Burden of Adults Hospitalized With Group B Streptococcal Infection.

BACKGROUND: The burden of noninvasive group B Streptococcus (GBS) infections in adults is unknown. We determined population-based rates of hospitalization where invasive or noninvasive GBS infections were identified among US adults in a defined catchment area. METHODS: We identified adults with clinical and laboratory-confirmed evidence of GBS infection from January 2014 through December 2016 from 6 hospitals in Louisville, Kentucky. Invasive disease was defined as GBS isolated from a normally sterile site. RESULTS: Among 1076 adults with GBS infection, the median age was 52 years, 51% were male, and 89% had ≥1 chronic medical condition. The most prevalent infection sites were skin and soft tissue (39%), urinary tract (23%), bone and joint (16%), and bloodstream (11%). Forty percent of infections were polymicrobial. The annual incidence of GBS-associated hospitalization was 73 per 100 000 adults and 68 and 100 per 100 000 for patients aged 18-64 and ≥ 65 years, respectively. For every invasive GBS infection, 3.7 noninvasive infections occurred. CONCLUSIONS: Our population-based study outlines the full burden of GBS-associated hospitalization in adults and found incidence rates comparable to those of pneumococcal disease, where vaccines are recommended. Noninvasive disease was 3-4 times more common than invasive disease, suggesting that the GBS burden among adults is considerably greater than previously recognized.

Expanded Analysis of 20 Pneumococcal Serotypes Associated With Radiographically Confirmed Community-acquired Pneumonia in Hospitalized US Adults.

BACKGROUND: Streptococcus pneumoniae is a causative agent of community-acquired pneumonia (CAP). The 13-valent pneumococcal conjugate vaccine (PCV13) has significantly decreased the burden of PCV13-serotype pneumococcal disease; however, disease from nonvaccine serotypes remains substantial. A recent study documented the persistence of PCV13 serotypes among US adults hospitalized with radiographically confirmed CAP. The current analysis used a recently developed urinary antigen detection (UAD) assay (UAD2) to extend these results to additional serotypes included in an investigational PCV20 vaccine. METHODS: This prospective study enrolled adults aged ≥18 years hospitalized with radiographically confirmed CAP between October 2013 and September 2016. Presence of S pneumoniae was determined by blood and respiratory sample culture, BinaxNOW urine testing, and UAD. In addition to Quellung on cultured isolates when available, serotypes were identified from urine specimens using UAD1 for PCV13 serotypes and UAD2 for 7 PCV20-unique serotypes (8, 10A, 11A, 12F, 15B, 22F, and 33F) and 4 additional serotypes (2, 9N, 17F, and 20). RESULTS: Among 12 055 subjects with radiographically confirmed CAP, 1482 were positive for S pneumoniae. PCV13- and PCV20-unique serotypes were associated with 37.7% (n = 559) and 27.0% (n = 400) of cases, respectively; 288 subjects were exclusively diagnosed as positive for S pneumoniae by UAD2. Demographic and clinical disease characteristics were similar between subjects with CAP caused by PCV13 and PCV20-unique serotypes. CONCLUSIONS: The current analysis using UAD2 identified a sizeable proportion of hospitalized adult CAP associated with PCV20-unique serotypes. PCV20 may therefore address the burden of CAP caused by the additional serotypes present in the vaccine.

Effectiveness of oseltamivir treatment on clinical failure in hospitalized patients with lower respiratory tract infection.

