Publications by authors named "Pragnesh Patel"

34 Publications

Trends in Incidence, and Mortality of Acute Exacerbation of Chronic Obstructive Pulmonary Disease in the United States Emergency Department (2010-2018).

COPD 2021 10 16;18(5):567-575. Epub 2021 Sep 16.

Division of Pulmonary and Critical Care Medicine, Wayne State University, Detroit, MI, USA.

Literature regarding trends of incidence, mortality, and complications of acute exacerbation of chronic obstructive pulmonary disease (COPD) in the emergency departments (ED) is limited. What are trends of COPD exacerbation in ED? Data were obtained from the Nationwide Emergency Department Sample (NEDS) that constitutes a 20% sample of hospital-owned EDs and inpatient sample in the US. All ED encounters were included in the analysis. Complications of AECOPD were obtained by using ICD codes. Out of 1.082 billion ED encounters, 5,295,408 (mean age 63.31 ± 12.63 years, females 55%) presented with COPD exacerbation. Among these patients, 353,563(6.7%) had AECOPD-plus (features of pulmonary embolism, acute heart failure and/or pneumonia) while 4,941,845 (93.3%) had exacerbation without associated features or precipitating factors which we grouped as AECOPD. The AECOPD-plus group was associated with statistically significantly higher proportion of cardiovascular complications including AF (5.6% vs 3.5%;  < 0.001), VT/VF (0.14% vs 0.06%;  < 0.001), STEMI (0.22% vs 0.11%;  < 0.001) and NSTEMI (0.65% vs 0.2%;  < 0.001). The in-hospital mortality rates were greater in the AECOPD-plus population (0.7% vs 0.1%;  < 0.001). The incidence of both AECOPD and AECOPD-plus had worsened (-trend 0.004 and 0.0003) and the trend of mortality had improved (-trend 0.0055 and 0.003, respectively). The prevalence of smoking for among all COPD patients had increased (-value 0.004), however, the prevalence trend of smoking among AECOPD groups was static over the years 2010-2018. There was an increasing trend of COPD exacerbation in conjunction with smoking; however, mortality trends improved significantly. Moreover, the rising burden of AECOPD would suggest improvement in diagnostics and policy making regarding management.
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http://dx.doi.org/10.1080/15412555.2021.1979500DOI Listing
October 2021

Merkel Cell Carcinoma in the Setting of Chronic Lymphocytic Leukemia and Diffuse Large B-Cell Lymphoma.

Cureus 2021 Aug 15;13(8):e17204. Epub 2021 Aug 15.

Internal Medicine, Wayne State University School of Medicine, Detroit, USA.

Merkel cell carcinoma (MCC) is a rare, rapidly growing, and highly malignant cutaneous tumor that typically presents in elderly males as an erythematous or violaceous plaque or nodule in sun-exposed areas. Risk factors include long-term ultraviolet (UV) exposure, Merkel cell polyomavirus (MCV) infection, immunosuppression, and lymphoproliferative disorders such as chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Given the aggressive nature of this tumor, patients may present with nodal and distal metastasis. Locoregional disease can be managed with definitive radiotherapy or surgery with or without adjuvant radiotherapy, depending on the case. Disseminated disease, on the other hand, often requires a multidisciplinary tumor board consultation to individually tailor the treatment. Possible treatments include systemic therapy with chemotherapy or immunotherapy, radiotherapy, and surgery. Here we report a case of a patient with a medical history significant for chronic lymphocytic leukemia and diffuse large B-cell lymphoma who presented with a rapidly growing lesion that contained neighboring MCC and CLL/SLL on biopsy. Management included immunotherapy with pembrolizumab and radiotherapy to limit the tumor's growth and spread. To the best of our knowledge, the coexistence of all three malignancies in a person is rare and has not been reported previously.
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http://dx.doi.org/10.7759/cureus.17204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8380460PMC
August 2021

Letter to the editor: Vitamin D levels in acute illness and clinical severity in COVID-19 patients.

Respir Res 2021 04 9;22(1):102. Epub 2021 Apr 9.

Department of Endocrinology, Wayne State University, Detroit, MI, USA.

We would like to comment on the recently published article titled: "Circulating Vitamin D levels status and clinical prognostic indices in COVID-19 patients" by Ricci et al. The authors grouped the patients into two groups according to the vitamin D levels measured at the time of admission into the hospital and reported that lower vitamin D levels are associated with elevated D-dimer and IL-6 levels, low CD4/CD8 ratio and compromised clinical findings with elevated LIPI and SOFA scores. However, review of recent literature shows this association to be debatable. The 25-hydroxyvitamin D levels in the initial phase of critical illness have been reported to drop rapidly and hence consideration of the time of measurement from symptom onset would have enhanced the clinical relevance of these findings. Inferred association between vitamin D levels and disease severity based on SOFA score in COVID-19 patients, needs to be further explored in the light of the recent literature which casts doubt on using SOFA score at admission to predict mortality in COVID-19.
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http://dx.doi.org/10.1186/s12931-021-01703-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032551PMC
April 2021

Cardiovascular Risk Among Patients ≥65 Years of Age with Parkinson's Disease (From the National Inpatient Sample).

Am J Cardiol 2020 12 15;136:56-61. Epub 2020 Sep 15.

Division of Cardiology, University of California, San Francisco, California.

