Association Between Hemagglutination Inhibition Antibody Titers and Protection Against Reverse-Transcription Polymerase Chain Reaction-Confirmed Influenza Illness in Children 6-35 Months of Age: Statistical Evaluation of a Correlate of Protection.

BACKGROUND: Data from a randomized controlled efficacy trial of an inactivated quadrivalent influenza vaccine in children 6-35 months of age were used to determine whether hemagglutination inhibition (HI) antibody titer against A/H1N1 and A/H3N2 is a statistical correlate of protection (CoP) for the risk of reverse-transcription polymerase chain reaction (RT-PCR)-confirmed influenza associated with the corresponding strain. METHODS: The Prentice criteria were used to statistically validate strain-specific HI antibody titer as a CoP. The probability of protection was identified using the Dunning model corresponding to a prespecified probability of protection at an individual level. The group-level protective threshold was identified using the Siber approach, leading to unbiased predicted vaccine efficacy (VE). A case-cohort subsample was used for this exploratory analysis. RESULTS: Prentice criteria confirmed that HI titer is a statistical CoP for RT-PCR-confirmed influenza. The Dunning model predicted a probability of protection of 49.7% against A/H1N1 influenza and 54.7% against A/H3N2 influenza at an HI antibody titer of 1:40 for the corresponding strain. Higher titers of 1:320 were associated with >80% probability of protection. The Siber method predicted VE of 61.0% at a threshold of 1:80 for A/H1N1 and 46.6% at 1:113 for A/H3N2. CONCLUSIONS: The study validated HI antibody titer as a statistical CoP, by demonstrating that HI titer is correlated with clinical protection against RT-PCR-confirmed influenza associated with the corresponding influenza strain and is predictive of VE in children 6-35 months of age. CLINICAL TRIALS REGISTRATION: NCT01439360.

The nutritional landscape of host plants for a specialist insect herbivore.

Nutrition has far-reaching effects on both the ecology and evolution of species. A substantial body of work has examined the role of host plant quality on insect herbivores, with a particular focus on specialist-generalist dynamics, the interaction of growth and other physiological attributes on fitness and tritrophic effects. Measures of plant quality usually involve one or two axes of nutritional space: typically secondary metabolites or elemental proxies (N and C) of protein and carbohydrates, respectively.Here, we describe the nutrient space of seven host plants of the specialist insect herbivore, Manduca sexta, using an approach that measures physiologically relevant sources of nutrition, soluble protein and digestible carbohydrates. We show that plant species differ markedly in their nutrient content, offering developing insect herbivores a range of available nutrient spaces that also depend on the age of the leaves being consumed.The majority of host-plant species produce diets that are suboptimal to the herbivore, likely resulting in varying levels of compensatory feeding for M. sexta to reach target levels of protein to ensure successful growth and development. Low-quality diets can also impact immune function leading to complex patterns of optimization of plant resources that maximizes both growth and the ability to defend from parasitoids and pathogens. This study is the first to quantify the nutrient space of a suite of host plants used by an insect herbivore using physiologically relevant measures of nutrition.

Epidemiology of bisphosphonate-related osteonecrosis of the jaws: the utility of a national registry.

PURPOSE: Little is known about the epidemiology of osteonecrosis of the jaws. To date, no population-based studies have rigorously evaluated risk factors, treatment factors, or outcomes. We aimed to perform such a study. MATERIALS AND METHODS: We reviewed the literature for epidemiologic studies on osteonecrosis of the jaws. RESULTS: Current epidemiologic information is generally derived from anecdotal reports or case series from small institutions. Estimates that have been provided in some reports have questionable validity because of a lack of standardized case definitions, clearly defined source populations, and clear methods for obtaining (or confirming) full reporting. Population-based prospective registries are capable of answering and informing several of the outstanding questions about bisphosphonate-related osteonecrosis of the jaws/osteonecrosis of the jaws. CONCLUSION: A population-based registry that collects systematic information on patient characteristics, treatments, and outcomes is essential to filling the gaps in our knowledge and understanding of bisphosphonate-related osteonecrosis of the jaws.

Assessing the costs of chronic obstructive pulmonary disease: the state medicaid perspective.

