Impact of antiviral treatment and hospital admission delay on risk of death associated with 2009 A/H1N1 pandemic influenza in Mexico

Background Increasing our understanding of the factors affecting the severity of the 2009 A/H1N1 influenza pandemic in different regions of the world could lead to improved clinical practice and mitigation strategies for future influenza pandemics. Even though a number of studies have shed light into the risk factors associated with severe outcomes of 2009 A/H1N1 influenza infections in different populations (e.g., [1-5]), analyses of the determinants of mortality risk spanning multiple pandemic waves and geographic regions are scarce. Between-country differences in the mortality burden of the 2009 pandemic could be linked to differences in influenza case management, underlying population health, or intrinsic differences in disease transmission [6]. Additional studies elucidating the determinants of disease severity globally are warranted to guide prevention efforts in future influenza pandemics. In Mexico, the 2009 A/H1N1 influenza pandemic was characterized by a three-wave pattern occurring in the spring, summer, and fall of 2009 with substantial geographical heterogeneity [7]. A recent study suggests that Mexico experienced high excess mortality burden during the 2009 A/H1N1 influenza pandemic relative to other countries [6]. However, an assessment of potential factors that contributed to the relatively high pandemic death toll in Mexico are lacking. Here, we fill this gap by analyzing a large series of laboratory-confirmed A/H1N1 influenza cases, hospitalizations, and deaths monitored by the Mexican Social Security medical system during April 1 through December 31, 2009 in Mexico. In particular, we quantify the association between disease severity, hospital admission delays, and neuraminidase inhibitor use by demographic characteristics, pandemic wave, and geographic regions of Mexico. Methods We analyzed a large series of laboratory-confirmed pandemic A/H1N1 influenza cases from a prospective surveillance system maintained by the Mexican Social Security system, April-December 2009. We considered a spectrum of disease severity encompassing outpatient visits, hospitalizations, and deaths, and recorded demographic and geographic information on individual patients. We assessed the impact of neuraminidase inhibitor treatment and hospital admission delay (≤ \u3e 2 days after disease onset) on the risk of death by multivariate logistic regression. Results Approximately 50% of all A/H1N1-positive patients received antiviral medication during the Spring and Summer 2009 pandemic waves in Mexico while only 9% of A/H1N1 cases received antiviral medications during the fall wave (P \u3c 0.0001). After adjustment for age, gender, and geography, antiviral treatment significantly reduced the risk of death (OR = 0.52 (95% CI: 0.30, 0.90)) while longer hospital admission delays increased the risk of death by 2.8-fold (95% CI: 2.25, 3.41). Conclusions Our findings underscore the potential impact of decreasing admission delays and increasing antiviral use to mitigate the mortality burden of future influenza pandemics

Polymerized-Type I Collagen Downregulates Inflammation and Improves Clinical Outcomes in Patients with Symptomatic Knee Osteoarthritis Following Arthroscopic Lavage: A Randomized, Double-Blind, and Placebo-Controlled Clinical Trial

Objectives. Polymerized-type I collagen (polymerized collagen) is a downmodulator of inflammation and cartilage regenerator biodrug. Aim. To evaluate the effect of intraarticular injections of polymerized collagen after arthroscopic lavage on inflammation and clinical improvement in patients with knee osteoarthritis (OA). Methods. Patients (n = 19) were treated with 6 intraarticular injections of 2 mL of polymerized collagen (n = 10) or 2 mL of placebo (n = 9) during 3 months. Followup was 3 months. The primary endpoints included Lequesne index, pain on a visual analogue scale (VAS), WOMAC, analgesic usage, the number of Tregs and proinflammatory/anti-inflammatory cytokine-expressing peripheral cells. Secondary outcomes were Likert score and drug evaluation. Clinical and immunological improvement was determined if the decrease in pain exceeds 20 mm on a VAS, 20% of clinical outcomes, and inflammatory parameters from baseline. Urinary levels of C-terminal crosslinking telopeptide of collagen type II (CTXII) and erythrocyte sedimentation rate (ESR) were determined. Results. Polymerized collagen was safe and well tolerated. Patients had a statistically significant improvement (P < 0.05) from baseline versus polymerized collagen and versus placebo at 6 months on Lequesne index, VAS, ESR, Tregs IL-1β, and IL-10 peripheral-expressing cells. Urinary levels of CTXII were decreased 44% in polymerized collagen versus placebo. No differences were found on incidence of adverse events between groups. Conclusion. Polymerized collagen is safe and effective on downregulation of inflammation in patients with knee OA

Characterizing the Epidemiology of the 2009 Influenza A/H1N1 Pandemic in Mexico

Gerardo Chowell and colleagues address whether school closures and other social distancing strategies were successful in reducing pandemic flu transmission in Mexico by analyzing the age- and state-specific incidence of influenza morbidity and mortality in 32 Mexican states

Recrudescent wave of pandemic A/H1N1 influenza in Mexico, winter 2011-2012: Age shift and severity

Backgroun

Weekly number of new laboratory-confirmed A/H1N1 influenza outpatients, inpatients, and deaths by dates of symptoms onset, August-December 2009 in Mexico.

<p>Weekly number of new laboratory-confirmed A/H1N1 influenza outpatients, inpatients, and deaths by dates of symptoms onset, August-December 2009 in Mexico.</p

Characteristics of A/H1N1-positive and A/H1N1-negative inpatients and all ARI inpatients by age, gender, geography, 2008–2009 seasonal influenza vaccine status, and comorbidities and other medical conditions, Mexico, August-December 2009.

<p>Characteristics of A/H1N1-positive and A/H1N1-negative inpatients and all ARI inpatients by age, gender, geography, 2008–2009 seasonal influenza vaccine status, and comorbidities and other medical conditions, Mexico, August-December 2009.</p

Frequency of clinical characteristics of laboratory-confirmed A/H1N1inpatients and fatal cases, Mexico, August-December 2009.

a<p>adjusted by age, gender, and geography.</p

Results of a multivariate logistic regression analysis of the risk of death among inpatients based on A/H1N1-positive inpatients and A/H1N1-negative inpatients (controls) after adjusting for age, gender, geography, antiviral treatment, admission delays, 2008–2009 seasonal influenza vaccine, comorbidities, and other medical conditions.

<p>The effects of model predictors were measured using odds ratios and corresponding 95% CIs.</p

Frequency of risk factors and adjusted odds ratios for risk of death among laboratory-confirmed A/H1N1 inpatients, Mexico, August-December 2009.

a<p>Adjusted by age, gender, geography, admission delay, antiviral treatment, and 2008–2009 seasonal influenza vaccine status.</p>b<p>Pregnant case denominators include all female patients of childbearing age (15–49 y).</p