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Optimizing hepatitis C virus treatment through pharmacist interventions: Identification and management of drug-drug interactions

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World journal of Gastroenterology 2017年第9期23卷 1618-1626页

作者： jacob A Langness Matthew Nguyen Amanda Wieland Gregory T Everson jennifer j kiser Hepatology and Transplant Clinic University of Colorado Hospital Department of Pharmacy University of Colorado Hospital University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences Department of Gastroenterology School of MedicineUniversity of Colorado

AIM To quantify drug-drug-interactions(DDIs) encountered in patients prescribed hepatitis C virus(HCV) treatment, the interventions made, and the time spent in this process.METHODS As standard of care, a clinical pharmacist screened for DDIs in patients prescribed direct acting antiviral(DAA) HCV treatment between November 2013 and july 2015 at the University of Colorado Hepatology Clinic. HCV regimens prescribed included ledipasvir/sofosbuvir(LDV/SOF), paritaprevir/ritonavir/ombitasvir/dasabuvir(OBV/PTV/r + DSV), simeprevir/sofosbuvir (SIM/SOF), and sofosbuvir/ribavirin (SOF/RBV). This retrospective analysis reviewed the work completed by the clinical pharmacist in order to measure the aims identified for the study. The number and type of DDIs identified were summarized with descriptive statistics.RESULTS Six hundred and sixty four patients(83.4% Caucasian, 57% male, average 56.7 years old) were identified; 369 for LDV/SOF, 48 for OBV/PTV/r + DSV, 114 for SIM/SOF, and 133 for SOF/RBV. Fifty-one point five per cent of patients were cirrhotic. Overall, 5217 medications were reviewed (7.86 medications per patient) and 781 interactions identified (1.18 interactions per patient). The number of interactions were fewest for SOF/RBV (0.17 interactions per patient) and highest for OBV/PTV/r + DSV (2.48 interactions per patient). LDV/SOF and SIM/SOF had similar number of interactions (1.28 and 1.48 interactions per patient, respectively). Gastric acid modifiers and vitamin/herbal supplements commonly caused interactions with LDV/SOF. Hypertensive agents, analgesics, and psychiatric medications frequently caused interactions with OBV/PTV/r + DSV and SIM/SOF. To manage these interactions, the pharmacists most often recommended discontinuing the medication (28.9%), increasing monitoring for toxicities (24.1%), or separating administration times (18.2%). The pharmacist chart review for each patient usually took approximately 30 min, with additional time for more complex patients. CONCLUSION DDIs are common with HCV medication

关键词：临床的药剂师药药相互作用丙肝病毒治疗

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Neuroprotection by resveratrol-glucuronide and quercetin-glucuronide via binding to polyphenol-and glycosaminoglycan-binding sites in the laminin receptor

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Neural Regeneration Research 2025年第3期20卷 819-820页

作者： Rayudu Gopalakrishna jennifer Aguilar Emily Lee William j.Mack Department of Integrative Anatomical Sciences Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCAUSA Department of Neurological Surgery Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCAUSA

The dietary polyphenolic compounds resveratrol and quercetin prevent neurodegenerative diseases in experimental models;however, they reach the brain only in nanomolar concentrations in the glucuronidated and sulfated ... 详细信息

关键词： resveratrol molar dated

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Implementation of an international medical student pen-pal club:survey outcomes of perceptions in cultural competency and global health

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Global Health journal 2024年第1期8卷 11-15页

作者： Max j.Goodman jennifer Livschitz ji Won Kim Megan L.Schultz Medical College of Wisconsin MilwaukeeWI 53226USA Department of Pediatrics Division of Emergency MedicineMedical College of WisconsinMilwaukeeWI53226USA

