Rachel Isba

Cellular immune responses against hepatitis C virus: the evidence base 2002.

Hepatitis C virus (HCV) is an RNA virus which is estimated to persistently infect about 170 million people worldwide. After acute infection, there is an initial period during which long‐term outcome is decided. There is strong evidence that the cellular immune responses, involving both CD4+ and CD8+ T lymphocytes, are involved at this stage and it is their effectiveness which determines outcome. What is not understood is what determines their effectiveness. The most important component of this is likely to be some aspect of epitope selection, itself dictated by host MHC. Thus, to understand host immunity to HCV, we need to have a detailed understanding of the peptides involved in T lymphocyte responses. In this review, we discuss the peptide epitopes that have been identified so far, and their potential significance. We relate this to a scheme of host defence which may be useful for understanding natural and vaccine‐induced immunity.

Influenza vaccination for immunocompromised patients: systematic review and meta-analysis from a public health policy perspective.

Background Immunocompromised patients are vulnerable to severe or complicated influenza infection. Vaccination is widely recommended for this group. This systematic review and meta-analysis assesses influenza vaccination for immunocompromised patients in terms of preventing influenza-like illness and laboratory confirmed influenza, serological response and adverse events. Methodology/Principal Findings Electronic databases and grey literature were searched and records were screened against eligibility criteria. Data extraction and risk of bias assessments were performed in duplicate. Results were synthesised narratively and meta-analyses were conducted where feasible. Heterogeneity was assessed using I2 and publication bias was assessed using Beggs funnel plot and Eggers regression test. Many of the 209 eligible studies included an unclear or high risk of bias. Meta-analyses showed a significant effect of preventing influenza-like illness (odds ratio [OR] = 0.23; 95% confidence interval [CI] = 0.16–0.34; p<0.001) and laboratory confirmed influenza infection (OR = 0.15; 95% CI = 0.03–0.63; p = 0.01) through vaccinating immunocompromised patie nts compared to placebo or unvaccinated controls. We found no difference in the odds of influenza-like illness compared to vaccinated immunocompetent controls. The pooled odds of seroconversion were lower in vaccinated patients compared to immunocompetent controls for seasonal influenza A(H1N1), A(H3N2) and B. A similar trend was identified for seroprotection. Meta-analyses of seroconversion showed higher odds in vaccinated patients compared to placebo or unvaccinated controls, although this reached significance for influenza B only. Publication bias was not detected and narrative synthesis supported our findings. No consistent evidence of safety concerns was identified. Conclusions/Significance Infection prevention and control strategies should recommend vaccinating immunocompromised patients. Potential for bias and confounding and the presence of heterogeneity mean the evidence reviewed is generally weak, although the directions of effects are consistent. Areas for further research are identified.

World Health Organization guideline development: an evaluation.

Background Research in 2007 showed that World Health Organization (WHO) recommendations were largely based on expert opinion, rarely used systematic evidence-based methods, and did not follow the organizations own “Guidelines for Guidelines”. In response, the WHO established a “Guidelines Review Committee” (GRC) to implement and oversee internationally recognized standards. We examined the impact of these changes on WHO guideline documents and explored senior staffs perceptions of the new procedures. Methods and Findings We used the AGREE II guideline appraisal tool to appraise ten GRC-approved guidelines from nine WHO departments, and ten pre-GRC guidelines matched by department and topic. We interviewed 20 senior staff across 16 departments and analyzed the transcripts using the framework approach. Average AGREE II scores for GRC-approved guidelines were higher across all six AGREE domains compared with pre-GRC guidelines. The biggest changes were noted for “Rigour of Development” (up 37.6%, from 30.7% to 68.3%) and “Editorial Independence” (up 52.7%, from 20.9% to 73.6%). Four main themes emerged from the interviews: (1) high standards were widely recognized as essential for WHO credibility, particularly with regard to conflicts of interest; (2) views were mixed on whether WHO needed a single quality assurance mechanism, with some departments purposefully bypassing the procedures; (3) staff expressed some uncertainties in applying the GRADE approach, with departmental staff concentrating on technicalities while the GRC remained concerned the underlying principles were not fully institutionalized; (4) the capacity to implement the new standards varied widely, with many departments looking to an overstretched GRC for technical support. Conclusions Since 2007, WHO guideline development methods have become more systematic and transparent. However, some departments are bypassing the procedures, and as yet neither the GRC, nor the quality assurance standards they have set, are fully embedded within the organization.

