High resistance barrier and prophylactic protection in preclinical models of SARS-CoV-2 with two siRNA combination.

RNA interference is a natural antiviral mechanism that could be harnessed to combat SARS-CoV-2 infection by targeting and destroying the viral RNA. We identified potent lipophilic small interfering RNA (siRNA) conjugates targeting highly conserved regions of SARS-CoV-2 outside of the spike-encoding region capable of achieving ≥3-log viral reduction. Serial passaging studies demonstrated that a two-siRNA combination prevented development of resistance compared to a single siRNA approach.

Restoration of the activated Rig-I pathway in hepatitis C virus (HCV) replicon cells by HCV protease, polymerase, and NS5A inhibitors in vitro at clinically relevant concentrations.

Development of persistent hepatitis C virus (HCV) infection may be mediated by HCV NS3 · 4A protease-dependent inhibition of host innate immunity. When double-stranded RNA (dsRNA) is detected in virus-infected cells, host innate immunity mounts an antiviral response by upregulating production of type I interferons (α/β interferon [IFN-α/β]); HCV counters by cleaving the IFN-β stimulator 1 (IPS-1) adaptor protein, decreasing synthesis of IFN-α/β. We evaluated HCV protease (telaprevir, boceprevir, and TMC435350), polymerase (HCV-796 and VX-222), and NS5A (BMS-790052) inhibitors for the ability to restore IPS-1-mediated Rig-I signaling by measuring Sendai virus-induced IFN-β promoter activation in HCV replicon cells after various exposure durations.

Pathway to dry skin prevention and treatment.

Background: This article presents an evidence-supported clinical pathway for dry skin prevention and treatment.

Objective: The development of the pathway involved the following: a literature review was conducted and demonstrated that literature on dry skin is scarce. To compensate for the gap in the available literature, a modified Delphi method was used to collect information on prevention and treatment practice through a panel, which included 10 selected dermatologists who currently provide medical care for dermatology patients in Ontario.

Guideline-based antibiotics and mortality in healthcare-associated pneumonia.

Background: Guidelines recommend administration of antibiotics with activity against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa for treatment of healthcare-associated pneumonia (HCAP). It is unclear if this therapy improves outcomes for patients with HCAP.

Objective: To determine if administration of guideline-similar therapy (GST) was associated with a reduction in 30-day mortality for HCAP.

Predicting antibiotic resistance to community-acquired pneumonia antibiotics in culture-positive patients with healthcare-associated pneumonia.

Objective: To develop and validate a model to predict resistance to community-acquired pneumonia antibiotics (CAP-resistance) among patients with healthcare-associated pneumonia (HCAP), and to compare the model's predictive performance to a model including only guideline-defined criteria for HCAP.

Design: Retrospective cohort study.

Setting: Six Veterans Affairs Medical Centers in the northwestern United States.

Gender differences in veterans health administration mental health service use: effects of age and psychiatric diagnosis.

Purpose: The objective of this study was to compare gender differences in mental health disease burden and outpatient mental health utilization among veterans utilizing Veterans Health Administration (VHA) mental health services in fiscal year 1999 (FY99), after the first Gulf War and significant restructuring of VHA services.

Methods: We used logistic regression to examine the relationships among gender, age, diagnostic groups, and utilization of mental health and specialty mental health services in a national sample of veterans. The sample included 782,789 veterans with at least 1 outpatient visit in the VHA in FY99 associated with a mental health or substance abuse (SA) diagnosis.

Efficacy of oral beta-lactam versus non-beta-lactam treatment of uncomplicated cellulitis.

Background: Preferred therapy for purulent skin and soft tissue infections is incision and drainage, but many infections cannot be drained. Empiric therapies for these infections are ill-defined in the era of community-acquired methicillin-resistant Staphylococcus aureus.

Methods: A multicenter retrospective cohort study of outpatients treated for cellulitis was conducted to compare clinical failure rates of oral beta-lactam and non-beta-lactam treatments.

Racial differences in the evaluation and treatment of hepatitis C among veterans: a retrospective cohort study.

Objectives: We examined the association between race and hepatitis C virus (HCV) evaluation and treatment of veterans in the Northwest Network of the Department of Veterans Affairs (VA).

