Meta-analysis comparing the reported mortality from “early enrollment” (the Wave 1 for each individual country) during the H1N1 pandemic with studies describing prolonged enrollment from the same countries.

<p>We evaluated the differences in the reported mortality among studies from individual countries by using both a fixed-effects and a random-effects model.</p

Global Variability in Reported Mortality for Critical Illness during the 2009-10 Influenza A(H1N1) Pandemic: A Systematic Review and Meta-Regression to Guide Reporting of Outcomes during Disease Outbreaks

<div><p>Purpose</p><p>To determine how patient, healthcare system and study-specific factors influence reported mortality associated with critical illness during the 2009–2010 Influenza A (H1N1) pandemic.</p><p>Methods</p><p>Systematic review with meta-regression of studies reporting on mortality associated with critical illness during the 2009–2010 Influenza A (H1N1) pandemic.</p><p>Data Sources</p><p>Medline, Embase, LiLACs and African Index Medicus to June 2009-March 2016.</p><p>Results</p><p>226 studies from 50 countries met our inclusion criteria. Mortality associated with H1N1-related critical illness was 31% (95% CI 28–34). Reported mortality was highest in South Asia (61% [95% CI 50–71]) and Sub-Saharan Africa (53% [95% CI 29–75]), in comparison to Western Europe (25% [95% CI 22–30]), North America (25% [95% CI 22–27]) and Australia (15% [95% CI 13–18]) (P<0.0001). High income economies had significantly lower reported mortality compared to upper middle income economies and lower middle income economies respectively (P<0.0001). Mortality for the first wave was non-significantly higher than wave two (P = 0.66). There was substantial variability in reported mortality among the specific subgroups of patients: unselected critically ill adults (27% [95% CI 24–30]), acute respiratory distress syndrome (37% [95% CI 32–44]), acute kidney injury (44% [95% CI 26–64]), and critically ill pregnant patients (10% [95% CI 5–19]).</p><p>Conclusion</p><p>Reported mortality for outbreaks and pandemics may vary substantially depending upon selected patient characteristics, the number of patients described, and the region and economic status of the outbreak location. Outcomes from a relatively small number of patients from specific regions may lead to biased estimates of outcomes on a global scale.</p></div

Differences in reported mortality based on subgroups of patients with different severity of illness (need for mechanical ventilation), critical illness associated organ failure (ARDS; AKI) or co-presenting conditions (pregnancy).

<p>The black squares represent the point estimate and 95% confidence intervals (CIs) around the mortality for each subgroup. The black diamond is the summary or overall combined estimate of mortality associated with the 2009 Influenza A (H1N1) pandemic</p

Preferred reporting items for systematic reviews and meta-analyses (PRISMA) flow diagram.

<p>Study identification and selection process.</p

System and study based characteristics described in 226 studies compared to the studies selected for the meta-regression and hierarchical model respectively.

<p>System and study based characteristics described in 226 studies compared to the studies selected for the meta-regression and hierarchical model respectively.</p

Reported mortality associated with 2009 Influenza A (H1N1) associated critical illness.

<p>We describe the mortality based on temporal (early, late and prolonged enrollment), study (study size, single center compared to multicenter and adults compared to pediatrics), and the geographic location and socioeconomic development from the included studies. The black squares represent the point estimate and 95% confidence intervals (CIs) around the mortality for each subgroup. The black diamond is the summary or overall combined estimate of mortality associated with the 2009 Influenza A (H1N1) pandemic.</p

Differences in reported mortality based on different geographic variables for the included countries (hemisphere, continent and World Bank designated geographical region).

<p>The Black squares represent the point estimate and 95% confidence intervals (CIs) around the mortality for each subgroup. The black diamond is the summary or overall combined estimate of mortality associated with the 2009 Influenza A (H1N1) pandemic. The use of geographical regions is associated with the best discriminative power to report the differences in mortality in a global context.</p

Clinical course of critically Ill patients with confirmed 2009/2010 influenza A(H1N1) infection by ethnicity, n = 647 ^a.

<p>Clinical course of critically Ill patients with confirmed 2009/2010 influenza A(H1N1) infection by ethnicity, n = 647 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0184013#t003fn002" target="_blank">^a</a>.</p

Outcomes of critically Ill patients with confirmed 2009/2010 influenza A(H1N1) infection by ethnicity, n = 64 ^a.

<p>Outcomes of critically Ill patients with confirmed 2009/2010 influenza A(H1N1) infection by ethnicity, n = 64 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0184013#t004fn002" target="_blank">^a</a>.</p

Demographic characteristics of critically Ill patients with confirmed or probable 2009/2010 influenza A(H1N1) infection, n = 647.

<p>Demographic characteristics of critically Ill patients with confirmed or probable 2009/2010 influenza A(H1N1) infection, n = 647.</p