Multicenter Development and Validation of the Vocal Cord Paralysis Experience (CoPE), a Patient-Reported Outcome Measure for Unilateral Vocal Fold Paralysis-Specific Disability.

Importance: Unilateral vocal fold paralysis (UVFP) is a common and life-changing complication of cancer, trauma, and an estimated 500 000 head, neck, and chest surgeries performed annually in the US, among other causes (eg, idiopathic). Consequent disabilities are profound and often permanent and can include severe voice, swallowing, and breathing dysfunction and concomitant anxiety, isolation, and fear. Physiological measures often correlate poorly with patient-reported disability. The measure described herein was designed to be a comprehensive, psychometrically sound UVFP-specific patient-reported outcome measure (PROM) for use in clinical trials or at point of care. Objective: To evaluate the reliability and validity of the CoPE (vocal Cord Paralysis Experience) PROM in a nationally representative sample for both clinical and research use. Design, Setting, and Participants: This survey validation study was performed at 34 tertiary care centers across the US and included English-speaking adults with unilateral vocal fold immobility confirmed via laryngoscopy. Main Outcomes and Measures: Reliability (internal consistency, alternate form, and test-retest) and validity (convergent and known-group). Results: In total, 613 patients (mean [SD] age, 58 [15.3] years; 394 [64.5%] women) were recruited, and 555 (92.3%) completed surveys for all time points. Internal consistency was high in the overall 22-item PROM and psychosocial, swallow, and voice subscales (Cronbach α > 0.91). Intraclass correlations for individuals between the baseline and 2-week administrations were moderate for the overall score and subscales (intraclass correlations range, 0.66-0.80). There were significant differences between the online and 2-week paper administrations for the overall score and voice and psychosocial subscales (overall scale mean: 54.4 [95% CI, 49.7-59.1] vs 48.9 [95% CI, 43.7-54.0] at 2 weeks). The confirmatory model was found to be suitably fitted based on average r2 values 0.5 or greater for subscale and overall scores. Correlations between subscales and existing PROMs (Voice-Related Quality of Life, Eating Assessment Tool, and Communication Participation Item Bank) were all greater than 0.69, and mean PROM subscale scores were significantly different across known quartiles of existing PROMs. Conclusions and Relevance: The findings of this survey validation study suggest that the CoPE PROM could serve as a psychometrically sound, comprehensive measure of UVFP-attributed disability suitable for use in clinical and research settings to assess within-person changes. The results will inform a user manual to facilitate use in clinical trials comparing the effectiveness and durability of treatments including behavioral (speech therapy), temporary (eg, injection augmentation), and permanent surgical treatments for UVFP.

Study protocol to develop a patient-reported outcome measuring disability associated with unilateral vocal fold paralysis: a mixed-methods approach with the CoPE collaborative.

INTRODUCTION: Patient-reported outcome (PRO) measures are increasingly developed with multisite, representative patient populations so that they can serve as a primary endpoint in clinical trials and longitudinal studies. Creating multisite infrastructure during PRO measure development can facilitate future comparative effectiveness trials. We describe our protocol to simultaneously develop a PRO measure and create a collaborative of tertiary care centres to address the needs of patients with unilateral vocal fold paralysis (UVFP). We describe the stakeholder engagement, information technology and regulatory foundations for PRO measure development and how the process enables plans for multisite trials comparing treatments for this largely iatrogenic condition. METHODS AND ANALYSIS: The study has three phases: systematic review, measure development and measure validation. Systematic reviews and qualitative interviews (n=75) will inform the development of a conceptual framework. Qualitative interviews with patients with UVFP will characterise the lived experience of the condition. Candidate PRO measure items will be derived verbatim from patient interviews and refined using cognitive interviews and expert input. The PRO measure will be administered to a large, multisite cohort of adult patients with UVFP via the CoPE (vocal Cord Paralysis Experience) Collaborative. We will establish CoPE to facilitate measure development and to create preliminary infrastructure for future trials, including online data capture, stakeholder engagement, and the identification of barriers and facilitators to participation. Classical test theory psychometrics and grounded theory characterise our approach, and validation includes assessment of latent structure, reliability and validity. ETHICS AND DISSEMINATION: Our study is approved by the University of Wisconsin Health Sciences Institutional Review Board. Findings from this project will be published in open-access journals and presented at international conferences. Subsequent use of the PRO measure will include comparative effectiveness trials of treatments for UVFP at CoPE Collaborative sites.

NSAID Use and Incident Cognitive Impairment in a Population-based Cohort.

Nonsteroidal anti-inflammatory drugs (NSAIDs) may prevent dementia, but previous studies have yielded conflicting results. This study estimated the association of prior NSAID use with incident cognitive impairment in the population-based Epidemiology of Hearing Loss Study (EHLS, n=2422 without cognitive impairment in 1998-2000). Prospectively collected medication data from 1988-1990, 1993-1995, and 1998-2000 were used to categorize NSAID use history at the cognitive baseline (1998-2000). Aspirin use and nonaspirin NSAID use were separately examined. Cox regression models were used to estimate the associations between NSAID use history at baseline and incident cognitive impairment in 2003-2005 or 2009-2010. Logistic regression analyses were used to estimate associations with a second outcome, mild cognitive impairment/dementia, available in 2009-2010. Participants using aspirin at baseline but not 5 years prior were more likely to develop cognitive impairment (adjusted hazard ratio=1.77; 95% confidence interval=1.11, 2.82; model 2), with nonsignificant associations for longer term use. Nonaspirin NSAID use was not associated with incident cognitive impairment or mild cognitive impairment/dementia odds. These results provided no evidence to support a potential protective effect of NSAIDs against dementia.

