Immunogenicity and safety of a quadrivalent inactivated influenza virus vaccine compared with a comparator quadrivalent inactivated influenza vaccine in a pediatric population: A phase 3, randomized noninferiority study.

BACKGROUND: Seqirus 2010 Southern Hemisphere split-virion trivalent inactivated influenza vaccine (IIV3) was associated with increased febrile reactions in children. Studies in vitro concluded that increasing concentrations of splitting agent decreased residual lipids and attenuated proinflammatory cytokine signals associated with fever. We assessed immunogenicity and safety of a quadrivalent inactivated influenza vaccine (IIV4; produced using higher concentration of splitting agent) versus a United States-licensed comparator IIV4 in healthy children aged 5-17years. METHODS: Participants (N=2278) were randomized 3:1 and stratified by age (5-8years; 9-17years) to receive IIV4 (n=1709) or comparator IIV4 (n=569). Primary objective was to demonstrate noninferiority of IIV4 versus comparator IIV4 as assessed by hemagglutination inhibition (HI) geometric mean titer (GMT) ratio (upper bound of two-sided 95% confidence interval [CI]≤1.5) and difference in seroconversion rate (upper bound of two-sided 95% CI≤10%) for all four vaccine strains. HI antibody titers were assessed at baseline and 28days postvaccination. Solicited and unsolicited adverse events were assessed during each 7- and 28-day postvaccination period, respectively. RESULTS: IIV4 met immunogenicity criteria for noninferiority. Adjusted GMT ratios (comparator IIV4/IIV4) for A/H1N1, A/H3N2, B/Yamagata, and B/Victoria strains were 1.01 (95% CI; 0.93, 1.09), 1.05 (0.96, 1.15), 0.89 (0.81, 0.98), and 0.92 (0.83, 1.02), respectively. Corresponding values for differences (95% CI) in seroconversion rates (comparator IIV4 minus IIV4) were -3.1 (-8.0, 1.8), 0.4 (-4.5, 5.3), -3.4 (-8.3, 1.5), and -2.0 (-6.9, 2.9). Fever rates were numerically higher, but not statistically different, with IIV4 versus comparator IIV4. No new safety signals were reported. CONCLUSION: IIV4 demonstrated immunological noninferiority to the comparator IIV4 with a clinically acceptable safety profile in children aged 5-17years. Increased levels of virus splitting agent seem to have reduced fever rates observed in children with Seqirus IIV3, particularly those aged 5-8years. FUNDING: Seqirus Pty Ltd; Clinicaltrials.gov identifier: NCT02545543.

Use of saliva as a lubricant in anal sexual practices among homosexual men.

OBJECTIVES: Compared with other sexually active adults, men who have sex with men (MSM) are more frequently infected with several pathogens including cytomegalovirus, hepatitis B virus, and Kaposi sarcoma-associated herpesvirus. Because one common element between these organisms is their presence in saliva, we evaluated saliva exposure among MSM in a heretofore relatively unrecognized route-via use of saliva as a lubricant in anal sex. METHODS: MSM in a San Francisco population-based cohort were interviewed regarding use of saliva by the insertive partner as a lubricant in various anal sexual practices. RESULTS: Among 283 MSM, 87% used saliva as a lubricant in insertive or receptive penile-anal intercourse or fingering/fisting at some point during their lifetime; 31%-47% did so, depending upon the act, in the prior 6 months. Saliva use as a lubricant was more common among younger men and among HIV-infected men when with HIV-infected partners. Even among MSM following safe sex guidelines by avoiding unprotected penile-anal intercourse, 26% had anal exposure to saliva via use as a lubricant. CONCLUSIONS: Among MSM, use of saliva as a lubricant is a common, but not ubiquitous, practice in anal sex. The findings provide the rationale for formal investigation of whether saliva use in this way contributes to transmission of saliva-borne pathogens in MSM.

Hyponatremia and hospital outcomes among patients with pneumonia: a retrospective cohort study.

