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1.
J Opioid Manag ; 15(6): 479-485, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31850509

RESUMO

INTRODUCTION: In response to the US opioid epidemic, the Centers for Disease Control and Prevention issued a guideline (CDCG) for prescribing opioids for chronic pain. Successful implementation of the CDCG requires identification of the information, skills, and support physicians need to carry out its recommendations. However, such data are currently lacking. METHODS: The authors performed one-on-one interviews with nine practicing physicians regarding their needs and perspectives for successful CDCG implementation, including the perceived barriers, focusing on communication strategies. Interviews were audio recorded, transcribed, and a thematic qualitative analysis was performed. FINDINGS: Three major themes were identified: communication, knowledge, and information technology (IT). Physicians reported that open communication with patients about opioids was difficult and burdensome, but essential; they shared their communication strategies. Knowledge gaps included patient-specific topics (eg, availability of/insurance coverage for non-opioid treatments) and more general areas (eg, opioid dosing/equivalencies, prescribing naloxone). Finally, physicians discussed the importance of innovation in IT, focusing on the electronic medical record for decision support and to allow safer opioid prescribing within the time constraints of clinical practice. DISCUSSION: These qualitative data document practical issues that should be considered in the development of implementation plans for safer opioid prescribing practices. Specifically, healthcare systems may need to provide opioid-relevant communication strategies and training, education on key topics such as naloxone prescribing, resources for referrals to appropriate nonpharmacologic treatments, and innovative IT solutions. Future research is needed to establish that such measures will be effective in producing better outcomes for patients on opioids for chronic pain.


Assuntos
Analgésicos Opioides , Comunicação , Registros Eletrônicos de Saúde , Transtornos Relacionados ao Uso de Opioides/prevenção & controle , Padrões de Prática Médica , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Tomada de Decisões , Humanos , Naloxona , Médicos , Pesquisa Qualitativa
2.
AIDS Care ; : 1-8, 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31870170

RESUMO

It is widely acknowledged that the growing opioid epidemic and associated increase in overdose deaths necessitates a reexamination of processes and procedures related to an opioid prescription for the treatment of chronic pain. However, the perspectives of patients, including those at the highest risk for opioid-related harms, are largely missing from this reexamination. To partially address the gap, we conducted a pair of one-day public deliberations on opioid prescribing in the context of HIV care. Results included recommendations and perspectives from people living with HIV that detail how providers can best assess patient needs, communicate regarding opioids, and reduce the risk of misuse. Participants emphasized the importance of building trust with patients and taking an extensive patient history prior to making decisions about whether to initiate or end an opioid prescription. This trust - together with an understanding of the origin of a patient's pain, history of drug use and other therapies tried - was perceived as essential to effective monitoring and pain management, as well as promotion of positive health outcomes. Ensuring that such patient perspectives are incorporated into the operationalization of guidelines for safe opioid prescribing may help to improve outcomes and quality of care for people living with HIV.

3.
Contemp Clin Trials Commun ; 16: 100468, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31701042

RESUMO

Many people with HIV (PWH) experience chronic pain that limits daily function and quality of life. PWH with chronic pain have commonly been prescribed opioids, sometimes for many years, and it is unclear if and how the management of these legacy patients should change in light of the current US opioid epidemic. Guidelines, such as the Centers for Disease Control and Prevention Guideline for Prescribing Opioids for Chronic Pain (CDCG), provide recommendations for the management of such patients but have yet to be translated into easily implementable interventions; there is also a lack of strong evidence that adhering to these recommendations improves patient outcomes such as amount of opioid use and pain levels. Herein we describe the development and preliminary testing of a theory-based intervention, called TOWER (TOWard SafER Opioid Prescribing), designed to support HIV primary care providers in CDCG-adherent opioid prescribing practices with PWH who are already prescribed opioids for chronic pain. TOWER incorporates the content of the CDCG into the theoretical and operational framework of the Information Motivation and Behavioral Skills (IMB) model of health-related behavior. The development process included elicitation research and incorporation of feedback from providers and PWH; testing is being conducted via an adaptive feasibility clinical trial. The results of this process will form the basis of a large, well-powered clinical trial to test the effectiveness of TOWER in promoting CDCG-adherent opioid prescribing practices and improving outcomes for PWH with chronic pain.