In this study, we aimed to investigate the relationship between Parkinson's disease (PD) and vascular disease and risk factors using a nationally representative sample. The National Inpatient Sample was queried for all patients aged ≥65 who were diagnosed with PD during the year 2016. Patients were identified using the International Classification of Diseases-Tenth Revision (ICD-10) diagnosis code: "G20." Each patient diagnosed with PD was frequency-matched to controls at a 1:4 ratio by age and gender. Study outcomes were hypertension, hyperlipidemia, diabetes mellitus, coronary artery disease, and stroke. Outcomes were modeled using logistic regression analysis and further validation was obtained using a propensity score-matched analysis. A total of 57,914 patients (weighted: 289,570) with PD were included. Most patients were of Caucasian race (80.8%). Females were 42.4% and the mean age was 79 years, standard error of the mean (0.03). PD correlated with lower odds for hyperlipidemia adjusted odd ratio (a-OR): 0.77 (95% confidence interval [CI]: 0.75 to 0.79) p <0.001, diabetes mellitus a-OR 0.73 (95% CI 0.71 to 0.75) p <0.001, hypertension a-OR 0.68 (95% CI: 0.67 to 0.70) p <0.001, coronary artery disease a-OR 0.64 (95% CI: 0.63 to 0.66) p <0.001 and higher odds for stroke a-OR: 1.27 (95% CI: 1.24 to 1.31) p <0.001. Following propensity score matching, identical findings were found. In conclusion, patients with PD have a distinct cardiovascular profile with higher rates of stroke and lower rates of coronary artery disease and vascular disease risk factors.
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http://dx.doi.org/10.1016/j.amjcard.2020.09.021DOI Listing
December 2020

Impact of Malnutrition on Hospitalization Outcomes for Older Adults Admitted for Sepsis.

Am J Med 2021 02 15;134(2):221-226.e1. Epub 2020 Aug 15.

Division of Geriatrics, Wayne State University, MI, USA.

Background: Malnutrition is a major determinant of health outcomes among the older adult population. Our goal was to evaluate the impact of malnutrition on hospitalization outcomes for older adults who were admitted with a diagnosis of sepsis.

Methods: The National Inpatient Sample was queried for all patients who were admitted with a primary diagnosis of sepsis from January to December 2016. These patients were identified using the International Classification of Diseases, Tenth Revision (ICD-10) diagnosis code A419. Patients who were diagnosed with malnutrition were identified using ICD-10 codes E43, E440, E441, E45, and E46. Outcomes of hospitalization were modeled using logistic regression for binary outcomes and generalized linear models for continuous outcomes.

Results: Overall, a total of 808,030 patients were admitted for sepsis. Those diagnosed with malnutrition were 15.6% (126,335) of the total. The mean age (standard error of the mean) was 78 years (0.03). On multivariate analysis, malnutrition correlated with increased odds for mortality: adjusted OR (aOR) 1.20; 95% confidence interval [CI], 1.15-1.26; P < .001; septic shock: aOR 1.50; 95% CI, 1.44-1.57; P < .001; and intubation: aOR 1.45; 95% CI, 1.38-1.52; P < .001. It was also associated with higher odds for acute kidney injury and stroke. Malnutrition correlated with a 53% increase in the length of stay, with mean ratio 1.53; 95% CI, 1.51-1.56; P < .01; and a 54% increase in cost, with mean cost ratio 1.54; 95% CI, 1.51-1.58; P < .001.

Conclusion: Among the geriatric population diagnosed with sepsis, malnutrition is an independent predictor for poor hospitalization outcomes.
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http://dx.doi.org/10.1016/j.amjmed.2020.06.044DOI Listing
February 2021

A Case of COVID-19 Infection With Delayed Thromboembolic Complication on Warfarin.

Cureus 2020 Jun 26;12(6):e8847. Epub 2020 Jun 26.

Internal Medicine, Wayne State University, Detorit, USA.

Novel coronavirus disease 2019 (COVID-19) pandemic has posed an unprecedented threat to humanity with more than eight million infections and 450,000 deaths reported worldwide so far. The spectrum of the disease varies from mild asymptomatic infection to severe disease with rapid progression to acute respiratory distress syndrome and multiorgan failure. It is associated with a prothrombotic state and hence there is a risk of thromboembolic complications in critically ill patients, even after recovery. However, the duration of prothrombotic risk after recovery is yet to be determined. We present the case of a 78-year-old man with a history of atrial fibrillation on warfarin who had been recently discharged to a nursing home after recovering from COVID-19 pneumonia and presented to the emergency department a month later with worsening shortness of breath and cough. He was found to have worsening respiratory failure with multiple segmental pulmonary emboli, despite being on warfarin, and supratherapeutic international normalized ratio (INR). He required mechanical ventilation and was started on steroids and therapeutic enoxaparin anticoagulation. This case highlights the risk of delayed thromboembolic complications in patients with COVID-19 infection and the need to identify the subgroup of patients with a higher risk of thromboembolism, such as discharges to nursing homes and those in need of oxygen requirement; and those with underlying comorbid conditions that may require anticoagulation for a longer duration. The role of heparin is being increasingly investigated in patients with COVID-19 infection; however, the role of other anticoagulants such as warfarin is yet to be defined.
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http://dx.doi.org/10.7759/cureus.8847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325392PMC
June 2020

Relation of Age to Survival in Patients with Obstructive Sleep Apnea who Develop an Acute Coronary Event (from the National Inpatient Sample).

Am J Cardiol 2020 05 5;125(10):1571-1576. Epub 2020 Mar 5.

Advocate Illinois Masonic Medical Center, Chicago, Illinois; University of California, San Francisco, California.

