Optimizing warfarin and dual oral anticoagulation practices in an academic clinic during a merger amid the COVID-19 pandemic in a marginalized population.

BACKGROUND: The closure of a pharmacy-led anticoagulation clinic, which provided point-of-care (POC) international normalized ratio (INR) testing and face-to-face visits, coupled with the transition to an academic physician-led clinic without POC INR testing and reliance on telephone communication, created significant challenges for warfarin management during the Coronavirus disease 2019 pandemic. The aim of this quality control project was to increase the percentage of patients on warfarin within the optimal time in therapeutic range (TTR) from 52.30% to 65.00%, sustain baseline quarterly cumulative percentage TTR to 59.00%, and transition 20% of eligible patients from warfarin to dual oral anticoagulation (DOAC) within 12 months. METHODS: A multidisciplinary team employed a Fishbone diagram, stakeholder analysis, process flow map, and a driver diagram. Significant barriers included knowledge gaps, fear of blood draws, lack of POC INR testing, and noninteroperable electronic health records (EHRs). Primary outcome measures included quarterly cumulative percentage TTR, 2-monthly percentage TTR, and the percentage of eligible patients switched to DOAC. Process measures included INR completion rates. Key interventions involved educating patients and the care team, transitioning patients to DOAC, improving EHRs, and optimizing processes. Data analysis utilized run charts. RESULTS: Monthly INR completion rates rose from 63% to 87% within 12 months and reached 92% during the 6 months post-project period. Among 143 patients, 40.55% (58) were eligible for a DOAC switch, with 51.72% (30/58) successfully transitioning during the project and the 6-month post-project period. Two-monthly TTR rates improved from the baseline of 52.30% to 62.00% during the study period and remained sustainable at 62.80% in the post-project phase. Quarterly cumulative TTR rates remained stable at 59.20% during the study period in 2021. The quarterly cumulative TTR rates continued to increase at 60.50% and 64.40% in 2022 and 2023, respectively, during the post-project period. No bleeding episodes occurred during the 15-month post-project period. CONCLUSION: Multi-faceted strategies significantly improved warfarin safety during the project and maintained these improvements for 24 months. Transitioning from warfarin to DOACs was crucial for optimizing anticoagulation management with limited resources. The lead physician and team used various tools to address barriers to effective warfarin management, ensure appropriate DOAC prescribing, and enhance practices for DOAC prescriptions. This project effectively addressed barriers, improved population health, and provided a model for anticoagulation management in primary care settings.

Emergent and urgent ventral hernia repair: comparing recurrence rates amongst procedures utilizing mesh versus no mesh.

BACKGROUND: The decision for emergent and urgent ventral hernia repair (VHR) is driven by acute symptomatology, concern for incarceration and strangulation, and perforation. Although mesh has been established to reduce hernia recurrences, the potential for mesh complications may impact the decision for utilization in emergent repairs. This study evaluates hernia repair outcomes in the emergent setting with/without mesh. METHODS: An IRB-approved review of NSQIP and retrospective chart review data of emergent/urgent VHRs performed between 2013 and 2017 was conducted at a single academic institution. Six-month postoperative emergency department and surgery clinic visits, hospital readmissions, and hernia recurrences were recorded. Patients were grouped based on mesh utilization. Perioperative and outcome variables were compared using Chi-square, Fisher's exact, and t-tests. RESULTS: Among 94 patients, 41 (44%) received mesh; 53 (56%) did not. Synthetic mesh was used in 27 cases (65.9%); bioresorbable or biologic mesh was used in 14 cases (34.1%). ASA class (p = 0.016) was higher in the no-mesh group, as were emergent vs. urgent cases (p ≤ 0.001). Preoperative SIRS/Sepsis, COPD, and diabetes were increased in the no-mesh group. Hernia recurrence was significantly higher in the no-mesh group vs. the mesh group (24.5% vs. 7.3%, p = 0.03). No difference was found in wound complications between groups. ED visits occurred almost twice as often in the mesh group (42% vs. 23%, p = 0.071). Postoperative surgery clinic visits were more frequent among the mesh group (> 1 visit 61% vs. 24%, p = 0.004). CONCLUSIONS: Mesh-based hernia repairs in the urgent/emergent patient population are performed in fewer than half of patients in our tertiary care referral center. Repairs without mesh were associated with over a three-fold increase in recurrence without a difference in the risk of infectious complications. Efforts to understand the rationale for suture-based repair compared to mesh repair are needed to reduce hernia recurrences in the emergent population.

