New developments in the treatment and management of phenylketonuria (PKU) as well as advances in molecular testing have emerged since the National Institutes of Health 2000 PKU Consensus Statement was released. An NIH State-of-the-Science Conference was convened in 2012 to address new findings, particularly the use of the medication sapropterin to treat some individuals with PKU, and to develop a research agenda. Prior to the 2012 conference, five working groups of experts and public members met over a 1-year period. The working groups addressed the following: long-term outcomes and management across the lifespan; PKU and pregnancy; diet control and management; pharmacologic interventions; and molecular testing, new technologies, and epidemiologic considerations. In a parallel and independent activity, an Evidence-based Practice Center supported by the Agency for Healthcare Research and Quality conducted a systematic review of adjuvant treatments for PKU; its conclusions were presented at the conference. The conference included the findings of the working groups, panel discussions from industry and international perspectives, and presentations on topics such as emerging treatments for PKU, transitioning to adult care, and the U.S. Food and Drug Administration regulatory perspective. Over 85 experts participated in the conference through information gathering and/or as presenters during the conference, and they reached several important conclusions. The most serious neurological impairments in PKU are preventable with current dietary treatment approaches. However, a variety of more subtle physical, cognitive, and behavioral consequences of even well-controlled PKU are now recognized. The best outcomes in maternal PKU occur when blood phenylalanine (Phe) concentrations are maintained between 120 and 360 μmol/L before and during pregnancy. The dietary management treatment goal for individuals with PKU is a blood Phe concentration between 120 and 360 μmol/L. The use of genotype information in the newborn period may yield valuable insights about the severity of the condition for infants diagnosed before maximal Phe levels are achieved. While emerging and established genotype-phenotype correlations may transform our understanding of PKU, establishing correlations with intellectual outcomes is more challenging. Regarding the use of sapropterin in PKU, there are significant gaps in predicting response to treatment; at least half of those with PKU will have either minimal or no response. A coordinated approach to PKU treatment improves long-term outcomes for those with PKU and facilitates the conduct of research to improve diagnosis and treatment. New drugs that are safe, efficacious, and impact a larger proportion of individuals with PKU are needed. However, it is imperative that treatment guidelines and the decision processes for determining access to treatments be tied to a solid evidence base with rigorous standards for robust and consistent data collection. The process that preceded the PKU State-of-the-Science Conference, the conference itself, and the identification of a research agenda have facilitated the development of clinical practice guidelines by professional organizations and serve as a model for other inborn errors of metabolism.

BACKGROUND: Antiviral treatment is recommended for hospitalized patients with suspected and confirmed influenza, but evidence is limited among children. We evaluated the effect of antiviral treatment on hospital length of stay (LOS) among children hospitalized with influenza. METHODS: We included children <18 years hospitalized with laboratory-confirmed influenza in the US Influenza Hospitalization Surveillance Network. We collected data for 2 cohorts: 1 with underlying medical conditions not admitted to the ICU (n = 309, 2012-2013) and an ICU cohort (including children with and without underlying conditions; n = 299, 2010-2011 to 2012-2013). We used a Cox model with antiviral receipt as a time-dependent variable to estimate hazard of discharge and a Kaplan-Meier survival analysis to determine LOS. RESULTS: Compared with those not receiving antiviral agents, LOS was shorter for those treated ≤2 days after illness onset in both the medical conditions (adjusted hazard ratio: 1.37, P = .02) and ICU (adjusted hazard ratio: 1.46, P = .007) cohorts, corresponding to 37% and 46% increases in daily discharge probability, respectively. Treatment ≥3 days after illness onset had no significant effect in either cohort. In the medical conditions cohort, median LOS was 3 days for those not treated versus 2 days for those treated ≤2 days after symptom onset (P = .005). CONCLUSIONS: Early antiviral treatment was associated with significantly shorter hospitalizations in children with laboratory-confirmed influenza and high-risk medical conditions or children treated in the ICU. These results support Centers for Disease Control and Prevention recommendations for prompt empiric antiviral treatment in hospitalized patients with suspected or confirmed influenza.