This study was undertaken to investigate whether obstructive sleep apnea (OSA) produces a survival advantage in acute coronary syndrome (ACS), and to evaluate the mechanism of any benefit, including the impact of age and other risk factors. The National Inpatient Sample was queried for all patients who were admitted for ACS during the years 2013 to 2014. The primary outcomes were all-cause in-hospital mortality and cardiogenic shock (CS). Multivariable logistic regression was used for analysis. A total of 1,080,340 patients with ACS were included, 63,255 patients had OSA. The majority of patients were males (60.3%) and of Caucasian race (75%). The mean age was 67 years (SEM: 0.1). Despite a higher burden of risk factors and older age, OSA patients had a lower risk for mortality and cardiogenic shock adjusted OR 0.68 (95%CI 0.61-0.75), p <0.001 and 0.81 (95%CI: 0.74 to 0.89), p <0.001 respectively. Age was an important effect modifier. Survival advantage and lower risk for CS arises at the age above 55 and become more apparent with increasing age. In conclusion, despite a higher CV risk profile, and older age, OSA produces a survival benefit in ACS. Age is a significant modifier of risk in OSA patients with ACS. Ischemic preconditioning might explain these results.
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http://dx.doi.org/10.1016/j.amjcard.2020.02.011DOI Listing
May 2020

Association of Hospital Readmissions and Survivability With Frailty and Palliative Performance Scores Among Long-Term Care Residents.

Am J Hosp Palliat Care 2020 Sep 1;37(9):716-720. Epub 2020 Mar 1.

Department of Internal Medicine/Geriatrics, Wayne State University School of Medicine, Detroit, MI, USA.

Background: Frailty and palliative performance scores are 2 markers used in the measurement of functional decline in oncology and hospice care.

Objective: To evaluate the frailty and palliative performance scores of a long-term care resident community and determine whether frailty and palliative performance scores can predict hospital readmissions (HR) and survivability of the long-term care resident.

Methods: One hundred seventy-one long-term care residents from 2 urban facilities were evaluated for functional decline using the Clinical Frailty Scale (CFS) and Palliative Performance Scale (PPS). Sociodemographic, HR, and survival data for 1 year from study initiation were recorded.

Results: The 171 long-term care residents, of lower socioeconomic status, primarily Medicare/Medicaid or dual-eligible, evaluated for functional decline using the CFS and PPS, had mean age of 73.1 years, 52.6% female, 94.7% African American, with 18.1% having HR and 87.1% surviving more than a year. There was a negative association between age and HR ( = .384). Among functional evaluation scales, CFS was positively associated with age ( = .013) but not PPS ( = .673). The residents scored 6.0 ± 1.2 on CFS and 52.8 ± 13.2 on PPS (%) with those residents readmitted to hospital having poorer outcomes. Readmission to hospital and survivability of the long-term care resident were both strongly associated with CFS ( = .001) and PPS ( = .001).

Conclusion: There is a strong association between the 2 markers used in the measurement of functional decline- measured by CFS and measured by PPS. Frailty and palliative performance scores can strongly predict HR and survivability of the long-term care resident.
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http://dx.doi.org/10.1177/1049909120907602DOI Listing
September 2020

Detecting Prefrailty: Comparing Subjective Frailty Assessment and the Paulson-Lichtenberg Frailty Index.

Gerontol Geriatr Med 2020 Jan-Dec;6:2333721420904234. Epub 2020 Feb 1.

Wayne State University, Detroit, MI, USA.

We examined the level of agreement between subjective frailty assessments (SFA) and frailty classifications derived from the validated Paulson-Lichtenberg Frailty Index (PLFI). Clinic patients ( = 202) were classified as healthy, prefrail, or frail first by screening using the PLFI and later by two geriatric nurses and two geriatricians according to SFA. Of the 202 participants (mean age = 76.7 ± 8.6), 52 (26%) were prefrail and 57 (28%) were frail based on the PLFI. Geriatrician SFA aligned with the PLFI in 43.0% of prefrail and 65.7% of frail cases. Nurse SFA aligned with the PLFI in 43.9% of prefrail and 17.0% of frail cases. There was slight-to-fair agreement between SFA and PLFI (geriatrician: Cohen's κ = .23; 95% confidence interval (CI) = [.11, .35], < .001; nurse: Cohen's κ = .20; 95% CI = [.08, .33], = .001). Clinician SFA did not align well with PLFI classifications.
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http://dx.doi.org/10.1177/2333721420904234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003161PMC
February 2020

Feasibility of a Habit Formation Intervention to Delay Frailty Progression Among Older African Americans: A Pilot Study.

Gerontologist 2020 09;60(7):1353-1363

School of Medicine, Wayne State University, Detroit, Michigan.

Background And Objectives: Older African Americans are at high risk for becoming frail in later life. Interventions can reverse or delay frailty, yet African Americans have largely been excluded from such research. Many interventions are also time- and resource-intensive, and thus inaccessible to socially disadvantaged older African Americans. We evaluated the feasibility of a low-dose frailty prevention intervention integrated with primary care among 60 community-dwelling, prefrail older African Americans aged 55+ recruited from a primary care clinic.

Research Design And Methods: We conducted a 2-arm randomized control trial. Participants were assigned to a 4-session intervention (1 session per month), delivered by an occupational therapist, or enhanced usual care. Feasibility criteria were set a priori at 75% for participant retention (including attrition due to death/hospitalization), 80% for session engagement, 2 participants/week for mean participant accrual, and 90% for program satisfaction.

Results: Participants were 65% female with an average age of 76.6 years, 51.7% lived alone and 39.1% reported <$10,000 in yearly income. Feasibility metrics were met. The study recruited, a mean of, 2.5 participants per week and retained 75% of participants who attended 95% of scheduled sessions. The mean satisfaction score was 29.75 (range = 0-32; SD .25). Changes in physical activity and dietary habit formation as well as changes in secondary outcomes were largely in the expected direction.

