Advancing health equity in improving breast cancer screening with the use of a mobile mammography bus in marginalised population: quality improvement project.

BACKGROUND: Breast cancer, the second leading cause of cancer-related deaths in women in the USA, is effectively treated through early detection and screening. This quality improvement (QI) project aimed to improve mammography screening rates from the baseline of 50% to 60% within 12 months for patients aged 50-74 years at an Internal Medicine Clinic. METHODS: We used the Plan, Do, Study, Act (PDSA) model. A multidisciplinary team used a fishbone diagram to identify barriers to suboptimal screening. The QI team created a driver diagram and process flow map. The mammogram screening rate was the outcome measure. Mammogram order and completion rates were the process measures. We implemented six PDSA cycles. Major interventions included the use of a nurse navigator, enhancements in health information technology, and education to patients, providers, and nursing staff. Mammograms were offered in a mobile bus, located in the hospital campus and in under-resourced inner-city neighbourhoods to improve the access. Data analysis was performed using monthly statistical process control charts. RESULTS: The project exceeded its initial goal, achieving a breast cancer screening rate of 66% (n=490 of 744) during the study period and was sustainable at 69%, 3 months post-project. The mammogram order rate was 58% (n=432 of 744) and completion rate was 53% (n=231 of 432) within 12 months. CONCLUSIONS: We attributed the success of this QI project to the education of patients, nurses and physicians, the use of a nurse navigator and engagement of a multidisciplinary team. Access to mobile mammography bus addressed the social determinants of health barriers in a marginalised population.

An immunoregulator nanomedicine approach for the treatment of tuberculosis.

Introduction: A nanoparticle composed of a poly (lactic-co-glycolic acid) (PLGA) core and a chitosan (CS) shell with surface-adsorbed 1,3 ß-glucan (ß-glucan) was synthesized. The exposure response of CS-PLGA nanoparticles (0.1 mg/mL) with surface-bound ß-glucan at 0, 5, 10, 15, 20, or 25 ng or free ß-glucan at 5, 10, 15, 20, or 25 ng/mL in macrophage in vitro and in vivo was investigated. Results: In vitro studies demonstrate that gene expression for IL-1ß, IL-6, and TNFα increased at 10 and 15 ng surface-bound ß-glucan on CS-PLGA nanoparticles (0.1 mg/mL) and at 20 and 25 ng/mL of free ß-glucan both at 24 h and 48 h. Secretion of TNFα protein and ROS production increased at 5, 10, 15, and 20 ng surface-bound ß-glucan on CS-PLGA nanoparticles and at 20 and 25 ng/mL of free ß-glucan at 24 h. Laminarin, a Dectin-1 antagonist, prevented the increase in cytokine gene expression induced by CS-PLGA nanoparticles with surface-bound ß-glucan at 10 and 15 ng, indicating a Dectin-1 receptor mechanism. Efficacy studies showed a significant reduction in intracellular accumulation of mycobacterium tuberculosis (Mtb) in monocyte-derived macrophages (MDM) incubated with on CS-PLGA (0.1 mg/ml) nanoparticles with 5, 10, and 15 ng surface-bound ß-glucan or with 10 and 15 ng/mL of free ß-glucan. ß-glucan-CS-PLGA nanoparticles inhibited intracellular Mtb growth more than free ß-glucan alone supporting the role of ß-glucan-CS-PLGA nanoparticles as stronger adjuvants than free ß-glucan. In vivo studies demonstrate that oropharyngeal aspiration (OPA) of CS-PLGA nanoparticles with nanogram concentrations of surface-bound ß-glucan or free ß-glucan increased TNFα gene expression in alveolar macrophages and TNFα protein secretion in bronchoalveolar lavage supernatants. Discussion: Data also demonstrate no damage to the alveolar epithelium or changes in the murine sepsis score following exposure to ß-glucan-CS-PLGA nanoparticles only, indicating safety and feasibility of this nanoparticle adjuvant platform to mice by OPA.

Mitochondrial Dynamics in SARS-COV2 Spike Protein Treated Human Microglia: Implications for Neuro-COVID.

