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1.
Semin Immunopathol ; 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33608820

RESUMO

Spondyloarthritis (SpA) is a chronic inflammatory disorder with complex etiology and pathogenesis. Its pathogenesis likely involves a combination of different factors. These factors include host genetics, environmental triggers, and immune and microbiota dysregulation. One of the strongest genetic associations with SpA is HLA-B27, implicating the involvement of cytotoxic T lymphocytes (CTLs) in SpA pathogenesis. Despite this discovery dating back decades ago, the CTL compartment that underlies SpA inflammation has yet to be fully defined until recently. Indeed, recent published studies support a significant role that CTLs play in contributing to chronic joint inflammation, which is a hallmark of SpA pathology. In this review chapter, we discuss emerging evidence that supports a newfound role of CTLs in SpA pathogenesis. This emerging evidence includes enrichment of CTL-related genes from genome-wide association studies, overrepresentation of pathogenic synovial CTL phenotype, clonal expansion, and immune dysregulation of CTLs. The discoveries of this mounting evidence suggest that CTL homeostasis is altered, and a disrupted adaptive immunity underlies the chronic inflammatory features seen in SpA pathology.

3.
J Palliat Med ; 2020 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-33351714

RESUMO

Background: Prescription drug monitoring programs (PDMPs) help maintain electronic records of controlled substances and are a resource to help direct patient care. As the use of these electronic programs expands, limitations of their use are becoming more apparent. We present two cases that illustrate the effects and the need to interpret the PDMPs with caution. Cases Description: Case 1: A male in his 60s presented with metastatic lung cancer who was being managed by our team for pain management along with oncology for cancer directed care. The PDMP erroneously reported that he had filled methadone, thereby impacting the provider-patient relationship. The second case was a female patient in her 40s who had metastatic lung cancer currently receiving cancer directed therapy and also followed with the Supportive Care Clinic for the management of cancer associated pain. The patient had demonstrated nonmedical opioid use behaviors in past visits so a careful monitoring approach had been implemented by the clinic to help safely prescribe opioids. The patient was wearing a fentanyl patch that was found only on physical examination during a clinic visit, because it was not noted in the PDMP. Conclusion: The PDMP has been found to assist physicians in decision making but there are limitations with its use. Enhanced real-time reporting of opioid prescribing information, increased integration into electronic health systems, and universal interstate sharing of prescribing data are some of the ways to improve their effectiveness. More research is needed to further examine the deficiencies and improve on its utility in routine chronic opioid therapy.

4.
Curr Oncol Rep ; 23(1): 6, 2020 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-33219861

RESUMO

PURPOSE OF REVIEW: Pain is a multi-faceted symptom. Effective pain assessment involves properly defining the pain syndrome, utilizing various assessment tools, and recognizing different conditions which may affect the expression and the management of pain. RECENT FINDINGS: Pain results from multiple physical and psychosocial etiological interplay. It has traditionally been categorized as acute or chronic with chronic pain having been categorized further into 6 categories in ICD 11. At the same time, the opioid epidemic and the recent surge in cannabis popularity further complicates pain assessment and effective pain management. Adequate management of pain begins with proper assessment including conducting extensive medical and psychosocial history and physical examination, and utilizing various pain and substance risk assessment tools. An interdisciplinary team approach may be more effective in managing complex pain behaviors compared to a solo approach.

5.
Cancer ; 2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33231885

RESUMO

BACKGROUND: There is limited information regarding the true frequency of nonmedical opioid use (NMOU) among patients receiving opioid therapy for cancer pain. Data to guide patient selection for urine drug testing (UDT) as well as the timing and frequency of ordering UDT are insufficient. This study examined the frequency of abnormal UDT among patients with cancer who underwent random UDT and their characteristics. METHODS: Demographic and clinical information for patients with cancer who underwent random UDT were retrospectively reviewed and compared with a historical cohort that underwent targeted UDT. Random UDT was ordered regardless of a patient's risk potential for NMOU. Targeted UDT was ordered on the basis of a physician's estimation of a patient's risk for NMOU. RESULTS: In all, 552 of 573 eligible patients (96%) underwent random UDT. Among these patients, 130 (24%) had 1 or more abnormal results; 38 of the 88 patients (43%) who underwent targeted UDT had 1 or more abnormal results. When marijuana was excluded, 15% of the random group and 37% of the targeted group had abnormal UDT findings (P < .001). It took a shorter time from the initial consultation to detect 1 or more abnormalities with the random test than the targeted test (median, 130 vs 274 days; P = .02). Abnormal random UDT was independently associated with younger age (P < .0001), male sex (P = .03), Cut Down, Annoyed, Guilty, and Eye Opener-Adapted to Include Drugs positivity (P = .001), and higher Edmonton Symptom Assessment System anxiety (P = .01). CONCLUSIONS: Approximately 1 in 4 patients receiving opioids for cancer pain at a supportive care clinic who underwent random UDT had 1 or more abnormalities. Random UDT detected abnormalities earlier than the targeted test. These findings suggest that random UDT is justified among patients with cancer pain.