BACKGROUND: Influenza is associated with excess morbidity and mortality of individuals each year. Few therapies exist for treatment of influenza infection, and each require initiation as early as possible in the course of infection, making efficacy difficult to estimate in the hospitalized patient with lower respiratory tract infection. Using causal machine learning methods, we re-analyze data from a randomized trial of oseltamivir versus standard of care aimed at reducing clinical failure in hospitalized patients with lower respiratory tract infection during the influenza season. METHODS: This was a secondary analysis of the Rapid Empiric Treatment with Oseltamivir Study (RETOS). Conditional average treatment effects (CATE) and 95% confidence intervals were computed from causal forest including 85 clinical and demographic variables. RETOS was a multicenter, randomized, unblinded, trial of adult patients hospitalized with lower respiratory tract infections in Kentucky from 2009 through 2012. Adult hospitalized patients with lower respiratory tract infection were randomized to standard of care or standard of care plus oseltamivir as early as possible after hospital admission but within 24 h of enrollment. After randomization, oseltamivir was initiated in the treatment arm per package insert. The primary outcome was clinical failure, a composite measure including failure to reach clinical improvement within 7 days, transfer to intensive care 24 h after admission, or rehospitalization or death within 30 days. RESULTS: A total of 691 hospitalized patients with lower respiratory tract infections were included in the study. The only subgroup of patients with a statistically significant CATE was those with laboratory-confirmed influenza infection with a 26% lower risk of clinical failure when treated with oseltamivir (95% CI 3.2-48.0%). CONCLUSIONS: This study suggests that addition of oseltamivir to standard of care may decrease clinical failure in hospitalized patients with influenza-associated lower respiratory tract infection versus standard of care alone. These results are supportive of current recommendations to initiate antiviral treatment in hospitalized patients with confirmed or suspected influenza as soon as possible after admission. Trial registration Original trial: Clinical Trials.Gov; Rapid Empiric Treatment With Oseltamivir Study (RETOS) (RETOS); ClinicalTrials.gov Identifier: NCT01248715 https://clinicaltrials.gov/ct2/show/NCT01248715.

The elevated systemic cytokine levels in HIV patients are not associated with an elevated pulmonary cytokine environment.

BACKGROUND: HIV-positive patients on anti-retroviral therapy (ART) are at higher risk of developing many non-AIDS related chronic diseases, including chronic obstructive pulmonary disease (COPD), compared to HIV-negative individuals. While the mechanisms are not clear, a persistent pro-inflammatory state appears to be a key contributing factor. The aims of this study were to investigate whether HIV-positive patients without COPD present evidence of potentially predisposing abnormal pulmonary cytokine/chemokine environment and to explore the relationship between pulmonary and systemic cytokine levels. METHODS: This study included 39 HIV-seropositive and 34 HIV-seronegative subjects without COPD. All were subjected to outpatient bronchoscopy with bronchoalveolar lavage fluid (BALF) aspiration and blood sample collection. The levels of 21 cytokines and chemokines were measured in plasma and BALF using a bead-based multi-analyte assay. RESULTS: In plasma, HIV-infected patients showed significantly increased circulating levels of pro-inflammatory (TNFα) and Th1-associated cytokines (IL-12p70) as well as several chemokines (CXCL11 and CX3CL1). However, no statistically significant differences were found in the numbers of cells, the concentrations of protein and urea as well as cytokine levels in the BALFs of HIV-positive patients when compared to controls. Correlation analysis indicated a potential modulatory effect of the BMI in HIV-seropositive individuals. CONCLUSIONS: While our results are consistent with the existence of a systemic pro-inflammatory state in HIV-infected patients, they did not detect significant differences in cytokine levels and other inflammatory markers in the lungs of HIV-positive individuals when compared to HIV-negative controls.

A phase 2b/3b MenACWY-TT study of long-term antibody persistence after primary vaccination and immunogenicity and safety of a booster dose in individuals aged 11 through 55 years.

BACKGROUND: A previous phase 2 study demonstrated the immunogenicity of a single dose of meningococcal A, C, W, Y-tetanus toxoid conjugate (MenACWY-TT) or polysaccharide (MenACWY-PS) vaccine for up to 5 years in individuals aged 11-55 years. This follow-up study evaluated long-term antibody persistence up to 10 years and the immunogenicity and safety of a single MenACWY-TT booster dose given 10 years after primary vaccination. METHODS: Blood draws were conducted annually in Years 7-10. At Year 10, all subjects received a MenACWY-TT booster dose. Blood was drawn at 1 month and safety data were collected ≤6 months postbooster. Study endpoints included immunogenicity during the persistence phase (primary), and immunogenicity and safety during the booster phase (secondary). Statistical analyses were descriptive. RESULTS: A total of 311 subjects were enrolled in the persistence phase (MenACWY-TT, 235; MenACWY-PS, 76); 220 were enrolled in the booster phase (MenACWY-TT, 164; MenACWY-PS, 56). Descriptive analyses indicated that at Years 7-10, the percentages of subjects achieving serum bactericidal antibody assay using baby rabbit complement (rSBA) titers ≥1:8 and ≥1:128 were higher for serogroups A, W, and Y in the MenACWY-TT versus MenACWY-PS group; percentages were similar across groups for serogroup C. rSBA geometric mean titers (GMTs) for serogroups A, W, and Y were higher in the MenACWY-TT group and slightly higher in the MenACWY-PS group for serogroup C. One month postbooster, all primary MenACWY-TT and ≥98.1% of primary MenACWY-PS recipients had rSBA titers ≥1:8. For all serogroups, rSBA GMTs postbooster were higher in the MenACWY-TT versus MenACWY-PS group. Most local and general reactogenicity events were similar between groups and mild to moderate in severity. Adverse events at 1 month postbooster were 9.1% for the MenACWY-TT and 3.6% for the MenACWY-PS groups; all were nonserious. CONCLUSIONS: Immune responses to a single MenACWY-TT primary dose administered at age 11-55 years persisted in >70% of individuals evaluated at Years 7-10. A MenACWY-TT booster dose administered at Year 10 was safe and immunogenic with no new safety signals observed. These results provide important insights regarding long-term protection from primary vaccination and the benefits of booster dosing. TRIAL REGISTRATION: Clinicaltrials.gov, NCT01934140. Registered September 2013.