Emerging clinical data from the current COVID-19 pandemic suggests that ~ 40% of COVID-19 patients develop neurological symptoms attributed to viral encephalitis while in COVID long haulers chronic neuro-inflammation and neuronal damage result in a syndrome described as Neuro-COVID. We hypothesize that SAR-COV2 induces mitochondrial dysfunction and activation of the mitochondrial-dependent intrinsic apoptotic pathway, resulting in microglial and neuronal apoptosis. The goal of our study was to determine the effect of SARS-COV2 on mitochondrial biogenesis and to monitor cell apoptosis in human microglia non-invasively in real time using Raman spectroscopy, providing a unique spatio-temporal information on mitochondrial function in live cells. We treated human microglia with SARS-COV2 spike protein and examined the levels of cytokines and reactive oxygen species (ROS) production, determined the effect of SARS-COV2 on mitochondrial biogenesis and examined the changes in molecular composition of phospholipids. Our results show that SARS- COV2 spike protein increases the levels of pro-inflammatory cytokines and ROS production, increases apoptosis and increases the oxygen consumption rate (OCR) in microglial cells. Increases in OCR are indicative of increased ROS production and oxidative stress suggesting that SARS-COV2 induced cell death. Raman spectroscopy yielded significant differences in phospholipids such as Phosphatidylinositol (PI), phosphatidylserine (PS), phosphatidylethanolamine (PE) and phosphatidylcholine (PC), which account for ~ 80% of mitochondrial membrane lipids between SARS-COV2 treated and untreated microglial cells. These data provide important mechanistic insights into SARS-COV2 induced mitochondrial dysfunction which underlies neuropathology associated with Neuro-COVID.

HIV Neuroinflammation: The Role of Exosomes in Cell Signaling, Prognostic and Diagnostic Biomarkers and Drug Delivery.

Fifty to sixty percent of HIV-1 positive patients experience HIV-1 associated neurocognitive disorders (HAND) likely due to persistent inflammation and blood-brain barrier (BBB) dysfunction. The role that microglia and astrocytes play in HAND pathogenesis has been well delineated; however, the role of exosomes in HIV neuroinflammation and neuropathogenesis is unclear. Exosomes are 50-150 nm phospholipid bilayer membrane vesicles that are responsible for cell-to-cell communication, cellular signal transduction, and cellular transport. Due to their diverse intracellular content, exosomes, are well poised to provide insight into HIV neuroinflammation as well as provide for diagnostic and predictive information that will greatly enhance the development of new therapeutic interventions for neuroinflammation. Exosomes are also uniquely positioned to be vehicles to delivery therapeutics across the BBB to modulate HIV neuroinflammation. This mini-review will briefly discuss what is known about exosome signaling in the context of HIV in the central nervous system (CNS), their potential for biomarkers as well as their potential for vehicles to deliver various therapeutics to treat HIV neuroinflammation.

Melatonin multifaceted pharmacological actions on melatonin receptors converging to abrogate COVID-19.

Data indicate that controlling inflammatory responses to COVID-19 may be as important as antiviral therapies or could be an important adjunctive approach. Melatonin possesses anti-inflammation, antioxidation, and immune-enhancing features directly and/or indirectly through its own receptor signaling and is therefore well suited to reduce the severity of COVID-19. Studies have proposed that melatonin regulates COVID-19-associated proteins directly through regulation of molecules such as calmodulin (CALM) 1 and CALM 2, calreticulin (CalR), or myeloperoxidase (MPO) and/or indirectly through actions on GPCR (eg, MTNR1A, MTNR1B) and nuclear (eg, RORα, RORß) melatonin receptor signaling. However, the exact mechanism(s) and doses by which melatonin reduces the severity of COVID-19 is still open for debate, warranting the need for further testing of melatonin in placebo-controlled randomized clinical trials for COVID-19.

Hybrid Curdlan Poly(γ -Glutamic Acid) Nanoassembly for Immune Modulation in Macrophage.