Background:Pen-pal clubs(PPC)are used worldwide for students to learn about different cultures and other skillsets without the need for travel.Many medical students are interested in global health opportunities abroad but costs,scheduling,and other barriers allow few to participate in such experiences.It is important that medical students have nuanced global medical perspectives and can contribute to the global medical community.Objective:The purpose of this study is to demonstrate that an international medical student PPC improves medical students'perspectives of cultural competency and global health engagement.Methods:In 2021,a novel medical student PPC was established that began between an American and japanese medical school.Following a shareholders meeting,it was decided that the number of medical schools involved globally be expanded through previous institutional affiliations and online presences.In total,the club connected 50 American medical students and 52 medical students from 17 high-and middle-income countries.The primary form of communication was online;pen-pals were encouraged to communicate monthly using provided topics,although frequency and way of communication was their discretion.In February 2022,American PPC members were emailed a qualitative survey to assess the PPC's impact.Results:The survey was completed by 42%of American PPC members,95%of which were 22-26 years.Participants were preclinical medical students,60%whom were female and the majority either white(47%)or Asian(43%).Overall,the PPC positively influenced American medical students'perception of global medicine,medical education,and their cultural competency after joining the PPC compared to prior(P=0.004).Conclusion:PPCs encourage medical students to think from a global perspective and foster open-mindedness within varying social and cultural contexts.Having a global communication platform for students during medical school education may be an additional way to train aspiring global leaders.

关键词： Pen-pals Medical student Global health Cultural competency

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Phase 3 trial of first generation protease inhibitor therapy for hepatitis C virus/human immunodeficiency virus coinfection

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World journal of Hepatology 2017年第4期9卷 217-223页

作者： Kenneth E Sherman Minhee Kang Richard Sterling Triin Umbleja Kristen Marks jennifer j kiser Beverly Alston-Smith Wayne Greaves Adeel A Butt 无 Division of Digestive Diseases University of Cincinnati College of Medicine harvard T.h. Chan School of Public health Department of Gastroenterology Virginia Commonwealth University Division of Infectious Disease Weill Cornell Medical School University of Colorado School of Pharmacy NIAID-Division of AIDS Merck and Co Inc. University of Pittsburgh School of Medicine hamad healthcare Quality Institute the ACTG 5294 BIRTH Study Team

AIM To evaluate efficacy/safety of hepatitis C virus(HCV) protease inhibitor boceprevir with pegylated interferon(PEG-IFN) alfa and weight-based ribavirin(RBV) in a phase 3 trial. METHODS A prospective, multicenter, phase 3, open-label, singlearm study of PEG-IFN alfa, weight-based RBV, and boceprevir, with a PEG-IFN/RBV lead-in phase was performed. The HCV/human immunodeficiency virus coinfected study population included treatment na?ve(TN) and treatment experienced(TE) patients. Treatment duration ranged from 28 to 48 wk dependent upon response-guided criteria. All patients had HCV Genotype 1 with a viral load > 10000 IU/ml. Compensated cirrhosis was allowed. Sample size was determined to establish superiority to historical(PEG-IFN plus RBV) rates in sustained viral response(SVR). RESULTS A total of 257 enrolled participants were analyzed(135 TN and 122 TE). In the TN group, 81.5% were male and 54.1% were black. In the TE group, 76.2% were male and 47.5% were white. Overall SVR12 rates(HCV RNA jects(P = 0.002). Among the TN, SVR12 was 42.1% among whites and 27.4% among blacks(P = 0.09). CONCLUSION The trial met its hypothesis of improved SVR compared to historical controls but overall SVR rates were low. All-oral HCV treatments will mitigate these difficulties.

关键词：人的免疫不全病毒丙肝病毒 Boceprevir Pegylated 干扰素 A Ribavirin

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Are there sex-based disparities in cataract surgery?