BACKGROUND: Community-acquired (CAP) and nosocomial pneumonias contribute substantially to morbidity and hospital resource utilization. Hyponatremia, occurring in >1/4 of patients with CAP, is associated with greater disease severity and worsened outcomes. METHODS: To explore how hyponatremia is associated with outcomes in hospitalized patients with pneumonia, we analyzed a large administrative database with laboratory component from January 2004 to December 2005. Hyponatremia was defined as at least two [Na+] < 135 mEq/L within 24 hours of admission value. RESULTS: Of 7,965 patients with pneumonia, 649 (8.1%) with hyponatremia were older (72.4 +/- 15.7 vs. 68.0 +/- 22.0, p < 0.01), had a higher mean Deyo-Charlson Comorbidity Index Score (1.7 +/- 1.7 vs. 1.6 +/- 1.6, p = 0.02), and higher rates of ICU (10.0% vs. 6.3%, p < 0.001) and MV (3.9% vs. 2.3%, p = 0.01) in the first 48 hours of hospitalization than patients with normal sodium. Hyponatremia was associated with an increased ICU (6.3 +/- 5.6 vs. 5.3 +/- 5.1 days, p = 0.07) and hospital lengths of stay (LOS, 7.6 +/- 5.3 vs. 7.0 +/- 5.2 days, p < 0.001) and a trend toward increased hospital mortality (5.4% vs. 4.0%, p = 0.1). After adjusting for confounders, hyponatremia was associated with an increased risk of ICU (OR 1.58, 95% CI 1.20-2.08), MV (OR 1.75 95% CI 1.13-2.69), and hospital death (OR 1.3, 95% CI 0.90-1.87) and with increases of 0.8 day to ICU and 0.3 day to hospital LOS, and over $1,300 to total hospital costs. CONCLUSION: Hyponatremia is common among hospitalized patients with pneumonia and is associated with worsened clinical and economic outcomes. Studies in this large population are needed to explore whether prompt correction of [Na+] may impact these outcomes.

Awareness of Kaposi's sarcoma-associated herpesvirus among men who have sex with men.

BACKGROUND: Despite burgeoning scientific knowledge about Kaposi's sarcoma-associated herpesvirus (KSHV), the etiologic agent of Kaposi's sarcoma (KS), little is known about awareness of this virus in the general community. This is particularly the case for men who have sex with men (MSM), the group at greatest risk for infection. METHODS: The California Health Interview Survey was a random digit- dial survey of over 50,000 households. Men aged 18 to 64 years who self-identified as gay or bisexual were subsequently recontacted for a follow-up study of HIV-related knowledge and behavior in which they were asked if they had heard of KS and to describe the cause of KS. RESULTS: Of 398 MSM interviewed, 73.0% (95% CI 65.0-79.7) had heard of KS. However, only 6.4% (95% CI 4.4-9.2) of participants correctly identified that KS is caused by KSHV or a virus other than HIV. Postgraduate education, urban residence, and concurrent HIV infection were all independently associated with greater awareness of the viral origin of KS. CONCLUSION: Awareness of KSHV is very low, overall, among MSM and only somewhat higher, but still unacceptably low, among HIV-infected MSM. Significant efforts are needed to increase awareness of KSHV as a sexually transmitted infection in this population.

Epidemiology, clinical and economic outcomes of admission hyponatremia among hospitalized patients.

BACKGROUND: Hyponatremia, the most frequent electrolyte derangement identified among hospitalized patients, is associated with worsened outcomes in patients with pneumonia, heart failure and other disorders. RESEARCH DESIGN AND METHODS: We performed a retrospective cohort study of hospitalized patients to quantify the attributable influence of admission hyponatremia on hospital costs and outcomes. Data were derived from a large administrative database with laboratory components, representing 198,281 discharges from 39 US hospitals from January 2004 to December 2005. Hyponatremia was defined as admission serum [Na(+)]<135 mEq/L. RESULTS: The incidence of hyponatremia at admission was 5.5% (n=10,899). Patients with hyponatremia were older (65.7+/-19.6 vs. 61.5+/-21.8, p<0.001) and had a higher Deyo-Charlson Comorbidity Index score (1.8+/-2.1 vs. 1.3+/-1.8, p<0.001) than those with normal [Na(+)]. A higher proportion of hyponatremic patients required intensive care unit (ICU) (17.3% vs. 10.9%, p<0.001) and mechanical ventilation (MV) (5.0% vs. 2.8%, p<0.001) within 48 hours of hospitalization. Hospital mortality (5.9% vs. 3.0%, p<0.001), mean length of stay (HLOS, 8.6+/-8.0 vs. 7.2+/-8.2 days, p<0.001) and costs ($16,502+/-$28,984 vs. $13,558+/-$24,640, p<0.001) were significantly greater among patients with hyponatremia than those without. After adjusting for confounders, hyponatremia was independently associated with an increased need for ICU (OR 1.64, 95% CI 1.56-1.73) and MV (OR 1.68, 95% CI 1.53-1.84), and higher hospital mortality (OR 1.55, 95% CI 1.42-1.69). Hyponatremia also contributed an increase in HLOS of 1.0 day and total hospital costs of $2,289. CONCLUSIONS: Hyponatremia is common at admission among hospitalized patients and is independently associated with a 55% increase in the risk of death, substantial hospital resource utilization and costs. Potential for bias inherent in the retrospective cohort design is the main limitation of our study. Studies are warranted to explore how prompt normalization of [Na(+)] may impact these outcomes.