Howard Johnson

Investigation of an association between onset of narcolepsy and vaccination with pandemic influenza vaccine, Ireland April 2009-December 2010.

In 2011, the Irish Medicines Board received reports of onset of narcolepsy following vaccination against influenza A(H1N1)pdm09 with Pandemrix. A national steering committee was convened to examine the association between narcolepsy and pandemic vaccination. We conducted a retrospective population-based cohort study. Narcolepsy cases with onset from 1 April 2009 to 31 December 2010 were identified through active case finding. Narcolepsy history was gathered from medical records. Pandemic vaccination status was obtained from vaccination databases. Two independent experts classified cases using the Brighton case definition. Date of onset was defined as date of first healthcare contact for narcolepsy symptoms. Incidence of narcolepsy in vaccinated and non-vaccinated individuals was compared. Of 32 narcolepsy cases identified, 28 occurred in children/adolescents and for 24 first healthcare contact was between April 2009 and December 2010. Narcolepsy incidence was 5.7 (95% confidence interval (CI): 3.4–8.9) per 100,000 children/adolescents vaccinated with Pandemrix and 0.4 (95% CI: 0.1–1.0) per 100,000 unvaccinated children/adolescents (relative risk: 13.9; absolute attributable risk: 5.3 cases per 100,000 vaccinated children/adolescents). This study confirms the crude association between Pandemrix vaccination and narcolepsy as observed in Finland and Sweden. The vaccine is no longer in use in Ireland. Further studies are needed to explore the immunogenetic mechanism of narcolepsy.

Mechanisms and mediation in survival analysis: towards an integrated analytical framework

BackgroundA wide-ranging debate has taken place in recent years on mediation analysis and causal modelling, raising profound theoretical, philosophical and methodological questions. The authors build on the results of these discussions to work towards an integrated approach to the analysis of research questions that situate survival outcomes in relation to complex causal pathways with multiple mediators. The background to this contribution is the increasingly urgent need for policy-relevant research on the nature of inequalities in health and healthcare.MethodsThe authors begin by summarising debates on causal inference, mediated effects and statistical models, showing that these three strands of research have powerful synergies. They review a range of approaches which seek to extend existing survival models to obtain valid estimates of mediation effects. They then argue for an alternative strategy, which involves integrating survival outcomes within Structural Equation Models via the discrete-time survival model. This approach can provide an integrated framework for studying mediation effects in relation to survival outcomes, an issue of great relevance in applied health research. The authors provide an example of how these techniques can be used to explore whether the social class position of patients has a significant indirect effect on the hazard of death from colon cancer.ResultsThe results suggest that the indirect effects of social class on survival are substantial and negative (-0.23 overall). In addition to the substantial direct effect of this variable (-0.60), its indirect effects account for more than one quarter of the total effect. The two main pathways for this indirect effect, via emergency admission (-0.12), on the one hand, and hospital caseload, on the other, (-0.10) are of similar size.ConclusionsThe discrete-time survival model provides an attractive way of integrating time-to-event data within the field of Structural Equation Modelling. The authors demonstrate the efficacy of this approach in identifying complex causal pathways that mediate the effects of a socio-economic baseline covariate on the hazard of death from colon cancer. The results show that this approach has the potential to shed light on a class of research questions which is of particular relevance in health research.

Influence of socioeconomic status on allograft and patient survival following kidney transplantation

Whether socioeconomic status confers worse outcomes after kidney transplantation is unknown. Its influence on allograft and patient survival following kidney transplantation in Ireland was examined.

Causes and outcomes of emergency presentation of rectal cancer

Emergency presentation of rectal cancer carries a relatively poor prognosis, but the roles and interactions of causative factors remain unclear. We describe an innovative statistical approach which distinguishes between direct and indirect effects of a number of contextual, patient and tumour factors on emergency presentation and outcome of rectal cancer. All patients diagnosed with rectal cancer in Ireland 2004–2008 were included. Registry information, linked to hospital discharge data, provided data on patient demographics, comorbidity and health insurance; population density and deprivation of area of residence; tumour type, site, grade and stage; treatment type and optimality; and emergency presentation and hospital caseload. Data were modelled using a structural equation model with a discrete‐time survival outcome, allowing us to estimate direct and mediated effects of the above factors on hazard, and their inter‐relationships. Two thousand seven hundred and fifty patients were included in the analysis. Around 12% had emergency presentations, which increased hazard by 80%. Affluence, private patient status and being married reduced hazard indirectly by reducing emergency presentation. Older patients had more emergency presentations, while married patients, private patients or those living in less deprived areas had fewer than expected. Patients presenting as an emergency were less likely to receive optimal treatment or to have this in a high caseload hospital. Apart from stage, emergency admission was the strongest determinant of poor survival. The factors contributing to emergency admission in this study are similar to those associated with diagnostic delay. The socio‐economic gradient found suggests that patient education and earlier access to endoscopic investigation for public patients could reduce emergency presentation.

