Measuring dengue illness intensity: Development and content validity of the dengue virus daily diary (DENV-DD).

BACKGROUND: Dengue is the most prevalent arboviral infection causing an estimated 50-60 million cases of febrile illness globally per year, exacting considerable disease burden. Few instruments exist to assess the patient illness experience, with most based on healthcare provider assessment, lacking standardization in timepoints and symptom assessment. This study aimed to evaluate the content validity of the novel 'Dengue Virus Daily Diary (DENV-DD)', designed to measure symptom intensity and disease burden within outpatient infant to adult populations. METHODS: The Dengue Illness Index Report Card was used as a foundation to create the DENV-DD, consisting of patient- and observer-reported outcome (PRO/ObsRO) instruments. In two South American dengue-endemic communities, qualitative combined concept elicitation and cognitive debriefing interviews were conducted among individuals and caregivers of children with symptomatic laboratory-confirmed dengue. Interviews were conducted across two rounds allowing DENV-DD modifications. A small-scale quantitative assessment of the DENV-DD was also conducted with data from an independent Dengue Human Infection Model (DHIM) to generate early evidence of feasibility of DENV-DD completion, instrument performance and insight into the sign/symptom trajectory over the course of illness. RESULTS: Forty-eight participants were interviewed (20 adults, 20 older children/adolescents with their caregivers, 8 caregivers of younger children). A wide spectrum of signs/symptoms lasting 3-15 days were reported with fever, headache, body ache/pain, loss of appetite, and body weakness each reported by > 70% participants. DENV-DD instructions, items and response scales were understood, and items were considered relevant across ages. DHIM data supported feasibility of DENV-DD completion. CONCLUSIONS: Findings demonstrate content validity of the DENV-DD (PRO/ObsRO instruments) in dengue-endemic populations. Psychometric and cultural validity studies are ongoing to support use of the DENV-DD in clinical studies.

Dengue is the most common viral infection transmitted to humans by mosquitos, and affects an estimated 50­60 million individuals globally per year. However, there are few resources for understanding and capturing the patient experience of dengue throughout illness. Most research studies are based on healthcare provider assessment, which lack consistency in terms of assessment time points and the signs/symptoms assessed. The 'Dengue Illness Index Report Card (DII-RC)' was used as a foundation to create the new 'Dengue Virus Daily Diary (DENV-DD)' to better capture the patient experience of symptom intensity and dengue disease burden for the duration of illness. Forty-eight individuals and caregivers of younger children from Peru and Ecuador who recently had symptomatic dengue were interviewed to understand the patient experience over the time of illness and to test whether the DENV-DD is understood by patients and caregivers and includes all relevant and important signs/symptoms and health-related quality of life impacts. Nine individuals with active dengue infection also completed the DENV-DD daily for 28-days as part of a clinical study. We found that > 70% of patients experienced fever, headache, body ache/pain, loss of appetite and body weakness. The DENV-DD instructions, questions and response option(s) were well understood, feasible to complete and the concepts assessed by the DENV-DD were relevant to the dengue experience. Our study adds to the understanding of the dengue illness experience and supports the DENV-DD for use in future dengue studies as an assessment of signs/symptoms throughout the duration of illness.

Design and validation of the biliary atresia research consortium histologic assessment system for cholestasis in infancy.

BACKGROUND & AIMS: Pathologists participating in the National Institutes of Health-sponsored Biliary Atresia Research Consortium (BARC) developed and then evaluated a standardized system for histologic reporting of liver biopsies from infants with cholestasis. METHODS: A set of 97 anonymous liver biopsy samples was sent to 10 pathologists at BARC centers. A semiquantitative scoring system that had 16 histologic features was developed and then used by the pathologists, who had no knowledge of clinical history, imaging results, or laboratory data. Interobserver agreement was evaluated statistically. Agreement on scoring of each feature and on the pathologists' diagnosis, compared with the final clinical diagnosis, was evaluated by using weighted kappa statistics. RESULTS: There was moderate to substantial interobserver agreement in identification of bile plugs in ducts, giant-cell transformation, extramedullary hematopoiesis, and bile duct proliferation. The pathologists' diagnosis of obstruction in clinically proven cases of biliary atresia (BA) ranged from 79%-98%, with a positive predictive value of 90.7%. Histologic features that best predicted BA, on the basis of logistic regression, included bile duct proliferation, portal fibrosis, and absence of sinusoidal fibrosis (each P<.0001). CONCLUSIONS: The BARC histologic assessment system identified features of liver biopsies from cholestatic infants, with good interobserver agreement, that might be used in diagnosis and determination of prognosis. The system diagnosed BA with a high level of sensitivity and identified infants with biliary obstruction with reasonable interobserver agreement. However, distinguishing between BA and disorders such as total parenteral nutrition-associated liver disease and alpha(1)-antitrypsin deficiency is not possible without adequate clinical information.