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International journal of Ophthalmology(English edition) 2024年第1期17卷 137-143页

作者： Matthew D.Geiger Anne M.Lynch Alan G.Palestine Nathan C.Grove Karen L.Christopher Richard S.Davidson Michael j.Taravella Naresh Mandava jennifer L.Patnaik Department of Ophthalmology University of Colorado School of MedicineAuroraCO 80045USA

AIM:To investigate sex-based differences in the occurrence of intra-operative and post-operative complications and associated visual outcomes following cataract surgery.METHODS:This was a retrospective study of patients who had phacoemulsification cataract surgery at the University of Colorado School of Medicine.Data collected included the patient’s health history,ocular comorbidities,operative and post-operative complications,and the post-operative best corrected visual acuity(BCVA).The data were analyzed using univariate and multivariable logistic regression with generalized estimating equations to account for the correlation of some patients having two eyes included in the study.RESULTS:A total of 11977 eyes from 7253 patients were included in the study.Ocular comorbidities differed by sex,with males having significantly higher percentages of traumatic cataracts(males 0.7%vs females 0.1%),prior ocular surgery(6.7%vs 5.5%),and mature cataracts(2.8%vs 1.9%).Conversely,females had significantly higher rates of pseudoexfoliation(2.0%vs 3.2%).In unadjusted analysis,males had higher rates of posterior capsular rupture(0.8%vs 0.4%)and vitreous loss(1.0%vs 0.6%),but this difference was not significant after adjustment for confounders.Males had a significantly increased risk of post-operative retinal detachment,but in multivariable analysis this was no longer significant.Males were significantly less likely to undergo post-operative neodymium-doped yttrium aluminum garnet(Nd:YAG)laser capsulotomy for posterior capsule opacification(OR=0.8,95%CI=0.7-0.9,P=0.0005).The BCVA was slightly worse for males pre-operatively;but post-operatively,both sexes exhibited similar visual acuity of Snellen equivalent 20/25.CONCLUSION:The study finds that in a cohort of patients presenting for cataract surgery,sex differences exist in pre-operative comorbidities and surgical characteristics that contribute to higher rates of some complications for males.However,observed surgical complication rates exhibit almost no difference by sex afte

关键词： cataract surgery sex-based disparity phacoemulsification outcomes

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A functional tacrolimus-releasing nerve wrap for enhancing nerve regeneration following surgical nerve repair

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Neural Regeneration Research 2025年第1期20卷 291-304页

作者： Simeon C.Daeschler Katelyn j.W.So Konstantin Feinberg Marina Manoraj jenny Cheung jennifer Zhang Kaveh Mirmoeini jPaul Santerre Tessa Gordon Gregory HBorschel SickKids Research Institute Neuroscience and Mental Health ProgramTorontoONCanada Institute of Biomaterials and Biomedical Engineering University of TorontoTorontoONCanada Indiana University School of Medicine IndianapolisINUSA Division of Plastic and Reconstructive Surgery the Hospital for Sick ChildrenTorontoONCanada Translational Biology and Engineering Program Ted Rogers Centre for Heart ResearchInstitute of Biomedical EngineeringFaculty of DentistryUniversity of TorontoTorontoONCanada

Axonal regeneration following surgical nerve repair is slow and often incomplete,resulting in poor functional recovery which sometimes contributes to lifelong disability.Currently,there are no FDA-approved therapies available to promote nerve regeneration.Tacrolimus accelerates axonal regeneration,but systemic side effects presently outweigh its potential benefits for peripheral nerve surgery.The authors describe herein a biodegradable polyurethane-based drug delivery system for the sustained local release of tacrolimus at the nerve repair site,with suitable properties for scalable production and clinical application,aiming to promote nerve regeneration and functional recovery with minimal systemic drug exposure.Tacrolimus is encapsulated into co-axially electrospun polycarbonate-urethane nanofibers to generate an implantable nerve wrap that releases therapeutic doses of bioactive tacrolimus over 31 days.Size and drug loading are adjustable for applications in small and large caliber nerves,and the wrap degrades within 120 days into biocompatible byproducts.Tacrolimus released from the nerve wrap promotes axon elongation in vitro and accelerates nerve regeneration and functional recovery in preclinical nerve repair models while off-target systemic drug exposure is reduced by 80%compared with systemic delivery.Given its surgical suitability and preclinical efficacy and safety,this system may provide a readily translatable approach to support axonal regeneration and recovery in patients undergoing nerve surgery.