The influence of socioeconomic status on patient survival on chronic dialysis

Socioeconomic status (SES) has been linked to worse end‐stage kidney disease survival. The effect of SES on survival on chronic dialysis, including the impact of transplantation, was examined. A retrospective, observational study investigated the association of SES with dialysis patient survival, with censoring at time of transplantation. Adult patients commencing dialysis from 1990 to 2009 in an Irish tertiary center received a spatial SES score using the 2011 Pobal Haase‐Pratschke Deprivation Index and were compared by quartile. Cox proportional hazard models and Kaplan–Meier survival analysis examined any association of SES with survival. The 1794 patients included had a median follow‐up of 3.8 years. Patients in the lowest SES area quartile were significantly younger than the highest, mean age 56.7 vs. 59 years, P = 0.006, respectively. There was no association between SES area score and survival in an unadjusted model (hazard ratio [HR] 1.00, 95% confidence interval [CI] 0.99–1.01). Survival in the highest SES area quartile was superior to the lowest SES in a multivariable adjusted model including age, gender, and dialysis modality (HR 0.83, 95% CI 0.70–0.99, P = 0.04). These results were only mildly attenuated by censoring at time of transplantation (highest SES area quartile deprived vs. lowest SES area quartile, HR 0.85, 95% CI 0.70–1.03, P = 0.09). Superior patient survival was identified in the highest SES areas compared with the lowest following age‐adjusted analyses, despite the older population in the most affluent areas. Further research should focus on identifying modifiable targets for intervention that account for this socioeconomic‐related survival advantage.

Temporal trends in acute kidney injury across health care settings in the Irish health system: a cohort study.

Abstract Background Complete ascertainment of the true rates of acute kidney injury (AKI) and emerging trends are essential for planning of preventive strategies within health systems. Methods We conducted a retrospective cohort study from 2005 to 2014 using data from regional laboratory information systems to determine incidence rates of AKI and severity Stages 1–3 in the Irish health system. Multivariable models were developed to explore annual trends and the contributions of demographic factors, clinical measures, geographic factors and location of medical supervision expressed as adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Results From 2005 to 2014, incidence rates of AKI increased from 6.1% (5.8–6.3) to 13.2% (12.7–13.8) per 100 patient-years in men and from 5.0% (4.8–5.2) to 11.5% (11.0–12.0) in women, P < 0.001. Stage 1 AKI accounted for the greatest growth in incidence, from 4.4% (95% CI 4.3–4.6) in 2005 to 10.1% (95% CI 9.8–10.5) in 2014 (P < 0.001 for trend). Compared with 2005, patients in 2014 were more likely to experience AKI [OR 4.53 (95% CI 4.02–5.1) for Stage 1, OR 5.22 (4.16–6.55) for Stage 2 and OR 4.11 (3.05–5.54) for Stage 3], adjusting for changing demographic and clinical profiles. Incidence rates of AKI increased in all locations of medical supervision during the period of observation, but were greatest for inpatient [OR 19.11 (95% CI 17.69–20.64)] and emergency room settings [OR 5.97 (95% CI 5.56–6.42)] compared with a general practice setting (referent). Conclusion Incidence rates of AKI have increased substantially in the Irish health system, which were not accounted for by changing demographic patterns, clinical profiles or location of medical supervision.

Affluence and Private Health Insurance Influence Treatment and Survival in Non-Hodgkin's Lymphoma.

Background The aim of this study was to investigate inequalities in survival for non-Hodgkin’s lymphoma (NHL), distinguishing between direct and indirect effects of patient, social and process-of-care factors. Methods All cases of NHL diagnosed in Ireland in 2004–2008 were included. Variables describing patient, cancer, stage and process of care were included in a discrete-time model of survival using Structural Equation Modelling software. Results Emergency admissions were more common in patients with co-morbid conditions or with more aggressive cancers, and less frequent for patients from more affluent areas. Aggressive morphology, female sex, emergency admission, increasing age, comorbidity, treatment in a high caseload hospital and late stage were associated with increased hazard of mortality. Private patients had a reduced hazard of mortality, mediated by systemic therapy, admission to high caseload hospitals and fewer emergency admissions. Discussion The higher rate of emergency presentation, and consequent poorer survival, of uninsured patients, suggests they face barriers to early presentation. Social, educational and cultural factors may also discourage disadvantaged patients from consulting with early symptoms of NHL. Non-insured patients, who present later and have more emergency admissions would benefit from better access to diagnostic services. Older patients remain disadvantaged by sub-optimal treatment, treatment in non-specialist centres and emergency admission.