A nanoformulation composed of curdlan, a linear polysaccharide of 1,3-ß-linked d-glucose units, hydrogen bonded to poly(γ -glutamic acid) (PGA), was developed to stimulate macrophage. Curdlan/PGA nanoparticles (C-NP) are formulated by physically blending curdlan (0.2 mg mL-1 in 0.4 m NaOH) with PGA (0.8 mg mL-1 ). Forster resonance energy transfer (FRET) analysis demonstrates a heterospecies interpolymer complex formed between curdlan and PGA. The 1 H-NMR spectra display significant peak broadening as well as downfield chemical shifts of the hydroxyl proton resonances of curdlan, indicating potential intermolecular hydrogen bonding interactions. In addition, the cross peaks in 1 H-1 H 2D-NOESY suggest intermolecular associations between the OH-2/OH-4 hydroxyl groups of curdlan and the carboxylic-/amide-groups of PGA via hydrogen bonding. Intracellular uptake of C-NP occurs over time in human monocyte-derived macrophage (MDM). Furthermore, C-NP nanoparticles dose-dependently increase gene expression for TNF-α, IL-6, and IL-8 at 24 h in MDM. C-NP nanoparticles also stimulate the release of IL-lß, MCP-1, TNF-α, IL-8, IL-12p70, IL-17, IL-18, and IL-23 from MDM. Overall, this is the first demonstration of a simplistic nanoformulation formed by hydrogen bonding between curdlan and PGA that modulates cytokine gene expression and release of cytokines from MDM.

Impact of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in the Nervous System: Implications of COVID-19 in Neurodegeneration.

Coronavirus Disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2), began in December 2019, in Wuhan, China and was promptly declared as a pandemic by the World Health Organization (WHO). As an acute respiratory disease, COVID-19 uses the angiotensin-converting enzyme 2 (ACE2) receptor, which is the same receptor used by its predecessor, SARS-CoV, to enter and spread through the respiratory tract. Common symptoms of COVID-19 include fever, cough, fatigue and in a small population of patients, SARS-CoV-2 can cause several neurological symptoms. Neurological malaise may include severe manifestations, such as acute cerebrovascular disease and meningitis/encephalitis. Although there is evidence showing that coronaviruses can invade the central nervous system (CNS), studies are needed to address the invasion of SARS-CoV-2 in the CNS and to decipher the underlying neurotropic mechanisms used by SARS-CoV-2. This review summarizes current reports on the neurological manifestations of COVID-19 and addresses potential routes used by SARS-CoV-2 to invade the CNS.

Deprescribing Proton Pump Inhibitors in an Academic, Primary Care Clinic: Quality Improvement Project.

GOAL: The goal of this study was to reduce the percentage of inappropriately prescribed proton pump inhibitors (PPIs) in patients aged 50 and older from 80% (baseline) to 60% within 12 months in an academic, internal medicine clinic. BACKGROUND: The use of PPIs has increased drastically worldwide. Internal medicine clinic patients had inappropriate use of PPIs for an average of 4 to 5 years. STUDY: A multidisciplinary quality improvement team used the Plan-Do-Study-Act Model of health care improvement and performed a root cause analysis to identify barriers to inappropriate use of PPIs. The outcome measure was the percentage of patients inappropriately prescribed PPI. Process measures were completion rates of PPI risk assessment and esophagogastroduodenoscopy. Interventions included the creation of customized electronic health record templates and education to providers and patients. Analysis was performed using monthly statistical process control charts. RESULTS: The average rate of PPI discontinuation was 51.1% (n=92/180), which corresponds to 30.0% inappropriate PPI usage within 12 months. The mean PPI discontinuation rate in the 1-year prestudy, study and 6 months poststudy period was 2.0%, 32.0%, and 49.7%, respectively. The mean esophagogastroduodenoscopy completion rate was 49.8% from the baseline of <30%. CONCLUSIONS: We achieved a statistically significant and sustainable reduction of inappropriate PPI use to 30% from the baseline rates of 80% and surpassed our goal within 12 months. This quality improvement was unique as no pharmacy personnel was utilized in this process. The multifaceted strategies in a safety-net internal medicine clinic resulted in successful deprescribing of PPI and can be replicated in other setting.

Multifaceted strategies to improve blood pressure control in a primary care clinic: A quality improvement project.