Discussion And Implications: The intervention was feasible to deliver. Qualitative findings from exit interviews suggested changes to the program dose, structure, and content that could improve it for future use.
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http://dx.doi.org/10.1093/geront/gnz143DOI Listing
September 2020

Gastric Siderosis and Ulceration from Intravenous Iron Supplementation Manifesting as Chronic Upper Gastrointestinal Bleeding: A Case Report and Review of the Literature.

Case Rep Gastrointest Med 2019 18;2019:1790686. Epub 2019 Apr 18.

Houston Methodist Hospital, Department of Pathology and Genomic Medicine, 6550 Fannin St., Houston, TX 77030, USA.

Iron deficiency is the most common etiology of anemia worldwide and is often managed with varying methods of iron supplementation. Although rare, oral iron supplementation can perpetuate iron deficiency anemia by causing gastric ulceration and upper gastrointestinal bleeding in high-risk populations. However, this complication has not been previously described with intravenous iron supplementation. We present a case of a 63-year-old male with severe iron deficiency anemia on biweekly intravenous iron infusions and weekly packed red blood cell transfusions who presented with melena over several months. Upper endoscopy demonstrated a clean-based gastric body ulcer and nonbleeding gastric varices. Histology of the gastric ulcer was suggestive of iron-induced gastric mucosal injury. This case demonstrates that frequent utilization of intravenous iron and packed red blood cell transfusions may predispose certain patients to the development of iron-induced gastritis and ulceration.
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http://dx.doi.org/10.1155/2019/1790686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6500599PMC
April 2019

Liposomes produced by microfluidics and extrusion: A comparison for scale-up purposes.

Nanomedicine 2019 06 13;18:146-156. Epub 2019 Mar 13.

Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University/OHSU, Portland, OR, USA. Electronic address:

Successful liposomal formulations in the clinic are severely limited due to poor translational capability of the traditional bench techniques to clinical production settings. The gold standard for liposome bench manufacturing is a multi-step and parameter dependent extrusion method. Moreover, these parameters need re-optimization for clinical production. The microfluidics technique utilizes vigorous mixing of fluids at a nanoliter scale to produce liposomes in batches from milliliters to a couple liters. The fine control of process parameters results in improved reproducibility between batches. It is inherently scalable; however, the characteristics of liposomes produced by microfluidics both in vitro and in vivo have never been compared to those produced using extrusion. In this manuscript, we describe the comparison between the traditional extrusion method to microfluidics, the new paradigm in liposome production and scale-up.
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http://dx.doi.org/10.1016/j.nano.2019.02.019DOI Listing
June 2019

Liposomal formulation of hypoxia activated prodrug for the treatment of ovarian cancer.

J Control Release 2018 12 16;291:169-183. Epub 2018 Oct 16.

Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University/OHSU, Portland, OR, USA. Electronic address:

In this work, a new sphingomyelin-cholesterol liposomal formulation (CPD100Li) for the delivery of a hypoxia activated prodrug of vinblastine, mon-N-oxide (CPD100), is developed. The optimized liposomal formulation uses an ionophore (A23187) mediated pH-gradient method. Optimized CPD100Li is characterized for size, drug loading, and stability. The in vitro toxicity of CPD100Li is assessed on different aspects of cell proliferation and apoptosis of ES2 ovarian cancer under normoxic and hypoxic conditions. The pharmacokinetics of CPD100Li in mice as well as the influence of A23187 on the retention of CPD100 are assessed. The dose limiting toxicity (DLT) and maximum tolerated dose (MTD) for CPD100Li are evaluated in nude mice. CPD100 is loaded in the liposome at 5.5 mg/mL. The sizes of CPD100Li using DLS, qNano and cryo-TEM techniques are 155.4 ± 4.2 nm, 132 nm, and 112.6 ± 19.8 nm, respectively. There is no difference between the in vitro characterization of CPD100Li with and without ionophore. Freshly prepared CPD100Li with ionophore are stable for 48 h at 4 °C, while the freeze-dried formulation is stable for 3 months under argon at 4 °C. The hypoxic cytotoxicity ratios (HCR) of CPD100 and CPD100Li are 0.16 and 0.11, respectively. CPD100Li under hypoxic conditions has a 9.2-fold lower IC value as compared to CPD100Li under normoxic conditions, confirming the hypoxia dependent activation of CPD100. CPD100Li treated ES2 cells show a time dependent enhanced cell death, along with caspase production and an increase in the number of cells in G/G and higher cell arrest. The blood concentration profile of CPD100Li in mice without A23187 has a 12.6-fold lower area under the curve (AUC) and 1.6-fold lower circulation time compared to the CPD100Li with A23187. The DLT for both CPD100 and CPD100Li is 45 mg/kg and the MTD is 40 mg/kg in nude mice. Based on the preliminary data obtained, we clearly show that the presence of ionophore affects the in vivo stability of CPD100. CPD100Li presents a unique opportunity to develop a first-in-kind chemotherapy product based on achieving selective drug activation through the hypoxic physiologic microenvironment of solid tumors.
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http://dx.doi.org/10.1016/j.jconrel.2018.10.021DOI Listing
December 2018

Health literacy, preventive health screening, and medication adherence behaviors of older African Americans at a PCMH.

Am J Manag Care 2018 09;24(9):428-432

9D - Wayne State University Health Center, 4201 Saint Antoine Dr, Detroit, MI 48201-2153. Email:

Objectives: To determine the health literacy (HL) of older African Americans (AAs) and establish whether associations exist between HL and preventive health screening (PHS) behaviors, disease control (DC), and medication adherence (MA).

Study Design: A prospective study using a clustered sampling of older AAs.

Methods: A total of 99 older AAs seeking care at a patient-centered medical home were given the Newest Vital Sign (NVS), Short Test of Functional Health Literacy in Adults (STOFHLA), and Morisky Medication Adherence Scale (MMAS). Sociodemographic and clinical data were obtained.