关键词： biodegradable local drug delivery nerve injury nerve regeneration nerve wrap tacrolimus

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Diagnostic accuracy of ePOS score in predicting DNR labeling after ICU admission:A prospective observational study(ePOS-DNR)

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journal of Intensive Medicine 2024年第2期4卷 216-221页

作者： Omar E.Ramadan Ahmed F.Mady Mohammed A.Al-Odat Ahmed N.Balshi Ahmed W.Aletreby Taisy j.Stephen Sheena R.Diolaso jennifer Q.Gano Waleed Th.Aletreby Department of Critical Care King Saud Medical CityRiyadhSaudi Arabia Anesthesia Department Faculty of MedicineAin Shams UniversityCairoEgypt Anesthesia Department Faculty of MedicineTanta UniversityTantaEgypt Faculty of Medicine Alexandria UniversityAlexandriaEgypt Nursing Department King Saud Medical CityRiyadhSaudi Arabia

Background Resuscitation can sometimes be futile and making a do-not-resuscitate(DNR)decision is in the best interest of the patient.The electronic poor outcome screening(ePOS)score was developed to predict 6-month poor outcomes of critically ill patients.We explored the diagnostic accuracy of the ePOS score in predicting DNR decisions in the intensive care unit(ICU).Methods This study was conducted at the ICU of a tertiary referral hospital in Saudi Arabia between March and May 2023.Prospectively,we calculated ePOS scores for all eligible consecutive admissions after 48 h in the ICU and recorded the DNR orders.The ability of the score to predict DNR was explored using logistic regression.Youden's ideal cut-off value was calculated using the DeLong method,and different diagnostic accuracy measures were generated with corresponding 95%confidence intervals(CIs).Results We enrolled 857 patients,125 received a DNR order and 732 did not.The average ePOS score of DNR and non-DNR patients was 28.2±10.7 and 15.2±9.7,respectively.ePOS score,as a predictor of DNR order,had an area under receiver operator characteristic(AUROC)curve of 81.8%(95%CI:79.0 to 84.3,P17 was associated with a sensitivity of 87.2(95%CI:80.0 to 92.5,P17 may help guide clinical decisions to withhold or commence resuscitative measures.

关键词： Do-not-resuscitate(DNR) Resuscitation Intensive care unit(ICU) Diagnostic accuracy Sensitivity Specificity

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Inflammasome links traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease

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Neural Regeneration Research 2025年第6期 1644-1664页

作者： Gabriela Seplovich Yazan Bouchi juan Pablo de Rivero Vaccari jennifer C.Munoz Pareja Andrew Reisner Laura Blackwell Yehia Mechref Kevin K.Wang j.Adrian Tyndall Binu Tharakan Firas Kobeissy Department of Surgery Morehouse School of Medicine Department of Neurobiology Center for Neurotrauma Multiomics & Biomarkers (CNMB) Neuroscience Institute Morehouse School of Medicine Department of Neurological Surgery and the Miami Project to Cure Paralysis University of Miami Miller School of Medicine Division of Pediatric Critical Care Department of Pediatrics University of Miami Miller School of Medicine Department of Pediatrics Emory University Department of Neurosurgery Children's Healthcare of Atlanta Department of Chemistry and Biochemistry Texas Tech University Morehouse School of Medicine

Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.

