High-content, arrayed compound screens with rhinovirus, influenza A virus and herpes simplex virus infections.

Viruses are genetically and structurally diverse, and outnumber cells by orders of magnitude. They can cause acute and chronic infections, suppress, or exacerbate immunity, or dysregulate survival and growth of cells. To identify chemical agents with pro- or antiviral effects we conducted arrayed high-content image-based multi-cycle infection screens of 1,280 mainly FDA-approved compounds with three human viruses, rhinovirus (RV), influenza A virus (IAV), and herpes simplex virus (HSV) differing in genome organization, composition, presence of an envelope, and tropism. Based on Z'-factors assessing screening quality and Z-scores ranking individual compounds, we identified potent inhibitors and enhancers of infection: the RNA mutagen 5-Azacytidine against RV-A16; the broad-spectrum antimycotic drug Clotrimazole inhibiting IAV-WSN; the chemotherapeutic agent Raltitrexed blocking HSV-1; and Clobetasol enhancing HSV-1. Remarkably, the topical antiseptic compound Aminacrine, which is clinically used against bacterial and fungal agents, inhibited all three viruses. Our data underscore the versatility and potency of image-based, full cycle virus propagation assays in cell-based screenings for antiviral agents.

Methylene blue, Mycophenolic acid, Posaconazole, and Niclosamide inhibit SARS-CoV-2 Omicron variant BA.1 infection of human airway epithelial organoids.

Sublineages of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) Omicron variants continue to amass mutations in the spike (S) glycoprotein, which leads to immune evasion and rapid spread of the virus across the human population. Here we demonstrate the susceptibility of the Omicron variant BA.1 (B.1.1.529.1) to four repurposable drugs, Methylene blue (MB), Mycophenolic acid (MPA), Posaconazole (POS), and Niclosamide (Niclo) in post-exposure treatments of primary human airway cell cultures. MB, MPA, POS, and Niclo are known to block infection of human nasal and bronchial airway epithelial explant cultures (HAEEC) with the Wuhan strain, and four variants of concern (VoC), Alpha (B.1.1.7), Beta (B.1.351), Gamma (B.1.1.28), Delta (B.1.617.2) (Weiss et al., 2021, Murer et al., 2022). Our results here not only reinforce the broad anti-coronavirus effects of MB, MPA, POS and Niclo, but also demonstrate that the Omicron variant BA.1 (B.1.1.529.1) sheds infectious virus from HAEEC over at least 15 d, and maintains both intracellular and extracellular viral genomic RNA without overt toxicity, suggesting viral persistence. The data emphasize the potential of repurposable drugs against COVID-19.

Does diabetes double the risk of depression?

PURPOSE: In this study, we compared the rate of depression diagnoses in adults with and without diabetes mellitus, while carefully controlling for number of primary care visits. METHODS: We matched adults with incident diabetes (n = 2,932) or prevalent diabetes (n = 14,144) to nondiabetic control patients based on (1) age and sex, or (2) age, sex, and number of outpatient primary care visits. Logistic regression analysis was used to assess the association between various predictors and a diagnosis of depression in each diabetes cohort relative to matched nondiabetic control patients. RESULTS: With matching for age and sex alone, patients with prevalent diabetes having few primary care visits were significantly more likely to have a new depression diagnosis than matched control patients (odds ratio [OR] = 1.46, 95% confidence interval [CI], 1.19-1.80), but this relationship diminished when patients made more than 10 primary care visits (OR = 0.95, 95% CI, 0.77-1.17). With additional matching for number of primary care visits, patients with prevalent diabetes mellitus with few primary care visits were more likely to have a new diagnosis of depression than those in control group (OR = 1.32, 95% CI, 1.07-1.63), but this relationship diminished and reversed when patients made more than 4 primary care visits (OR = 0.99, 95% CI, 0.80-1.23). Similar results were observed in the subset of patients with incident diabetes and their matched control patients. CONCLUSIONS: Patients with diabetes have little or no increase in the risk of a new diagnosis of depression relative to nondiabetic patients when analyses carefully control for the number of outpatient visits. Studies showing such an association may have inadequately adjusted for comorbidity or for exposure to the medical care system.

Managing fecal incontinence: self-care practices of older adults.