Results: The group was 75.8% female, with means of 75 years of age, 12.7 years education, and 29.5 kg/m2 body mass index and good control over disease markers: For blood pressure, 62.6% had good control; for blood glucose, 82.8%; and for total lipids/cholesterol, 63.6% (high-density lipoprotein, 81.8%; low-density lipoprotein, 73.7%). Compliance rates for primary PHS behaviors were 61.6% for influenza vaccine and 57.7% for pneumococcal vaccine. For secondary PHS behaviors, compliance rates for mammography were 97.3% among women; for colonoscopy, 84%; and for bone densitometry (BD), 62.8%. Performance differences were observed on HL scales, with 31.3% and 73.7% obtaining an adequate NVS score and STOFHLA score, respectively, but no gender differences were noted. HL scales showed positive association among themselves (P = .001), patient education (NVS, P = .001; STOFHLA, P = .004), MMAS (P = .001 and P = .563, respectively), anthropometry measurements, primary PHS procedures, and 1 secondary PHS procedure (mammography), but they exhibited negative association with colonoscopy and BD. DC achieved using a PHS approach to clinical care was not associated with HL.

Conclusions: HL was positively associated with patient education, some PHS behaviors, and MA. Performance on HL scales may not enable positive identification of PHS behaviors, DC, and MA. Thus, HL may have limited efficacy as a tool to assess PHS behaviors and DC among older AAs.
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September 2018

Insomnia in the Elderly: A Review.

J Clin Sleep Med 2018 06 15;14(6):1017-1024. Epub 2018 Jun 15.

Department of Geriatrics, Wayne State University School of Medicine, Detroit, Michigan.

Background: Insomnia remains one of the most common sleep disorders encountered in the geriatric clinic population, frequently characterized by the subjective complaint of difficulty falling or maintaining sleep, or nonrestorative sleep, producing significant daytime symptoms including difficulty concentrating and mood disturbances.

Methods: A search of the literature was conducted to review the epidemiology, definition, and age-related changes in sleep, as well as factors contributing to late-life insomnia and scales utilized for the assessment of insomnia in older people. The aim is to summarize recent diagnostic guidelines and both nonpharmacological and pharmacological strategies for the management of insomnia in the older population.

Results: Insomnia remains a clinical diagnosis. There are several demographic, psychosocial, biologic, and behavioral factors that can contribute to late-life insomnia. Older adults are at higher risk for the medical and psychiatric effects of insomnia.

Conclusions: The most important aspect in evaluation of insomnia is detailed history taking and thorough physical examination. Nonpharmacological treatment options have favorable and enduring benefits compared to pharmacological therapy.
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http://dx.doi.org/10.5664/jcsm.7172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5991956PMC
June 2018

Apnea in Older Adults.

Sleep Med Clin 2018 Mar 10;13(1):21-37. Epub 2017 Nov 10.

Sleep Medicine Section, John D. Dingell VA Medical Center, Detroit, MI 48201, USA; Department of Medicine, Wayne State University, Detroit, MI 48201, USA.

Sleep-disordered breathing (SDB) is a highly prevalent chronic disease in older adults. A growing body of evidence demonstrates that SDB in older adults is linked to many adverse cardiovascular, neurocognitive, and metabolic sequelae. However, several unanswered questions remain regarding the diagnosis, consequences, and treatment of SDB in older adults. This review presents the current evidence pertaining to the management of SDB in older adults and identifies crucial gaps in knowledge that need further investigation.
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http://dx.doi.org/10.1016/j.jsmc.2017.09.003DOI Listing
March 2018

High-Resolution Single Particle Zeta Potential Characterisation of Biological Nanoparticles using Tunable Resistive Pulse Sensing.

Sci Rep 2017 12 12;7(1):17479. Epub 2017 Dec 12.

Izon Science Limited, 8C Homersham Place, PO Box 39168, Burnside, Christchurch 8053, New Zealand.

Physicochemical properties of nanoparticles, such as size, shape, surface charge, density, and porosity play a central role in biological interactions and hence accurate determination of these characteristics is of utmost importance. Here we propose tunable resistive pulse sensing for simultaneous size and surface charge measurements on a particle-by-particle basis, enabling the analysis of a wide spectrum of nanoparticles and their mixtures. Existing methodologies for measuring zeta potential of nanoparticles using resistive pulse sensing are significantly improved by including convection into the theoretical model. The efficacy of this methodology is demonstrated for a range of biological case studies, including measurements of mixed anionic, cationic liposomes, extracellular vesicles in plasma, and in situ time study of DNA immobilisation on the surface of magnetic nanoparticles. The high-resolution single particle size and zeta potential characterisation will provide a better understanding of nano-bio interactions, positively impacting nanomedicine development and their regulatory approval.
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http://dx.doi.org/10.1038/s41598-017-14981-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5727177PMC
December 2017

Use of quantitative endoscopic ultrasound elastography for diagnosis of pancreatic neuroendocrine tumors.

Endosc Ultrasound 2016 Sep-Oct;5(5):342-345

Department of Gastroenterology, Hepatology and Nutrition, Ertan Digestive Disease Center, Memorial Hermann Hospital, University of Texas Health Science Center at Houston, Houston, Texas, USA.

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http://dx.doi.org/10.4103/2303-9027.191680DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5070294PMC
November 2016

Thymic carcinoma diagnosed by using endoscopic ultrasound with fine-needle aspiration.

Endosc Ultrasound 2016 May-Jun;5(3):206-9

Department of Gastroenterology and Hepatology, University of Texas Health Science Center at Houston, Texas, USA.

