Showing papers by "Kristin L. Nichol published in 2010"

Sensitivity analyses to estimate the potential impact of unmeasured confounding in causal research

Abstract: BACKGROUND: The impact of unmeasured confounders on causal associations can be studied by means of sensitivity analyses. Although several sensitivity analyses are available, these are used infrequently. This article is intended as a tutorial on sensitivity analyses, in which we discuss three methods to conduct sensitivity analysis. METHODS: Each method is based on assumed associations between confounder and exposure, confounder and outcome and the prevalence of the confounder in the population at large. In the first method an unmeasured confounder is simulated and subsequently adjusted. The other two methods are analytical methods, in which either the (adjusted) effect estimate is multiplied with a factor based on assumed confounder characteristics, or the (adjusted) risks for the outcome among exposed and unexposed subjects are adjusted by such a factor. These methods are illustrated with a clinical example on influenza vaccine effectiveness. RESULTS: When applied to a dataset constructed to assess the effect of influenza vaccination on mortality, the three reviewed methods provided similar results. After adjustment for observed confounders, influenza vaccination reduced mortality by 42% [odds ratio (OR) 0.58, 95% confidence interval (CI) 0.46-0.73]. To arrive at a 95% CI including one requires a very common confounder (40% prevalence) with strong associations with both vaccination status and mortality, respectively OR or =3.0 (OR 0.79, 95% CI 0.62-1.00). CONCLUSIONS: In every non-randomized study on causal associations the robustness of the results with respect to unmeasured confounding can, and should, be assessed using sensitivity analyses.

Modeling seasonal influenza outbreak in a closed college campus: impact of pre-season vaccination, in-season vaccination and holidays/breaks.

Abstract: Background College and university students experience substantial morbidity from influenza and influenza-like illness, and they can benefit substantially from vaccination. Public health authorities encourage vaccination not only before the influenza season but also into and even throughout the influenza season. We conducted the present study to assess the impact of various vaccination strategies including delayed (i.e., in-season) vaccination on influenza outbreaks on a college campus.

Attending work while sick: implication of flexible sick leave policies.

Abstract: Objective:To examine the impact of various flexible sick leave policies (FSLPs) on workplace attendance of employees with self-reported “severe” influenza-like-illness (ILI) symptoms.Methods:This is a prospective study of employees from three US employers, which involved collection of information on

Workshop on Immunizations in Older Adults: Identifying Future Research Agendas

Abstract: Goals for immunization in older adults may differ from those in young adults and children, in whom complete prevention of disease is the objective. Often, reduced hospitalization and death but also averting exacerbation of underlying chronic illness, functional decline, and frailty are important goals in the older age group. Because of the effect of age on dendritic cell function, T cell-mediated immune suppression, reduced proliferative capacity of T cells, and other immune responses, the efficacy of vaccines often wanes with advanced age. This article summarizes the discussion and proceedings of a workshop organized by the Association of Specialty Professors, the Infectious Diseases Society of America, the American Geriatrics Society, the National Institute on Aging, and the National Institute of Allergy and Infectious Diseases. Leading researchers and clinicians in the fields of immunology, epidemiology, infectious diseases, geriatrics, and gerontology reviewed the current status of vaccines in older adults, identified knowledge gaps, and suggest priority areas for future research. The goal of the workshop was to identify what is known about immunizations (efficacy, effect, and current schedule) in older adults and to recommend priorities for future research. Investigation in the areas identified has the potential to enhance understanding of the immune process in aging individuals, inform vaccine development, and lead to moreeffective strategies to reduce the risk of vaccine-preventable illness in older adults. J Am Geriatr Soc 58:765–776, 2010.