6.
Palliat Support Care ; : 1-3, 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33118907

RESUMO

BACKGROUND: Recognizing and managing existential suffering remains challenging. We present two cases demonstrating how existential suffering manifests in patients and how to manage it to alleviate suffering. CASE DESCRIPTION: Case 1: A 69-year-old man with renal cell carcinoma receiving end-of-life care expressed fear of lying down "as he may not wake up." He also expressed concerns of not being a good Christian. Supportive psychotherapy and chaplain support were provided, with anxiolytic medications as needed. He was able to express his fear of dying and concern about his family, and Edmonton Symptom Assessment System scores improved. He died peacefully with family at bedside. Case 2: A 71-year-old woman presented with follicular lymphoma and colonic obstruction requiring nasogastric drain of fecaloid matter. Initially, she felt that focusing on comfort rather than cure symbolized giving up but eventually felt at peace. Physical symptoms were well-controlled but emotionally she became more distressed, repeatedly asking angrily, "Why is it taking so long to die?." She was supported by her family through Bible readings and prayers, but she was distressed about being a burden to them. An interdisciplinary approach involving expressive supportive counseling, spiritual care, and integrative medicine resulted in limited distress relief. Owing to increasing agitation, the patient and family agreed to titrate chlorpromazine to sedation. Her family was appreciative that she was restful until her death. CONCLUSION: Existential suffering manifests through multiple domains in each patient. A combination of pharmacologic and non-pharmacologic techniques may be needed to relieve end-of-life suffering.

8.
Int J Infect Dis ; 100: 470-472, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32979587

RESUMO

OBJECTIVES: Tenofovir alafenamide (TAF) is a preferred nucleotide reverse transcriptase inhibitor used in the treatment of HIV. Co-administration of TAF with rifabutin (RFB) is not recommended due to concerns that RFB decreases TAF gastrointestinal absorption. The objective of this study was to determine the efficacy of antiretroviral therapy regimens that include the co-administration of TAF and RFB. METHODS: Persons with HIV (PWH) who received TAF-RFB co-administration for ≥1 month were identified retrospectively. The primary outcome was the maintenance of HIV viral load <200 copies/mL (cpm) for those already on HIV therapy at RFB initiation, or suppression of viral load to <200 cpm for those with unsuppressed HIV viral load prior to TAF-RFB co-administration. RESULTS: Twenty-two PWH met the inclusion criteria. Four out of five patients (80%) maintained a viral load <200 cpm and 15/17 (88%) achieved a viral load <200 cpm during TAF-RFB co-administration. After the exclusion of patients who self-discontinued therapy or were lost to follow-up, 19/19 (100%) met the combined primary endpoint of HIV viral load <200 cpm. CONCLUSIONS: This study suggests that TAF-RFB co-administration may be effective despite concerns that RFB could reduce TAF absorption.

10.
JAMA Pediatr ; 174(6): 519-520, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32250416
11.
BMJ Open ; 10(3): e034305, 2020 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-32161159

RESUMO

OBJECTIVES: To describe an approach using concomitant medication log records for the construction of treatment episodes. Concomitant medication log records are routinely collected in clinical studies. Unlike prescription and dispensing records, concomitant medication logs collect utilisation data. Logs can provide information about drug safety and drug repurposing. DESIGN: A prospective multicentre, multicohort observational study. SETTING: Twenty-one clinical sites in the USA, Europe, Israel and Australia. PARTICIPANTS: 415 subjects from the de novo cohort of the Parkinson's Progression Markers Initiative. METHODS: We construct treatment episodes of concomitant medication use. The proposed approach treats temporal gaps as a stoppage of medication and temporal overlaps as simultaneous use or changes in dose. Log records with no temporal gaps were combined into a single treatment episode. RESULTS: 5723 concomitant medication log records were used to construct 3655 treatment episodes for 65 medications. There were 405 temporal gaps representing a stoppage of medication; 985 temporal overlaps representing simultaneous regimens of the same medication and 2696 temporal overlaps representing a change in dose regimen. The median episode duration was 37 months (IQ interval: 11-73 months). CONCLUSIONS: The proposed approach for constructing treatment episodes offers a method of estimating duration and dose of treatment from concomitant medication log records. The accompanying recommendations guide log data collection to improve their quality for drug safety and drug repurposing.

