The burden of influenza B: a structured literature review.

We reviewed the epidemiology, clinical characteristics, disease severity, and economic burden of influenza B as reported in the peer-reviewed published literature. We used MEDLINE to perform a systematic literature review of peer-reviewed, English-language literature published between 1995 and 2010. Widely variable frequency data were reported. Clinical presentation of influenza B was similar to that of influenza A, although we observed conflicting reports. Influenza B-specific data on hospitalization rates, length of stay, and economic outcomes were limited but demonstrated that the burden of influenza B can be significant. The medical literature demonstrates that influenza B can pose a significant burden to the global population. The comprehensiveness and quality of reporting on influenza B, however, could be substantially improved. Few articles described complications. Additional data regarding the incidence, clinical burden, and economic impact of influenza B would augment our understanding of the disease and assist in vaccine development.

Water quality monitoring records for estimating tap water arsenic and nitrate: a validation study.

BACKGROUND: Tap water may be an important source of exposure to arsenic and nitrate. Obtaining and analyzing samples in the context of large studies of health effects can be expensive. As an alternative, studies might estimate contaminant levels in individual homes by using publicly available water quality monitoring records, either alone or in combination with geographic information systems (GIS). METHODS: We examined the validity of records-based methods in Washington State, where arsenic and nitrate contamination is prevalent but generally observed at modest levels. Laboratory analysis of samples from 107 homes (median 0.6 microg/L arsenic, median 0.4 mg/L nitrate as nitrogen) served as our "gold standard." Using Spearman's rho we compared these measures to estimates obtained using only the homes' street addresses and recent and/or historical measures from publicly monitored water sources within specified distances (radii) ranging from one half mile to 10 miles. RESULTS: Agreement improved as distance decreased, but the proportion of homes for which we could estimate summary measures also decreased. When including all homes, agreement was 0.05-0.24 for arsenic (8 miles), and 0.31-0.33 for nitrate (6 miles). Focusing on the closest source yielded little improvement. Agreement was greatest among homes with private wells. For homes on a water system, agreement improved considerably if we included only sources serving the relevant system (rho = 0.29 for arsenic, rho = 0.60 for nitrate). CONCLUSIONS: Historical water quality databases show some promise for categorizing epidemiologic study participants in terms of relative tap water nitrate levels. Nonetheless, such records-based methods must be used with caution, and their use for arsenic may be limited.

A Proposed Framework for Patient-Focused Policy at the U.S. Food and Drug Administration.

Medical product sponsors are encouraged to include the patient perspective in their medical product development strategy to inform product design, augment regulatory submissions, argue for alternative clinical trial designs, or to support indications in specific patient populations. The goal is to create a patient-focused ecosystem that enables industry to integrate the patient voice throughout the medical product lifecycle. To this end, the U. S. Food and Drug Administration (FDA) has published several guidance documents to provide industry with the expectations and opportunities for conducting patient-focused activities. From an industry perspective, the Center for Devices and Radiologic Health (CDRH) and the Center for Drug Evaluation and Research (CDER)/Center for Biologics Evaluation and Research (CBER) patient-focused policies are complementary. The basic tenets promoted in all FDA patient-focused guidance could apply across therapeutic areas. However, there remain differences in these guidance documents across FDA centers, and there is no framework in place to provide industry with consistent recommendations. Without a coordinated patient-focused policy from the FDA, there is the potential for confusion and a lack of consistency among industry and regulatory decision-makers. The objective of this paper was to propose an alternative framework for patient-focused policy at the FDA, which recognizes the potential for different types of patient input to be used across therapeutic areas and medical product types. Further, these policies need to provide greater clarity on how patient input data is used, so that sponsors may navigate the opportunities to use patient input regardless of the FDA center under which their product is regulated. Creating consistent, coherent, and transparent FDA patient-focused policy will encourage sponsors to obtain patient input more often and with greater certainty of the value that these data may have to their medical product strategies.

Measuring participation in people living with multiple sclerosis: a comparison of self-reported frequency, importance and self-efficacy.