Future Research Directions in Pneumonia. NHLBI Working Group Report.

Pneumonia is a complex pulmonary disease in need of new clinical approaches. Although triggered by a pathogen, pneumonia often results from dysregulations of host defense that likely precede infection. The coordinated activities of immune resistance and tissue resilience then dictate whether and how pneumonia progresses or resolves. Inadequate or inappropriate host responses lead to more severe outcomes such as acute respiratory distress syndrome and to organ dysfunction beyond the lungs and over extended time frames after pathogen clearance, some of which increase the risk for subsequent pneumonia. Improved understanding of such host responses will guide the development of novel approaches for preventing and curing pneumonia and for mitigating the subsequent pulmonary and extrapulmonary complications of pneumonia. The NHLBI assembled a working group of extramural investigators to prioritize avenues of host-directed pneumonia research that should yield novel approaches for interrupting the cycle of unhealthy decline caused by pneumonia. This report summarizes the working group's specific recommendations in the areas of pneumonia susceptibility, host response, and consequences. Overarching goals include the development of more host-focused clinical approaches for preventing and treating pneumonia, the generation of predictive tools (for pneumonia occurrence, severity, and outcome), and the elucidation of mechanisms mediating immune resistance and tissue resilience in the lung. Specific areas of research are highlighted as especially promising for making advances against pneumonia.

Examining age as a moderating effect on the relationship between alcohol use and viral suppression among women living with HIV.

This study sought to examine if age moderated the effect of alcohol on viral suppression among women living with HIV. A secondary data analysis, using data from the 550 Clinic Women's HIV Cohort Study was completed. Individuals were included if they were HIV positive, sought care in an urban clinic in Kentucky between 2009 and 2012, and had ≥1 year of follow-up. The primary independent variable was current alcohol use; the moderating variable was age (<50 years versus ≥50 years); and the outcome was suppression. Logistic regression models examined the interaction between age and alcohol. Among 360 women (average age 45.8 ± 10.1 years, 38 percent were ≥50 years), approximately 32.0 percent had consumed alcohol, and 40 percent achieved suppression. Women aged ≥50 years were more likely to achieve suppression than younger women. Age interacted significantly with alcohol (p = .038). Stratified by age, alcohol was associated with poor viral suppression among older women; for older women, alcohol users had lower odds of suppression compared to nonusers (odds ratio = 0.37; 95 percent confidence interval = 0.14-0.99). Alcohol may impede the opportunity for older women to achieve suppression. Further study is needed to examine alcohol use among older women, specifically addressing quantity and frequency and their impact on suppression.

A Randomized Study Evaluating the Effectiveness of Oseltamivir Initiated at the Time of Hospital Admission in Adults Hospitalized With Influenza-Associated Lower Respiratory Tract Infections.