BACKGROUND: State Medicaid programs provide insurance coverage to over 40 million Americans. However, estimates of the annual cost of chronic obstructive pulmonary disease (COPD) from the Medicaid perspective are lacking. METHODS: This retrospective cohort study used Medicaid administrative claims data from California and Florida to estimate COPD expenditures using two alternative methods: (1) excess costs (comparing a COPD cohort to a matched comparison cohort); and (2) attributable costs (COPD-related expenditures within a COPD cohort, inclusive of respiratory medications). The COPD cohort in each state included Medicaid recipients not dually eligible for Medicare who were 40+ years of age with at least one medical claim for COPD during 2001. The comparison cohort consisted of patients with medical claims during 2001 for conditions other than chronic respiratory disease, matched by age, sex, and race to the COPD cohort. RESULTS: A total of 6,738 Medicaid recipients in California and 18,017 in Florida were included in the COPD cohort, with mean ages of 56 and 60 years, respectively. Comorbidities, especially congestive heart failure and vascular disease, were more common in the COPD cohort than among matched controls. The mean excess cost of COPD per-patient was estimated to be approximately 6,500 US dollars in California Medicaid and 5,200 US dollars in Florida Medicaid. Mean attributable costs of COPD were similar in the two Medicaid programs (approximately 2,200 US dollars and 2,300 US dollars per patient, respectively). CONCLUSIONS: COPD places a substantial financial burden on State Medicaid programs. These findings may be of interest to clinicians and policy-makers involved in preventing or managing this chronic disease.

Population antibiotic susceptibility for Streptococcus pneumoniae and treatment outcomes in common respiratory tract infections.

PURPOSE: Antibiotic-resistant Streptococcus pneumoniae potentially threatens the successful treatment of common respiratory tract infections (RTIs); however, the relationship between antibiotic resistance and treatment outcomes remains unclear. We aimed to test the hypothesis that higher in vitro penicillin and erythromycin nonsusceptibility levels among clinical isolates of S. pneumoniae are associated with higher risk of treatment failure in suppurative acute otitis media (AOM), acute sinusitis, and acute exacerbation of chronic bronchitis (AECB). METHODS: We conducted a population-level analysis using treatment outcomes data from a national, managed-care claims database, and antibiotic susceptibility data from a national repository of antimicrobial susceptibility results between 1997 and 2000. Treatment outcomes in patients with suppurative AOM, acute sinusitis, or AECB receiving selected macrolides or beta-lactams were assessed. Associations between RTI-specific treatment outcomes and antibiotic nonsusceptibility were determined using Spearman correlation coefficients with condition-specific paired outcome and susceptibility data for each region and each year. RESULTS: There were 649 552 available RTI outcomes and 7252 susceptibility tests performed on S. pneumoniae isolates. There were no statistically significant trends across time for resolution proportions following treatment by either beta-lactams or macrolides among any of the RTIs. Correlation analyses found no statistically significant association between S. pneumoniae susceptibility and RTI treatment outcomes apart from a significant positive association between of erythromycin nonsusceptibility in ear isolates and macrolide treatment resolution for suppurative AOM. CONCLUSION: On the population level, in vitro S. pneumoniae nonsusceptibility to macrolide or beta-lactam antibiotics was not associated with treatment failure in conditions of probable S. pneumoniae etiology.

A cost-minimization analysis comparing azithromycin-based and levofloxacin-based protocols for the treatment of patients hospitalized with community-acquired pneumonia: results from the CAP-IN trial.

BACKGROUND: A randomized trial was performed comparing azithromycin and levofloxacin for treating moderately to severely ill patients hospitalized with community-acquired pneumonia. This is a cost-minimization analysis comparing those regimens. METHODS: The cost-minimization analysis compares 81 patients receiving sequential therapy with IV azithromycin plus IV ceftriaxone followed by oral azithromycin with 82 patients receiving IV levofloxacin followed by oral levofloxacin, all with complete economic data over approximately 30 days, including information about hospitalization, study medications, home care, postdischarge utilization, and lost productivity. Units of utilization were multiplied by unit prices in order to estimate cost per patient. These total costs were compared using a two-sample t test. RESULTS: Direct medical costs of the azithromycin group were 2,481 US dollars less than the corresponding costs in the levofloxacin group (p = 0.03; 95% confidence interval, 238 US dollars to 4,724 US dollars). Most of the cost difference (2,300 US dollars) is attributable to hospital days, with the majority of these days being spent on the general medicine wards. The precise magnitude of the cost advantage attributable to azithromycin, if any, depends on both the reduction in length of hospital stay and its associated daily cost. CONCLUSIONS: Azithromycin was no more costly than levofloxacin, and perhaps less so. Cost is but one of many factors that should be considered by clinicians in decisions involving any individual patient.

Excess mortality, length of stay, and costs associated with serious fungal infections among elderly cancer patients: findings from linked SEER-Medicare data.

