Content validity of visual analog scales to assess symptom severity of acute angioedema attacks in adults with hereditary angioedema : an interview study

Background: Hereditary angioedema (HAE) is a rare, debilitating, potentially life-threatening condition characterized by recurrent acute attacks of edema of the skin, face/upper airway, and gastrointestinal and urogenital tracts. During a laryngeal attack, people with HAE may be at risk of suffocation, while other attacks are often associated with intense pain, disfigurement, disability, and/or vomiting. The intensity of some symptoms is known only to the person experiencing them. Thus, interview studies are needed to explore such experience and patient-reported outcome measures (PROMs) are required for systematic assessment of symptoms in the clinical setting and in clinical trials of treatments for acute HAE attacks.

Objective: The aim of this interview study was to assess the content validity and suitability of four visual analog scale (VAS) instruments for use in clinical studies. The VAS instruments were designed to assess symptoms at abdominal, oro-facial-pharyngeal-laryngeal, peripheral, and urogenital attack locations. This is the first known study to report qualitative data about the patient's experience of the rare disorder, HAE.

Methods: Semi-structured exploratory and cognitive debriefing interviews were conducted with 27 adults with a confirmed clinical/laboratory diagnosis of HAE (baseline plasma level of functional plasma protein C1 esterase inhibitor [C1INH] <50% of normal without evidence for acquired angioedema). There were 17 participants from the US and 10 from Italy, with mean age 42.5 (SD 14.5) years, range 18–72 years, mean HAE duration 21.3 (SD 14.1) years, range 1–45 years, 67% female, and 44% VAS-naïve. Experience of acute angioedema attacks was first explored, noting spontaneous mentions by participants of HAE symptomatology. Cognitive debriefing of the VAS instruments was undertaken to assess the suitability, comprehensibility, and relevance of the VAS items. Asymptomatic participants completed the VAS instruments relevant to their angioedema experience, reporting as if they were experiencing an acute angioedema attack at the time. Interviews were conducted in the clinic setting in the US and Italy over an 8-month period.

Results: Participants mentioned spontaneously almost all aspects of acute angioedema attacks covered by the four VAS instruments, thus providing strong support for inclusion of nearly all VAS items, with no important symptoms missing. Predominant symptoms found to be associated with acute angioedema attacks were edema and pain, and there was evidence of varying degrees of disruption to everyday activities supporting the inclusion of an overall severity item reflecting the disabling effects of HAE symptoms. VAS item wording was understood by participants.

Conclusion: This interview study explored and reported the patient experience of HAE attacks. It demonstrated the content validity of the four anatomical location HAE VAS instruments and their suitability for use in clinical trials of recombinant human C1INH (rhC1INH) treatment for ascertaining trial participants' assessments of the severity of acute angioedema symptoms.

Blind alleys, blinding and blinded aliens : mapping the outer limits of the technical image

Marcia Jane's installation work is situated along a historic line of critical enquiry traceable back to Goethe. her energy field series re-tools for digital use the formal erasures of sturcturalist film, where the relationship between the signifier and the signified are inverted.

Racialized urban America and Holocaust film : negotiating the limits of representation

Sidney Lumet’s influential film The Pawnbroker (1964) is one of the earliest films to consider the encounter between Holocaust narratives and low-income, urban American racial minorities. As much concerned with contemporary ‘race relations’ in the United States as it is with the Nazis’ persecution of Europe’s Jews, the film intertwines the story of Holocaust survivor Sol Nazerman with the social tensions of 1960s America, represented in his relationship with the young Puerto Rican shop assistant Jesus Oritz. The film stylistically juxtaposes raw footage of concentration camp existence with dismal images of New York slum life. Against these backdrops, the protagonist’s climactic ‘silent scream’ emblematically merges the repressed trauma of the survivor with the filmmaker’s interest in race relations, a theme that has undergone various transformations in a number of films since. One film that contemporizes this encounter is Richard LaGravenese’s Freedom Writers (2007). As opposed to the tragic outcome of the pawnbroker’s induction into urban America, here the Holocaust is a redemptive tool that permits inner-city Black and Latino youth to contextualize their own suffering. After reading The Diary of Anne Frank, this group of ‘at-risk’ sophomores to inspired to collaborate on an ultimately successful effort to bring Miep Geis, the woman who sheltered Anne Frank, to speak at their high school. Foregrounded by the 1992 Los Angeles riots, gentiles teacher Erin Gruwell and savior Miep Geis transform the Holocaust from an amplified parallel of American slums into an event that permits the children of American postcoloniality to triumph in spite of their socio-economic circumstances. Underlining the tension between the Jewish specificity and unprecedented nature of the Holocaust, and the need to generate Holocaust narratives that intersect with intrinsically racialized American narratives, such films have significant implications for how collective memories of suffering are constructed and contested.