12.
Arthritis Rheumatol ; 72(3): 428-434, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31599089

RESUMO

OBJECTIVE: Ankylosing spondylitis (AS) is an inflammatory arthritis in which men have a higher risk of developing progressive axial disease than women. Transcriptomic studies have shown reduced expression of cytotoxic cell genes in the blood of AS patients. HLA-B27 contributes the greatest risk for AS, suggesting a role for CD8+ T cells. This study was undertaken to profile AS patient cytotoxic cells with the hypothesis that an alteration in CD8+ T cells might explain the aberrant cytotoxic profile observed in patients. METHODS: Whole blood was examined for GZM and PRF1 gene expression by quantitative polymerase chain reaction. Serum and synovial fluid (SF) were examined for granzyme and perforin 1 expression by bead array, and blood and SF mononuclear cells were examined for granzyme and perforin 1 expression by fluorescence-activated cell sorting (FACS). RESULTS: GZM and PRF1 gene expression were both reduced in AS patients compared to healthy controls, especially in men. Perforin 1, but not granzyme, protein levels were reduced in AS patient serum. Granzymes were elevated in AS SF, but not in rheumatoid arthritis or osteoarthritis SF. FACS revealed a reduction in granzyme-positive and perforin 1-positive lymphocytes, but not an intrinsic defect in CD8+ T cell granzyme or perforin 1 production. CD8+ T cell frequency was reduced in the blood and increased in the SF of AS patients. CONCLUSION: Our findings indicate that AS patients have an altered cytotoxic T cell profile. These data suggest that CD8+ T cells with a cytotoxic phenotype are recruited to the joints, where they exhibit an activated phenotype. Thus, a central role for CD8+ T cells in AS may have been overlooked and deserves further study.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Citotoxicidade Imunológica/genética , Granzimas/imunologia , Perforina/imunologia , Espondilite Anquilosante/imunologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Espondilite Anquilosante/genética
13.
Support Care Cancer ; 28(1): 295-301, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31044305

RESUMO

BACKGROUND: An international panel achieved consensus on 9 need-based and 2 time-based major referral criteria to identify patients appropriate for outpatient palliative care referral. To better understand the operational characteristics of these criteria, we examined the proportion and timing of patients who met these referral criteria at our Supportive Care Clinic. METHODS: We retrieved data on consecutive patients with advanced cancer who were referred to our Supportive Care Clinic between January 1, 2016, and February 18, 2016. We examined the proportion of patients who met each major criteria and its timing. RESULTS: Among 200 patients (mean age 60, 53% female), the median overall survival from outpatient palliative care referral was 14 (95% confidence interval 9.2, 17.5) months. A majority (n = 170, 85%) of patients met at least 1 major criteria; specifically, 28%, 30%, 20%, and 8% met 1, 2, 3, and ≥ 4 criteria, respectively. The most commonly met need-based criteria were severe physical symptoms (n = 140, 70%), emotional symptoms (n = 36, 18%), decision-making needs (n = 26, 13%), and brain/leptomeningeal metastases (n = 25, 13%). For time-based criteria, 54 (27%) were referred within 3 months of diagnosis of advanced cancer and 63 (32%) after progression from ≥ 2 lines of palliative systemic therapy. The median duration from patient first meeting any criterion to palliative care referral was 2.4 (interquartile range 0.1, 8.6) months. CONCLUSIONS: Patients were referred early to our palliative care clinic and a vast majority (85%) of them met at least one major criteria. Standardized referral based on these criteria may facilitate even earlier referral.


