The public health value of vaccines beyond efficacy: methods, measures and outcomes.

BACKGROUND: Assessments of vaccine efficacy and safety capture only the minimum information needed for regulatory approval, rather than the full public health value of vaccines. Vaccine efficacy provides a measure of proportionate disease reduction, is usually limited to etiologically confirmed disease, and focuses on the direct protection of the vaccinated individual. Herein, we propose a broader scope of methods, measures and outcomes to evaluate the effectiveness and public health impact to be considered for evidence-informed policymaking in both pre- and post-licensure stages. DISCUSSION: Pre-licensure: Regulatory concerns dictate an individually randomised clinical trial. However, some circumstances (such as the West African Ebola epidemic) may require novel designs that could be considered valid for licensure by regulatory agencies. In addition, protocol-defined analytic plans for these studies should include clinical as well as etiologically confirmed endpoints (e.g. all cause hospitalisations, pneumonias, acute gastroenteritis and others as appropriate to the vaccine target), and should include vaccine-preventable disease incidence and 'number needed to vaccinate' as outcomes. Post-licensure: There is a central role for phase IV cluster randomised clinical trials that allows for estimation of population-level vaccine impact, including indirect, total and overall effects. Dynamic models should be prioritised over static models as the constant force of infection assumed in static models will usually underestimate the effectiveness and cost-effectiveness of the immunisation programme by underestimating indirect effects. The economic impact of vaccinations should incorporate health and non-health benefits of vaccination in both the vaccinated and unvaccinated populations, thus allowing for estimation of the net social value of vaccination. CONCLUSIONS: The full benefits of vaccination reach beyond direct prevention of etiologically confirmed disease and often extend across the life course of a vaccinated person, prevent outcomes in the wider community, stabilise health systems, promote health equity, and benefit local and national economies. The degree to which vaccinations provide broad public health benefits is stronger than for other preventive and curative interventions

Refractory septic shock in children: a European Society of Paediatric and Neonatal Intensive Care definition

PURPOSE: Although overall paediatric septic shock mortality is decreasing, refractory septic shock (RSS) is still associated with high mortality. A definition for RSS is urgently needed to facilitate earlier identification and treatment. We aim to establish a European society of paediatric and neonatal intensive care (ESPNIC) experts' definition of paediatric RSS. METHODS: We conducted a two-round Delphi study followed by an observational multicentre retrospective study. One hundred and fourteen paediatric intensivists answered a clinical case-based, two-round Delphi survey, identifying clinical items consistent with RSS. Multivariate analysis of these items in a development single-centre cohort (70 patients, 30 % mortality) facilitated development of RSS definitions based on either a bedside or computed severity score. Both scores were subsequently tested in a validation cohort (six centres, 424 patients, 11.6 % mortality). RESULTS: From the Delphi process, the draft definition included evidence of myocardial dysfunction and high blood lactate levels despite high vasopressor treatment. When assessed in the development population, each item was independently associated with the need for extracorporeal life support (ECLS) or death. Resultant bedside and computed septic shock scores had high discriminative power against the need for ECLS or death, with areas under the receiver operating characteristics curve of 0.920 (95 % CI 0.89-0.94), and 0.956 (95 % CI 0.93-0.97), respectively. RSS defined by a bedside score equal to or higher than 2 and a computed score equal to or higher than 3.5 was associated with a significant increase in mortality. CONCLUSIONS: This ESPNIC definition of RSS accurately identifies children with the most severe form of septic shock

Exploring key-stakeholder perceptions on non-communicable disease care during the COVID-19 pandemic in Kenya

Introduction: over one third of total Disability-Adjusted-Life-Years lost in Kenya are due to non-communicable diseases (NCD). In response, the Government declared significant commitment towards improving NCD care. The COVID-19 pandemic increased the burden on the already overstretched health systems in Kenya. The aims of this study are to assess whether health care providers perceived NCD care to be optimal during the pandemic and explore how to improve responses to future emergencies. Methods: this cross-sectional online survey included healthcare personnel with non-clinical roles (public health workers and policy-makers) and those delivering health care (doctors and nurses). Respondents were recruited between May and September 2021 by random sampling, completed by snowball sampling. Results: among 236 participants (42% in clinical, 58% in non-clinical roles) there was an overall consensus between respondents on NCD care being disrupted and compromised during the pandemic in Kenya. Detracted supplies, funding, and technical resources affected the continuity of NCDs’ response, despite government efforts. Respondents agreed that the enhanced personnel capacity and competencies to manage COVID-19 patients were positive, but noted a lack of guidance for redirecting care for chronic diseases, and advocated for digital innovation as a solution. Conclusion: this paper explores the perceptions of key stakeholders involved in the management of NCDs in Kenya to improve planning for future emergency responses. Gaps were identified in health system response and preparedness capacity during the pandemic including the perceived need to strengthen NCD services, with solutions offered to guide resilience efforts to protect the health system from disruption

Refractory septic shock in children: an European Society of Paediatric and Neonatal Intensive Care definition

10.1007/s00134-016-4574-2Intensive Care Medicine42121948-195