BACKGROUND: Timing of influenza spread across the United States is dependent on factors including local and national travel patterns and climate. Local epidemic intensity may be influenced by social, economic and demographic patterns. Data are needed to better explain how local socioeconomic factors influence both the timing and intensity of influenza seasons to result in national patterns. METHODS: To determine the spatial and temporal impacts of socioeconomics on influenza hospitalization burden and timing, we used population-based laboratory-confirmed influenza hospitalization surveillance data from the CDC-sponsored Influenza Hospitalization Surveillance Network (FluSurv-NET) at up to 14 sites from the 2009/2010 through 2013/2014 seasons (n = 35,493 hospitalizations). We used a spatial scan statistic and spatiotemporal wavelet analysis, to compare temporal patterns of influenza spread between counties and across the country. RESULTS: There were 56 spatial clusters identified in the unadjusted scan statistic analysis using data from the 2010/2011 through the 2013/2014 seasons, with relative risks (RRs) ranging from 0.09 to 4.20. After adjustment for socioeconomic factors, there were five clusters identified with RRs ranging from 0.21 to 1.20. In the wavelet analysis, most sites were in phase synchrony with one another for most years, except for the H1N1 pandemic year (2009-2010), wherein most sites had differential epidemic timing from the referent site in Georgia. CONCLUSIONS: Socioeconomic factors strongly impact local influenza hospitalization burden. Influenza phase synchrony varies by year and by socioeconomics, but is less influenced by socioeconomics than is disease burden.

BACKGROUND: Hospitalized immunocompromised (IC) adults with influenza may have worse outcomes than hospitalized non-immunocompromised adults. METHODS: We identified adults (>/=18 years) hospitalized with laboratory-confirmed influenza during 2011-2015 seasons through CDC's Influenza Hospitalization Surveillance Network. IC patients had >/=1: HIV/AIDS, cancer, stem cell or organ transplantation, non-steroid immunosuppressive therapy, immunoglobulin deficiency, asplenia, or other rare conditions. We compared demographic and clinical characteristics of IC and non-IC adults using descriptive statistics and used multivariable logistic regression and Cox proportional hazards models to control for confounding by patient demographic characteristics, pre-existing medical conditions, influenza vaccination, and other factors. RESULTS: Among 35,348 adults, 3633 (10%) were IC; cancer (44%), non-steroid immunosuppressive therapy (44%), and HIV (17%) were most common. IC patients were more likely than non-IC patients to have received influenza vaccination (53% vs. 46%; p<0.001), and ~85% of both groups received antivirals. In multivariable analysis, IC adults had higher mortality (adjusted odds ratio (aOR) [95% confidence interval (CI)]: 1.46 [1.20-1.76]). Intensive care was more likely among IC patients 65-79 years (aOR [95% CI]: 1.25 [1.06-1.48]) and >80 years (aOR [95% CI]: 1.35 [1.06-1.73]) compared with non-IC patients in those age groups. IC patients were hospitalized longer (adjusted hazard ratio of discharge [95% CI]: 0.86 [0.83-0.88]) and were more likely to require mechanical ventilation (aOR [95% CI] 1.19 [1.05-1.36]). CONCLUSIONS: Substantial morbidity and mortality occurred among IC adults hospitalized with influenza. Influenza vaccination and antiviral administration could be increased in both IC and non-IC adults.

BACKGROUND: Influenza hospitalizations result in substantial morbidity and mortality each year. Little is known about the association between influenza hospitalization and census tract-based socioeconomic determinants beyond the effect of individual factors. OBJECTIVE: To evaluate if census tract-based determinants such as poverty and household crowding would contribute significantly to the risk of influenza hospitalization above and beyond individual level determinants. METHODS: We analyzed 33,515 laboratory-confirmed influenza-associated hospitalizations that occurred during the 2009-2010 through 2013-2014 influenza seasons using a population-based surveillance system at 14 sites across the United States. RESULTS: Using a multilevel regression model, we found that individual factors were associated with influenza hospitalization with the highest adjusted odds ratio (AOR) of 9.20 (95% CI 8.72-9.70) for those >=65 versus 5-17 years old. African Americans had an AOR of 1.67 (95% CI 1.60-1.73) compared to Whites, and Hispanics had an AOR of 1.21 (95% CI 1.16-1.26) compared to non-Hispanics. Among census tract-based determinants, those living in a tract with >=20% versus <5% of persons living below poverty had an AOR of 1.31 (95% CI 1.16-1.47), those living in a tract with >=5% versus <5% of persons living in crowded conditions had an AOR of 1.17 (95% CI 1.11-1.23) and those living in a tract with >=40% versus <5% female heads of household had an AOR of 1.32 (95% CI 1.25-1.40). CONCLUSION: Census tract-based determinants account for 11% of the variability in influenza hospitalization. This article is protected by copyright. All rights reserved.