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.

The Effect of Lung Lavage Volume Return on the Diagnosis of Ventilator-Associated Pneumonia.

BACKGROUND: Bronchoalveolar lavage (BAL) is a commonly used tool in the diagnosis of ventilator-associated pneumonia (VAP). Previous protocols recommend 30% lavage return, though no studies have investigated this relationship. This study aims to assess the influence of BAL volume return on VAP diagnosis. MATERIALS AND METHODS: A retrospective review was performed of a prospectively maintained database for BAL performed from January 2015 to January 2016 in the trauma and surgical ICU at a level 1 trauma center. In total, 147 ventilated patients with clinical suspicion for pneumonia underwent 264 BALs. A protocol was used with five aliquots of 20 cc of saline instilled. Quantitative cultures were performed with 10ˆ5 colony-forming organisms as the threshold for VAP diagnosis. BAL was repeated at 6-8 d on 50 patients. Univariate and multivariate regression analyses were performed to investigate the predictors of VAP diagnosis. RESULTS: Patients with >40% lavage return had increased rates of VAP diagnosis (odds ratio [OR] 2.86, P = 0.002). Increasing volume return also trended toward a lower false-negative rate. Temperature, leukocytosis, and X-ray infiltrate were not associated with increased VAP diagnosis. Concurrent antibiotic therapy at the time of BAL predicted decreased VAP diagnosis (OR 0.58, P = 0.04). On multivariable analysis, only >40% return remained associated with increased rate of VAP diagnosis (OR 4.00, P = 0.004). CONCLUSIONS: This study found that >40% lavage volume return was associated with increased VAP diagnosis. Clinicians should consider the reliability of a negative BAL if clinical suspicion of VAP is high and lavage return is <40%. Additional investigation is needed to further elucidate this association.

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.

Characterisation of utrophin modulator SMT C1100 as a non-competitive inhibitor of firefly luciferase.

Firefly luciferase (FLuc) is a powerful tool for molecular and cellular biology, and popular in high-throughput screening and drug discovery. However, FLuc assays have been plagued with positive and negative artefacts due to stabilisation and inhibition by small molecules from a range of chemical classes. Here we disclose Phase II clinical compound SMT C1100 for the treatment of Duchenne muscular dystrophy as an FLuc inhibitor (KD of 0.40 ±â€¯0.15 µM). Enzyme kinetic studies using SMT C1100 and other non-competitive inhibitors including resveratrol and NFκBAI4 identified previously undescribed modes of inhibition with respect to FLuc's luciferyl adenylate intermediate. Employing a photoaffinity strategy to identify SMT C1100's binding site, a photolabelled SMT C1100 probe instead underwent FLuc-dependent photooxidation. Our findings support novel binding sites on FLuc for non-competitive inhibitors.

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.

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.

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.

BET bromodomain ligands: Probing the WPF shelf to improve BRD4 bromodomain affinity and metabolic stability.

Ligands for the bromodomain and extra-terminal domain (BET) family of bromodomains have shown promise as useful therapeutic agents for treating a range of cancers and inflammation. Here we report that our previously developed 3,5-dimethylisoxazole-based BET bromodomain ligand (OXFBD02) inhibits interactions of BRD4(1) with the RelA subunit of NF-κB, in addition to histone H4. This ligand shows a promising profile in a screen of the NCI-60 panel but was rapidly metabolised (t½â€¯= 39.8 min). Structure-guided optimisation of compound properties led to the development of the 3-pyridyl-derived OXFBD04. Molecular dynamics simulations assisted our understanding of the role played by an internal hydrogen bond in altering the affinity of this series of molecules for BRD4(1). OXFBD04 shows improved BRD4(1) affinity (IC50 = 166 nM), optimised physicochemical properties (LE = 0.43; LLE = 5.74; SFI = 5.96), and greater metabolic stability (t½â€¯= 388 min).