4.
Clin Infect Dis ; 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31587032

RESUMO

BACKGROUND: Cognitive dysfunction in HIV has decreased, but milder forms of HIV-associated neurocognitive disorders (HAND) persist along with motor dysfunction. The HIV Motor Scale (HMS) is a validated tool which captures motor abnormalities on routine neurologic examination, and which is associated with cognitive impairment in HIV. In this study, we applied a modified HMS (MHMS) to a nationwide cohort of people with longstanding HIV to characterize and understand the factors contributing to motor dysfunction. METHODS: The National NeuroAIDS Tissue Consortium (NNTC) is a nationwide longitudinal cohort study. Participants undergo regular assessments including neurological examination, neuropsychological testing and immunovirologic data collection. Data from examinations were used to calculate the MHMS score which was then correlated with history of AIDS-related CNS disorders (ARCD; e.g. prior CNS opportunistic infection), cerebrovascular disease (CVD) and HIV-associated neurocognitive disorder (HAND). RESULTS: Sixty-nine percent of participants showed an abnormality on the MHMS, with 27% classified as severe. Results did not vary based on demographic or immunologic variables. The most common abnormalities seen were gait (54%) followed by coordination (39%) and strength (25%), and these commonly co-occurred. CVD (p=0.02), history of ARCD (p=0.001), and HAND (p=0.001) were all associated with higher (i.e. worse) HMS in univariate analyses; CVD and ARCD persisted in multivariate analyses. CVD was also marginally associated with symptomatic HAND. CONCLUSIONS: Complex motor dysfunction remains common in HIV and is associated with CVD, ARCD and to a lesser extent HAND. Future studies are needed to understand the longitudinal trajectory of HIV-associated motor dysfunction, its neural substrates and impact on quality of life.

5.
J Neurovirol ; 25(4): 551-559, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31098925

RESUMO

Small intestinal bacterial overgrowth (SIBO) is common among patients with HIV-associated autonomic neuropathies (HIV-AN) and may be associated with increased bacterial translocation and elevated plasma inflammatory biomarkers. Pyridostigmine is an acetylcholinesterase inhibitor which has been used to augment autonomic signaling. We sought preliminary evidence as to whether pyridostigmine could improve proximal gastrointestinal motility, reduce SIBO, reduce plasma sCD14 (a marker of macrophage activation and indirect measure of translocation), and reduce the inflammatory cytokines IL-6 and TNFα in patients with HIV-AN. Fifteen participants with well-controlled HIV, HIV-AN, and SIBO were treated with 8 weeks of pyridostigmine (30 mg PO TID). Glucose breath testing for SIBO, gastric emptying studies (GES) to assess motility, plasma sCD14, IL-6, and TNFα, and gastrointestinal autonomic symptoms were compared before and after treatment. Thirteen participants (87%) experienced an improvement in SIBO following pyridostigmine treatment; with an average improvement of 50% (p = 0.016). There was no change in gastrointestinal motility; however, only two participants met GES criteria for gastroparesis at baseline. TNFα and sCD14 levels declined by 12% (p = 0.004) and 19% (p = 0.015), respectively; there was no significant change in IL-6 or gastrointestinal symptoms. Pyridostigmine may ameliorate SIBO and reduce levels of sCD14 and TNFα in patients with HIV-AN. Larger placebo-controlled studies are needed to definitively delineate how HIV-AN affects gastrointestinal motility, SIBO, and systemic inflammation in HIV, and whether treatment improves clinical outcomes.

6.
AIDS ; 33(3): 475-481, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30702516

RESUMO

BACKGROUND: During antiretroviral therapy, HIV RNA can be detected in cerebrospinal fluid (CSF) when it is undetectable in plasma, a condition termed 'CSF viral escape'. The aim of the current study was to determine the prevalence and risk factors for CSF viral escape in two large cohorts in the USA. METHODS: A total of 1264 HIV-infected volunteers enrolled in two US cohorts at their most recent visit between 2003 and 2011 were included in this cross-sectional analysis if their HIV RNA level in plasma was less than 50 copies/ml while receiving stable antiretroviral therapy (ART) (>6 months) and if they had HIV RNA measured in CSF at their most recent visit between 2003 and 2011. Potential risk factors were identified using univariable and multivariable regression. RESULTS: CSF viral escape was detected in 55 adults (4.4%; 95% CI: 3.4-5.6), who had a median CSF HIV RNA of 155 copies/ml [interquartile range (IQR: 80-283)]. Patients with or without CSF viral escape had similar rates of neurocognitive impairment (38.2 vs. 37.7%; P = 0.91). CSF viral escape was independently associated with the use of ritonavir-boosted protease inhibitors [odds ratio (OR): 2.0; 95% CI: 1.1-3.8] or unboosted atazanavir (OR: 5.1; 95% CI: 1.3-16.1), CSF pleocytosis (OR: 7.6; 95% CI: 4.2-13.7) and abnormal CSF total protein (OR: 2.1; 95% CI: 1.1-3.7). CONCLUSIONS: In this large study of aviremic patients receiving ART, CSF viral escape was uncommon and was linked to evidence of central nervous system inflammation and the use of protease inhibitors, but not with worse neurocognitive performance.