Background: Influenza-associated hospitalizations result in high morbidity and mortality. We sought to determine if early empiric anti-influenza therapy improves outcomes of hospitalized patients with influenza-associated lower respiratory tract infections (I-LRTIs). Methods: This was a randomized, unblinded, trial of adult patients hospitalized with I-LRTIs in Kentucky during 2009-2012. Patients were randomized to group A (standard of care) or group B (standard of care plus oseltamivir as early as possible but within 24 hours of enrollment). The primary outcome was development of clinical failure (composite variable including failure to reach clinical improvement within 7 days, transfer to intensive care 24 hours after admission, or rehospitalization or death within 30 days). Intent-to-treat (ITT) (all LRTI) and per-protocol (PP) (I-LRTI) analyses were done. Results: A total of 1107 patients were enrolled and included in the ITT analysis, 556 in group A and 551 in group B. The median time from symptom onset to hospital admission was 5 days (interquartile range, 5) for both groups; oseltamivir was initiated median day 6 in group B. There was no difference in the development of clinical failure (group A, 25%, and group B, 24%; P = .561). In the PP analysis, 11 of 45 (24%) patients in group A and 4 of 29 (14%) patients in group B had clinical failure (P = .414). Conclusions: Initiation of oseltamivir more than 5 days after illness onset did not reduce clinical failures among hospitalized patients with I- LRTIs. However, we did not enroll our projected sample size of I-LRTI. Clinical Trials Registration: NCT01248715.

Effectiveness of 13-Valent Pneumococcal Conjugate Vaccine Against Hospitalization for Community-Acquired Pneumonia in Older US Adults: A Test-Negative Design.

Background: Following universal recommendation for use of 13-valent pneumococcal conjugate vaccine (PCV13) in US adults aged ≥65 years in September 2014, we conducted the first real-world evaluation of PCV13 vaccine effectiveness (VE) against hospitalized vaccine-type community-acquired pneumonia (CAP) in this population. Methods: Using a test-negative design, we identified cases and controls from a population-based surveillance study of adults in Louisville, Kentucky, who were hospitalized with CAP. We analyzed a subset of CAP patients enrolled 1 April 2015 through 30 April 2016 who were aged ≥65 years and consented to have their pneumococcal vaccination history confirmed by health insurance records. Cases were defined as hospitalized CAP patients with PCV13 serotypes identified via culture or serotype-specific urinary antigen detection assay. Remaining CAP patients served as test-negative controls. Results: Of 2034 CAP hospitalizations, we identified PCV13 serotypes in 68 (3.3%) participants (ie, cases), of whom 6 of 68 (8.8%) had a positive blood culture. Cases were less likely to be immunocompromised (29.4% vs 46.4%, P = .02) and overweight or obese (41.2% vs 58.6%, P = .01) compared to controls, but were otherwise similar. Cases were less likely to have received PCV13 than controls (3/68 [4.4%] vs 285/1966 [14.5%]; unadjusted VE, 72.8% [95% confidence interval, 12.8%-91.5%]). No confounding was observed during adjustment for patient characteristics, including immunocompromised status, body mass index, and history of influenza and pneumococcal polysaccharide vaccination (adjusted VE range, 71.1%-73.3%). Conclusions: Our study is the first to demonstrate real-world effectiveness of PCV13 against vaccine-type CAP in adults aged ≥65 years following introduction into a national immunization program.

Detailed Transmission Network Analysis of a Large Opiate-Driven Outbreak of HIV Infection in the United States.

In January 2015, an outbreak of undiagnosed human immunodeficiency virus (HIV) infections among persons who inject drugs (PWID) was recognized in rural Indiana. By September 2016, 205 persons in this community of approximately 4400 had received a diagnosis of HIV infection. We report results of new approaches to analyzing epidemiologic and laboratory data to understand transmission during this outbreak. HIV genetic distances were calculated using the polymerase region. Networks were generated using data about reported high-risk contacts, viral genetic similarity, and their most parsimonious combinations. Sample collection dates and recency assay results were used to infer dates of infection. Epidemiologic and laboratory data each generated large and dense networks. Integration of these data revealed subgroups with epidemiologic and genetic commonalities, one of which appeared to contain the earliest infections. Predicted infection dates suggest that transmission began in 2011, underwent explosive growth in mid-2014, and slowed after the declaration of a public health emergency. Results from this phylodynamic analysis suggest that the majority of infections had likely already occurred when the investigation began and that early transmission may have been associated with sexual activity and injection drug use. Early and sustained efforts are needed to detect infections and prevent or interrupt rapid transmission within networks of uninfected PWID.

Adults Hospitalized With Pneumonia in the United States: Incidence, Epidemiology, and Mortality.