Background: We investigated the effect of influenza vaccination on disease severity in adults hospitalized with laboratory-confirmed influenza during 2013-14, a season in which vaccine viruses were antigenically similar to those circulating. Methods: We analyzed data from the 2013-14 influenza season, and used propensity score matching to account for the probability of vaccination within age strata (18-49, 50-64 and ≥65 years). Death, intensive care unit (ICU) admission, and hospital and ICU lengths of stay (LOS) were outcome measures for severity. Multivariable logistic regression and competing risk models were used to compare disease severity between vaccinated and unvaccinated patients, adjusting for timing of antiviral treatment and time from illness onset to hospitalization. Results: Influenza vaccination was associated with a reduction in the odds of in-hospital death among patients aged 18-49 years (adjusted odds ratios [aOR] =0.21; 95% confidence interval [CI], 0.05 to 0.97), 50-64 years (aOR=0.48; 95% CI, 0.24 to 0.97), and ≥65 years (aOR=0.39; 95% CI, 0.17 to 0.66). Vaccination also reduced ICU admission among patients aged 18-49 years (aOR=0.63; 95% CI, 0.42 to 0.93) and ≥65 years (aOR=0.63; 95% CI, 0.48 to 0.81), and shortened ICU LOS among those 50-64 years (adjusted relative hazards [aRH]=1.36; 95% CI, 1.06 to 1.74) and ≥65 years (aRH=1.34; 95% CI, 1.06 to 1.73), and hospital LOS among 50-64 years (aRH=1.13; 95% CI, 1.02 to 1.26) and ≥65 years (aRH=1.24; 95% CI, 1.13 to 1.37). Conclusions: Influenza vaccination during 2013-14 influenza season attenuated adverse outcome among adults that were hospitalized with laboratory-confirmed influenza.

Using population-based surveillance data, we analyzed antiviral treatment among hospitalized patients with laboratory-confirmed influenza. Treatment increased after the influenza A(H1N1) 2009 pandemic from 72% in 2010-2011 to 89% in 2014-2015 (P < .001). Overall, treatment was higher in adults (86%) than in children (72%); only 56% of cases received antivirals on the day of admission.

BACKGROUND: Invasive group A Streptococcus (GAS) infections cause significant morbidity and mortality. We report the epidemiology and trends of invasive GAS over 8 years of surveillance. METHODS: From January 2005 through December 2012, we collected data from the Centers for Disease Control and Prevention's Active Bacterial Core surveillance (ABCs), a population-based network of 10 geographically diverse U.S. sites (2012 population, 32.8 million). We defined invasive GAS as isolation of GAS from a normally sterile site or from a wound in a patient with necrotizing fasciitis (NF) or streptococcal toxic shock syndrome (STSS). Available isolates were emm typed. We calculated rates and made age- and race-adjusted national projections using census data. RESULTS: We identified 9557 cases (3.8 cases per 100,000 persons per year) with 1116 deaths (case-fatality ratio [CFR]: 11.7%). CFRs for septic shock, STSS and NF were 45%, 38%, and 29%, respectively. Annual incidence was highest among persons aged ≥65 years (9.4 per 100,000), persons aged <1 year (5.3), and blacks (4.7). National rates remained steady over 8 years of surveillance. Factors independently associated with death included increasing age, residence in a nursing home, recent surgery, septic shock, NF, meningitis, isolated bacteremia, pneumonia, emm type 1 or 3, and underlying chronic illness or immunosuppression. An estimated 10,649-13,434 cases of invasive GAS infections occur in the U.S. annually, resulting in 1,136-1,607 deaths. emm types in a 30-valent M-protein vaccine accounted for 91% of isolates. CONCLUSIONS: The burden of invasive GAS infection in the U.S. remains substantial. Vaccines under development could have a considerable public health impact.