PURPOSE: To compare three dimensions related to participation in everyday situations in community-dwelling adults with multiple sclerosis (MS). METHODS: Mail survey was obtained from 112 respondents. Data were analyzed using Kendall's tau-b correlation coefficients between responses to participation items relative to three question dimensions (importance, frequency, and self-efficacy) and criterion variables (mobility, depression, general health, fatigue and pain). RESULTS: No significant associations were found between item responses in the importance dimension and the criterion variables. Weak associations were found for items in the frequency dimension, and stronger associations were found for items in the self-efficacy dimension. CONCLUSIONS: Different dimensions of participation in specific life situations yielded different responses and associations of those responses with key criterion measures. Subjective importance of participating in everyday situations is relatively independent of measures of mobility, general health, depression, fatigue and pain. Subjective judgments of self-efficacy for participation are more closely linked to these criterion measures. Caution is warranted when interpreting scales of participation because participation is a complex construct, potentially composed of several dimensions.

Patient Experience Data in US Food and Drug Administration (FDA) Regulatory Decision Making:: A Policy Process Perspective.

BACKGROUND: The influence of patient advocates on FDA regulatory decision making has increased. Despite enhanced engagement with FDA, there remain challenges to achieving the regulatory goals of patients within FDA's regulatory framework. Gaps exist between patient advocates' knowledge of the agency's processes and FDA's need for rigorous, clinically meaningful patient experience data. This study examined the policy process in which patient experience data are collected by patient advocates and provided to FDA for regulatory decision making. METHODS: Semistructured, narrative interviews were conducted with 14 professionals working in patient advocacy or at FDA. The purpose was to examine, in depth, participants' perceptions and experiences regarding this new regulatory process. Interviews were coded and examined for themes. RESULTS: The use of patient experience data by FDA is an evolving regulatory process. Participants identified a number of barriers and contributors to regulatory success. Well-organized and sophisticated patient advocacy groups with access to scientific and policy expertise are more likely to find success meeting FDA's patient experience data requirements. A conceptual model of this regulatory process was developed. CONCLUSIONS: Use of patient experience data by FDA has the potential to positively influence the regulation of medical products in the United States. Success within this new regulatory process will depend on clear guidance from FDA regarding the collection, analysis, and use of patient experience data. Patient advocacy groups must enhance internal capacity and expertise while engaging in substantive collaborations with FDA and other stakeholders in order to meaningfully contribute to the regulatory review of new therapeutics.

Fetal deaths and proximity to hazardous waste sites in Washington State.

BACKGROUND: The in utero period is one of increased susceptibility to environmental effects. The effects of prenatal exposure to environmental toxicants on various adverse pregnancy outcomes, including fetal death, are not well understood. OBJECTIVE: We examined the risk of fetal death in relation to maternal residential proximity to hazardous waste sites. METHODS: We conducted a population-based case-control study using Washington State vital records for 1987-2001. Cases were women with fetal deaths at > or = 20 weeks (n = 7,054). Ten controls per case were randomly selected from live births. Locations of 939 hazardous waste sites were identified from the Department of Ecology registry. We measured distance from maternal residence at delivery to the nearest hazardous waste site, and calculated odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The risk of fetal death for women residing < or = 0.5 miles, relative to > 5 miles, from a hazardous waste site was not increased (adjusted OR = 1.06; 95% CI, 0.90-1.25). No associations were observed for any proximity categories < or = 5 miles from sites with contaminated air, soil, water, solvents, or metals; however, fetal death risk increased among women residing < or = 1 mile from pesticide-containing sites (OR = 1.28; 95% CI, 1.13-1.46). CONCLUSION: These results do not suggest that fetal death is associated with residential proximity to hazardous waste sites overall; however, close proximity to pesticide-containing sites may increase the risk of fetal death.

Survey of SLP caseloads in Washington State schools: implications and strategies for action.

PURPOSE: To document statewide and regional caseloads and to examine workload management strategies by surveying speech-language pathologists (SLPs) in Washington State public schools. METHOD: All school SLPs who were registered with the Office of the Superintendent of Public Instruction were mailed a detailed survey in May, 2001 and a brief follow-up survey 1 year later. RESULTS: Response rates were 43% (N=431) and 47% (N=464), respectively. Caseload findings showed a statewide mean of 59 students, with regional variation as high as 30%. IMPLICATIONS: There was no systematic evidence that caseloads were managed through state, district, or local limits or by distributing clients on the basis of the severity of impairment or SLP experience ortraining. There was significant evidence, however, that clinicians with larger caseloads were more likely to have assistants and to conduct a higher proportion of group sessions than were clinicians with smaller caseloads. The authors discuss the implication of these findings for and other states with no caseload limits and a shortage of SLPs. There is an appeal for more research using newly established measures of workload as well as a call to action to address the challenges that these findings represent.