Solving the surgeon ergonomic crisis with surgical exosuit.

INTRODUCTION: The widespread adoption of laparoscopic surgery has put new physical demands on the surgeon leading to increased musculoskeletal disorders and injuries. Shoulder, back, and neck pains are among the most common complaints experienced by laparoscopic surgeons. Here, we evaluate the feasibility and efficacy of a non-intrusive progressive arm support exosuit worn by surgeons under the sterile gown to reduce pain and fatigue during surgery. METHODS AND PROCEDURES: This is a prospective randomized crossover study approved by the Internal Review Board (IRB). The study involves three phases of testing. In each phase, general surgery residents or attendings were randomized to wearing the surgical exosuit at the beginning or at the crossover point. The first phase tests for surgeon manual dexterity wearing the device using the Minnesota Dexterity test, the Purdue Pegboard test, and the Fundamentals of Laparoscopic Surgery (FLS) modules. The second phase tests the effect of the device on shoulder pain and fatigue while operating the laparoscopic camera. The third phase rates surgeon experience in the operating room between case-matched operating days. RESULTS: Twenty subjects were recruited for this study. Surgeons had the similar dexterity scores and FLS times whether or not they wore the exosuit (p value ranges 0.15-0.84). All exosuit surgeons completed 15 min of holding laparoscopic camera compared to three non-exosuit surgeons (p < 0.02). Exosuit surgeons experienced significantly less fatigue at all time periods and arm pain (3.11 vs 5.88, p = 0.019) at 10 min. Surgeons wearing the exosuit during an operation experienced significant decrease in shoulder pain and 85% of surgeons reported some form of pain reduction at the end of the operative day. CONCLUSION: The progressive arm support exosuit can be a minimally intrusive device that laparoscopic surgeons wear to reduce pain and fatigue of surgery without significantly interfering with operative skills or manual dexterity.

Immunomodulatory activities of curcumin-stabilized silver nanoparticles: Efficacy as an antiretroviral therapeutic.

We synthesized and characterized curcumin-stabilized silver nanoparticles (Cur-AgNP) and found them to be 45 nm by dynamic light scattering with a maximum absorbance at 406 nm. We evaluated Cur-AgNP for immunomodulatory activities and their potential as an antiretroviral agent. The antiretroviral effects of Cur-AgNP were determined in ACH-2 cells latently infected with human immunodeficiency virus (HIV)-1. ACH-2 cells, 200,000/ml, were treated with Cur-AgNP for 24-48 h. Expression of HIV-1 LTR and p24, the pro-inflammatory cytokines, IL-1ß, TNF-α, and NF-κB was quantitated. Treatment of ACH-2 cells latently infected with HIV-1 with Cur-AgNP produced no toxic effects but significantly inhibited the expression of HIV-1 LTR (-73%, P < 0.01) and p24 (-57%, P < 0.05), IL-1ßα (-61%, P < 0.01), TNF-αα (-54%, P < 0.05), IL-6 (-68%, P < 0.01), and NF-κB (-79%, P < 0.0001) as compared to untreated controls. Thus, Cur-AgNP have therapeutic potential as direct antiretroviral agents, as well as having immunomodulatory activities inhibiting the expression of pro-inflammatory mediators induced by infection with HIV-1. Experimental controls, such as curcumin alone, and conventional silver nanoparticles capped with citric acid, produced no similar biological effects. We conclude that treatment of HIV-1 infected cells with Cur-AgNP significantly reduced replication of HIV by inhibition of NF-κB nuclear translocation and the downstream expression of the pro-inflammatory cytokines IL-1ß, TNF-α, and IL-6. Subsequent in vivo studies with Cur-AgNP using a humanized mouse model of HIV infection are underway.

Efficacy of magnetic sphincter augmentation in patients with large hiatal hernias.