7.
J Stroke Cerebrovasc Dis ; 28(1): 84-89, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30297169

RESUMO

BACKGROUND: Rate of ischemic strokes and transient ischemic attacks (TIAs) increases with age. There is lack of evidence on how age affects treatment strategies and outcomes. Our aim is to compare epidemiology of ischemic strokes and TIAs in adult and geriatric populations including risk factors, treatment delivered, and outcomes. DESIGN: We designed a retrospective cross-sectional review of patients admitted to neurology with diagnosis of stroke or TIA from 2010 to 2015. Obtained variables were: age, sex, risk factors, acute therapy, National Institutes of Health Stroke Scale on admission and discharge, and disposition. Means, confidence intervals, or percentages were calculated as appropriate. RESULTS: Around 1,457 patients were divided into two groups: younger than 80 (n = 968) and 80 and older (n = 487). Rates of stroke and TIA were similar across younger and older groups (11% versus 12% TIA and 89% versus 88% stroke, respectively). Younger patients had lower admission National Institutes of Health Stroke Scale (mean 4.64 versus 7.84 in older group) and greater improvement on discharge (mean change -1.51 versus -1.29 accordingly). Older patients received tissue-type plasminogen activator (tPA) more often than younger patients, but no difference in rates of thrombectomy between groups. Older patients were more likely to have hypertension, atrial fibrillation, coronary artery disease, and less likely to be a smoker. On discharge, younger patients with stroke were discharged home or to acute rehab more frequently, regardless of tPA administration. CONCLUSIONS: Older patients had more comorbidities, received tPA more often, and had worse outcomes regardless of use of intravenous tPA or thrombectomy, and were more frequently institutionalized after discharge.


Assuntos
Isquemia Encefálica/epidemiologia , Isquemia Encefálica/terapia , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/terapia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Estudos Transversais , Feminino , Humanos , Masculino , Alta do Paciente , Estudos Retrospectivos , Resultado do Tratamento
9.
AIDS ; 32(9): 1147-1156, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29596112

RESUMO

OBJECTIVE: Chronic inflammation in HIV-infected individuals drives disease progression and the development of comorbidities, despite viral suppression with combined antiretroviral therapy. Here, we sought evidence that vagal dysfunction, which occurs commonly as part of HIV-associated autonomic neuropathy, could exacerbate inflammation through gastrointestinal dysmotility, small intestinal bacterial overgrowth (SIBO), and alterations in patterns of soluble immune mediators. DESIGN: This is a cross-sectional observational study. METHODS: Forty participants on stable combined antiretroviral therapy with gastrointestinal symptoms, and no causes for vagal or gastrointestinal dysfunction other than HIV, underwent autonomic testing, hydrogen/methane breath testing for SIBO, and gastric emptying scintigraphy. A panel of 41 cytokines, high-mobility group box 1, and markers of bacterial translocation (lipopolysaccharide) and monocyte/macrophage activation (sCD14 and sCD163) were tested in plasma. RESULTS: We found that participants with vagal dysfunction had delayed gastric emptying and higher prevalence of SIBO. SIBO was associated with IL-6, but not sCD14; lipopolysaccharide could not be detected in any participant. We also found alteration of cytokine networks in participants with vagal dysfunction, with stronger and more numerous positive correlations between cytokines. In the vagal dysfunction group, high mobility group box 1 was the only soluble mediator displaying strong negative correlations with other cytokines, especially those cytokines that had numerous other strong positive correlations. CONCLUSION: The current study provides evidence that the vagal component of HIV-associated autonomic neuropathy is associated with changes in immune and gastrointestinal function in individuals with well treated HIV. Further study will be needed to understand whether therapies targeted at enhancing vagal function could be of benefit in HIV.


Assuntos
Síndrome da Alça Cega/epidemiologia , Infecções por HIV/complicações , Inflamação/fisiopatologia , Doenças do Nervo Vago/complicações , Adolescente , Adulto , Idoso , Translocação Bacteriana/imunologia , Testes Respiratórios , Estudos Transversais , Citocinas/sangue , Esvaziamento Gástrico , Motilidade Gastrointestinal , Humanos , Ativação de Macrófagos , Pessoa de Meia-Idade , Prevalência , Adulto Jovem
10.
Pain Med ; 19(7): 1445-1450, 2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-29024980