Getting the work done: a qualitative study of individuals with multiple sclerosis.

THE PROBLEM: Work can be defined as an activity performed to accomplish something in the presence of obstacles that may make accomplishing the goal difficult. For individuals with MS, work is not only limited by physical impairments but also by factors such as fatigue and cognitive changes PURPOSE: The aim of this study is to examine the experiences of individuals with mild to moderate MS as they carry out everyday work activities both inside and outside the home. METHOD: Eleven women and three men were recruited from the community to participate in a series of semi-structured interviews. Using qualitative research methodology that examined the experiences of the participants, two major themes and seven subthemes emerged. RESULTS: The first theme, Defining the work, included Priorities: seeing what's important; Plans: learning about resources and requirements; and PERSPECTIVES: fixing it yourself. The second theme, Changing how things get done, includes Precipitating factors; Awareness; Constructing the strategies; and Evaluating the strategies. CONCLUSIONS: Individuals with MS develop strategies and utilize resources in order to get the work done. Comparisons are made between existing intervention theories or programmes and the experiences described by participants in this study.

Validation of chest X-ray comparisons for unknown decedent identification.

Comparing skeletal structures between antemortem and postmortem chest radiographs is widely used by forensic specialists from many disciplines to positively identify unknown decedents. However, validity assessments of this method have been fairly limited. This study had three objectives: 1) to quantify the reliability of ante- and postmortem chest radiograph comparison for decedent identification; 2) to identify useful radiologic features supporting decedent identification; and 3) to recognize sources of error in decedent identification related to use of comparative radiographs. A forensic pathologist, a forensic anthropologist, and two radiologists participated in the study. Our results showed that chest radiograph comparisons proved reliable, if basic decedent information was provided, and antemortem and postmortem radiographs were adequately positioned and exposed. A "morphological approach" using normal anatomical structures for comparison may provide the most efficient method for accurate identification.

An evaluation of semi-quantitative test strips for the measurement of nitrate in drinking water in epidemiologic studies.

Consumption of nitrate and nitrite is associated with a variety of health outcomes. Commercially available test strips that allow semi-quantitative estimation of these contaminants in drinking water are inexpensive relative to laboratory testing, and are simple to use. To examine the accuracy of a nitrate/nitrite test strip, we recruited Washington State residents to estimate levels of these contaminants in their tap water using these strips, and simultaneously provide a tap water sample for laboratory analysis. Paired results were available from 102 homes. On the basis of laboratory assay, nitrate levels as nitrogen ranged from no nitrate (27%) to 40.5 mg/l (median 0.4 mg/l). Spearman's correlation coefficient between test strip- and laboratory-measured nitrate indicated moderate precision overall (r=0.72). Correlation was similar for homes inside and outside city/town limits, but differed by primary source of water for the purveyor indicated by residents (r=0.72 for groundwater and r=0.34 for surface water). Seven (7%) participants reported difficulty in distinguishing colors (contaminant levels) when using the test strip; and among the samples with nitrate, the laboratory assay indicated higher nitrate levels than the test strip for 81%. Nitrite was not detected by laboratory assay; in comparison, five (5%) subjects reported any nitrite according to the test strip. Nitrate/nitrite test strips may be useful in some epidemiologic studies, but should be used with caution, preferably as a screening tool or when laboratory assays are not feasible.

Risk of malformations associated with residential proximity to hazardous waste sites in Washington State.

Hazardous waste sites often contain substances harmful to fetal development. Using linked birth-hospital discharge and hazardous sites data for Washington State, we evaluated the association between malformation occurrence and maternal residential proximity to hazardous waste sites. Cases (N=63,006) were infants born 1987-2001 with malformations. Controls (N=315,030) were randomly selected infants without malformations born during these years. Distance between maternal residence and nearest hazardous waste site was measured using geographic information systems (GIS) software. Odds ratio (OR) estimates of the relative risk of malformation at varying distances were calculated. Relative to living >5 miles from a site, living < or = 5 miles was associated with increased risk of any malformations in offspring (for >2- < or = 5 miles: OR 1.15: 95% Confidence Interval (CI): 1.10, 1.21; for >1- < or = 2 miles: OR 1.26, 95% CI: 1.20, 1.32; for >0.5- < or = 1 miles: OR 1.28, 95% CI: 1.22, 1.35; for < or = 0.5 miles: OR 1.33, 95% CI: 1.27, 1.40.) Risk estimates varied by urban vs. rural maternal residence and by specific malformation type. Hazardous waste sites are often located within populated areas. Thus, the possibility of increased malformation occurrence among those in close proximity deserves closer scrutiny.