Little is known about the ways in which community-dwelling elderly individuals manage fecal incontinence (FI) in their daily lives. In this study, community-dwelling elderly individuals were surveyed at clinics of a health maintenance organization (HMO) to describe the self-care practices used to manage FI and to examine factors that influenced the number of self-care practices used and the reporting of FI to a health care practitioner. Responses of 242 elderly individuals who reported that they had FI several times per year were analyzed. The self-care practices used most commonly were changing diet, wearing a sanitary pad/brief, and reducing activity or exercise. Elderly women and those with a greater severity of FI and more chronic health problems engaged in more self-care practices. Factors associated with reporting FI to a clinician were considering FI to be a problem, uncertainty about the cause of FI, and changing diet to avoid FI. There is a need to promote effective management strategies for FI to older individuals living in the community.

Severity of fecal incontinence in community-living elderly in a health maintenance organization.

An anonymous survey containing questions about the severity of fecal incontinence (FI)--frequency, amount, and type--and its correlates was distributed to community-living elderly at four managed-care clinics. Completed surveys were received from 1,352 respondents whose mean (+/-standard deviation) age was 75 +/- 6 years and 60% of whom were female. Approximately 19% reported having FI one or more times within the past year. Incontinence that soiled underwear or was of loose or liquid consistency was most common. More frequent FI and a greater amount of FI were significantly associated with loose or liquid stool consistency, defecation urgency, bowel surgery, and chronic health conditions. Therapies aimed at normalizing stool consistency or reducing urgency may be beneficial in lessening FI severity.

Treatment of elderly and other adult patients for depression in primary care.

OBJECTIVES: To determine whether depression is treated differently in older and younger patients in primary care clinics. DESIGN: Administrative data were used to identify patients with a depression diagnosis code. The sources of data were baseline and 3-month follow-up surveys, the health plan electronic database, and chart audits. SETTING: Nine primary care clinics owned by a health maintenance organization in the Midwest. PARTICIPANTS: The study sample (N=1023) consisted of adult patients, aged 19 to 93, and was divided into six age groups, from young adult, under age 35, to old old, 75 or older. MEASUREMENTS: Independent variables were a series of dummy variables: age groups, baseline depression severity, sex, and incident depression. Outcomes were defined as care processes (assessment, resources) and improvement in depression symptoms (Center for Epidemiologic Studies-Depression scale short form). Univariate and multivariate logistic regression analyses were used to analyze patient characteristics, depression symptoms, and care process variables. Significance level was reported based on the chi-square test of probability, P

Community-based care and risk of nursing home placement.

OBJECTIVE: To test the substitution hypothesis, that community-based care reduces the probability of institutional placement for at-risk elderly. RESEARCH DESIGN: The closure of the Social Health Maintenance Organization (Social HMO) at HealthPartners (HP) in Minnesota in 1994 and the continuation of the Social HMO at Kaiser Permanente Northwest (KPNW) in Oregon/Washington comprised a "natural experiment." Using multinomial logistic regression analyses, we followed cohorts of Social HMO enrollees for up to 5 years, 1995 to 1999. To adjust for site effects and secular trends, we also followed age- and gender-matched Medicare-Tax Equity and Fiscal Responsibility Act (TEFRA) cohorts, enrolled in the same HMOs but not in the Social HMOs. SUBJECTS: All enrollees in the Social HMO for at least 4 months in 1993 and an age-gender matched sample of Medicare-TEFRA enrollees. To be included, individuals had to be alive and have a period out of an institution after January 1, 1995 (total n = 18,143). MEASURES: The primary data sources were the electronic databases at HP and KPNW. The main outcomes were long-term nursing home placement (90+ days) or mortality. Covariates were age, gender, a comorbidity index, and geographic site effect. RESULTS: Adjusting for variations in the 2 sites, we found no difference in probability of mortality between the 2 cohorts, but approximately a 40% increase in long-term institutional placement associated with the termination of the Social HMO at HealthPartners (odds ratio, 1.43; 95% confidence interval, 1.15-1.79). CONCLUSIONS: The Social HMO appears to help at-risk elderly postpone long-term nursing home placement.

When depression is the diagnosis, what happens to patients and are they satisfied?