BACKGROUND: Magnetic sphincter augmentation (MSA) has demonstrated long-term safety and efficacy in the treatment of patients with gastroesophageal reflux (GERD), but its efficacy in patients with large hiatal hernias has yet to be proven. The aim of our study was to assess outcomes of MSA in patients with hiatal hernias ≥3 cm. METHODS: We retrospectively reviewed all patients who underwent MSA at our institutions over a 6-year period. Information obtained consisted of patient demographics, symptoms of GERD, preoperative GERD Health-Related Quality-of-Life (HRQL) scores, perioperative details, and implantation of the MSA device. Primary endpoints included postoperative GERD-HRQL scores, proton-pump inhibitor (PPI) use, symptom change, and procedure-related complications. A large hiatal hernia was defined as a hernia measuring ≥3 cm by intraoperative measurement. RESULTS: A total of 192 patients were reviewed. Median follow-up was 20 months (3-75 months). Mean GERD-HRQL scores in the overall population before and after MSA were 18.9 and 5.0, respectively (p < 0.001). In the majority of patients symptoms improved or resolved (N = 177, p < 0.001). Fifty-two patients (27.0 %) had a hiatal hernia ≥3 cm (range 3-7 cm). Their mean GERD-HRQL score decreased from 20.5 to 3.6 (p < 0.001) following MSA. When compared to patients with smaller hernias, patients with large hiatal hernias had decreased postoperative PPI requirement (9.6 vs. 26.6 %, p = 0.011) and lower mean postoperative GERD-HRQL scores (3.6 vs. 5.6, p = 0.027). The percent of patients requiring postoperative intervention for dysphagia was similar (13.5 vs. 17.9 %, p = 0.522), as was the incidence of symptom resolution or improvement (98.1 vs. 91.3 %, p = 0.118). CONCLUSION: MSA in patients with large hiatal hernias demonstrates decreased postoperative PPI requirement and mean GERD-HRQL scores compared to patients with smaller hernias. The incidence of symptom resolution or improvement and the percentage of patients requiring intervention for dysphagia are similar. Short-term outcomes of MSA are encouraging in patients with gastroesophageal reflux disease and large hiatal hernias.

Nanotherapy silencing the interleukin-8 gene produces regression of prostate cancer by inhibition of angiogenesis.

Interleukin-8 (IL-8) is a pro-angiogenic cytokine associated with aggressive prostate cancer (CaP). We detected high levels of IL-8 in sera from patients with CaP compared with healthy controls and patients with benign prostatic hypertrophy. This study examines the role of IL-8 in the pathogenesis of metastatic prostate cancer. We developed a biocompatible, cationic polylactide (CPLA) nanocarrier to complex with and efficiently deliver IL-8 small interfering RNA (siRNA) to CaP cells in vitro and in vivo. CPLA IL-8 siRNA nanocomplexes (nanoplexes) protect siRNA from rapid degradation, are non-toxic, have a prolonged lifetime in circulation, and their net positive charge facilitates penetration of cell membranes and subsequent intracellular trafficking. Administration of CPLA IL-8 siRNA nanoplexes to immunodeficient mice bearing human CaP tumours produced significant antitumour activities with no adverse effects. Systemic (intravenous) or local intra-tumour administration of IL-8 siRNA nanoplexes resulted in significant inhibition of CaP growth. Magnetic resonance imaging and ultrasonography of experimental animals demonstrated reduction of tumour perfusion in vivo following nanoplex treatment. Staining of tumour sections for CD31 confirmed significant damage to tumour neovasculature after nanoplex therapy. These studies demonstrate the efficacy of IL-8 siRNA nanotherapy for advanced, treatment-resistant human CaP.