BACKGROUND: We describe the impact of early antiviral treatment among pregnant women hospitalized with laboratory-confirmed influenza (2010-14 influenza seasons). METHODS: Severe influenza was defined as intensive care unit admission, mechanical ventilation, respiratory failure, pulmonary embolism, sepsis, or death. Within severity stratum, we used parametric survival analysis to compare length of stay (LOS) by timing of antiviral treatment, adjusting for underlying conditions, influenza vaccination, and pregnancy trimester. RESULTS: Among 865 pregnant women, median age was 27 years (interquartile range [IQR], 23-31). Most (68%) were healthy, and 85% received antiviral treatment. Sixty-three (7%) women had severe influenza, 4 died. Severity was associated with preterm delivery and fetal loss. Women with severe influenza were less likely to be vaccinated than those without (14% vs. 26%, p=0.03). Comparing women treated with antivirals ≤2 vs. >2 days from illness onset, median LOS (days) was respectively 2.2 (IQR 0.9-5.8; n=8) vs. 7.8 (IQR 3.0-20.6; n=7) for severe (p=0.03), and 2.4 (IQR 2.3-2.5; n=153) vs. 3.1 (IQR 2.8-3.5; n=62) for non-severe influenza (p<0.01). CONCLUSIONS: Early influenza antiviral treatment for pregnant women hospitalized with influenza may reduce LOS, especially if severe influenza. Influenza during pregnancy is associated with maternal and infant morbidity and annual influenza vaccination is warranted.

Annual influenza vaccine is recommended for all persons aged ≥6 months in the United States, with recognition that some persons are at risk for more severe disease. However, there might be previously unrecognized demographic groups that also experience higher rates of serious influenza-related disease that could benefit from enhanced vaccination efforts. Socioeconomic status (SES) measures that are area-based can be used to define demographic groups when individual SES data are not available. Previous surveillance data analyses in limited geographic areas indicated that influenza-related hospitalization incidence was higher for persons residing in census tracts that included a higher percentage of persons living below the federal poverty level. To determine whether this association occurs elsewhere, influenza hospitalization data collected in 14 FluSurv-NET sites covering 27 million persons during the 2010-11 and 2011-12 influenza seasons were analyzed. The age-adjusted incidence of influenza-related hospitalizations per 100,000 person-years in high poverty (≥20% of persons living below the federal poverty level) census tracts was 21.5 (95% confidence interval [CI]: 20.7-22.4), nearly twice the incidence in low poverty (<5% of persons living below the federal poverty level) census tracts (10.9, 95% CI: 10.3-11.4). This relationship was observed in each surveillance site, among children and adults, and across racial/ethnic groups. These findings suggest that persons living in poorer census tracts should be targeted for enhanced influenza vaccination outreach and clinicians serving these persons should be made aware of current recommendations for use of antiviral agents to treat influenza.

BACKGROUND: Invasive group A Streptococcus (iGAS) infections cause significant morbidity and mortality worldwide. We analyzed whether obesity and diabetes were associated with iGAS infections and worse outcomes among an adult US population. METHODS: We determined the incidence of iGAS infections using 2010-2012 cases in adults aged ≥18 years from Active Bacterial Core surveillance (ABCs), a population-based surveillance system, as the numerator. For the denominator, we used ABCs catchment area population estimates from the 2011-2012 Behavioral Risk Factor Surveillance System (BRFSS) survey. The relative risk (RR) of iGAS was determined by obesity and diabetes status after adjusting for age group, gender, race and other underlying conditions through binomial logistic regression. Multivariable logistic regression was used to determine whether obesity or diabetes was associated with increased odds of death due to iGAS compared to normal weight and non-diabetic patients, respectively. RESULTS: Between 2010 and 2012, 2927 iGAS cases were identified. Diabetes was associated with an increased risk of iGAS in all racial groups (adjusted (a)RR ranged from 2.71-5.08). Grade 3 obesity (body mass index [BMI] ≥40) was associated with an increased risk of iGAS for whites (aRR=3.47; 95% confidence interval [CI] =3.00-4.01). Grades 1-2 (BMI= 30.0-<40.0) and grade 3 obesity were associated with an increased odds of death (OR=1.55, [95% CI=1.05, 2.29] and OR=1.62 [95% CI=1.01, 2.61], respectively) when compared to normal weight patients. CONCLUSIONS: These results may help target vaccines against GAS that are currently under development. Efforts to develop enhanced treatment regimens for iGAS may improve prognoses for obese patients.