Methods: In our retrospective cohort study, we used medical records to determine antiviral treatment of 4263 HCV-infected patients from 8 VA medical centers. Secondary outcomes included specialty referrals, laboratory evaluation, viral genotype testing, and liver biopsy.

Outpatient treatment engagement and abstinence rates following inpatient opioid detoxification.

Many patients with chronic opioid dependence are referred to drug-free outpatient treatment following inpatient detoxification even though successful outpatient treatment engagement and abstinence from opioids occur only in a minority of cases. This retrospective cohort analysis of medical records documents the post-discharge outcome in a treatment setting that maximizes the support during transition to abstinence-oriented outpatient care, with comprehensive social, medical and mental health services, including the availability of naltrexone. Participants were male veterans (N = 112) admitted at an urban VA medical center.

Low serum testosterone and mortality in male veterans.

Background: Low serum testosterone is a common condition in aging associated with decreased muscle mass and insulin resistance. This study evaluated whether low testosterone levels are a risk factor for mortality in male veterans.

Methods: We used a clinical database to identify men older than 40 years with repeated testosterone levels obtained from October 1, 1994, to December 31, 1999, and without diagnosed prostate cancer.

Development and validation of a psychiatric case-mix system.

Background: Although difficulties in applying risk-adjustment measures to mental health populations are increasingly evident, a model designed specifically for patients with psychiatric disorders has never been developed.

Objective: Our objective was to develop and validate a case-mix classification system, the "PsyCMS," for predicting concurrent and future mental health (MH) and substance abuse (SA) healthcare costs and utilization.

Subjects: Subjects included 914,225 veterans who used Veterans Administration (VA) healthcare services during fiscal year 1999 (FY99) with any MH/SA diagnosis (International Classification of Diseases, 9th Revision, Clinical Modification [ICD-9-CM] codes 290.

Randomized trial of onsite versus referral primary medical care for veterans in addictions treatment.

Background: Patients presenting for treatment of substance use disorders (SUDs) often exhibit medical comorbidities that affect functional health status and healthcare costs. Providing primary care within addictions clinics (onsite care) may improve medical and SUD treatment outcomes in this population.

Objective: The objective of this study was to compare outcomes among Veterans' Administration (VA) patients who receive medical care within the SUD clinic and those referred to a general medicine clinic at the same facility.

CD155/PVR enhances glioma cell dispersal by regulating adhesion signaling and focal adhesion dynamics.

We recently identified the immunoglobulin-CAM CD155/PVR (the poliovirus receptor) as a regulator of cancer invasiveness and glioma migration, but the mechanism through which CD155/PVR controls these processes is unknown. Here, we show that expression of CD155/PVR in rat glioma cells that normally lack this protein enhances their dispersal both in vitro and on primary brain tissue. CD155/PVR expression also reduced substrate adhesion, cell spreading, focal adhesion density, and the number of actin stress fibers in a substrate-dependent manner.

Substantial weight gain during adulthood: the road to bariatric surgery.

We sought to examine the relationship of body mass index (BMI) at age 18 years with the degree and rate of rise in body weight during adulthood among the morbidly obese. We evaluated 196 patients with a standard medical history form and a structured interview with questions regarding weight at age 18 years. The study included 40 (20.

Functional proteomic screen identifies a modulating role for CD44 in death receptor-mediated apoptosis.

Apoptotic evasion is a hallmark of cancer and its resistance to chemotherapeutic drugs. Identification of cellular proteins that mediate apoptotic programs is a critical step toward the development of therapeutics aimed at overcoming apoptosis resistance. We developed an innovative high-throughput screen to identify proteins that modulate Fas ligand-mediated apoptosis using fluorophore-assisted light inactivation (HTS-FALIpop).

Cost effectiveness of testing strategies for chronic hepatitis C.

Objective: This paper compares nine strategies for determining hepatitis C antibody and viral status. They combine two tests for antibodies (enzyme immunoassays (EIA), recombinant immunoblot assays (RIBA)) and one for viremia (reverse transcription polymerase chain reaction (PCR)). Using optical density to divide EIA results into three categories (high positive, low positive, negative) was also considered.

Low testosterone levels predict incident depressive illness in older men: effects of age and medical morbidity.

