Replicative Fitness of Seasonal Influenza A Viruses With Decreased Susceptibility to Baloxavir.

Susceptibility of influenza A viruses to baloxavir can be affected by changes at amino acid residue 38 in the polymerase acidic (PA) protein. Information on replicative fitness of PA-I38-substituted viruses remains sparse. We demonstrated that substitutions I38L/M/S/T not only had a differential effect on baloxavir susceptibility (9- to 116-fold) but also on in vitro replicative fitness. Although I38L conferred undiminished growth, other substitutions led to mild attenuation. In a ferret model, control viruses outcompeted those carrying I38M or I38T substitutions, although their advantage was limited. These findings offer insights into the attributes of baloxavir-resistant viruses needed for informed risk assessment.

Cytotoxic Clerodane Diterpenoids from the Leaves of Casearia grewiifolia.

Two new clerodane diterpenoids (1 and 2) and the known compound caseanigrescen D (3) were isolated from the leaves of Casearia grewiifolia by bioassay-guided fractionation. Their structures were determined by analyses of MS and 2D NMR data. The absolute configurations of 1 and 3 were established by analysis of X-ray diffraction data. Compounds 1-3 were evaluated for their cytotoxicity against four cancer cell lines, KB (mouth epidermal carcinoma cells), HepG-2 (human liver hepatocellular carcinoma cells), LU-1 (human lung adenocarcinoma cells), and MCF-7 (human breast cancer cells). Caseagrewifolin B (2) had inhibitory activity against KB and HepG-2 cell lines with IC50 values of 6.2 to 7.0 µM, respectively. When tested against the normal cells (NIH/3T3), caseagrewifolin B (2) exhibited a significant selective inhibition against cancer cells in comparison with the normal cells. Caseanigrescen D (3) was cytotoxic against four cancer cell lines; however it had no selective inhibition compared with normal cells.

Characterization of drug-resistant influenza A(H7N9) variants isolated from an oseltamivir-treated patient in Taiwan.

BACKGROUND: Patients contracting influenza A(H7N9) infection often developed severe disease causing respiratory failure. Neuraminidase (NA) inhibitors (NAIs) are the primary option for treatment, but information on drug-resistance markers for influenza A(H7N9) is limited. METHODS: Four NA variants of A/Taiwan/1/2013(H7N9) virus containing a single substitution (NA-E119V, NA-I222K, NA-I222R, or NA-R292K) recovered from an oseltamivir-treated patient were tested for NAI susceptibility in vitro; their replicative fitness was evaluated in cell culture, mice, and ferrets. RESULTS: NA-R292K led to highly reduced inhibition by oseltamivir and peramivir, while NA-E119V, NA-I222K, and NA-I222R caused reduced inhibition by oseltamivir. Mice infected with any virus showed severe clinical signs with high mortality rates. NA-I222K virus was the most virulent in mice, whereas virus lacking NA change (NA-WT) and NA-R292K virus seemed the least virulent. Sequence analysis suggests that PB2-S714N increased virulence of NA-I222K virus in mice; NS1-K126R, alone or in combination with PB2-V227M, produced contrasting effects in NA-WT and NA-R292K viruses. In ferrets, all viruses replicated to high titers in the upper respiratory tract but produced only mild illness. NA-R292K virus, showed reduced replicative fitness in this animal model. CONCLUSIONS: Our data highlight challenges in assessment of the replicative fitness of H7N9 NA variants that emerged in NAI-treated patients.

Older adults' use of care strategies in response to general and upper respiratory symptoms.

This study examined the use of complementary and medical treatments, both individually and in combination, to address common general and upper respiratory symptoms. Data for the analysis were collected from a series of 18 daily diary questionnaires administered to community-living older African American and white adults living in rural counties in North Carolina. Participants reported symptoms experienced on each diary day and the treatment strategies they used each day in response to the particular symptom(s). Older adults used diverse categories of strategies to treat symptoms; treatment strategies were used inconsistently across symptoms. Use of only complementary strategies, only medical conventional strategies, or both complementary and medical strategies to treat any one symptom rarely corresponded to the use of the same strategy to address other symptoms. Future research would benefit from analyzing how older adults use health care strategies across symptom categories.

Use of Complementary Therapies for Health Promotion Among Older Adults.