Influenza vaccination for immunocompromised patients: summary of a systematic review and meta-analysis

Vaccination of immunocompromised patients is recommended in many national guidelines to protect against severe or complicated influenza infection. However, due to uncertainties over the evidence base, implementation is frequently patchy and dependent on individual clinical discretion. We conducted a systematic review and meta‐analysis to assess the evidence for influenza vaccination in this patient group. Healthcare databases and grey literature were searched and screened for eligibility. Data extraction and assessments of risk of bias were undertaken in duplicate, and results were synthesised narratively and using meta‐analysis where possible. Our data show that whilst the serological response following vaccination of immunocompromised patients is less vigorous than in healthy controls, clinical protection is still meaningful, with only mild variation in adverse events between aetiological groups. Although we encountered significant clinical and statistical heterogeneity in many of our meta‐analyses, we advocate that immunocompromised patients should be targeted for influenza vaccination.

Social network analysis in medical education

Humans are fundamentally social beings. The social systems within which we live our lives (families, schools, workplaces, professions, friendship groups) have a significant influence on our health, success and well‐being. These groups can be characterised as networks and analysed using social network analysis.

Seasonal Influenza Vaccination amongst Medical Students: A Social Network Analysis Based on a Cross-Sectional Study

Introduction The Chief Medical Officer for England recommends that healthcare workers have a seasonal influenza vaccination in an attempt to protect both patients and NHS staff. Despite this, many healthcare workers do not have a seasonal influenza vaccination. Social network analysis is a well-established research approach that looks at individuals in the context of their social connections. We examine the effects of social networks on influenza vaccination decision and disease dynamics. Methods We used a social network analysis approach to look at vaccination distribution within the network of the Lancaster Medical School students and combined these data with the students’ beliefs about vaccination behaviours. We then developed a model which simulated influenza outbreaks to study the effects of preferentially vaccinating individuals within this network. Results Of the 253 eligible students, 217 (86%) provided relational data, and 65% of responders had received a seasonal influenza vaccination. Students who were vaccinated were more likely to think other medical students were vaccinated. However, there was no clustering of vaccinated individuals within the medical student social network. The influenza simulation model demonstrated that vaccination of well-connected individuals may have a disproportional effect on disease dynamics. Conclusions This medical student population exhibited vaccination coverage levels similar to those seen in other healthcare groups but below recommendations. However, in this population, a lack of vaccination clustering might provide natural protection from influenza outbreaks. An individual student’s perception of the vaccination coverage amongst their peers appears to correlate with their own decision to vaccinate, but the directionality of this relationship is not clear. When looking at the spread of disease within a population it is important to include social structures alongside vaccination data. Social networks influence disease epidemiology and vaccination campaigns designed with information from social networks could be a future target for policy makers.

When I say … micro learning environment.

There is increasing interest in learning environments and the roles they play in medical education. The body of evidence in this area is growing. Learning environments cut across all three aspects of the medical curriculum as we have come to understand it – formal, informal and hidden – although their influence is probably most powerfully felt (but least understood) in the context of this last element. The hidden curriculum is a complex phenomenon, made of many overlapping and interacting parts, and there remains much work to be done to investigate not only the nature of the hidden curriculum, but also the particular effects it may exert on learners.