Social organization of free-ranging ruffed lemurs, Varecia variegata variegata: mother-adult daughter relationship.

The relationship between a mother and an adult daughter is examined in a group of free-ranging ruffed lemurs (Varecia variegata) at the Duke University Primate Center (DUPC). Although the two females were affiliative during the birth season, interactions during the mating season were predominantly agonistic. The maturing daughter was dominant to the mother, as has been observed in many caged social groups at the DUPC. Although both mother and daughter produced offspring in the same group, the daughter subsequently aggressively evicted the mother from the enclosure. It was not possible to maintain more than one long-term resident breeding female in the same social group. This pattern contrasts with observations of affiliation among breeding females in the wild. © 1992 Wiley-Liss, Inc.

Activity Budgets, feeding behavior, and habitat use of pygmy chimpanzees at Lomako, Zaire.

Data from 250 hours of focal animal sampling in the Lomako Forest of central Zaire show pygmy chimpanzees spent 70% of feeding time on fruit and 25% on young leaves. Feeding and resting each accounted for about 40% and traveling less than 20% of the time. Sitting was the most frequent feeding posture. Locomotion was predominantly quadrupedal walking and quadrumanous climbing. Most feeding and resting occurred above 30 m. Pygmy chimpanzees spent most time in primary forest. Activity budgets varied with forest type. Most levels were used in each forest type. Pygmy chimpanzees spent most time in the canopy when in primary and slope (Bolafa) forests, and on the ground in secondary forest. These results show pygmy chimpanzees as arboreal, but habituation may have influenced the results. Pygmy chimpanzees at Lomako and Wamba have similar diets, despite differences in methods of data collection. At Wamba and Lomako, pygmy chimpanzees use secondary forest more and swamp forest less than expected given the abundance of each forest type at both sites.

Pygmy chimpanzee social organization: Variation with party size and between study sites.

Descriptions of social organization based on interactions are difficult for fission-fusion primates, such as pygmy chimpanzees, as interactions may depend on association in parties. Frequencies of male-male and male-female affiliative and female-male and female-female aggressive interactions among Lomako pygmy chimpanzees occurred in proportion to the presence of each sex in parties. Male-male aggression and female-male affiliation, however, were more frequent than expected on the basis of party membership. Females with small swellings received more grooming and less mating than expected. Patterns of interactions at Lomako also varied with party size. Female-female affiliation predominated in small parties, while male-female affiliation predominated in larger parties. This trend parallels observed differences between the Lomako and Wamba study sites. Male-female affiliation is more frequent at Wamba where party sizes are larger. Differences between study sites may also reflect provisioning, habituation, predator threat, and habitat. Provisioning at Wamba may result in higher frequencies of aggression among males and lower levels of aggression among females. Comparison between earlier and later Lomako studies suggests that increased habituation is associated with greater differences from, rather than more similarity to, results from Wamba. Differences between Lomako and Wamba in habitat, provisioning, and human (but not non-human) predation, by affecting party size and composition, most likely account for the observed differences in social organization between the two sites.

Census and preliminary observations on the ecology of the black-faced black spider monkey (Ateles paniscus chamek) in Manu National Park, Peru.

The black-faced black spider monkey, Ateles paniscus chamek, was studied at Cocha Cashu, Manu National Park, Peru, from June to August 1982. The density of independently locomoting individuals was found to be 31/km2, and the average party size was 3.15. Data on age and sex compositions of parties, activity patterns, and diet composition are presented. The spider monkeys spend approximately 30% of observed time feeding, 44% resting, and 25% moving. They ate 80% fruit and 17% new leaves. Spider monkeys appear to be important seed dispersers. The best dispersal observed was for fruits with few, relatively large seeds. A rough day-range of 2,400 m was estimated from measured travel times and distances. The social system of Ateles is discussed.