This article describes the types of complementary therapies used by older adults for health promotion, and delineates the predisposing, enabling, and need factors associated with their use. One-hundred ninety-five African American and White participants (age 65+) completed a baseline interview and up to six sets of three daily follow-up interviews at monthly intervals. Complementary therapies for health promotion included home remedies, specific foods or beverages, herbs, supplements, vitamins, over-the-counter (OTC) medicine, prayer, exercise, and being active. Although gender, ethnicity, education, and trust in doctors were associated with the use of complementary therapies for health promotion, health information seeking was the predisposing factor most often associated. The enabling factors were also associated with their use. Health information seeking, which reflects a wellness lifestyle, had the most consistent associations with complementary therapy use for health promotion. This health self-management for health promotion may have positive effects on future medical expenditures.

Care practices and traditional beliefs related to neonatal jaundice in northern Vietnam: a population-based, cross-sectional descriptive study.

BACKGROUND: The National Hospital of Pediatrics in Vietnam performed >200 exchange transfusions annually (2006-08), often on infants presenting encephalopathic from lower-level hospitals. As factors delaying care-seeking are not known, we sought to study care practices and traditional beliefs relating to neonatal jaundice in northern Vietnam. METHODS: We conducted a prospective, cross-sectional, population-based, descriptive study from November 2008 through February 2010. We prospectively identified mothers of newborns through an on-going regional cohort study. Trained research assistants administered a 78-item questionnaire to mothers during home visits 14-28 days after birth except those we could not contact or whose babies remained hospitalized at 28 days. RESULTS: We enrolled 979 mothers; 99% delivered at a health facility. Infants were discharged at a median age of 1.35 days. Only 11% received jaundice education; only 27% thought jaundice could be harmful. During the first week, 77% of newborns were kept in dark rooms. Only 2.5% had routine follow-up before 14 days. Among 118 mothers who were worried by their infant's jaundice but did not seek care, 40% held non-medical beliefs about its cause or used traditional therapies instead of seeking care. Phototherapy was uncommon: 6 (0.6%) were treated before discharge and 3 (0.3%) on readmission. However, there were no exchange transfusions, kernicterus cases, or deaths. CONCLUSIONS: Early discharge without follow-up, low maternal knowledge, cultural practices, and use of traditional treatments may limit or delay detection or care-seeking for jaundice. However, in spite of the high prevalence of these practices and the low frequency of treatment, no bad outcomes were seen in this study of nearly 1,000 newborns.

Patterns and Stability over Time of Older Adults' Diabetes-related Beliefs.

OBJECTIVES: We sought to identify coherent profiles of diabetes beliefs within discrete domains (ie causes, symptoms, consequences, self management, and medical management), and delineate consistency of belief profiles over one month. METHODS: Diabetes beliefs of rural-dwelling older adults were assessed with the Common Sense Model of Diabetes Inventory at baseline (N = 593) and one month later (N = 563). RESULTS: A discrete number of belief patterns were identified in each belief domain using latent class analysis. Belief patterns varied by the extent to which more popular or folk notions of diabetes encroached on biomedical understandings of the disease. Belief patterns were generally stable over time. CONCLUSIONS: A manageable number of belief patterns can be identified and used to strengthen patient-centered care and, potentially, enhance diabetes management.

Relationship between nonprescribed therapy use for illness prevention and health promotion and health-related quality of life.

OBJECTIVES: This study describes the nonprescribed therapy use (prayer, over-the-counter medications [OTC's], home remedies, vitamins, herbs and supplements, and exercise) for health promotion among rural elders. It also delineates the association of such therapy use with physical and mental health-related quality of life (HRQoL). METHOD: The sample (N = 200) consisted of African American and White elders from south-central North Carolina. Participants completed baseline interviews and repeated measures of nonprescribed therapy use over a 6-month follow-up. RESULTS: Prayer had the highest percentage (80.7%) of use for health promotion followed by OTC (54.3%); vitamins only (49.3%); herbs and supplements (40.5%); exercise (31.9%); and home remedies (5.2%). Exercise was significantly associated with better physical HRQoL (p < .05). However, elders who used nonprescribed therapies had poorer mental HRQoL than nonusers, adjusting for potential confounders. CONCLUSION: This analysis suggests that use of some nonprescribed therapies for health promotion is associated with poorer mental HRQoL.