Intraoperative assessment of the effects of laparoscopic sleeve gastrectomy on the distensibility of the lower esophageal sphincter using impedance planimetry.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has emerged as an effective weight-loss procedure for morbid obesity that is also effective for treating comorbidities such as diabetes. However, it has been associated with the development of GERD postoperatively. The pathophysiology of post-LSG GERD is unknown, and current studies have shown conflicting results. The aim of our study is to shed light on this issue by investigating the effect of LSG on the lower esophageal sphincter (LES) function and the relationship of LES function to GERD symptoms. METHODS: A prospective study of patients undergoing LSG from 10/2013 to 8/2014 at a single academic tertiary referral center was carried out. Patients undergoing a concomitant procedure such as hiatal hernia repair or laparoscopic gastric band removal were excluded. Distensibility of the LES was measured after pneumoperitoneum and after LSG. Baseline GERD-HRQL was obtained with follow-up GERD-HRQL and weight at 3 and 6 months. The primary outcomes measured were LES distensibility and GERD-HRQL scores after LSG. Our secondary outcome was a correlation between LES distensibility and GERD-HRQL scores after LSG. RESULTS: Fifteen subjects were enrolled (5M/10F). Mean age was 51 years (30-71 years), and mean BMI 45 kg/m2 (30-58). We were able to obtain follow-up data for all patients at 3 months. Mean LES distensibility increased from 1.2 before LSG to 2.2 after LSG (p = 0.017). Median GERD-HRQL was 0 before LSG and remained essentially negative at 1 and 0 (3 and 6 months postoperatively, respectively). Three (27 %) of the patients had de novo GERD at 3 months following LSG. One (25 %) patient had remission of GERD. There was no correlation between LES distensibility and GERD symptoms. CONCLUSION: While LSG weakens the LES immediately, it does not predictably affect postoperative GERD symptoms; therefore, distensibility is not the only factor affecting development of postoperative GERD, confirming the multifactorial nature of post-LSG GERD.

Charges, outcomes, and complications: a comparison of magnetic sphincter augmentation versus laparoscopic Nissen fundoplication for the treatment of GERD.

BACKGROUND: Magnetic sphincter augmentation (MSA) is approved for uncomplicated GERD. Multiple studies have shown MSA to compare favorably to laparoscopic Nissen fundoplication (LNF) in terms of symptom control with results out to 5 years. The MSA device itself, however, is an added cost to an anti-reflux surgery, and direct cost comparison studies have not been done between MSA and LNF. The aim of the study was to compare charges, complications, and outcome of MSA versus LNF at 1 year. METHODS: This is a retrospective analysis of all patients who underwent MSA or LNF for the treatment of GERD between January 2010 and June 2013. Patient charges were collected for the surgical admission. We also collected data on 30-day complications and symptom control at 1 year assessed by GERD-HRQL score and PPI use. RESULTS: There were 119 patients included in the study, 52 MSA and 67 LNF. There was no significant difference between the mean charges for MSA and LNF ($48,491 vs. $50,111, p = 0.506). There were significant differences in OR time (66 min MSA vs. 82 min LNF, p < 0.01) and LOS (17 h MSA vs. 38 h LNF, p < 0.01). At 1-year follow-up, mean GERD-HRQL was 4.3 for MSA versus 5.1 for LNF (p = 0.47) and 85 % of MSA patients versus 92 % of LNF patients were free from PPIs (p = 0.37). MSA patients reported less gas bloat symptoms (23 vs. 53 %, p ≤ 0.01) and inability to belch (10 vs. 36 %, p ≤ 0.01) and vomit (4 vs. 19 %, p ≤ 0.01). CONCLUSION: The side effect profile of MSA is better than LNF as evidenced by less gas bloat and increase ability to belch and vomit. LNF and MSA are comparable in symptom control, safety, and overall hospital charges. The charge for the MSA device is offset by less charges in other categories as a result of the shorter operative time and LOS.

Multi-institutional outcomes using magnetic sphincter augmentation versus Nissen fundoplication for chronic gastroesophageal reflux disease.