BACKGROUND: Understanding the burden of community-acquired pneumonia (CAP) is critical to allocate resources for prevention, management, and research. The objectives of this study were to define incidence, epidemiology, and mortality of adult patients hospitalized with CAP in the city of Louisville, and to estimate burden of CAP in the US adult population. METHODS: This was a prospective population-based cohort study of adult residents in Louisville, Kentucky, from 1 June 2014 to 31 May 2016. Consecutive hospitalized patients with CAP were enrolled at all adult hospitals in Louisville. The annual population-based CAP incidence was calculated. Geospatial epidemiology was used to define ecological associations among CAP and income level, race, and age. Mortality was evaluated during hospitalization and at 30 days, 6 months, and 1 year after hospitalization. RESULTS: During the 2-year study, from a Louisville population of 587499 adults, 186384 hospitalizations occurred. A total of 7449 unique patients hospitalized with CAP were documented. The annual age-adjusted incidence was 649 patients hospitalized with CAP per 100000 adults (95% confidence interval, 628.2-669.8), corresponding to 1591825 annual adult CAP hospitalizations in the United States. Clusters of CAP cases were found in areas with low-income and black/African American populations. Mortality during hospitalization was 6.5%, corresponding to 102821 annual deaths in the United States. Mortality at 30 days, 6 months, and 1 year was 13.0%, 23.4%, and 30.6%, respectively. CONCLUSIONS: The estimated US burden of CAP is substantial, with >1.5 million unique adults being hospitalized annually, 100000 deaths occurring during hospitalization, and approximately 1 of 3 patients hospitalized with CAP dying within 1 year.

Macrolide Use and Neutrophil Function/Cytokine Levels in Hospitalized Patients with Community-Acquired Pneumonia: A Pilot Study.

PURPOSE: The objective of this study was to measure plasma cytokine levels and blood neutrophil functions as well as clinical outcomes in hospitalized patients with community-acquired pneumonia (CAP) treated with or without macrolide use--a known modulator of inflammatory response. METHODS: Subjects with CAP had peripheral blood analyzed for some neutrophil functions (degranulation of secretory vesicles and specific granules, respiratory burst response and phagocytosis) and ten cytokine levels measured in serum and sputum supernatants. Neutrophil function in healthy volunteers was also measured for reference. Values were measured on the day of enrollment, days 2-4 and 5-7, depending on a patient's length of stay. Early and late clinical outcomes were also evaluated. All values were compared between those treated with or without a macrolide. RESULTS: A total of 40 subjects were in this study; 14 received macrolide treatment, and 26 did not. Neutrophil function in the macrolide group was not significantly different compared to the non-macrolide group. None of the median cytokine levels or IQRs were statistically significant between the groups. However, a trend toward decreased IL-6, IL-8, and IFN-γ levels, and favorable clinical outcomes were present in the macrolide group. CONCLUSIONS: This pilot study showed no statistical difference between cytokine levels or neutrophil activity for CAP patients prescribed a macrolide containing regimen. Considering the trend of lower cytokine levels in the macrolide group when comparing the 5- to 7-day time period with the non-macrolide group, a full study with an appropriate sample size may be warranted.

Comparing posteroanterior with lateral and anteroposterior chest radiography in the initial detection of parapneumonic effusions.

BACKGROUND: It is unclear whether anteroposterior (AP) or posteroanterior with lateral (PA/Lat) chest radiographs are superior in the early detection of clinically relevant parapneumonic effusions (CR-PPEs). The objective of this study was to identify which technique is preferred for detection of PPEs using chest computed tomography (CCT) as a reference standard. METHODS: A secondary analysis of a pneumonia database was conducted to identify patients who received a CCT within 24 hours of presentation and also received AP or PA/Lat chest radiographs within 24 hours of CCT. Sensitivity and specificity were then calculated by comparing the radiographic diagnosis of PPEs of both types of radiographs compared with CCT by using the existing attending radiologist interpretation. Clinical relevance of effusions was determined by CCT effusion measurement of >2.5 cm or presence of loculation. RESULTS: There was a statistically significant difference between the sensitivity of AP (67.3%) and PA/Lat (83.9%) chest radiography for the initial detection of CR-PPE. Of 16 CR-PPEs initially missed by AP radiography, 7 either required drainage initially or developed empyema within 30 days, whereas no complicated PPE or empyema was found in those missed by PA/Lat radiography. CONCLUSIONS: PA/Lat chest radiography should be the initial imaging of choice in pneumonia patients for detection of PPEs because it appears to be statistically superior to AP chest radiography.

What is the best therapeutic approach to methicillin-resistant Staphylococcus aureus pneumonia?