We sought to assess diagnostic practices for influenza and other respiratory virus in a survey of hospitals and laboratories participating in the US Influenza Hospitalization Surveillance Network in 2012-13. Of the 240 participating laboratories, 67% relied only on commercially-available rapid influenza diagnostic tests to diagnose influenza. Few reported the availability of molecular diagnostic assays for detection of influenza (26%) and other viral pathogens (≤ 20%) in hospitals and commercial laboratories. Reliance on insensitive assays to detect influenza may detract from optimal clinical management of influenza infections in hospitals.

BACKGROUND: Patients hospitalized with influenza may require extended care upon discharge. We aimed to explore predictors for extended care needs and the potential mitigating effect of antiviral treatment among community-dwelling adults aged ≥65 years hospitalized with influenza. METHODS: We used laboratory-confirmed influenza hospitalizations from 3 influenza seasons. Extended care was defined as new placement in a skilled nursing home/long-term/rehabilitation facility upon hospital discharge. We focused on those treated with antiviral agents to explore the effect of early treatment on extended care and hospital length of stay (LOS) using logistic regression and competing risk survival analysis, accounting for time from illness onset to hospitalization. Treatment was categorized as early (≤4 days) and late (>4 days) in reference to date of illness onset. RESULTS: Among 6,593 community-dwelling adults aged ≥65 years hospitalized for influenza, 18% required extended care at discharge. Need for care increased with age and neurologic disorders, ICU admission, and pneumonia were predictors of care needs. Early treatment reduced the odds of extended care after hospital discharge for those hospitalized ≤2 or >2 days from illness onset (adjusted odds ratio [aOR] 0.38; 95% confidence interval [CI] 0.17, 0.85, and aOR 0.75; 95% CI 0.56, 0.97 respectively). Early treatment was also independently associated with reduction in LOS for those hospitalized ≤2 days from illness onset (adjusted hazard ratio [aHR] 1.81; 95% CI 1.43, 2.30) or >2 days (aHR 1.30; 95% CI 1.20, 1.40). CONCLUSIONS: Prompt antiviral treatment decreases the impact of influenza on older adults through shorten hospitalization and reduced extended care needs.

Diagnostic test sensitivity affects rate estimates for laboratory-confirmed influenza-associated hospitalizations. We used data from FluSurv-NET, a national population-based surveillance system for laboratory-confirmed influenza hospitalizations, to capture diagnostic test type by patient age and influenza season. We calculated observed rates by age group and adjusted rates by test sensitivity. Test sensitivity was lowest in adults >65 years of age. For all ages, reverse transcription PCR was the most sensitive test, and use increased from <10% during 2003-2008 to approximately 70% during 2009-2013. Observed hospitalization rates per 100,000 persons varied by season: 7.3-50.5 for children <18 years of age, 3.0-30.3 for adults 18-64 years, and 13.6-181.8 for adults >65 years. After 2009, hospitalization rates adjusted by test sensitivity were approximately 15% higher for children <18 years, approximately 20% higher for adults 18-64 years, and approximately 55% for adults >65 years of age. Test sensitivity adjustments improve the accuracy of hospitalization rate estimates.