Self-reported sleep difficulties and self-care strategies among rural older adults.

This study examined the use of self-care strategies to address difficulty sleeping among community-dwelling older adults. Data were collected from a series of 18 questionnaires administered to 195 rural African American and white older adults in North Carolina. Participants reported whether they had experienced difficulty sleeping and strategies used to respond to the symptom. The most widely used strategies included ignoring the symptom, staying in bed or resting, and praying. Herb and supplement use were not reported. Ethnicity, income, and education were associated with use of specific self-care strategies for sleep. This variation suggests that older adults may draw on cultural understandings to interpret the significance of difficulty sleeping and influence their use of self-care strategies, including complementary and alternative medicine use. This information may enable health care providers to communicate with the older patients about sleep difficulty strategies to minimize sleep problems.

The relationship between cognitive function and non-prescribed therapy use in older adults.

OBJECTIVES: To examine the association of cognitive function with use of non-prescribed therapies for managing acute and chronic conditions, and to determine whether use of non-prescribed therapies changes over time in relation to baseline cognitive function. METHODS: 200 community-dwelling adults aged 65 and older were recruited from three counties in south central North Carolina. Repeated measures of daily symptoms and treatment were collected on three consecutive days at intervals of at least one month. The Mini-Mental State Examination, the primary cognitive measure, was collected as part of the baseline survey. Data were collected on the daily use of common non-prescribed therapies (use of prayer, ignore symptoms, over-the-counter remedies, food and beverage therapies, home remedies, and vitamin, herb, or supplements) on each of the three days of the follow-up interviews for up to six consecutive months. RESULTS: Older adults with poorer cognitive function were more likely to pray and ignore symptoms on days that they experienced acute symptoms. Poorer cognitive function was associated with increased use of home remedies for treating symptoms related to existing chronic conditions. CONCLUSIONS: Cognitive function may play a role in why older patients use some non-prescribed therapies in response to acute and chronic conditions.

Daily use of complementary and other therapies for symptoms among older adults: study design and illustrative results.

OBJECTIVE: This article describes research designed to specify complementary therapies used among older adults by obtaining daily use data and the specific purposes for use. DESIGN: Two hundred African American and White participants completed a baseline interview and up to six sets of three daily-diary interviews at monthly intervals. RESULTS: Participants provided retrospective information on complementary therapy use and information on the use of therapies for specific symptoms experienced across 3,070 person days. Retrospective information indicated that most participants used complementary therapies (e.g., 85.0% used home remedies in the past year). The use of complementary or other therapies and the number of days the therapies were used varied for specific symptoms. For example, home remedies were used on 86 (9.1%) of the 944 person days for which joint pain was reported. DISCUSSION: The daily-diary design provides detailed information for delineating how elders include complementary and other therapies in their health self-management.

Effects of complementary therapy on health in a national U.S. sample of older adults.

OBJECTIVES: The study objectives were to identify types of complementary therapy that are most predictive of health outcomes, including functional status, physical health-related quality of life (HRQoL), and mental HRQoL among older adults. DESIGN: This was a prospective study. SETTINGS/LOCATION: The study comprised computer-assisted interviews conducted in participants' homes. SUBJECTS: Subjects included 1683 adults aged 55 and older who participated in the 2002 National Health Interview Survey and the 2003 Medical Expenditure Panel Survey. INTERVENTION: None. OUTCOME MEASURES: Functional status, physical HRQoL, and mental HRQoL at 1-year follow-up. RESULTS: The use of biologically based therapies predicted better functional status, such that users reported less functional impairment than nonusers (p < 0.01), adjusting for age, gender, race/ethnicity, education, health insurance, household income, and comorbid conditions. Users of manipulative and body-based methods reported less functional impairment (p < 0.05). They also reported better physical and mental health-related quality of life, though these relationships were marginally significant. Other groups of therapies, alternative medical systems, mind-body therapies, and prayer were not predictive of either functional status or HRQoL. CONCLUSIONS: Favorable effects were observed among users of biologically based therapies and users of manipulative and body-based methods. Other types of complementary therapy had no effects on health status over a 1-year follow-up period.