Development of the Flu-PRO: a patient-reported outcome (PRO) instrument to evaluate symptoms of influenza.

BACKGROUND: To develop content validity of a comprehensive patient-reported outcome (PRO) measure following current best scientific methodology to standardize assessment of influenza (flu) symptoms in clinical research. METHODS: Stage I (Concept Elicitation): 1:1 telephone interviews with influenza-positive adults (≥18 years) in the US and Mexico within 7 days of diagnosis. Participants described symptom type, character, severity, and duration. Content analysis identified themes and developed the draft Flu-PRO instrument. Stage II (Cognitive Interviewing): The Flu-PRO was administered to a unique set of influenza-positive adults within 14 days of diagnosis; telephone interviews addressed completeness, respondent interpretation of items and ease of use. RESULTS: Samples: Stage I: N = 46 adults (16 US, 30 Mexico); mean (SD) age: 38 (19), 39 (14) years; % female: 56%, 73%; race: 69% White, 97% Mestizo. Stage II: N = 34 adults (12 US, 22 Mexico); age: 37 (14), 39 (11) years; % female: 50%, 50%; race: 58% White, 100% Mestizo. SYMPTOMS: Symptoms identified by >50%: coughing, weak or tired, throat symptoms, congestion, headache, weakness, sweating, chills, general discomfort, runny nose, chest (trouble breathing), difficulty sleeping, and body aches or pains. No new content was uncovered during Stage II; participants easily understood the instrument. CONCLUSIONS: Results show the 37-item Flu-PRO is a content valid measure of influenza symptoms in adults with a confirmed diagnosis of influenza. Research is underway to evaluate the suitability of the instrument for children and adolescents. This work can form the basis for future quantitative tests of reliability, validity, and responsiveness to evaluate the measurement properties of Flu-PRO for use in clinical trials and epidemiology studies.

Beyond intuition: patient fever symptom experience.

CONTEXT: Fever is an important sign of inflammation recognized by health care practitioners and family caregivers. However, few empirical data obtained directly from patients exist to support many of the long-standing assumptions about the symptoms of fever. Many of the literature-cited symptoms, including chills, diaphoresis, and malaise, have limited scientific bases, yet they often represent a major justification for antipyretic administration. OBJECTIVES: To describe the patient experience of fever symptoms for the preliminary development of a fever assessment questionnaire. METHODS: Qualitative interviews were conducted with 28 inpatients, the majority (86%) with cancer diagnoses, who had a recorded temperature of ≥38°C within approximately 12 hours before the interview. A semi-structured interview guide was used to elicit patient fever experiences. Thematic analyses were conducted by three independent research team members, and the data were verified through two rounds of consensus building. RESULTS: Eleven themes emerged. The participants reported experiences of feeling cold, weakness, warmth, sweating, nonspecific bodily sensations, gastrointestinal symptoms, headaches, emotional changes, achiness, respiratory symptoms, and vivid dreams/hallucinations. CONCLUSION: Our data not only confirm long-standing symptoms of fever but also suggest new symptoms and a level of variability and complexity not captured by the existing fever literature. Greater knowledge of patients' fever experiences will guide more accurate assessment of symptoms associated with fever and the impact of antipyretic treatments on patient symptoms in this common condition. Results from this study are contributing to the content validity of a future instrument that will evaluate patient outcomes related to fever interventions.

Microalbuminuria in HIV disease.

BACKGROUND/AIMS: Microalbuminuria is a marker for early kidney disease and cardiovascular risk. The purposes of this study were to determine the prevalence of microalbuminuria in an HIV-infected clinic population, to test the predictive value of a single urine albumin/creatinine ratio (ACR) to identify persistent microalbuminuria and to examine covariates of microalbuminuria. METHODS: We conducted a prospective cohort study of HIV-infected subjects (n = 182) without proteinuria (urine protein/creatinine ratio ≥0.5 g/g), elevated serum creatinine, diabetes, or chronic inflammatory conditions. Subjects completed three research visits within 9 months. Microalbuminuria was defined as the geometric mean ACR of 25-355 mg/g for females and 17-250 mg/g for males. RESULTS: The prevalence of microalbuminuria was 14%. The negative predictive value of a single urine ACR determination was 98%, whereas the positive predictive value was only 74%. Microalbuminuria was similar among Black (15%) and non-Black (14%) subjects (p = 0.8). Subjects with microalbuminuria were more likely to have hypertension (p = 0.02) and metabolic syndrome (p = 0.03). While duration of HIV infection and the level of HIV viremia were similar between groups, those with microalbuminuria were more likely to have a CD4 count <200 cells/µl (p = 0.0003). In a multivariate logistic regression analysis, the only significant independent predictors of microalbuminuria were low CD4 count (p = 0.018) and current ritonavir exposure (p = 0.04). CONCLUSION: The prevalence of microalbuminuria in an HIV-infected clinic population was similar to earlier reports, and was associated with hypertension and impaired immune function. A single normal ACR determination effectively excludes microalbuminuria, whereas an elevated ACR requires confirmation.