Objective: Prior studies found that chronic low testosterone levels are associated with an increased risk of depression. We investigated whether low testosterone levels in older men predict depressive illness over 2 years, while controlling for age and medical morbidity.

Method: Participants were 748 men, aged 50 years or older, without prior ICD-9-diagnosed depressive illness, with a testosterone level obtained between 1995 and 1997.

The Addiction Severity Index medical and psychiatric composite scores measure similar domains as the SF-36 in substance-dependent veterans: concurrent and discriminant validity.

Background: Recently attention has focused on the assessment of functional health status in substance-dependent individuals. The addiction severity index (ASI) is a widely used assessment instrument that includes scales to reflect current medical and psychiatric status. This study examines the concurrent validity of these ASI composite scores in relation to the short form 36-item health survey (SF-36), a well-established measure of health-related quality of life/functional health status.

CD155/PVR plays a key role in cell motility during tumor cell invasion and migration.

Background: Invasion is an important early step of cancer metastasis that is not well understood. Developing therapeutics to limit metastasis requires the identification and validation of candidate proteins necessary for invasion and migration.

Methods: We developed a functional proteomic screen to identify mediators of tumor cell invasion.

Use of electronic medical record data for quality improvement in schizophrenia treatment.

An understanding of the strengths and limitations of automated data is valuable when using administrative or clinical databases to monitor and improve the quality of health care. This study discusses the feasibility and validity of using data electronically extracted from the Veterans Health Administration (VHA) computer database (VistA) to monitor guideline performance for inpatient and outpatient treatment of schizophrenia. The authors also discuss preliminary results and their experience in applying these methods to monitor antipsychotic prescribing using the South Central VA Healthcare Network (SCVAHCN) Data Warehouse as a tool for quality improvement.

Hepatitis C tested prevalence and comorbidities among veterans in the US Northwest.

Goals: (1) Investigate the epidemiology of hepatitis C virus infection among patients seen in the Veterans Administration Northwest Network; (2) examine time trends in testing practices and results; and (3) estimate the prevalence of hepatitis C virus infection among active patients.

Background: Hepatitis C virus infection causes chronic hepatitis and cirrhosis and is a leading cause of end-stage liver disease. Hepatitis C virus antibodies are estimated to be present in 1.

Increased incidence of diagnosed depressive illness in hypogonadal older men.

Context: Age-associated hypogonadism (testosterone deficit) occurs in 30% of men after the age of 55; it is associated with decreased muscle mass, bone mineral density, and libido, and with anorexia, fatigue, and irritability. Although some of these symptoms overlap with those of depression, the association between the 2 disorders is unclear.

Objective: To determine if hypogonadal men have an increased incidence of depressive illness compared with eugonadal men.

Case-mix adjusting performance measures in a veteran population: pharmacy- and diagnosis-based approaches.

Objective: To compare the rankings for health care utilization performance measures at the facility level in a Veterans Health Administration (VHA) health care delivery network using pharmacy- and diagnosis-based case-mix adjustment measures.

Data Sources/study Setting: The study included veterans who used inpatient or outpatient services in Veterans Integrated Service Network (VISN) 20 during fiscal year 1998 (October 1997 to September 1998; N = 126,076). Utilization and pharmacy data were extracted from VHA national databases and the VISN 20 data warehouse.

How well do automated performance measures assess guideline implementation for new-onset depression in the Veterans Health Administration?

Background: Because most guidelines focus on patients with new episodes of depression, algorithms to identify such samples must be accurate. This study examined whether the Veterans Health Administration's (VHA's) electronic medical record database could identify valid cases of new-onset depression.

Results: Of 109 individuals receiving outpatient care at one of three VHA medical centers who were identified with newly diagnosed depressive disorder, 39 (35.

Smoking cessation treatment among dually diagnosed individuals: preliminary evaluation of different pharmacotherapies.

This descriptive, observational pilot study evaluated a smoking cessation intervention using open-label bupropion and nicotine replacement within an addiction treatment center for patients with high rates of comorbid psychiatric diagnoses. Participants were 115 veterans receiving substance abuse treatment at a Veterans Administration outpatient program who voluntarily sought smoking cessation treatment. Three fourths of participants had a psychiatric diagnosis in addition to substance dependence (i.