BACKGROUND: Approximately 80% of patients with hypertension in the Internal Medicine Clinic were uncontrolled (BP > 130/80 mmHg), according to the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) hypertension guidelines, leading to increased morbidity and mortality. The aim of this quality improvement (QI) was to improve BP control <130/80 from the baseline rates of 20%-30% and <140/90 from the baseline rates of 40%-60% between ages of 18-75 years, within 12 months. METHODS: We used the Plan-Do-Study-Act method. A multidisciplinary QI team identified barriers by fish bone diagram. Barriers included: 1) Physicians' knowledge gap and clinical inertia in optimization of medications, and 2) Patients' nonadherence to medication and appointments. The outcome measures were the percentage of patients with BP < 140/90 and < 130/80. Process measures included: 1) attendance rates of physician and nurses at educational sessions, 2) medication reconciliation completion rates and 3) care guide order rates. Key interventions were: 1) physicians and nurses' education regarding ACC/AHA guidelines, 2) patient education and engagement and 3) enhancement of health information technology. Data analysis was performed using monthly statistical process control charts. RESULTS: We achieved 62.6% (n = 885/1426) for BP < 140/90 and 24.47% (n = 349/1426) for BP < 130/80 within 12 months project period. We sustained and exceeded at 72.64% (n = 945/1301) for BP < 140/90 and 44.58% (n = 580/1301) for BP < 130/80 during the 10 months post-project period. CONCLUSIONS: Overcoming physician clinical inertia, enhancing patient adherence to appointments and medications, and a high functioning multidisciplinary team were the key drivers for the success.

Transmigration of Tetraspanin 2 (Tspan2) siRNA Via Microglia Derived Exosomes across the Blood Brain Barrier Modifies the Production of Immune Mediators by Microglia Cells.

Microglia are implicated in the neuropathogenesis of HIV. Tetraspanin 2 (Tspan2) is closely related to CD9 and CD81 proteins, and are expressed on microglia cells. They have been implicated in cell fusion and adhesion and in the immune response, and neuroinflammation. Developing therapeutics that target microglia remains a challenge as these therapeutics must cross the Blood-Brain Barrier (BBB). Our goal was to use microglia derived exosomes as a vehicle to deliver siRNA across the BBB to target human telomerase reverse transcriptase immortalized human microglial cells (HTHU) latently infected by HIV (HTHU-HIV) and to evaluate if the knockdown of Tspan2 gene expression in changes the activation state of microglia cells, thereby modulating the neuroinflammatory response. A blood brain barrier (BBB) model that closely mimics and accurately reflects the characteristics and functional properties of the in vivo BBB was used to examine HTHU microglia exosome effects on BBB permeability, and their ability to migrate across the and delivery small interfering RNA (siRNA) to cells on the CNS side of the BBB model. Exosomes were loaded with Texas-Red control siRNA (20 pmol) or Cy5-Tspan2 siRNA and then placed in the apical side of the BBB model, 24 h after incubation, HTHU-HIV cells microglial cells on the lower chamber were either imaged for siRNA uptake or analyzed for gene expression induced modifications. HTHU exosomes transmigrate from the apical side of the BBB to deliver Texas-Red control siRNA or Cy5-Tspan2 siRNA to HTHU-HIV microglia cells on the CNS side of the BBB model. A dose dependent (5-40 pmol) increase in Cy5-Tspan2 uptake with a corresponding decrease in gene expression for Tspan2 occurred in HTHU-HIV microglia. A decrease in Tspan2 gene expression as a consequence of knockdown with Tspan2 siRNA at both 20 and 40 pmol concentrations resulted in a significant decrease in C-X-C motif chemokine 12 (CXCL12) and C-X-C chemokine receptor type 4 (CXCR4) gene expression in HTHU-HIV microglia. Furthermore, a decrease in the gene expression levels of the Interleukins, IL-13 and IL-10 and an increase in the gene expression levels for the Fc gamma receptor 2A(FCGR2A) and TNF-α occurred in HTHU-HIV microglial cells These data demonstrate that HTHU exosomes cross the BBB and are efficient delivery vehicles to the CNS. Moreover, modifying the expression levels of Tspan2, has downstream consequences that includes alterations in cytokines and microglia biomarkers. Graphical Abstract Microglia-derived exosomes loaded with Tspan2 siRNA transmigrate across the BBB and knockdown Tspan2 gene expression in human microglial cells latently infected by HIV. This knockdown increases CXCL12, CXCR4, FCGR2A and TNF-α while decreasing IL-13 and IL-10 gene expression in HTHU-HIV microglial cells. Modulating Tspan2 modulates microglia cytokines and phenotype biomarkers.

Optimisation of diagnosis and treatment of heart failure in a primary care setting.