Symptom burden in persons with spinal cord injury.

OBJECTIVE: To determine (1) the frequency, severity, and reported course of 7 symptoms in persons with spinal cord injury (SCI) and (2) the association between these symptoms and patient functioning. DESIGN: Postal survey. SETTING: Community. INTERVENTION: A survey that included measures of the frequency, severity, and recalled course of pain, fatigue, numbness, weakness, shortness of breath, vision loss, and memory loss, as well as a measure of community integration and psychologic functioning was mailed to a sample of persons with SCI. One hundred forty-seven usable surveys were returned (response rate, 43% of surveys mailed). MAIN OUTCOME MEASURES: The frequency and average severity of each symptom was computed, and the frequencies of each type of reported course were noted. Analyses estimated the associations among the symptoms, and between symptom severity and measures of patient functioning. RESULTS: The most common symptoms were pain, weakness, fatigue, and numbness. All symptoms were reported to remain the same or to get worse more often than they were reported to improve once they began. Pain, weakness, fatigue, and memory loss were the symptoms most closely associated with patient functioning. CONCLUSIONS: Patients with SCI must deal with a number of secondary complications in addition to any disability caused by the injury itself. Of 7 symptoms studied, pain, weakness, and fatigue appeared to be most common and most closely linked to patient social and mental health functioning. Research is needed to identify the causal relationships between perceived symptoms and quality of life in patients with SCI and to identify effective treatments for those symptoms shown to impact patient functioning.

Maternal and birth characteristics in relation to childhood leukaemia.

Our objective was to investigate the association of childhood leukaemia with selected maternal and birth characteristics by conducting a population-based case-control study using linked cancer registry and birth certificate records for Washington State. We compared maternal and infant characteristics of 595 Washington-born residents <20 years old with leukaemia diagnosed during 1981-2003, and 5,950 control children, using stratified analysis and logistic regression. Maternal age 35+ years (odds ratio [OR] 1.5; 95% confidence interval [CI] 1.1, 2.0), infant birthweight 4,000+ g (OR 1.4; 95% CI 1.1, 1.8), neonatal jaundice (OR 1.5; 95% CI 1.1, 2.1), and Down's syndrome (OR 31.3; 95% CI 6.4, 153.4) were associated with an increased risk of leukaemia. Among women with 2+ pregnancies, having at least two prior early (<20 weeks' gestation) fetal deaths was also associated with an increased risk (OR 1.5; 95% CI 0.97, 2.1). Maternal unmarried status (OR 0.7; 95% CI 0.6, 0.9) and African American race (OR 0.5; 95% CI 0.3, 0.9) were associated with a decreased risk. These results were more marked for acute lymphocytic leukaemia (ALL) than for acute myeloid leukaemia (AML), and for leukaemia diagnosed <5 years of age. These results may provide clues to the aetiology of childhood leukaemia. Genetic epidemiological studies are needed to expand our knowledge of inherent and possibly prenatal influences on the occurrence of this disease.

The cost and benefits of employment: a qualitative study of experiences of persons with multiple sclerosis.

OBJECTIVE: To attain a better understanding of the benefits and barriers faced by persons with multiple sclerosis (MS) in the workplace. DESIGN: Qualitative research methodology comprising a series of semistructured interviews. SETTING: Community-based setting. PARTICIPANTS: Fourteen women and 2 men with MS living in the community who were employed or recently employed at the time of interviews. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Accounts of personal experiences related to employment. RESULTS: Four themes emerged: the cost-benefit economy of working; fatigue and cognitive changes; stress in the workplace; and accommodations made to address barriers. Although participants valued work highly, they were also aware of the cost of being employed. The consequences of unemployment or changing jobs were considered negative and appeared stressful. For persons with MS, employment had both costs and significant benefits. Accommodations in the workplace and modifications of roles and responsibilities at home made it possible for individuals to continue working. CONCLUSIONS: Health care providers must consider the complexity and timing of decisions by people with MS to continue or leave employment before recommending either action. Identifying critical periods of intervention to stabilize this cost-benefit balance is a critical next step for understanding issues of employment and MS.