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Do people with low back pain walk differently? A systematic review and meta-analysis

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journal of Sport and Health Science 2022年第4期11卷 450-465页

作者： jo Armour Smith Heidi Stabbert jennifer j.Bagwell Hsiang-Ling Teng Vernie Wade Szu-Ping Lee Department of Physical Therapy Chapman UniversityIrvineCA 92618USA Department of Physical Therapy California State UniversityLong BeachCA 90840USA Department of Physical Therapy University of NevadaLas VegasNV 89154USA

Background:The biomechanics of the trunk and lower limbs during walking and running gait are frequently assessed in individuals with low back pain(LBP).Despite substantial research,it is still unclear whether consistent and generalizable changes in walking or running gait occur in association with LBP.The purpose of this systematic review was to identify whether there are differences in biomechanics during walking and running gait in individuals with acute and persistent LBP compared with back-healthy controls.Methods:A search was conducted in PubMed,CINAHL,SPORTDiscus,and PsycINFO in june 2019 and was repeated in December 2020.Studies were included if they reported biomechanical characteristics of individuals with and without LBP during steady-state or perturbed walking and running.Biomechanical data included spatiotemporal,kinematic,kinetic,and electromyography variables.The reporting quality and potential for bias of each study was assessed.Data were pooled where possible to compare the standardized mean differences(SMD)between back pain and back-healthy control groups.Results:Ninety-seven studies were included and reviewed.Two studies investigated acute pain and the rest investigated persistent pain.Nine studies investigated running gait.Of the studies,20%had high reporting quality/low risk of bias.In comparison with back-healthy controls,individuals with persistent LBP walked slower(SMD=-0.59,95%confidence interval(95%CI):-0.77 to-0.42)and with shorter stride length(SMD=-0.38,95%CI:-0.60 to-0.16).There were no differences in the amplitude of motion in the thoracic or lumbar spine,pelvis,or hips in individuals with LBP.During walking,coordination of motion between the thorax and the lumbar spine/pelvis was significantly more in-phase in the persistent LBP groups(SMD=-0.60,95%CI:-0.90 to-0.30),and individuals with persistent LBP exhibited greater amplitude of activation in the paraspinal muscles(SMD=0.52,95%CI:0.23-0.80).There were no consistent differences in running biomechanics between groups.Conclusion:The

关键词： Biomechanics Low back pain Running Walking

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Ultraviolet light exposure and its penetrance through the eye in a porcine model

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International journal of Ophthalmology(English edition) 2023年第2期16卷 172-177页

作者： Hideki Fukuoka Helena E.Gali jennifer j.Bu Ruti Sella Natalie A.Afshari Shiley Eye Institute Viterbi Family Department of OphthalmologyUniversity of California San DiegoLa JollaCA 92093USA

AIM:To determine the amount of ultraviolet(UV)light irradiance that various layers of the eye receive as sunlight passes through the eye,and to investigate the protective benefits of UV light-blocking contact lenses.METHODS:Twenty-four porcine eyes were prepared in one of three ways:isolated cornea,cornea and lens together,or whole eye preparation.UV light irradiance was measured with a UV-A/B light meter before and after the eye preparations were placed over the meter to measure UV light penetration in each eye structure.In the whole eye preparation,a hole was placed in the fovea to measure light as it passed through the vitreous.Subsequently,UVprotective contact lenses were placed over the structures,and UV light penetrance was measured.Measurements of UV light exposure were taken outdoors at various locations and times.RESULTS:Cornea absorbed 63.56%of UV light that reached the eye.Cornea and lens absorbed 99.34%of UV light.Whole eye absorbed 99.77%of UV light.When UV-protective contact lenses were placed,absorption was 98.90%,99.55%,and 99.87%,respectively.UV light exposure was dependent on directionality and time of day,and was greatest in areas of high albedo that reflect significant amounts of light,such as a beach.CONCLUSION:Cornea absorbs the majority of UV light that reaches the eye in this model.UV-protective contact lenses reduce UV exposure to the eye.Locations with high albedo expose the eye to higher levels of UV light.

关键词： ultraviolet light penetrance contact lens cornea lens

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