BACKGROUND: Heart failure (HF) is one of the leading causes of emergency department visits and hospital admissions in the USA. We identified a gap in the diagnosis and the use of guideline-directed medical therapy in patients with HF at the internal medicine clinic. AIM: To improve the diagnosis and treatment of HF, as well as to reduce emergency department visits and hospitalisation over 12 months in patients aged 40-75 years. METHODS: The multidisciplinary quality improvement (QI) team performed a root cause analysis and identified barriers to optimal guideline-directed medical therapy. Rates of patients on guideline-directed medical therapy with systolic HF diagnosis, emergency department visits and hospital admissions were the outcome measures. The process measures included echocardiogram order and completion rates, and rates of accurate classification of HF from the baseline rate of less than 10%. We used the focus, analyse, develop, execute and evaluate (FADE) model with five improvement cycles. The major components of interventions included (1) leveraging health information technology; (2) optimising teamwork; and (3) providing education to patients, physicians and internal medicine clinic staff. Data were analysed using statistical process control and run charts. RESULTS: We observed a reduction in the total number of emergency department visits (160 vs 108), hospital admissions (117 vs 114) and observation visits (22 vs 16) comparing the 1-year preproject and 1-year postproject periods. An increase in the use of ACE inhibitors or angiotensin receptor blockers occurred from the baseline rate of 20%-37% during the second half of the project and was sustained at 71.4% (median) during 6 months of the postproject period. CONCLUSIONS: We achieved a sustainable increase in the accurate diagnosis of HF and achieved 80% diagnosis during the 6-month poststudy period.

Improving hepatitis C screening and diagnosis in patients born between 1945 and 1965 in a safety-net primary care clinic.

Individuals born between 1945-1965 represent 81% of all persons chronically infected with hepatitis C virus (HCV) in the USA and are largely unaware of their positive status. The baseline HCV screening rate in this population in an academic internal medicine clinic at a US hospital was less than 3.0%. The goal was to increase the rate of HCV screening in patients born between 1945 and 1965 to 20% within 24 months. The quality improvement team used the Plan Do Study Act Model. Outcome measures included HCV antibody screening, HCV RNA positive rate and linkage to hepatology care. Process measures included HCV antibody order and completion rates. The quality improvement team performed a root cause analysis and identified barriers for HCV screening and linkage to care. The key elements of interventions included redesigning nursing workflow, use of health information technology and educating patients, physicians and nursing staff about HCV. The HCV screening rate was 30.3% (391/1291) within 24 months. The HCV antibody positive rate was 43.5% (170/391), and HCV RNA positive rate was 95.3% (162/170). HCV infection was diagnosed in 12.5% (162/1291) of patients or 41.4% (162/391) of the screened population. Of those positive, 70% (114/162) were linked to hepatology care within the 24-month project timeframe. Eighty percent of patients seen by a hepatologist were treated with direct-acting antivirals agents. The HCV screening rate was sustained at 25.4% during the post-project 1-year period. Engagement of a multidisciplinary team and education to patients, physicians and nursing staff were the key drivers for success.

In vitro Pharmacokinetic Cell Culture System that Simulates Physiologic Drug and Nanoparticle Exposure to Macrophages.

PURPOSE: An in vitro dynamic pharmacokinetic (PK) cell culture system was developed to more precisely simulate physiologic nanoparticle/drug exposure. METHODS: A dynamic PK cell culture system was developed to more closely reflect physiologic nanoparticle/drug concentrations that are changing with time. Macrophages were cultured in standard static and PK cell culture systems with rifampin (RIF; 5 µg/ml) or ß-glucan, chitosan coated, poly(lactic-co-glycolic) acid (GLU-CS-PLGA) nanoparticles (RIF equivalent 5 µg/ml) for 6 h. Intracellular RIF concentrations were measured by UPLC/MS. Antimicrobial activity against M. smegmatis was tested in both PK and static systems. RESULTS: The dynamic PK cell culture system mimics a one-compartment elimination pharmacokinetic profile to properly mimic in vivo extracellular exposure. GLU-CS-PLGA nanoparticles increased intracellular RIF concentration by 37% compared to free drug in the dynamic cell culture system. GLU-CS-PLGA nanoparticles decreased M. smegmatis colony forming units compared to free drug in the dynamic cell culture system. CONCLUSIONS: The PK cell culture system developed herein enables more precise simulation of human PK exposure (i.e., drug dosing and drug elimination curves) based on previously obtained PK parameters.