Assuntos
Assistência Ambulatorial/organização & administração , Neoplasias/terapia , Cuidados Paliativos/organização & administração , Seleção de Pacientes , Encaminhamento e Consulta/organização & administração , Adulto , Idoso , Assistência Ambulatorial/métodos , Assistência Ambulatorial/estatística & dados numéricos , Instituições de Assistência Ambulatorial/organização & administração , Instituições de Assistência Ambulatorial/estatística & dados numéricos , Pré-Escolar , Consenso , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Neoplasias/patologia , Avaliação de Processos e Resultados em Cuidados de Saúde , Pacientes Ambulatoriais , Cuidados Paliativos/métodos , Cuidados Paliativos/estatística & dados numéricos , Encaminhamento e Consulta/estatística & dados numéricos
14.
Cranio ; 38(5): 312-319, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30265209

RESUMO

OBJECTIVE: Physical therapy (PT) has been shown to be one of the most effective conservative treatments for temporomandibular disorders (TMD). The objectives of this pilot study are to determine the self-perceived knowledge, adequacy of entry-level education, and the current confidence levels of PTs in Florida regarding TMD treatment. METHODS: An online questionnaire was used. The overall experience, education, and confidence regarding TMD treatment and its implications were discussed. RESULTS: A total of 247 PTs participated. Nearly 70% of the PTs responded that they did not believe they received adequate education in TMD, and 50% are not confident to treat these patients. Seventy-seven percent were interested in knowing more about PT for TMD. DISCUSSION: This pilot study shows the lack of confidence of PTs in Florida to treat TMD patients. More adequate training on TMD in the entry-level professional education is needed.


Assuntos
Fisioterapeutas , Transtornos da Articulação Temporomandibular , Humanos , Modalidades de Fisioterapia , Projetos Piloto , Inquéritos e Questionários
15.
J Health Care Poor Underserved ; 30(4): 1252-1258, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31680096

RESUMO

Behavioral health integration, including as used in Medicaid Accountable Care Organizations, can improve care and decrease costs. Our model strives to integrate fully its medical, behavioral health, and substance use disorder services into one primary care clinic. Merged management has decreased wait times, improved billing, and enabled several promising innovations.


Assuntos
Organizações de Assistência Responsáveis/organização & administração , Prestação Integrada de Cuidados de Saúde/organização & administração , Medicaid/organização & administração , Serviços de Saúde Mental/organização & administração , Arquitetura de Instituições de Saúde , Humanos , Cultura Organizacional , Inovação Organizacional , Atenção Primária à Saúde/organização & administração , Estados Unidos
16.
Nano Lett ; 19(10): 7293-7300, 2019 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-31499003

RESUMO

A variety of methods including tuning chemical compositions, structures, crystallinity, defects and strain, and electrochemical intercalation have been demonstrated to enhance the catalytic activity. However, none of these tuning methods provide direct dynamical control during catalytic reactions. Here we propose a new method to tune the activity of catalysts through solid-state ion gating manipulation and adjustment (SIGMA) using a catalysis transistor. SIGMA can electrostatically dope the surface of catalysts with a high electron concentration over 5 × 1013 cm-2 and thus modulate both the chemical potential of the reaction intermediates and their electrical conductivity. The hydrogen evolution reaction (HER) on both pristine and defective MoS2 were investigated as model reactions. Our theoretical and experimental results show that the overpotential at 10 mA/cm2 and Tafel slope can be in situ, continuously, dynamically, and reversibly tuned over 100 mV and around 100 mV/dec, respectively.

17.
Adv Mater ; 31(17): e1807001, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30773741

RESUMO

Electrochemical water splitting driven by sustainable energy such as solar, wind, and tide is attracting ever-increasing attention for sustainable production of clean hydrogen fuel from water. Leveraging these advances requires efficient and earth-abundant electrocatalysts to accelerate the kinetically sluggish hydrogen and oxygen evolution reactions (HER and OER). A large number of advanced water-splitting electrocatalysts have been developed through recent understanding of the electrochemical nature and engineering approaches. Specifically, strain engineering offers a novel route to promote the electrocatalytic HER/OER performances for efficient water splitting. Herein, the recent theoretical and experimental progress on applying strain to enhance heterogeneous electrocatalysts for both HER and OER are reviewed and future opportunities are discussed. A brief introduction of the fundamentals of water-splitting reactions, and the rationalization for utilizing mechanical strain to tune an electrocatalyst is given, followed by a discussion of the recent advances on strain-promoted HER and OER, with special emphasis given to combined theoretical and experimental approaches for determining the optimal straining effect for water electrolysis, along with experimental approaches for creating and characterizing strain in nanocatalysts, particularly emerging 2D nanomaterials. Finally, a vision for a future sustainable hydrogen fuel community based on strain-promoted water electrolysis is proposed.