PURPOSE OF REVIEW: The purpose of this review is to define what the best therapeutic approach is for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. RECENT FINDINGS: Although two meta-analyses reported conflicting findings, recent retrospective studies reported higher success rates in patients with MRSA pneumonia treated with linezolid when compared to vancomycin. Only registration trials are available for some anti-MRSA antibiotics, such as telavancin, ceftaroline, and ceftobiprole. Scarce information is available regarding the best therapeutic approach for MRSA community-acquired pneumonia. SUMMARY: Linezolid seems to be a better choice than vancomycin for the treatment of MRSA ventilator-associated pneumonia. It is still unclear whether this affirmation holds for other forms of MRSA pneumonia. Further research is needed to define whether newer antibiotics are better alternatives than currently recommended agents.

Predicting Mycobacterium tuberculosis in patients with community-acquired pneumonia.

The 22 risk factors suggested by the Centers for Disease Control and Prevention (CDC) to predict patients at risk for Mycobacterium tuberculosis have not been evaluated in hospitalised patients with community-acquired pneumonia (CAP). We evaluated which of the CDC risk factors best predict M. tuberculosis in these patients. To our knowledge, this is the first time a score has been developed assessing these risk factors. This was a secondary analysis of 6976 patients hospitalised with CAP enrolled in the Community-Acquired Pneumonia Organization International Cohort Study. Using Poisson regression, we selected the subset of risk factors that best predicted the presence of CAP due to M. tuberculosis. This subset was compared to the CDC risk factors using receiver operating characteristic (ROC) curve analysis. Five risk factors were found to best predict CAP due to M. tuberculosis: night sweats, haemoptysis, weight loss, M. tuberculosis exposure and upper lobe infiltrate. The area under the ROC curve for all CDC risk factors was 71% and 89% for the subset of five risk factors. The CDC-suggested risk factors are poor at predicting the presence of M. tuberculosis in hospitalised patients with CAP. With a subset of five risk factors identified in this study, we developed a new score, which will improve our capacity to isolate patients at risk of CAP due to M. tuberculosis at the time of hospitalisation.

Higher clinical success in patients with ventilator-associated pneumonia due to methicillin-resistant Staphylococcus aureus treated with linezolid compared with vancomycin: results from the IMPACT-HAP study.

INTRODUCTION: Controversy exists regarding optimal treatment for ventilator-associated pneumonia (VAP) due to methicillin-resistant Staphylococcus aureus (MRSA). The primary objective of this study was to compare clinical success of linezolid versus vancomycin for the treatment of patients with MRSA VAP. METHODS: This was a multicenter, retrospective, observational study of patients with VAP (defined according to Centers for Disease Control and Prevention criteria) due to MRSA who were treated with linezolid or vancomycin. MRSA VAP was considered when MRSA was isolated from a tracheal aspirate or bronchoalveolar lavage. Clinical success was evaluated by assessing improvement or resolution of signs and symptoms of VAP by day 14. After matching on confounding factors, logistic regression models were used to determine if an association existed between treatment arm and clinical success. RESULTS: A total of 188 patients were evaluated (101 treated with linezolid and 87 with vancomycin). The mean ± standard deviation Acute Physiology and Chronic Health Evaluation (APACHE) II score was 21 ± 11 for linezolid- and 19 ± 9 for vancomycin-treated patients (P = 0.041). Clinical success occurred in 85% of linezolid-treated patients compared with 69% of vancomycin-treated patients (P = 0.009). After adjusting for confounding factors, linezolid-treated patients were 24% more likely to experience clinical success than vancomycin-treated patients (P = 0.018). CONCLUSIONS: This study adds to the evidence indicating that patients with MRSA VAP who are treated with linezolid are more likely to respond favorably compared with patients treated with vancomycin.

From Qualitative Research to Quantitative Preference Elicitation: An Example in Invasive Meningococcal Disease.