There is a paucity of literature on the use of endoscopic ultrasound (EUS) for evaluating superior mediastinal structures, especially the thymus gland. We report a case of thymic carcinoma diagnosed by using EUS elastography with strain ratio and fine-needle aspiration (FNA). A 64-year-old woman presented with altered mental status and was diagnosed with autoimmune encephalitis. Further work-up suggested a superior mediastinal mass, for which she underwent EUS. A hypoechoic mass was found in the superior mediastinum at the level of the aortic arch. Real-time EUS elastography showed a predominantly blue hue to the mass concerning for malignancy. FNA of the mass was performed, which revealed numerous large neoplastic cells under a background of a small lymphoid infiltrate. Immunohistochemistry was strongly positive for PAX8, pancytokeratin, and CAM5.2. The pathologic and immunohistochemical stains were consistent with thymic carcinoma.
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http://dx.doi.org/10.4103/2303-9027.183975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4918306PMC
July 2016

Alcohol withdrawal syndrome in medical patients.

Cleve Clin J Med 2016 Jan;83(1):67-79

Clinical Pharmacist Specialist in Internal Medicine, Harper University Hospital, Detroit, MI, USA.

The authors provide a critical review focusing on pharmacotherapy of alcohol withdrawal syndrome in hospitalized patients who are not critically ill. They outline recommendations for patient assessment and monitoring.
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http://dx.doi.org/10.3949/ccjm.83a.14061DOI Listing
January 2016

Ameliorative Effects of Curcumin on Artesunate-Induced Subchronic Toxicity in Testis of Swiss Albino Male Mice.

Dose Response 2015 Apr-Jun;13(2):1559325815592393. Epub 2015 Jun 26.

Department of Zoology and BMT, Gujarat University, Ahmedabad, Gujarat, India.

India is one of the endemic areas where control of malaria has become a formidable task. Artesunate is the current antimalarial drug used to treat malaria, especially chloroquine resistant. The objective of the present study was to investigate the dose-dependent effect of oral administration of artesunate on the oxidative parameters in testes of adult male Swiss albino mice and ameliorative efficacy of curcumin, a widely used antioxidant. An oral dose of 150 mg/kg body weight (bwt; low dose) and 300 mg/kg bwt (high dose) of artesunate was administered for a period of 45 days to male mice, and ameliorative efficacy of curcumin was also assessed. The results revealed that artesunate caused significant alteration in oxidative parameters in dose-dependent manner. Administration of artesunate brought about significant decrease in activities of superoxide dismutase, glutathione, glutathione peroxidase, and glutathione reductase, whereas lipid peroxidation and glutathione-S-transferase activity were found to be significantly increased. The results obtained show that oxidative insult is incurred upon the intracellular antioxidant system of testis tissue by artesunate treatment. Further, administration of curcumin at the dose level of 80 mg/kg bwt along with both doses of artesunate attenuated adverse effects in male mice.
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http://dx.doi.org/10.1177/1559325815592393DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4674183PMC
December 2015

An unusual case of pneumoperitoneum, pneumomediastinum, and subcutaneous emphysema following colorectal stent placement.

Endoscopy 2015 30;47 Suppl 1 UCTN:E173-4. Epub 2015 Apr 30.

Division of Gastroenterology and Hepatology, University of Texas Health Science Center at Houston, Texas, United States.

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http://dx.doi.org/10.1055/s-0034-1391497DOI Listing
December 2015

Health literacy and cardiovascular disease risk factors among the elderly: a study from a patient-centered medical home.

Am J Manag Care 2015 Feb;21(2):140-5

Division of Geriatric Medicine, Ste 5C, Wayne State University Health Center, 4201 Saint Antoine Dr, Detroit, MI 48201-2153. E-mail:

Background: Health literacy (HL) influences the use of healthcare, facilitates comprehension of health risk behaviors and subsequent vulnerabilities, and provides an impetus to seek improved health outcomes with lower cost of care.

Objectives: To determine the HL level of elderly patients and establish whether an association exists between HL and cardiovascular disease risk factors (CVDRFs).

Methods: A total of 150 elderly patients seeking care at a patient-centered medical home (PCMH) were administered the Nutritional Literacy Scale (NLS) and Short Test of Functional Health Literacy in Adults (STOFHLA). Sociodemographic, physiological, biochemical, and disease profile data were obtained.

Results: The patients were 68.7% female, 67.3% African American, 4.7% smokers, and 72.5% overweight. They had a mean age of 74.6 years, 13.2 years education, body mass index of 28.9 kg/m2, systolic blood pressure of 138.5 mm Hg, diastolic blood pressure of 70.7 mm Hg, fasting blood glucose of 100.6 mg/dL, and glycated hemoglobin of 6.6%. Their mean lipid values were: total cholesterol (TC), 188.0 mg/dL; high-density lipoprotein cholesterol, 54.3 mg/dL; low-density lipoprotein (LDL) cholesterol, 111.8 mg/dL; and triglycerides, 115.8 mg/dL. The cohort had 88% hypertensives and 32% diabetics. They scored a mean of 20.9 on the NLS and 29.6 on STOFHLA, with 16% lacking adequate scores on both scales. Lower education attainment was linked to higher TC (P = .027) and LDL cholesterol (P = .023), but no association was observed between HL and all the independent CVDRFs evaluated.

Conclusions: The study shows that a majority of the participating elderly PCMH patients had a higher level of education (≥12 years) and an adequate level of HL. A higher level of education, but not HL, appears to be predictive of a better control of CVDRFs.
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February 2015

Dieulafoy-like lesion bleeding: in the loop.

Gastroenterol Hepatol (N Y) 2011 Apr;7(4):271-4

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3127032PMC
April 2011

Testing the utility of the newest vital sign (NVS) health literacy assessment tool in older African-American patients.

