The impact of upper facial lines and psychological impact of crow's feet lines: content validation of the Facial Line Outcomes (FLO-11) Questionnaire.

BACKGROUND: Treatments for upper facial lines (UFL), the most visible sign of aging, are of interest to patients and clinicians alike. Patient-reported outcomes (PROs) are valuable in evaluating the impact of such treatments; however, regulatory recommendations have stipulated that the patient perspective be central in developing these assessments. OBJECTIVES: (1) To evaluate the content validity of the Facial Lines Outcomes Questionnaire, a PRO instrument developed to assess upper facial line impacts, according to the regulatory guidance of the United States Food and Drug Administration and (2) assess whether it adequately measures the psychological impacts associated with crow's feet lines (CFL) (lateral canthal lines) from the patient perspective. METHODS: Two patient groups participated in face-to-face qualitative interviews. One group included patients with UFL (Group 1, n = 25 interviews), and the other included patients specifically with CFL (Group 2, n = 41 interviews). Each interview consisted of a concept elicitation and cognitive debriefing phase. RESULTS: Interviews with both groups elicited all key concepts of the instrument, including "bothered by facial lines"; "looking older"; "looking less attractive"; and looking "tired," "stressed," or "angry." Most Group 2 patients (n = 35, 85%) agreed that the instrument adequately assessed the psychological impacts associated with CFL. During cognitive debriefing, the majority of patients in both groups agreed the instrument was understandable, comprehensive, and easy to complete. CONCLUSIONS: The Facial Line Outcomes Questionnaire is an appropriate and valid tool to assess the impact of UFL and the psychological impacts associated with CFL.

European content validation of the Self-Assessment Goal Achievement (SAGA) questionnaire in patients with overactive bladder.

INTRODUCTION AND HYPOTHESIS: The Self-Assessment Goal Achievement (SAGA) questionnaire is a patient-completed instrument designed to assess goal attainment in the behavioral or pharmacologic treatment of lower urinary tract symptoms (LUTS), including overactive bladder (OAB). The SAGA questionnaire allows patients to identify and rank the importance of treatment goals before treatment is initiated; the follow-up SAGA questionnaire quantifies the achievement of these patient-identified goals. The objective of this qualitative research was to confirm the content validity of the German, Spanish, Swedish, and English (UK) language versions of the SAGA questionnaire in patients with OAB with or without other LUTS. METHODS: The SAGA questionnaire was translated to each language in accordance with a well-established forward and backward harmonization method. Patient interviews were then conducted according to a cognitive debriefing methodology. Qualitative analysis of patients' input allowed assessment of content validity of each linguistically adapted SAGA questionnaire. RESULTS: All patients (n = 29; six to eight per targeted country) found the SAGA questionnaire easy to understand and to complete. Most patients completed the nine prespecified (fixed) treatment goals and were able to add up to five personal goals in the open-ended portion and rate each goal by importance. Differences were identified in how the various languages communicated some of the concepts assessed with the SAGA questionnaire. Rewording of the translated versions of the questionnaire was necessary in some cases. CONCLUSIONS: This linguistic content validation study in four European languages indicates that SAGA is a comprehensive, easy-to-understand, and relevant questionnaire for patient-completed evaluation of LUTS/OAB symptoms and treatment goal attainment.

Development of a next day functioning measure to assess the impact of sleep disturbance due to restless legs syndrome: the restless legs syndrome-next day impact questionnaire.

OBJECTIVES: Symptoms of Restless Legs Syndrome (RLS) affect patients' quality and duration of sleep, which can have next day sequelae detrimental to daytime performance. To date, no measure sufficiently assesses such sequelae. This study aimed to develop a new self-reported outcome measure to assess the impact of disturbed sleep due to RLS on next day functioning and to support its content validity. METHODS: The development of the Restless Legs Syndrome-Next Day Impact (RLS-NDI) questionnaire included concept elicitation interviews with RLS patients in the United States (n=20); grounded theory data collection and analysis methods; and review by clinical and measurement experts to generate items, responses, and instructions. Cognitive interviews (n=15) were conducted to ensure understanding of the RLS-NDI, concept comprehensiveness, and identification of any necessary item revisions. RESULTS: Impacts on next day functioning attributed to disturbed sleep due to RLS symptoms included activities of daily living (i.e., work, household chores), cognitive functioning (i.e., concentration, forgetfulness, mental tiredness, alertness), emotional functioning (i.e., irritability, depressed mood), physical functioning (i.e., physical tiredness, active leisure activities), energy, daytime sleepiness, and social functioning (i.e., relationships, social activities/situations). The final measure consists of 14 items assessed "today" and rated on a numeric rating scale. CONCLUSIONS: The RLS-NDI is an evaluative tool with demonstrated content validity.