BACKGROUND: Magnetic sphincter augmentation (MSA) has emerged as an alternative surgical treatment of gastroesophageal reflux disease (GERD). The safety and efficacy of MSA has been previously demonstrated, although adequate comparison to Nissen fundoplication (NF) is lacking, and required to validate the role of MSA in GERD management. METHODS: A multi-institutional retrospective cohort study of patients with GERD undergoing either MSA or NF. Comparisons were made at 1 year for the overall group and for a propensity-matched group. RESULTS: A total of 415 patients (201 MSA and 214 NF) underwent surgery. The groups were similar in age, gender, and GERD-HRQL scores but significantly different in preoperative obesity (32 vs. 40 %), dysphagia (27 vs. 39 %), DeMeester scores (34 vs. 39), presence of microscopic Barrett's (18 vs. 31 %) and hiatal hernia (55 vs. 69 %). At a minimum of 1-year follow-up, 354 patients (169 MSA and 185 NF) had significant improvement in GERD-HRQL scores (pre to post: 21-3 and 19-4). MSA patients had greater ability to belch (96 vs. 69 %) and vomit (95 vs. 43 %) with less gas bloat (47 vs. 59 %). Propensity-matched cases showed similar GERD-HRQL scores and the differences in ability to belch or vomit, and gas bloat persisted in favor of MSA. Mild dysphagia was higher for MSA (44 vs. 32 %). Resumption of daily PPIs was higher for MSA (24 vs. 12, p = 0.02) with similar patient-reported satisfaction rates. CONCLUSIONS: MSA for uncomplicated GERD achieves similar improvements in quality of life and symptomatic relief, with fewer side effects, but lower PPI elimination rates when compared to propensity-matched NF cases. In appropriate candidates, MSA is a valid alternative surgical treatment for GERD management.

Morphine and galectin-1 modulate HIV-1 infection of human monocyte-derived macrophages.

Morphine is a widely abused, addictive drug that modulates immune function. Macrophages are a primary reservoir of HIV-1; therefore, they play a role in the development of this disease, as well as impact the overall course of disease progression. Galectin-1 is a member of a family of ß-galactoside-binding lectins that are soluble adhesion molecules and that mediate direct cell-pathogen interactions during HIV-1 viral adhesion. Because the drug abuse epidemic and the HIV-1 epidemic are closely interrelated, we propose that increased expression of galectin-1 induced by morphine may modulate HIV-1 infection of human monocyte-derived macrophages (MDMs). In this article, we show that galectin-1 gene and protein expression are potentiated by incubation with morphine. Confirming previous studies, morphine alone or galectin-1 alone enhance HIV-1 infection of MDMs. Concomitant incubation with exogenous galectin-1 and morphine potentiated HIV-1 infection of MDMs. We used a nanotechnology approach that uses gold nanorod-galectin-1 small interfering RNA complexes (nanoplexes) to inhibit gene expression for galectin-1. We found that nanoplexes silenced gene expression for galectin-1, and they reversed the effects of morphine on galectin-1 expression. Furthermore, the effects of morphine on HIV-1 infection were reduced in the presence of the nanoplex.

Multimodal nanoparticles that provide immunomodulation and intracellular drug delivery for infectious diseases.

Infectious diseases are a worldwide health concern. For some infections, a common feature is the intracellular residence of the pathogen and evasion of the host immune response. In the case of tuberculosis (TB), Mycobacterium tuberculosis evades clearance within macrophages through suppression of intracellular reactive oxygen and nitrogen species (ROS/RNS) and pro-inflammatory cytokines. We propose new nanoparticle designs for infectious diseases, functionalized with ligands able to modulate the cellular immune response and concurrently deliver drug. We have designed 1,3-ß-glucan functionalized chitosan shell, poly(lactide)co-glycolide core nanoparticles to stimulate ROS/RNS, pro-inflammatory cytokine secretion, and delivery of rifampicin inside human alveolar like macrophages (ALM). Nanoparticles significantly enhanced ALM secretion of IL-12p70 (2.9-fold), TNF-α (16-fold) and INF-γ (23-fold) compared to controls over 24h, and doubled ROS/RNS generation over 6h. Nanoparticles could deliver 4-fold greater rifampicin into ALM compared to rifampicin solution. These results provide proof-of-concept of multimodal nanoparticles and support their further development. FROM THE CLINICAL EDITOR: In this paper, a new nanoparticle design is proposed to address hard to treat infectious diseases such as TB, through the use of nanoparticles functionalized with ligands that are able to concurrently modulate the cellular immune response and deliver a drug. The authors have designed 1,3-ß-glucan functionalized chitosan shell - poly(lactide)co-glycolide core nanoparticles to stimulate reactive oxygen and nitrogen species production, pro-inflammatory cytokine secretion, and delivery of rifampicin inside human alveolar-like macrophages.

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.