RCTs). In light of these positive results, we recommend policy-makers consider expanding alternative practices such as yoga into prisons, in recognition of their contribution to the rehabilitation process through the development of personal and social strengths.


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