Faecal immunochemical testing implementation to increase colorectal cancer screening in primary care.

Colorectal cancer (CRC) is the second leading cause of cancer death in USA, and CRC screening remains suboptimal. The aim of this quality improvement was to increase CRC screening in the internal medicine clinic (IMC) patients, between the ages of 50-75 years, from a baseline rate of 50%-70% over 12 months with the introduction of faecal immunochemical test (FIT) testing. We used the Plan-Do-Study-Act (PDSA) method and performed a root cause analysis to identify barriers to acceptance of CRC screening. The quality improvement team created a driver diagram to identify and prioritise change ideas. We developed a process flow map to optimise opportunities to improve CRC screening. We performed eight PDSA cycles. The major components of interventions included: (1) leveraging health information technology; (2) optimising team work, (3) education to patient, physicians and IMC staff, (4) use of patient navigator for tracking FIT completion and (5) interactive workshops for the staff and physicians to learn motivational interview techniques. The outcome measure included CRC screening rates with either FIT or colonoscopy. The process measures included FIT order and completion rates. Data were analysed using a statistical process control and run charts. Four hundred and seven patients visiting the IMC were offered FIT, and 252 (62%) completed the test. Twenty-two (8.7%) of patients were FIT positive, 14 of those (63.6%) underwent a subsequent diagnostic colonoscopy. We achieved 75% CRC screening with FIT or colonoscopy within 12 months and exceeded our goal. Successful strategies included engaging the leadership, the front-line staff and a highly effective multidisciplinary team. For average-risk patients, FIT was the preferred method of screening. We were able to sustain a CRC screening rate of 75% during the 6-month postproject period. Sustainable annual FIT is required for successful CRC screening.

Optimisation of lipids for prevention of cardiovascular disease in a primary care.

The 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines focus on atherosclerotic cardiovascular disease (ASCVD) risk reduction, using a Pooled Cohort Equation to calculate a patient's 10-year risk score, which is used to guide initiation of statin therapy. We identified a gap of evidence-based treatment for hyperlipidaemia in the Internal Medicine Clinic. Therefore, the aim of this study was to increase calculation of ASCVD risk scores in patients between the ages of 40 and 75 years from a baseline rate of less than 1% to 10%, within 12 months, for primary prevention of ASCVD. Root cause analysis was performed to identify materials/methods, provider and patient-related barriers. Plan-Do-Study-Act cycles included: (1) creation of customised workflow in electronic health records for documentation of calculated ASCVD risk score; (2) physician education regarding guidelines and electronic health record workflow; (3) refresher training for residents and a chart alert and (4) patient education and physician reminders. The outcome measures were ASCVD risk score completion rate and percentage of new prescriptions for statin therapy. Process measures included lipid profile order and completion rates. Increase in patient wait time, and blood test and medications costs were the balanced measures. We used weekly statistical process control charts for data analysis. The average ASCVD risk completion rate was 14.2%. The mean ASCVD risk completion rate was 4.0%. In eligible patients, the average lipid profile completion rate was 18%. ASCVD risk score completion rate was 33% 1-year postproject period. A team-based approach led to a sustainable increase in ASCVD risk score completion rate. Lack of automation in ASCVD risk score calculation and physician prompts in electronic health records were identified as major barriers. Furthermore, the team identified multiple barriers to lipid blood tests and treatment of increased ASCVD risk based on ACC/AHA guidelines.

United States National Trends in Mortality, Length of Stay (LOS) and Associated Costs of Cognitive Impairment in HIV Population from 2005 to 2014.