The CD8+ HLA-DR+ T cells expanded in HIV-1 infection are qualitatively identical to those from healthy controls.

HIV-induced immune activation leads to expansion of a subset of human CD8(+) T cells expressing HLA-DR antigens. Expansion of CD8(+) HLA-DR(+) T cells can be also observed in non-HIV settings including several autoimmune diseases and aging. Although these cells are felt to represent "immune exhaustion" and/or to be anergic, their precise role in host defense has remained unclear. Here, we report that this subset of cells exhibits a restricted repertoire, shows evidence of multiple rounds of division, but lacks markers of recent TCR engagement. Detailed cell cycle analysis revealed that compared with their CD8(+) HLA-DR(-) counterpart, the CD8(+) HLA-DR(+) T-cell pool contained an increased fraction of cells in S-phase with elevated levels of the G2/M regulators: cyclin A2, CDC25C, Cdc2 (CDK1), indicating that these cells are not truly anergic but rather experiencing proliferation in vivo. Together, these data support a hypothesis that antigen stimulation leads to the initial expansion of a CD8(+) pool of cells in vivo that undergo further expansion independent of ongoing TCR engagement. No qualitative differences were noted between CD8(+) HLA-DR(+) cells from HIV(+) and HIV(-) donors, indicating that the generation of CD8(+) HLA-DR(+) T cells is a part of normal immune regulation that is exaggerated in the setting of HIV-1 infection.

Increased prevalence of albuminuria in HIV-infected adults with diabetes.

OBJECTIVE: HIV and type 2 diabetes are known risk factors for albuminuria, but no previous reports have characterized albuminuria in HIV-infected patients with diabetes. RESEARCH DESIGN AND METHODS: We performed a cross-sectional study including 73 HIV-infected adults with type 2 diabetes, 82 HIV-infected non-diabetics, and 61 diabetic control subjects without HIV. Serum creatinine >1.5 mg/dL was exclusionary. Albuminuria was defined as urinary albumin/creatinine ratio >30 mg/g. RESULTS: The prevalence of albuminuria was significantly increased among HIV-infected diabetics (34% vs. 13% of HIV non-diabetic vs. 16% diabetic control, p = 0.005). HIV status and diabetes remained significant predictors of albuminuria after adjusting for age, race, BMI, and blood pressure. Albumin/creatinine ratio correlated significantly with HIV viral load (r = 0.28, p = 0.0005) and HIV-infected subjects with albuminuria had significantly greater cumulative exposure to abacavir (p = 0.01). In an adjusted multivariate regression analysis of HIV-infected subjects, the diagnosis of diabetes (p = 0.003), higher HIV viral load (p = 0.03) and cumulative exposure to abacavir (p = 0.0009) were significant independent predictors of albuminuria. CONCLUSIONS: HIV and diabetes appear to have additive effects on albuminuria which is also independently associated with increased exposure to abacavir and HIV viral load. Future research on the persistence, progression and management of albuminuria in this unique at-risk population is needed.

A1C underestimates glycemia in HIV infection.

OBJECTIVE: The objective of this study was to determine the relationship between A1C and glycemia in HIV infection. RESEARCH DESIGN AND METHODS: We completed a prospective cross-sectional study of 100 HIV-infected adults with type 2 diabetes (77%) or fasting hyperglycemia (23%) with measured glucose, A1C, mean corpuscular volume (MCV), and fructosamine. A total of 200 HIV-uninfected type 2 diabetic subjects matched for key demographic characteristics served as control subjects. RESULTS: Relative to the control subjects, A1C underestimated glucose by 29 +/- 4 mg/dl in the HIV-infected subjects. Current nucleoside reverse transcriptase inhibitors (NRTIs), higher MCV and hemoglobin, and lower HIV RNA and haptoglobin were associated with greater A1C-glucose discordance. However, only MCV and current NTRI use, in particular abacavir, remained significant predictors in multivariate analyses. Fructosamine more closely reflected glycemia in the HIV-infected subjects. CONCLUSIONS: A1C underestimates glycemia in HIV-infected patients and is related to NRTI use. Use of abacavir and increased MCV were key correlates in multivariate analyses. Fructosamine may be more appropriate in this setting.

Cryotherapy for treatment of anogenital warts.

Human papillomavirus is a group of viruses that produce anogenital warts for which there is no cure. Untreated anogenital warts can spread and form large clusters that are bothersome, painful, and embarrassing to the patient as well as being a significant health risk. One of the infectious disease clinics of the authors' hospital sees an average of 200 HIV-positive individuals per month. Approximately 10% of these patients have anogenital warts. The attending physicians asked the clinical nursing staff if they would be willing to be trained to remove these warts using cryotherapy techniques, if patient efforts at other remedies failed. This request provoked a decision-making challenge for the staff. This article will describe the decision-making process and conclude with the procedure that was created as a result of the decision making.