Socialization, Indifference, and Convenience: Exploring the Uptake of Influenza Vaccine Among Medical Students and Early Career Doctors

The Chief Medical Officer recommends that all health care workers receive an influenza vaccination annually. High vaccination coverage is believed to be the best protection against the spread of influenza within a hospital, although uptake by health care workers remains low. We conducted semistructured interviews with seven medical students and nine early career doctors, to explore the factors informing their influenza vaccination decision making. Data collection and analysis took place iteratively, until theoretical saturation was achieved, and a thematic analysis was performed. Socialization was important although its effects were attenuated by participants’ previous experiences and a lack of clarity around the risks and benefits of vaccination. Many participants did not have strong intentions regarding vaccination. There was considerable disparity between an individual’s opinion of the vaccine, their intentions, and their vaccination status. The indifference demonstrated here suggests few are strongly opposed to the vaccination—there is potential to increase vaccination coverage.

A mixed methods study exploring early career doctors’ and medical students’ seasonal influenza vaccination

Seasonal influenza is an acute, contagious respiratory infection that causes considerable morbidity and mortality each year. The Chief Medical Officer for England recommends that healthcare workers have a seasonal influenza vaccination in an attempt to protect both patients and NHS staff. Despite current recommendations and campaigns targeted at improving vaccination uptake, many healthcare workers do not have a seasonal influenza vaccination. It is clear that more research is necessary to fully understand the vaccination decision of healthcare workers. This mixed methods thesis employed a range of novel methodological approaches to understanding the influences on the seasonal influenza vaccination decision by medical students and junior doctors. Social network analysis is a well-established research approach that looks at individuals in the context of their social connections. I used an outbreak simulation model to investigate to assess whether an individual’s risk of infection could be linked with their position in the social network. Expanding further on this, the auto-logistic regression model was applied to social network data to predict an individual’s likelihood of vaccinating given the behaviour of their peers. Finally, a qualitative approach was used to explore the factors informing vaccination decisions. Findings gathered throughout this programme of work were synthesised together to produce a more detailed evaluation of seasonal influenza vaccination amongst medical students and junior doctors. These have been disseminated widely, particularly to occupational health practitioners and the wider academic community – demonstrating that this public health research has impact in practice. By gaining a better understanding of the social effects on influenza vaccination it will be possible to improve seasonal influenza vaccination uptake by healthcare workers, in turn better protecting patients and staff.

Seasonal influenza vaccination in health-care workers: the influence of consultants on the uptake of vaccination by medical students and early career doctors

Abstract Background The Chief Medical Officer for England recommends that all health-care workers receive an influenza vaccination annually. Medical students are also encouraged to get vaccinated. High vaccination coverage is believed to be the best form of protection against the spread of influenza within hospital settings, protecting both staff and patients, and reducing virus transmission. However, uptake of seasonal influenza vaccination by health-care workers remains substantially lower than the target level of 75%. Our study aimed to provide a deeper insight into the influenza vaccination practices of health-care workers. Methods An opportunistic sampling strategy was used and participants recruited via compulsory teaching sessions. We conducted a series of semi-structured interviews with seven medical students and nine foundation doctors, to explore the factors informing their vaccination decisions. Interviews were transcribed and the data analysed thematically. Data collection and analysis took place as an iterative process, until theoretical saturation was achieved. Findings Of the 16 participants, ten had been vaccinated during the 2015–16 season. A number of key themes emerged, and there were inconsistencies between an individuals opinion of the vaccine, their intentions, and their vaccination status. For example, someone reporting negative opinions of the vaccine could have been vaccinated. Moreover, individuals did not necessarily vaccinate year on year. Participants were influenced by senior staff as role models, demonstrating both positive and negative attitudes towards the vaccine. Participants often presented this observation in the context of their own conflicting ideals of medical professionalism. The decision making processes around influenza vaccination seem to be finely balanced, take place within a culture of relative ambivalence, and can easily be tipped one way or the other by factors such as convenience. Interpretation The findings are drawn from a diverse sample, and are supported by the literature. This study suggests that senior staff have an important role in the vaccination practices of juniors. The influential role of consultants could be used as part of a future strategy to increase vaccination, since positive role models can facilitate a cultural shift in favour of vaccination uptake. Future research involving senior staff is necessary to understand the complexities behind their own vaccination practices. Funding Colt Foundation.