In 2003, surveillance for influenza in hospitalized persons was added to the Centers for Disease Control and Prevention Emerging Infections Program network. This surveillance enabled monitoring of the severity of influenza seasons and provided a platform for addressing priority questions associated with influenza. For enhanced surveillance capacity during the 2009 influenza pandemic, new sites were added to this platform. The combined surveillance platform is called the Influenza Hospitalization Surveillance Network (FluSurv-NET). FluSurv-NET has helped to determine the risk for influenza-associated illness in various segments of the US population, define the severity of influenza seasons and the 2009 pandemic, and guide recommendations for treatment and vaccination programs.

We examined seasonal influenza severity [artificial ventilation, intensive care unit (ICU) admission, and radiographic-confirmed pneumonia] by weight category among adults hospitalized with laboratory-confirmed influenza. Using multivariate logistic regression models, we found no association between obesity or severe obesity and artificial ventilation or ICU admission; however, overweight and obese patients had decreased risk of pneumonia. Underweight was associated with pneumonia (adjusted odds ratio 1.31; 95 % confidence interval 1.04, 1.64).

BACKGROUND: Some studies suggest that influenza vaccination might be protective against severe influenza outcomes in vaccinated persons who become infected. We used data from a large surveillance network to further investigate the effect of influenza vaccination on influenza disease severity in adults aged ≥50 years hospitalized with laboratory-confirmed influenza. METHODS: We analyzed influenza vaccination and influenza severity using Influenza Hospitalization Surveillance Network (FluSurv-NET) data for the 2012-13 influenza season. Intensive care unit (ICU) admission, death, diagnosis of pneumonia, and hospital and ICU lengths of stay served as measures of disease severity. Data were analyzed by multivariable logistic regression, parametric survival models and propensity score matching (PSM). RESULTS: Overall, no differences in severity were observed in the multivariable logistic regression model. Using PSM, adults aged 50-64 years (but not other age groups) who were vaccinated against influenza had a shorter ICU length of stay compared to those unvaccinated (HR for discharge=1.84, 95% CI: 1.12-3.01). CONCLUSION: Our findings show a modest effect of influenza vaccination on disease severity. Analysis of data from seasons with different predominant strains and higher estimates of vaccine effectiveness are needed.

OBJECTIVE: To describe antiviral use among older, hospitalized adults during six influenza seasons (2006-2012) in Davidson County, Tennessee, USA. METHODS: Among adults ≥50 years old hospitalized with symptoms of respiratory illness or non-localizing fever, we collected information on provider-initiated influenza testing and nasal/throat swabs for influenza by RT-PCR in a research laboratory, and calculated the proportion treated with antivirals. RESULTS: We enrolled 1753 adults hospitalized with acute respiratory illness. Only 26% (457/1753) of enrolled patients had provider-initiated influenza testing. Thirty-eight patients had a positive clinical laboratory test, representing 2.2% of total patients and 8.3% of tested patients. Among the 38 subjects with clinical laboratory-confirmed influenza, 26.3% received antivirals compared to only 4.5% of those with negative clinical influenza tests and 0.7% of those not tested (p<0.001). There were 125 (7.1%) patients who tested positive for influenza in the research laboratory. Of those with research laboratory-confirmed influenza, 0.9%, 2.7%, and 2.8% received antivirals (p=.046) during pre-pandemic, pandemic, and post-pandemic influenza seasons, respectively. Both research laboratory-confirmed influenza (adjusted odds ratio [AOR] 3.04 95%CI 1.26-7.35) and clinical laboratory-confirmed influenza (AOR 3.05, 95%CI 1.07-8.71) were independently associated with antiviral treatment. Severity of disease, presence of a high-risk condition, and symptom duration were not associated with antiviral use. CONCLUSIONS: In urban Tennessee, antiviral use was low in patients recognized to have influenza by the provider as well as those unrecognized to have influenza. The use of antivirals remained low despite recommendations to treat all hospitalized patients with confirmed or suspected influenza.