Long-term systemic inflammation and cognitive impairment in a population-based cohort.

OBJECTIVES: Evidence suggests inflammation is associated with cognitive impairment, but previous epidemiological studies have reported conflicting results. DESIGN: Prospective population-based cohort. SETTING: Epidemiology of Hearing Loss Study participants. PARTICIPANTS: Individuals without cognitive impairment in 1998-2000 (N = 2,422; 1,947 with necessary data). MEASUREMENTS: Cognitive impairment (Mini-Mental State Examination score <24 or diagnosis of dementia) was ascertained in 1998-2000, 2003-2005, and 2009-2010. Serum C-reactive protein (CRP) and interleukin-6 (IL-6) were measured in 1988-1990, 1998-2000, and 2009-2010; tumor necrosis factor-alpha was measured from 1998-2000. RESULTS: Participants with high CRP in 1988-1990 and 1998-2000 had lower risk of cognitive impairment than those with low CRP at both time points (hazard ratio (HR) = 0.46, 95% confidence interval (CI) = 0.26-0.80). Risk did not differ according to 10-year IL-6 profile or baseline inflammation category in the whole cohort. In sensitivity analyses restricted to statin nonusers, those with high IL-6 at both times had greater risk of cognitive impairment than those with low IL-6 at both times (HR = 3.35, 95% CI = 1.09-10.30). In secondary analyses, each doubling of IL-6 change over 20 years was associated with greater odds of cognitive impairment in 2009-2010 in the whole cohort (odds ratio (OR) = 1.40, 95% CI = 1.04-1.89), whereas a doubling of CRP change over 20 years was associated with cognitive impairment only in statin nonusers (OR = 1.32, 95% CI = 1.06-1.65). CONCLUSION: With data collected over 20 years, this study demonstrated greater likelihood of cognitive impairment in individuals with repeated high or increasing IL-6. The inconsistent CRP findings may reflect effects of statin medications, survival effects, or adverse effects associated with chronically low CRP. Further studies of long-term inflammation and cognitive impairment are needed.

Changes in environmental tobacco smoke exposure: the Beaver Dam experience.

OBJECTIVES: Environmental tobacco smoke (ETS) exposure has been associated with adverse health outcomes. Our goal was to determine if ETS exposure changed between 1998-2000 and 2003-2005 among participants in the population-based Epidemiology of Hearing Loss Study. METHODS: ETS exposure was ascertained using a cotinine-validated questionnaire at the 5-year (1998-2000) and 10-year follow-up examinations (2003-2005). Non-smoking participants with data from both visits were included (n=1898; ages 53-96 years at 5-yr follow-up). McNemar's test was used to test differences in ETS exposure overall and in 3 settings: home, work, and social settings. Generalized estimating equations (GEE) were used for multivariate logistic regression models of exposure. RESULTS: The proportion of nonsmokers with no or little ETS exposure increased from 80% to 88% (P< 0.0001). The percent living in a home with no indoor smokers increased from 94% to 97% (P<0.0001). The percent reporting no exposure at work increased from 91% to 95% (P<0.0001). The percent reporting the lowest frequency of social exposure increased from 65% to 77% (P<0.0001). In the GEE model, age was inversely associated with overall ETS exposure (Odds Ratio [OR] per 5 yr= 0.87, 95% CI= 0.81, 0.94), as was education (OR for college vs < high school=0.25, 95% CI=0.16, 0.37), female gender (ORI= 0.41, 95% CI= 0.33, 0.51), and later examination period (OR =0.62, 95% CI= 0.53, 0.73); current employment was positively associated with exposure (OR=1.44, 95% CI=1.14, 1.83). CONCLUSIONS: Between the late 1990s and the mid-2000s, ETS exposure in older adults decreased. Decreasing exposures suggest there may be future declines in ETS-related adverse health outcomes.

The prevalence and determinants of antepartum mental health problems among women in the USA: a nationally representative population-based study.

Mental health problems disproportionately affect women, particularly during childbearing years. We sought to estimate the prevalence of antepartum mental health problems and determine potential risk factors in a representative USA population. We examined data on 3,051 pregnant women from 11 panels of the 1996-2006 Medical Expenditure Panel Survey. Poor antepartum mental health was defined by self report of mental health conditions or symptoms or a mental health rating of "fair" or "poor." Multivariate regression analyses modeled the odds of poor antepartum mental health; 7.8% of women reported poor antepartum mental health. A history of mental health problems increased the odds of poor antepartum mental health by a factor of 8.45 (95% CI, 6.01-11.88). Multivariate analyses were stratified by history of mental health problems. Significant factors among both groups included never being married and self-reported fair/poor health status. This study identifies key risk factors associated with antepartum mental health problems in a nationally representative sample of pregnant women. Women with low social support, in poor health, or with a history of poor mental health are at an increased risk of having antepartum mental health problems. Understanding these risk factors is critical to improve the long-term health of women and their children.