OBJECTIVE: To calculate the excess mortality, length of stay, and costs attributable to serious fungal infections in hospitalized elderly patients with selected cancers. METHODS: This study involved a retrospective cohort analysis using linked data from the Surveillance, Epidemiology and End Results Program of the National Cancer Institute (SEER) and Medicare claims data. Study cohorts included patients aged 65 years and older who newly received a diagnosis of a selected cancer (acute myeloid leukemia [AML] or squamous cell carcinoma of the head and neck [SCCHN]) in a SEER registry between 1991 and 1996 and who had a subsequent diagnosis of a serious fungal infection during an inpatient hospitalization, and hospitalized controls without a fungal infection matched 1:1 by age, geographic region, receipt of recent chemotherapy, concomitant bacterial infection, timing of the index hospitalization, and cancer stage at diagnosis (for SCCHN patients only). RESULTS: Eighty AML patients and 52 SCCHN patients experienced a serious fungal infection involving hospitalization. Relative to matched controls, SCCHN patients with fungal infections had significantly higher all-cause mortality (40% vs. 14%, P = 0.002), while mortality rates did not differ between AML cohorts. Patients with fungal infections had significantly longer index hospitalizations regardless of cancer type (mean: 30 days vs. 19 days for AML patients; 20 days vs. 9 days for SCCHN patients), and correspondingly higher Medicare payments (mean +/- SD: 34,268 dollars +/- 31,811 dollars vs. 21,416 dollars +/- 22,449 dollars among AML patients, P < 0.0001; 25,942 dollars +/- 29,122 dollars vs. 10,131 dollars +/- 10,686 dollars among SCCHN patients, P < 0.0001). CONCLUSIONS: Efforts to prevent these infections and/or initiate early treatment may yield both clinical and economic benefits.

Medicaid prescription drug access restrictions: exploring the effect on patient persistence with hypertension medications.

OBJECTIVE: To compare rates of discontinuation of prescription therapy for hypertension in Medicaid patients with and without medication access restrictions. STUDY DESIGN: Retrospective cohort study. METHODS: Prescription data were extracted from a pharmacy claims database in a large state that implemented a Medicaid preferred drug list (PDL), both before and after the PDL was implemented. Prescriptions filled between June 2000 and May 2003 were included. RESULTS: Medicaid patients taking prescription medications commonly used to treat hypertension were 39% (odds ratio = 1.39; 95% confidence interval, 1.21, 1.6) more likely to discontinue hypertension therapy after the restriction was implemented compared with Medicaid patients 1 year earlier when there were no restrictions. Patients were classified as "discontinued" if they had therapy available less than 50% of the time during the 12 months after implementation of the PDL. Before the PDL, 17% of patients receiving treatment with hypertension medication discontinued therapy. After the PDL, 21% of Medicaid patients taking hypertension medication discontinued therapy. After the PDL, Medicaid patients were significantly more likely to switch medications from a restricted to an unrestricted drug. Those patients also were less likely to have a restricted drug added to their therapy regimen. CONCLUSIONS: After implementation of the PDL, Medicaid patients were more likely to discontinue filling prescriptions for antihypertensive medication. Because hypertension management is an important challenge within the Medicaid community, the potential connection between access restrictions and patient adherence to medication therapy is a worthy topic for further exploratory studies and quantitative outcomes research.

Ethnicity-related variation in breast cancer risk factors.

BACKGROUND: A variety of factors are predictors of breast cancer risk. However, the studies conducted to establish these risk factors have rarely included African American women. The few studies with sufficient numbers of African-American women suggest that risk factors for breast cancer among African-American women are similar to those of white women. Although risk factors may be similar for African-American and white women, differences in the prevalence of risk factors may explain the differences in patterns of incidence. METHODS: The authors reviewed the epidemiologic studies of breast cancer among African-American women and identified resources with information regarding the prevalence of risk factors among African American and white women. RESULTS: Considerable variation exists in the studies of breast cancer risk factors among African American women. Because few studies have included sufficient numbers of African-American women, no firm conclusions can be drawn regarding whether risk estimates for African American women differ from those of white women. Estimates of the prevalence of breast cancer risk factors indicate that African American and white women differ in terms of their ages at menarche, menstrual cycle patterns, birth rates, lactation histories, patterns of oral contraceptive use, levels of obesity, frequency of menopausal hormone use, physical activity patterns, and alcohol intake. CONCLUSIONS: The risk factor profile of African-American women appears to differ from that of white women. This may explain in part, the higher incidence rates for African Americans before age 45 years and the lower incidence rates at older ages. Discussions of these data at a workshop highlighted the need for future research on breast cancer risk among African Americans. This research should acknowledge the heterogeneous heritage, cultural beliefs, and cultural knowledge of African-American women. Studies conducted in collaboration with the African-American community of women and with the breast cancer advocacy community can benefit from assistance in the design of questionnaires and recruitment of participants.