Patient Educ Couns 2011 Dec 21;85(3):505-7. Epub 2011 Apr 21.

Department of Internal Medicine, Division of Geriatrics, Wayne State University, Detroit, MI, USA.

Objective: To evaluate utility of the newest vital sign (NVS) which can be completed in 3min compared to the short version test of functional literacy in adults (S-TOFHLA) that takes 7min for health literacy in the older African American patients.

Methods: We enrolled 62 older (age>65 years) African American patients and administered the NVS and the S-TOFHLA. A score of less than 4 for the NVS and less than 16 for the S-TOFHLA was indicative of limited health literacy.

Results: Mean age of our patients was 73.2+7.9 years with an average education level of twelfth grade. Using S-TOFHLA 51% of the subjects were deemed to be sufficiently literate, with a score of 23.0+8.6 compared to 56% on the NVS with a score of 3.0+1.9. The average time for completing the NVS was 11min in our patient population.

Conclusion: Based on our data, while health literacy level can be assessed with the NVS its practicality as a quick screening tool in the elderly population appears limited.

Practice Implications: Knowing the level of patient's health literacy may help physicians deliver health information in the format that patients can understand.
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http://dx.doi.org/10.1016/j.pec.2011.03.014DOI Listing
December 2011

Nanofiltered C1 inhibitor concentrate for treatment of hereditary angioedema.

N Engl J Med 2010 Aug;363(6):513-22

University of California, San Diego, USA.

Background: Hereditary angioedema due to C1 inhibitor deficiency is characterized by recurrent acute attacks of swelling that can be painful and sometimes life-threatening.

Methods: We conducted two randomized trials to evaluate nanofiltered C1 inhibitor concentrate in the management of hereditary angioedema. The first study compared nanofiltered C1 inhibitor concentrate with placebo for treatment of an acute attack of angioedema. A total of 68 subjects (35 in the C1 inhibitor group and 33 in the placebo group) were given one or two intravenous injections of the study drug (1000 units each). The primary end point was the time to the onset of unequivocal relief. The second study was a crossover trial involving 22 subjects with hereditary angioedema that compared prophylactic twice-weekly injections of nanofiltered C1 inhibitor concentrate (1000 units) with placebo during two 12-week periods. The primary end point was the number of attacks of angioedema per period, with each subject acting as his or her own control.

Results: In the first study, the median time to the onset of unequivocal relief from an attack was 2 hours in the subjects treated with C1 inhibitor concentrate but longer than 4 hours in those given placebo (P=0.02). In the second study, the number of attacks per 12-week period was 6.26 with C1 inhibitor concentrate given as prophylaxis, as compared with 12.73 with placebo (P<0.001); the subjects who received the C1 inhibitor concentrate also had significant reductions in both the severity and the duration of attacks, in the need for open-label rescue therapy, and in the total number of days with swelling.

Conclusions: In subjects with hereditary angioedema, nanofiltered C1 inhibitor concentrate shortened the duration of acute attacks. When used for prophylaxis, nanofiltered C1 inhibitor concentrate reduced the frequency of acute attacks. (Funded by Lev Pharmaceuticals; ClinicalTrials.gov numbers, NCT00289211, NCT01005888, NCT00438815, and NCT00462709.)
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http://dx.doi.org/10.1056/NEJMoa0805538DOI Listing
August 2010

Prevalence of GH and other anterior pituitary hormone deficiencies in adults with nonsecreting pituitary microadenomas and normal serum IGF-1 levels.

Clin Endocrinol (Oxf) 2008 Aug 25;69(2):292-8. Epub 2008 Jan 25.

Department of Endocrinology, Oregon Health and Science University, Portland, OR 97239-3098, USA.

Objective: GH is usually the first pituitary hormone to be affected following a pathological insult to the pituitary; however, data on the prevalence of GH deficiency in patients with nonsecreting pituitary microadenomas and normal serum IGF-1 levels are scarce. This study aims to evaluate the prevalence of GH and other anterior pituitary hormone deficiencies, and to determine whether microadenomas per se could be associated with reduced GH response rates to GHRH-arginine stimulation.

Design: Analytical, retrospective, two-site case-control study.

Patients And Methods: Thirty-eight patients with nonsecreting pituitary microadenomas (mean size 4.2 mm) and normal serum IGF-1 levels were studied. Anterior pituitary function testing, including the GHRH-arginine test to examine GH reserve, was performed in all patients. Serum IGF-1 levels and peak GH levels in the patients that passed the GHRH-arginine test were compared with 22 age- and BMI-matched healthy controls.

Results: Nineteen patients (50%) failed the GHRH-arginine test and had higher body mass index (BMI) than those that passed the GHRH-arginine test and healthy controls. Peak GH levels in patients that passed the GHRH-arginine test were lower compared to healthy controls and 19 patients (50%) had at least one other pituitary hormone deficit. A negative correlation (r = -0.42, P < 0.01) between peak GH levels and BMI was identified, but no correlations were found between peak GH and serum IGF-1 levels.

Conclusions: Our data demonstrated that a substantial number of patients with nonsecreting pituitary microadenomas failed the GHRH-arginine test despite normal serum IGF-1 levels, and had at least one other pituitary hormone deficiency, suggesting that nonsecreting microadenomas may not be clinically harmless. We therefore recommend long-term follow-up with periodic basal pituitary function testing, and to consider dynamic pituitary testing should clinical symptoms arise in these patients.
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http://dx.doi.org/10.1111/j.1365-2265.2008.03201.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2953553PMC
August 2008

Design and statistical optimization of glipizide loaded lipospheres using response surface methodology.