Measurement of immunoglobulin A in saliva by particle-enhanced nephelometric immunoassay: sample collection, limits of quantitation, precision, stability and reference range

Background: Total immunoglobulin A in saliva (s-IgA) is normally assayed using an enzyme-linked immunosorbent assay. We have investigated methodological issues relating to the use of particle-enhanced nephelometric immunoassay (PENIA)
to measure s-IgA in whole unstimulated saliva and determine its reference range.

Methods: Whole unstimulated resting saliva was collected to determine sample stability (temperature, time, effect of a protease inhibitor), limit of quantitation (LOQ), assay precision and analytical variation. The reference range for 134 healthy adults was determined.

Results: Linearity was excellent (4–10.3 mg L21, P, 0.001; R2 ¼ 0.997) and without significant bias (mean of 20.7%). The lowest intra- and inter-analytical coefficients of variation were 1.8% and 7.5% and LOQ was 1.4 mg L21. The concentration of s-IgA is stable at room temperature for up to 6 h, at 48C for 48 h, at 248C for two weeks and at 2808C for up to 1.3 yr. There is no evidence that a protease inhibitor increases the stability or that repeated freeze–thawing cycles degrade sample quality. The reference ranges for s-IgA concentration, s-IgA secretion, s-IgA:albumin and s-IgA:osmolality were 15.9–414.5 mg L21, 7.2–234.9 mg min21, 0.4–19 and 0.6–8.9, respectively.

Conclusion: Automated PENIA assay of s-IgA is precise and accurate. High stability of collected saliva samples and the ease and speed of the assay make this an ideal method for use in athletic and military training situations. The convenience of measuring albumin and IgA on the same analytical platform adds to the practicability of the test.

Prevalence of visual impairment and uncorrected refractive error - report from a Canadian urban population-based study

The prevalence of visual impairment due to uncorrected refractive error has not been previously studied in Canada. A population-based study was conducted in Brantford, Ontario. The target population included all people 40 years of age and older. Study participants were selected using a randomized sampling strategy based on postal codes. Presenting distance and near visual acuities were measured with habitual spectacle correction, if any, in place. Best corrected visual acuities were determined for all participants who had a presenting distance visual acuity of less than 20/25. Population weighted prevalence of distance visual impairment (visual acuity <20/40 in the better eye) was 2.7% (n = 768, 95% confidence interval (CI) 1.8–4.0%) with 71.8% correctable by refraction. Population weighted prevalence of near visual impairment (visual acuity <20/40 with both eyes) was 2.2% (95% CI 1.4–3.6) with 69.1% correctable by refraction. Multivariable adjusted analysis showed that the odds of having distance visual impairment was independently associated with increased age (odds ratio, OR, 3.56, 95% CI 1.22–10.35; ≥65 years compared to those 39–64 years), and time since last eye examination (OR 4.93, 95% CI 1.19–20.32; ≥5 years compared to ≤2 years). The same factors appear to be associated with increased prevalence of near visual impairment but were not statistically significant. The majority of visual impairment found in Brantford was due to uncorrected refractive error. Factors that increased the prevalence of visual impairment were the same for distance and near visual acuity measurements.