18.
Nat Commun ; 10(1): 32, 2019 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-30604776

RESUMO

We present a microkinetic model for CO(2) reduction (CO(2)R) on Cu(211) towards C2 products, based on energetics estimated from an explicit solvent model. We show that the differences in both Tafel slopes and pH dependence for C1 vs C2 activity arise from differences in their multi-step mechanisms. We find the depletion in C2 products observed at high overpotential and high pH to arise from the 2nd order dependence of C-C coupling on CO coverage, which decreases due to competition from the C1 pathway. We further demonstrate that CO(2) reduction at a fixed pH yield similar activities, due to the facile kinetics for CO2 reduction to CO on Cu, which suggests C2 products to be favored for CO2R under alkaline conditions. The mechanistic insights of this work elucidate how reaction conditions can lead to significant enhancements in selectivity and activity towards higher value C2 products.

19.
BMJ Open ; 8(12): e020372, 2018 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-30530471

RESUMO

OBJECTIVE: We describe steps to operationalise a published conceptual framework for a contiguous hospitalisation episode using acute care hospital discharge abstracts. We then quantified the degree of bias induced by a first abstract episode, which does not account for hospital transfers. DESIGN: Retrospective observational study. SETTING: All acute care hospitals in nine Canadian provinces. PARTICIPANTS: We retrieved acute hospitalisation discharge abstracts for 189 448 patients aged 65 years and older admitted to acute care with hip fracture between 2003 and 2013. PRIMARY AND SECONDARY OUTCOME MEASURES: The percentage of patients treated surgically, delayed to surgery (defined as two or more days after admission) and dying, between contiguous hospitalisation episodes and the first abstract episodes of care. RESULTS: Using contiguous hospitalisation episodes, 91.6% underwent surgery, 35.7% were delayed two or more days after admission and 6.7% died postoperatively, whereas, using the first abstract only, these percentages were 83.7%, 32.5% and 6.5%, respectively. CONCLUSION: We demonstrate that not accounting for hospital transfers when evaluating the association between surgical timing and death underestimates reporting of the percentage of patients treated surgically and delayed to surgery by 9%, and the percentage who die after surgery by 3%. Researchers must be aware of this potential and avoidable bias as, depending on the purpose of the study, erroneous inferences may be drawn.


Assuntos
Biologia Computacional/métodos , Bases de Dados como Assunto , Fraturas do Quadril/mortalidade , Fraturas do Quadril/cirurgia , Hospitalização , Idoso , Canadá , Humanos , Estudos Retrospectivos , Tempo para o Tratamento
20.
J Immunol ; 201(4): 1306-1314, 2018 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-29997124

RESUMO

The success of adoptive CTL therapy for cancer depends on interactions between tumor-infiltrating CTLs and cancer cells as well as other cells and molecules in the tumor microenvironment. Tumor dendritic cells (DCs) comprise several subsets: CD103+CD11b- DC1 and CD11b+CD64- DC2, which originate from circulating precursors of conventional DCs, and CD11b+CD64+ DC3, which arise from monocytes. It remains controversial which of these subset(s) promotes intratumor CTL proliferation, expansion, and function. To address this issue, we used the Zbtb46-DTR-transgenic mouse model to selectively deplete DC1 and DC2 from tumors and lymphoid tissues. Wild-type and Zbtb46-DTR bone marrow chimeras were inoculated with B16 melanoma cells that express OVA and were treated with OT-1 CTLs. We found that depletion of DCs derived from precursors of conventional DCs in Zbtb46-DTR bone marrow chimeras abolished CTL proliferation and expansion in tumor-draining lymph nodes. By contrast, intratumor CTL accumulation, proliferation, and IFN-γ expression were unaffected by their absence. We found that adoptive cell therapy increases the frequency of monocyte-derived tumor DC3, which possess the capacity to cross-present tumor Ags and induce CTL proliferation. Our findings support the specialized roles of different DC subsets in the regulation of antitumor CTL responses.


Assuntos
Células Dendríticas/imunologia , Melanoma Experimental/imunologia , Neoplasias Cutâneas/imunologia , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/transplante , Animais , Apresentação Cruzada/imunologia , Feminino , Imunoterapia Adotiva , Ativação Linfocitária/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Microambiente Tumoral/imunologia
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