BACKGROUND: Persons with influenza can develop complications that result in hospitalization and death. These are most commonly respiratory-related, but cardiovascular or neurologic complications or exacerbations of underlying chronic medical conditions may also occur. Patterns of complications observed during pandemics may differ from typical influenza seasons, and characterizing variations in influenza-related complications can provide a better understanding of the impact of pandemics and guide appropriate clinical management and planning for the future. METHODS: Using a population-based surveillance system, we compared clinical complications using ICD-9 discharge diagnosis codes in adults hospitalized with seasonal influenza (n=5,270) or 2009 pandemic influenza A(H1N1) (H1N1pdm09) (n=4,962). RESULTS: Adults hospitalized with H1N1pdm09 were younger (median age 47 years) than those with seasonal influenza (median: 68 years, p<0.01), and differed in the frequency of certain underlying medical conditions. While there was similar risk for many influenza-associated complications, after controlling for age and type of underlying medical condition adults hospitalized with H1N1pdm09 were more likely to have lower respiratory tract complications, shock/sepsis, and organ failure than those with seasonal influenza. They were also more likely to be admitted to the ICU, require mechanical ventilation, or die. Young adults, in particular, had 2-4 times the risk of severe outcomes from H1N1pdm09 than persons of the same ages with seasonal influenza. CONCLUSIONS: While thought of as a relatively mild pandemic, these data highlight the impact of the 2009 pandemic on the risk of severe influenza, especially among younger adults, and the impact this virus may continue to have.

We challenge the notion that influenza B virus infection is milder than influenza A virus infection by finding similar clinical characteristics and outcomes between adults hospitalized with these two types of influenza. Among patients treated with oseltamivir, length of stay and mortality did not differ by type of virus infection.

CONTEXT: Adolescence marks a time when many young people engage in risky behaviors with potential implications for long-term health. Interventions focused on adolescents' parents and other caregivers have the potential to affect adolescents across a variety of risk and health-outcome areas. EVIDENCE ACQUISITION: Community Guide methods were used to evaluate the effectiveness of caregiver-targeted interventions in addressing adolescent risk and protective behaviors and health outcomes. Sixteen studies published during the search period (1966-2007) met review requirements and were included in this review. EVIDENCE SYNTHESIS: Effectiveness was assessed based on changes in whether or not adolescents engaged in specified risk and protective behaviors; frequency of risk and protective behaviors, and health outcomes, also informed the results. Results from qualifying studies provided sufficient evidence that interventions delivered person-to-person (i.e., through some form of direct contact rather than through other forms of contact such as Internet or paper) and designed to modify parenting skills by targeting parents and other caregivers are effective in improving adolescent health. CONCLUSIONS: Interventions delivered to parents and other caregivers affect a cross-cutting array of adolescent risk and protective behaviors to yield improvements in adolescent health. Analysis from this review forms the basis of the recommendation by the Community Preventive Services Task Force presented elsewhere in this issue.

MMWR was established to disseminate the results of public health surveillance and owes much of its existence to the founder of modern surveillance, William Farr (1807--1883). In 1878, under the sway of Farr, Lemuel Shattuck, and other pioneers of surveillance, the U.S. government created the first precursor of MMWR and entered the business of publishing surveillance statistics. Farr's influence touched MMWR again in 1961 when one of his adherents, Alexander D. Langmuir (Figure 1), brought MMWR to Atlanta and CDC from a federal office in Washington, D.C. (1). Since its beginnings, MMWR has played a unique role in addressing emerging public health problems by working with state and local health departments to announce problems even before their cause is known, rapidly disseminating new knowledge about them weeks or months before articles appear in the medical literature, and publishing recommendations for their control and prevention. MMWR has played this role time after time---the discovery of Legionnaires disease in the 1970s, AIDS and toxic-shock syndrome in the 1980s, hantavirus pulmonary syndrome in the 1990s, and severe acute respiratory syndrome (SARS) in the 2000s. At the same time, MMWR also has reported on nearly all the major noninfectious public health problems of the day---environmental emergencies, chronic diseases, injuries, and new public health technologies. To a great extent, the history of MMWR is the history of disease and injury prevention and control in the United States