Acta Pharm 2007 Sep;57(3):269-85

Department of Pharmaceutical, K.L.E.S's College of Pharmacy, Bangalore-560010, India.

A 32 factorial design was employed to produce glipizide lipospheres by the emulsification phase separation technique using paraffin wax and stearic acid as retardants. The effect of critical formulation variables, namely levels of paraffin wax (X1) and proportion of stearic acid in the wax (X2) on geometric mean diameter (dg), percent encapsulation efficiency (% EE), release at the end of 12 h (rel12) and time taken for 50% of drug release (t50), were evaluated using the F-test. Mathematical models containing only the significant terms were generated for each response parameter using the multiple linear regression analysis (MLRA) and analysis of variance (ANOVA). Both formulation variables studied exerted a significant influence (p < 0.05) on the response parameters. Numerical optimization using the desirability approach was employed to develop an optimized formulation by setting constraints on the dependent and independent variables. The experimental values of dg, % EE, rel12 and t50 values for the optimized formulation were found to be 57.54 +/- 1.38 mum, 86.28 +/- 1.32%, 77.23 +/- 2.78% and 5.60 +/- 0.32 h, respectively, which were in close agreement with those predicted by the mathematical models. The drug release from lipospheres followed first-order kinetics and was characterized by the Higuchi diffusion model. The optimized liposphere formulation developed was found to produce sustained anti-diabetic activity following oral administration in rats.
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http://dx.doi.org/10.2478/v10007-007-0022-8DOI Listing
September 2007

Dieulafoy's lesion-like bleeding: an underrecognized cause of upper gastrointestinal hemorrhage in patients with advanced liver disease.

Dig Dis Sci 2007 Mar;52(3):722-6

Division of Gastroenterology, John D. Dingell Veterans Administration Medical Center and Wayne State University School of Medicine, Detroit, Michigan 48201, USA.

Dieulafoy's lesion is a gastrointestinal submucosal artery that ruptures into the lumen causing massive hemorrhage. Until recently, failure to diagnose and treat patients endoscopically may have necessitated blind gastrectomy. Because arteriolar spider nevi abound in patients with liver disease and bleeding from such lesions has been described in the upper gastrointestinal tract, we reviewed our experience to determine whether a diagnosis of advanced liver disease could facilitate recognition and treatment of this type of arterial bleeding. Endoscopy records from 1991 to 1996 for all cases of upper gastrointestinal bleeding at our institution were reviewed. Dieulafoy's lesion-like bleeding was defined as arterial-type bleeding with no evidence of mucosal ulceration or erosions. Advanced liver disease was defined as signs of portal hypertension and/or cirrhosis or infiltrative liver disease. Dieulafoy's lesion-like bleeding was the cause in 6 of 4569 cases (0.13%). Five patients with Dieulafoy's lesion-like gastrointestinal hemorrhage had advanced liver disease compared with 954 of 4569 of all patients endoscoped for gastrointestinal hemorrhage for the period evaluated (OR = 19.04; 95% CI 2.1-900.8; p < 0.002 by Fisher's exact test). Dieulafoy's lesion-like bleeding was treated successfully with epinephrine injection and endoscopic cauterization in 5 of 6 patients with 1 patient requiring surgery. No other clinical associations were evident. Dieulafoy's lesion-like bleeding occurs more commonly in patients with advanced liver disease and should be included as a potential cause for bleeding in advanced liver disease and aggressively sought.
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http://dx.doi.org/10.1007/s10620-006-9468-7DOI Listing
March 2007

Endocytosis of extracellular superoxide dismutase into endothelial cells: role of the heparin-binding domain.

Arterioscler Thromb Vasc Biol 2006 Sep 29;26(9):1985-90. Epub 2006 Jun 29.

Cardiovascular Center and Department of Internal Medicine, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA.

Objective: Extracellular superoxide dismutase (EC-SOD) is a secreted antioxidant enzyme that binds to the outer plasma membrane and extracellular matrix through its heparin-binding domain (HBD). Carriers of a common genetic variant of EC-SOD (EC-SOD(R213G), within the HBD) have higher plasma concentration of EC-SOD and increased risk for vascular disease. In the present study, we used confocal fluorescence microscopy to examine mechanisms of endocytosis of EC-SOD to determine whether EC-SOD translocates to the nucleus of endothelial cells, and to test the hypothesis that EC-SOD, but not EC-SOD(R213G), is endocytosed into endothelial cells.

Methods And Results: Mouse endothelial cells (MS-1) were incubated with EC-SOD, EC-SOD(R213G), or HBD-deleted EC-SOD (EC-SODdeltaHBD). Binding to MS-1 was observed only with EC-SOD, but not EC-SOD(R213G) or EC-SODdeltaHBD. Endocytosis of EC-SODs was monitored after coincubation of MS-1 cells with EC-SODs and BSA-Texas Red (BSA-TR), which marks endosomes and lysosomes. Only EC-SOD was endocytosed, colocalizing with BSA-TR. EC-SOD also colocalized with early endosome antigen 1 (EEA-1), a specific marker for endocytosis. Endocytosis of EC-SOD was inhibited by chlorpromazine, but not by methyl-beta-cyclodextrin or nystatin, which suggests that endocytosis of EC-SOD is mediated by clathrin but not by caveolae. Minimal or no localization of EC-SOD in the nucleus of MS-1 cells was detected.

Conclusions: Our findings indicate that EC-SOD, but not EC-SOD(R213G), is endocytosed into endothelial cells through clathrin-mediated pathway, but does not translocate to the nucleus. We speculate that impairment of endocytosis may contribute to high plasma levels of EC-SOD(R213G) in R213G carriers.
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http://dx.doi.org/10.1161/01.ATV.0000234921.88489.5cDOI Listing
September 2006
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