OBJECTIVES: To understand the process, outcomes, and patient satisfaction of usual primary care for patients given a diagnostic code for depression. STUDY DESIGN: Health plan data were used to identify patients with a diagnostic code for depression (and no such diagnosis in the preceding 6 months). Patients were surveyed by mail soon after the coded visit and again 3 months later about the care they had received; their charts were also audited. METHODS: The 274 patients in 9 primary care clinics who responded to both surveys reported on their personal characteristics, depression symptoms and history, the care received in that initial visit, and the follow-up care during the next 3 months. They also reported on their satisfaction with various aspects of that care. RESULTS: These patients were likely to be given antidepressant medications as their main or only treatment. Referral for mental health therapies was not used often, even though referral is readily available in this setting; other types of self-management recommendations and support were even less frequent. Patient outcomes and levels of satisfaction during a 3-month follow-up period were unimpressive. CONCLUSIONS: To successfully maintain a key role in the care of this important problem for their patients, primary care physicians may need to incorporate a more comprehensive and systematic approach to management that involves other team members and is more satisfying to patients.

Pharmaceutical care and health care utilization in an HMO.

CONTEXT: The belief that expanding the role of pharmacists in patient care could improve the safety and efficacy of drug therapy is growing. Specifically, pharmaceutical care programs through which pharmacists provide direct and ongoing counseling to patients have been introduced. Whether such programs reduce medication-related problems or health care utilization is unknown. OBJECTIVE: To assess whether a pharmaceutical care program decreases health care utilization, medication use, or charges. DESIGN: Nonrandomized, controlled trial. SETTING: Staff clinic and freestanding contract pharmacies affiliated with a large HMO in greater Minneapolis-St. Paul (6 intervention pharmacies, 143 control pharmacies). STUDY POPULATION: Adult HMO enrollees (n = 921) with heart or lung disease who used one of the selected pharmacies. INTERVENTION: Patients at intervention pharmacies were invited to participate in the pharmaceutical care program. The protocol-based program consisted of scheduled meetings between trained pharmacists and patients to assess drug therapy, plan goals, and intervene through counseling and/or consultation with other health professionals. OUTCOME MEASURES: Change in number of outpatient clinic visits, unique medications dispensed, and total charges over 1 year of follow-up. RESULTS: In an intention-to-treat analysis (after adjustment for gender, age, Charlson Comorbidity Index, disease category, and the baseline value of the utilization measure), the number of unique medications for patients in the pharmaceutical care group increased more than in the usual care group (1.0 vs. 0.4 unique medications; P = 0.03). There was no difference between the two groups in the change in total number of clinic visits or total costs. In secondary adherence analyses, participants were more likely than the usual care group to increase the number of clinic visits (1.2 vs. -0.9; P = < 0.01) and number of unique medications (1.0 vs. 0.2; P = 0.02). CONCLUSION: Pharmaceutical care for patients with chronic health conditions appears to be associated with a modest increase rather than a decrease in health care utilization.

Geriatric depression, antidepressant treatment, and healthcare utilization in a health maintenance organization.

OBJECTIVES: To assess the separate effects of depressive symptoms and antidepressant treatment on healthcare utilization and cost. SETTING: Social Health Maintenance Organization (HMO) at HealthPartners in Minnesota. PARTICIPANTS: Geriatric Social HMO enrollees were screened for depressive symptoms using the 30-item Geriatric Depression Scale. A stratified sample was created, composed of geriatric enrollees with depressive symptoms, with antidepressant prescriptions, or with neither (n = 516). DESIGN: Regression analyses were conducted with separate equations for utilization and charge outcome variables, both outpatient and inpatient (log-transformed). The Charlson Comorbidity Index, age, and gender served as covariates. MEASUREMENT: Depressive symptoms were identified through the Diagnostic Interview Schedule. Antidepressant treatment was determined from the HMO pharmacy database. RESULTS: Having depressive symptoms was associated with a 19 increase in the number of outpatient encounters and a 30 increase in total outpatient charges. Antidepressant treatment was associated with a 32 increase in total outpatient charges but was not significantly associated with number of outpatient encounters. Depressive symptoms and antidepressant therapy were not significantly associated with inpatient utilization or charges. CONCLUSION: This study found that patients with depressive symptoms generated more outpatient health care and higher charges but not necessarily more inpatient care. Our findings suggest that programs targeted to geriatric patients whose depression is comorbid with other chronic medical conditions might be cost-effective and particularly appropriate for geriatric care.