Pneumococcal Vaccination and Revaccination in the Elderly Population

Abstract: Pneumococcal disease remains a major cause of morbidity and mortality among elderly persons. Invasive infections including bacteremic pneumonia and meningitis are responsible for tens of thousands of hospitalizations and thousands of deaths in this age group each year. According to estimates from the Centers for Disease Control and Prevention, in the United States in 2008 approximately one-third of the 44,000 cases of invasive pneumococcal disease occurred among elderly persons, whereas more than one-half of the 4500 deaths were in this age group [1]. Vaccination with the 23-valent pneumococcal polysaccharide vaccine (PPSV23) is recommended as a critical component of efforts to reduce this burden of invasive pneumococcal disease (IPD) among elderly persons [2]. PPSV23 induces a significant, serotype-specific antibody response in most elderly persons receiving the vaccine for the first time, although certain subgroups (including those with very advanced age and those with serious comorbidities or higher frailty scores) may have diminished immune responses to the vaccine [3]. Vaccination has also been found to be safe and efficacious. In a recent update to a Cochrane Collaboration systematic review , overall pneumococcal polysaccha-ride vaccine efficacy against invasive pneu-mococcal disease among adults from the 10 randomized, controlled trials included in the study was found to be 74% (95% confidence interval [CI], 56%–85%). For the subgroup of otherwise healthy adults in high-income countries (most of whom were older or institutionalized adults), vaccine efficacy was 80% (95% CI, 59%– 90%). The authors also conducted an analysis of 5 observational studies that assessed pneumococcal vaccine effectiveness among immunocompetent older adults, with a pooled vaccine efficacy estimate of 68% (95% CI, 53%–78%) [4]. Although PPSV23 can protect against invasive pneumococcal disease, the duration of this protection may not be long-lasting. Antibody levels following initial vaccination in the elderly decline over time [3] and may approach prevaccination levels after ∼5 years [3, 5]. Furthermore, results from a large observational study suggested that clinical protection also declines over time. In this study of 1054 persons with laboratory documented IPD and 1054 matched controls, polyvalent pneu-mococcal vaccine effectiveness tended to vary both by increasing age and time since vaccination. For the 64–74-year age group, vaccine efficacy was 80% (95% CI, 51%– 92%) for !3 years since vaccination but only 58% (95% CI, Ϫ2% to 83%) for 15 years since vaccination. For persons aged у85 years, vaccine efficacy was 46% (95% CI, Ϫ31% to 78%) for !3 years since vaccination and …

Employees' willingness to pay to prevent influenza.

Abstract: OBJECTIVES To quantify employees' preferences, as measured by willingness to pay, to prevent influenza in themselves and in their child and adult household members and to examine factors associated with willingness to pay. STUDY DESIGN Prospective observational cohort study of a convenience sample of employees from 3 large US employers. Participants had at least 1 child (< or = 17 years) living in their household for at least 4 days per week. METHODS Each month from November 2007 to April 2008, employees completed Web-based surveys regarding acute respiratory illness in their household. In the final survey, employees were presented with descriptions of influenza and questions regarding their willingness to pay to prevent influenza. Factors associated with willingness to pay were examined using multivariate ordinary least squares regression analysis of the log of willingness to pay. RESULTS Among 2006 employees, 31.3% were female, the mean age was 41.7 years, 85.3% were of white race/ethnicity, and the mean household size was 4.0. Employees' median (mean) willingness to pay to prevent influenza was $25 ($72) for themselves, $25 ($82) for their adult household members, and $50 ($142) (P <.01) for children. However, influenza vaccination rates were approximately equal for children (27.5%), employees (31.5%), and other adult household members (24.5%). This finding may be explained by barriers such as cost, dislike of vaccinations, and disagreement with national influenza vaccination recommendations, which were significantly associated with lower willingness to pay for prevention of influenza (P <.05). CONCLUSION Employees expressed a stronger preference to prevent influenza in their children than in themselves or other household members; however, modifiable barriers depress vaccination rates.

Benefits and risks of live attenuated influenza vaccine in young children.

Abstract: OBJECTIVE To examine the benefit-risk profile of live attenuated influenza vaccine (LAIV) across a range of clinical scenarios in which we varied assumptions regarding both the percentage of children who would receive LAIV in lieu of trivalent inactivated influenza virus (TIV) and the extent of off-label use STUDY DESIGN Model of expected benefits and risks of immunization of young children against influenza METHODS We estimated expected numbers of cases of influenza illness (FLU), medically significant wheezing (MSW), and hospitalization in a single influenza season under alternative assumptions regarding use of LAIV in lieu of TIV, based on projections from a large phase III trial RESULTS Assuming no use of LAIV in nonindicated children (aged <24 months and those with history of recurrent wheezing or asthma), and 50% use in lieu of TIV among children in the indicated population, there would be 2099 fewer FLU cases per 100,000 children aged 12 to 59 months, and no change in MSW or hospitalization If LAIV also were used in lieu of TIV among 20% of children aged 12 to 23 months and 20% of children aged 24 to 59 months with a history of recurrent wheezing or asthma, there would be a further reduction of 397 FLU cases and 12 hospitalizations per 100,000 children aged 12 to 59 months, but 51 additional MSW cases CONCLUSIONS Our study suggests that even if LAIV were sometimes used inadvertently in clinical practice in young children for whom it is not indicated, the overall balance of expected benefits and risks would remain favorable