Hepatitis A vaccination has dramatically reduced the incidence of hepatitis A virus (HAV) infection, but new infections continue to occur. To identify human genetic variants conferring a risk for HAV infection among the three major racial/ethnic populations in the United States, we assess associations between 67 genetic variants (single nucleotide polymorphisms, 'SNPs') among 31 candidate genes and serologic evidence of prior HAV infection using a population-based, cross-sectional study of 6779 participants, including 2619 non-Hispanic whites, 2095 non-Hispanic blacks, and 2065 Mexican Americans, enrolled in phase 2 (1991-1994) of the Third National Health and Nutrition Examination Survey. Among the three racial/ethnic groups, the number (weighted frequency) of seropositivity for antibody to HAV (anti-HAV) was 958 (24.9%), 802 (39.2%), and 1540 (71.5%), respectively. No significant associations with any of the 67 SNPs were observed among non-Hispanic whites or non-Hispanic blacks. In contrast, among Mexican Americans, variants in two genes were found to be associated with an increased risk of HAV infection: TGFB1 rs1800469 (adjusted odds ratio [OR] = 1.38; 95% confidence interval [CI], 1.14-1.68; p-value adjusted for false discovery rate [FDR-P] = 0.017) and XRCC1 rs1799782 (OR = 1.57; 95% CI, 1.27-1.94; FDR-P = 0.0007). A decreased risk was found with ABCB1 rs1045642 (OR = 0.79; 95% CI, 0.71-0.89; FDR-P = 0.0007). CONCLUSIONS: Genetic variants in ABCB1, TGFB1, and XRCC1 appear to be associated with susceptibility to HAV infection among Mexican Americans. Replication studies involving larger population samples are warranted. (HEPATOLOGY 2011).

Many guidelines, including those produced by the World Health Organisation (WHO), have failed to adhere to rigorous methodological standards. Operational examples of guideline development processes may provide important lessons learned to improve the rigour and quality of future guidelines. To this end, this paper describes the process of developing WHO guidelines on prevention and care interventions for adults and adolescents living with HIV. Using a pragmatic, structured, evidence-based approach, we created an organising committee, identified topics, conducted systematic reviews, identified experts and distributed evidence summaries. Subsequently, 55 global HIV experts drafted and anonymously submitted guideline statements at the beginning of a conference. During the conference, participants voted on statements using scales evaluating appropriateness of the statements, strength of recommendation and level of evidence. After review of voting results, open discussion, re-voting and refinement of statements, a draft version of the guidelines was completed. A post-conference writing team refined the guidelines based on pre-determined guideline writing principles and incorporated external comments into a final document. Successes and challenges of the guideline development process were identified and are used to highlight current issues and debates in developing guidelines with a focus on implications for future guideline development at WHO.

The relationship between the blood lead concentration and cognitive function in children and adults with different VDR genotypes who participated in the third National Health and Nutrition Examination Survey was investigated. The relationship between blood lead and serum homocysteine concentrations was also investigated. In children 12 to 16years old, performance on the digit span and arithmetic tests as a function of the blood lead concentration varied by VDR rs2239185 and VDR rs731236 genotypes. Decreases in performance occurred in some genotypes, but not in others. In adults 20 to 59years old, performance on the symbol-digit substitution test as a function of the blood lead concentration varied by VDR rs2239185-rs731236 haplotype. In the 12 to 16year old children and adults 60 or more years old, the relationship between the serum homocysteine and blood lead concentrations varied by VDR genotype. The mean blood lead concentrations of the children and adults did not vary by VDR genotype.

The relationship between the blood lead concentration and cognitive function in children and adults with different ALAD genotypes who participated in the third National Health and Nutrition Examination Survey was investigated. The relationship between blood lead and serum homocysteine concentrations was also investigated. In children 12 to 16 years old, no difference in the relationship between cognitive function and blood lead concentration between genotypes was found. In adults 20 to 59 years old, mean reaction time decreased as the blood lead concentration increased in the ALAD rs1800435 CC/CG group. This represents an improvement in performance. In adults 60 years and older, no difference in the relationship between cognitive function and blood lead concentration between genotypes was found. The serum homocysteine concentration increased as the blood lead concentration increased in adults 20 to 59 years old and 60 years and older, but there were no differences between genotypes. The mean blood lead concentration of children with the ALAD rs1800435 CC/CG genotype was less than that of children with the GG genotype.