Excitatory neurotransmitters in brain regions in interictal migraine patients.

OBJECTIVE: To examine biochemical differences in the anterior cingulate cortex (ACC) and insula during the interictal phase of migraine patients. We hypothesized that there may be differences in levels of excitatory amino acid neurotransmitters and/or their derivatives in migraine group based on their increased sensitivity to pain. METHODS: 2D J-resolved proton magnetic resonance spectroscopy (1H-MRS) data were acquired at 4.0 Tesla (T) from the ACC and insula in 10 migraine patients (7 women, 3 men, age 43 +/- 11 years) and 8 age gender matched controls (7 women, 3 men, age 41 +/- 9 years). RESULTS: Standard statistical analyses including analysis of variance (ANOVA) showed no significant metabolite differences between the two subject cohorts in the ACC nor the insula. However, linear discriminant analysis (LDA) introduced a clear separation between subject cohorts based on N-acetyl aspartylglutamate (NAAG) and glutamine (Gln) in the ACC and insula. CONCLUSION: These results are consistent with glutamatergic abnormalities in the ACC and insula in migraine patients during their interictal period compared to healthy controls. An alteration in excitatory amino acid neurotransmitters and their derivatives may be a contributing factor for migraineurs for a decrease in sensitivity for migraine or a consequence of the chronic migraine state. Such findings, if extrapolated to other regions of the brain would offer new opportunities to modulate central system as interictal or preemptive medications in these patients.

Interictal dysfunction of a brainstem descending modulatory center in migraine patients.

BACKGROUND: The brainstem contains descending circuitry that can modulate nociceptive processing (neural signals associated with pain) in the dorsal horn of the spinal cord and the medullary dorsal horn. In migraineurs, abnormal brainstem function during attacks suggest that dysfunction of descending modulation may facilitate migraine attacks, either by reducing descending inhibition or increasing facilitation. To determine whether a brainstem dysfunction could play a role in facilitating migraine attacks, we measured brainstem function in migraineurs when they were not having an attack (i.e. the interictal phase). METHODS AND FINDINGS: Using fMRI (functional magnetic resonance imaging), we mapped brainstem activity to heat stimuli in 12 episodic migraine patients during the interictal phase. Separate scans were collected to measure responses to 41 degrees C and noxious heat (pain threshold+1 degrees C). Stimuli were either applied to the forehead on the affected side (as reported during an attack) or the dorsum of the hand. This was repeated in 12 age-gender-matched control subjects, and the side tested corresponded to that in the matched migraine patients. Nucleus cuneiformis (NCF), a component of brainstem pain modulatory circuits, appears to be hypofunctional in migraineurs. 3 out of the 4 thermal stimulus conditions showed significantly greater NCF activation in control subjects than the migraine patients. CONCLUSIONS: Altered descending modulation has been postulated to contribute to migraine, leading to loss of inhibition or enhanced facilitation resulting in hyperexcitability of trigeminovascular neurons. NCF function could potentially serve as a diagnostic measure in migraine patients, even when not experiencing an attack. This has important implications for the evaluation of therapies for migraine.

Colocalized structural and functional changes in the cortex of patients with trigeminal neuropathic pain.

BACKGROUND: Recent data suggests that in chronic pain there are changes in gray matter consistent with decreased brain volume, indicating that the disease process may produce morphological changes in the brains of those affected. However, no study has evaluated cortical thickness in relation to specific functional changes in evoked pain. In this study we sought to investigate structural (gray matter thickness) and functional (blood oxygenation dependent level - BOLD) changes in cortical regions of precisely matched patients with chronic trigeminal neuropathic pain (TNP) affecting the right maxillary (V2) division of the trigeminal nerve. The model has a number of advantages including the evaluation of specific changes that can be mapped to known somatotopic anatomy. METHODOLOGY/PRINCIPAL FINDINGS: Cortical regions were chosen based on sensory (Somatosensory cortex (SI and SII), motor (MI) and posterior insula), or emotional (DLPFC, Frontal, Anterior Insula, Cingulate) processing of pain. Both structural and functional (to brush-induced allodynia) scans were obtained and averaged from two different imaging sessions separated by 2-6 months in all patients. Age and gender-matched healthy controls were also scanned twice for cortical thickness measurement. Changes in cortical thickness of TNP patients were frequently colocalized and correlated with functional allodynic activations, and included both cortical thickening and thinning in sensorimotor regions, and predominantly thinning in emotional regions. CONCLUSIONS: Overall, such patterns of cortical thickness suggest a dynamic functionally-driven plasticity of the brain. These structural changes, which correlated with the pain duration, age-at-onset, pain intensity and cortical activity, may be specific targets for evaluating therapeutic interventions.