We evaluated national trends of in-hospital discharge rates, mortality outcomes, health care costs, length of stay in HIV patients with cognitive disorders. Neurological involvement in HIV is commonly associated with cognitive impairment termed as HIV-associated neurocognitive disorder (HAND) which includes a spectrum of neurocognitive dysfunction associated with HIV infection. Although severe and progressive neurocognitive impairment has become rare in HIV patients in the era of potent antiretroviral therapy, a majority of HIV patients have mild to moderate degree of neurocognitive impairment. Study population for this analysis was derived from the Nationwide Inpatient Sample from 2005 to 2014. Patients with ICD-9 code of HIV (042) with discharge diagnosis (Dx) listed top 1 through 5 were included in the analysis. Within this population, we identified patients with cognitive impairment using ICD-9 codes of 294 (persistent mental disorders; organic psychotic brain syndromes (chronic), 323.9 (encephalitis, myelitis, and encephalomyelitis), 331.83 (mild cognitive impairment) with Dx listed from 1 to 25. Patient variables obtained included: age, race, gender, length of stay, in-hospital mortality and insurance status. Hospital level variables included teaching status, location and region of country. SAS 9.4 software was used for data analysis. Comparisons of variables between hospitalized HIV patients with and without HAND showed significant increase in cost per hospital admissions, longer hospital stay and higher risk of mortality in patients with HAND.

Correlates of opiate misuse based on aberrant urine drug tests for patients on chronic opiate therapy in a safety-net, academic primary care clinic.

OBJECTIVE: Determine correlates of opiate misuse based on urine drug test (UDT) among patients on chronic opiate therapy (COT) for chronic noncancer pain. DESIGN: A cross-sectional study. SETTING: Urban, academic clinic. PARTICIPANTS: UDT performed in 206 patients on COT for at least 3 months duration within a one-year period. Patients were classified based on UDT results: (1) Appearance of Opiate Adherence: Positive UDT for prescribed opiate and negative for illicit drugs and nonprescribed control substances; (2) Opiate Misuse; Overt nonadherence: (a) Positive UDT for illicit drugs and/or nonprescribed controlled substances AND positive or negative for prescribed opiates (b) Overdose; (3) Possible opiate nonadherence: Negative for prescribed opiates and negative for illicit and nonprescribed controlled substances. INTERVENTIONS: None. MAIN OUTCOME MEASURES: UDT results, patient demographics, medical history, healthcare adherence, and utilization measures. RESULTS: Of the 206 records analyzed, 80 (38 percent) had appearance of opiate adherence, 91 (44 percent) had misuse, and 35 (17 percent) had possible opiate nonadherence. Analysis was performed comparing misuse and appearance of opiate adherence groups. In bivariate analyses, history of smoking (OR 3.90, 95% CI 1.69-9.03), substance use (OR 7.02, 95% CI 2.56-19.20), missed medical appointments (OR 2.85, 95% CI 1.44-5.63), and nonadherence to other medications correlated with misuse group (OR 18.86, 95% CI 8.73-40.74). In logistic regression, only substance use history (OR 4.32, 95% CI 1.27-14.64) and nonadherence with nonopiate medications (OR 13.22, 95% CI 5.81-30.10) correlated with misuse. CONCLUSIONS: Medication nonadherence and missed appointments for other chronic conditions were significant correlates of opiate misuse.

Role of Galectin-3 in the pathophysiology underlying allergic lung inflammation in a tissue inhibitor of metalloproteinases 1 knockout model of murine asthma.

Asthma is a chronic inflammatory respiratory disease characterized by airway inflammation, airway hyperresponsiveness and reversible airway obstruction. Understanding the mechanisms that underlie the various endotypes of asthma could lead to novel and more personalized therapies for individuals with asthma. Using a tissue inhibitor of metalloproteinases 1 (TIMP-1) knockout murine allergic asthma model, we previously showed that TIMP-1 deficiency results in an asthma phenotype, exhibiting airway hyperreactivity, enhanced eosinophilic inflammation and T helper type 2 cytokine gene and protein expression following sensitization with ovalbumin. In the current study, we compared the expression of Galectins and other key cytokines in a murine allergic asthma model using wild-type and TIMP-1 knockout mice. We also examined the effects of Galectin-3 (Gal-3) inhibition on a non-T helper type 2 cytokine interleukin-17 (IL-17) to evaluate the relationship between Gal-3 and the IL-17 axis in allergic asthma. Our results showed a significant increase in Gal-3, IL-17 and transforming growth factor-ß1 gene expression in lung tissue isolated from an allergic asthma murine model using TIMP-1 knockout. Gal-3 gene and protein expression levels were also significantly higher in lung tissue from an allergic asthma murine model using TIMP-1 knockout. Our data show that Gal-3 may regulate the IL-17 axis and play a pivotal role in the modulation of inflammation during experimental allergic asthma.