BACKGROUND: Qualitative research is fundamental for designing discrete choice experiments (DCEs) but is often underreported in the preference literature. We developed a DCE to elicit preferences for vaccination against invasive meningococcal disease (IMD) among adolescents and young people (AYP) and parents and legal guardians (PLG) in the United States. This article reports the targeted literature review and qualitative interviews that informed the DCE design and demonstrates how to apply the recent reporting guidelines for qualitative developmental work in preference studies. METHODS: This study included two parts: a targeted literature review and qualitative interviews. The Medline and Embase databases were searched for quantitative and qualitative studies on IMD and immunization. The results of the targeted literature review informed a qualitative interview guide. Sixty-minute, online, semi-structured interviews with AYP and PLG were used to identify themes related to willingness to be vaccinated against IMD. Participants were recruited through a third-party recruiter's database and commercial online panels. Interviews included vignettes about IMD and vaccinations and three thresholding exercises examining the effect of incidence rate, disability rate, and fatality rate on vaccination preferences. Participant responses related to the themes were counted. RESULTS: The targeted literature review identified 31 concepts that were synthesized into six topics for the qualitative interviews. Twenty AYP aged 16-23 years and 20 PLG of adolescents aged 11-17 years were interviewed. Four themes related to willingness to be vaccinated emerged: attitudes towards vaccination, knowledge and information, perception of IMD, and vaccine attributes. Most participants were concerned about IMD (AYP 60%; PLG 85%) and had positive views of vaccination (AYP 80%; PLG 60%). Ninety percent of AYP and 75% of PLG always chose vaccination over no vaccination, independent of IMD incidence rate, disability rate, or fatality rate. CONCLUSION: Willingness to be vaccinated against IMD was affected by vaccine attributes but largely insensitive to IMD incidence and severity. This article provides an example of how to apply the recent reporting guidelines for qualitative developmental work in preference studies, with 21 out of 22 items in the guidelines being considered.

Outcomes in females hospitalised with community-acquired pneumonia are worse than in males.

There is little recent information on sex-specific outcomes of patients with community-acquired pneumonia (CAP). The objective of this study was to determine whether female sex is associated with better clinical outcomes in hospitalised patients with CAP. A secondary analysis was conducted by the Community Acquired Pneumonia Organization regarding male and female patients with CAP from 80 hospitals in 17 countries from June 1, 2001 to August 2, 2011. Outcomes were time to clinical stability, length of stay and in-hospital and 28-day mortality. Propensity-adjusted, multivariate regression models were used to predict the probability of occurrence of each of the study outcomes. There were 6718 patients in this study, of whom 40% were female. The adjusted hazard ratio (HR) for time to clinical stability was 0.91 (95% CI 0.85-0.97; p=0.005). The adjusted HR for length of stay was 0.94 (95% CI 0.88-1.01; p=0.089). The adjusted risk ratio for in-hospital mortality was 1.04 (95% CI 0.86-1.24; p=0.717), and for 28-day mortality was 1.15 (95% CI 1.02-1.30; p=0.018). This study demonstrates that the epidemiology of CAP may be changing, and that females have worse outcomes for CAP than males. They are more likely to take longer to reach clinical stability, have longer hospital stays and are 15% more likely to have died after 28 days. Current pneumonia scoring systems may need to be revised regarding female mortality risk.

Criteria for clinical stability in hospitalised patients with community-acquired pneumonia.

The American Thoracic Society (ATS) and Infectious Diseases Society of America (IDSA) suggested two sets of criteria in 2001 and 2007 to define clinical stability in community-acquired pneumonia (CAP). The present study aimed to evaluate the level of agreement between these two sets of criteria and how well they can predict clinical outcomes. A retrospective cohort study was carried out of 487 consecutive patients hospitalised with CAP. Level of agreement was tested using a survival curve analysis, while prediction of outcomes at 30-day follow-up was evaluated through receiver operating characteristic (ROC) analysis. A discrepancy between ATS 2001 and ATS/IDSA 2007 criteria in identifying clinical stability was detected in 62% of the patients. The median (interquartile range) time to clinical stability was 2 (1-4) days based on ATS 2001 and 3 (2-5) days based on ATS/IDSA 2007 criteria (p = 0.012). The daily distribution of patients who reached clinical stability evaluated with both sets was different (p = 0.002). The ROC analysis showed an area under the curve of 0.705 for the ATS 2001 criteria and 0.714 for ATS/IDSA 2007 criteria (p = 0.645). ATS 2001 and ATS/IDSA 2007 criteria for clinical stability in hospitalised patients with CAP are clinically equivalent and both can be used in clinical practice as well as in clinical research.

A three-step critical pathway for community-acquired pneumonia reduces duration of hospital stay and intravenous antibiotic use by 2 days.

Implications for practice and research: Although early switch therapy and hospital discharge are well-recognised processes, current practices show that these practices are not well established worldwide. Pathways are useful tools to remind treating physicians about criteria for early switch and discharge. A behavioural change may be necessary in order to decrease the gap between national recommendations and current management of hospitalised patients with community-acquired pneumonia.