RESUMO

Objective: Peripheral neuropathy (PN) is a common complication of HIV. There is increasing awareness that some forms of PN, particularly small-fiber neuropathies, can be associated with chronic widespread pain syndromes. Given the high prevalence of both PN and chronic pain in HIV, we sought to determine whether patients with a diagnosis of HIV-PN were more likely to experience other chronic pain syndromes. Methods: Data were obtained from the Clinical Data Warehouse maintained by our institution. All HIV-infected patients receiving standard of care antiretroviral therapy in our institution's primary care HIV clinic (N = 638) were included. Diagnoses of HIV-PN and other chronic pain disorders were established based on clinician-assigned ICD-9/10 codes. Results: Sixty-eight patients (11%) had a diagnosis of HIV-PN. Patients with HIV-PN were more than twice as likely to have other chronic pain disorders (66% vs 32%, χ2 = 30.3, P < 0.001). Patients with HIV-PN were also older and more likely to have substance use and psychiatric disorders; however, the association of HIV-PN with other chronic pain disorders persisted after adjusting for relevant confounders (χ2(5) = 81.38, P < 0.001). Conclusions: Patients with HIV-PN commonly experience other chronic pain disorders. Clinicians managing HIV-PN should seek a broad understanding of patients' pain experience as this may alter management strategies. Researchers studying HIV-PN should consider how the presence of other pain disorders might affect outcomes.


Assuntos
Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Dor/diagnóstico , Dor/epidemiologia , Doenças do Sistema Nervoso Periférico/diagnóstico , Doenças do Sistema Nervoso Periférico/epidemiologia , Adulto , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome
11.
J Neuroimaging ; 28(2): 217-224, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28833868

RESUMO

BACKGROUND AND PURPOSE: Human immunodeficiency virus (HIV)-infected patients commonly have abnormalities in cerebral white matter that are visible on magnetic resonance imaging (MRI) as hyperintensities (WMHs). Visual rating scales (VRSs) have been used to quantify WMH in other diseases such as cerebral small vessel disease (CSVD), but not in HIV. Such scales are advantageous because they are applicable to routinely acquired MRIs and so are suitable for large-scale studies and clinical care. We sought to establish the utility of three VRSs (the Fazekas, Scheltens, and van Sweiten scales) in HIV. METHODS: The Manhattan HIV Brain Bank (MHBB) is a longitudinal cohort study that performs serial neurologic examinations and neuropsychological testing. All brain MRIs (n = 73) performed for clinical purposes on MHBB participants were scored using the three VRSs. We assessed reliability, validity, and correlation of the VRS with clinical factors relevant to HIV and CSVD. RESULTS: The VRSs all showed acceptable internal consistency and interrater reliability and were highly correlated with one another (r = 0.836-0.916, P < .001). The Fazekas and Scheltens scales demonstrated more WMH in periventricular regions, and the Scheltens scale also suggested a frontal to occipital gradient, with greater WMH frontally. All three VRSs correlated significantly with cognitive impairment (global T score). Age and hepatitis C virus antibody serostatus were the strongest clinical/demographic correlates of WMH, followed by African-American race. CONCLUSIONS: VRSs reliably quantify WMH in HIV-infected individuals and correlate with cognitive impairment. Future studies may find routinely acquired brain MRI quantified by VRS to be an accessible and meaningful neurologic outcome measure in HIV.


Assuntos
Encéfalo/diagnóstico por imagem , Infecções por HIV/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Substância Branca/diagnóstico por imagem , Adulto , Encéfalo/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Reprodutibilidade dos Testes , Substância Branca/patologia
12.
Curr Treat Options Neurol ; 18(7): 30, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27188699

RESUMO

OPINION STATEMENT: The cyclic hormonal underpinnings of catamenial seizure exacerbations are consistent with the neurophysiologic activity of estrogen and progesterone. For women with catamenial epilepsy who have regular menses, intermittent treatment approaches may be utilized. These interventions are targeted at adding or increasing anti-seizure treatments during established vulnerable days of the menstrual cycle, such as perimenstrually (C1 pattern), at ovulation (C2 pattern), and during the luteal phase (C3 pattern). The single large study of natural progesterone treatment showed benefit for women with clear perimenstrual seizure exacerbations (C1 pattern), but not for subjects with other catamenial patterns or for randomized women with epilepsy of reproductive age who did not have catamenial seizure exacerbations. In this protocol, natural progesterone was given at a high dose during the luteal phase and was generally well tolerated. Other intermittent cyclic treatments include benzodiazepine use, increasing the dose of an anti-seizure drug already in use, or acetazolamide. For women with irregular menses, or those in which the intermittent cyclic treatments are not effective, pharmacologically stopping the menstrual cycle altogether by using synthetic hormones such as medroxyprogesterone (Depo-Provera) or sustained oral contraceptives may be considered.

13.
J Neurosci ; 29(14): 4498-511, 2009 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-19357275

RESUMO

Neuronal activity largely depends on two key components on the membrane: the Na,K-ATPase (NKA) that maintains the ion gradients and sets the foundation of excitability, and the ionotropic glutamatergic AMPA receptors (AMPARs) through which sodium influx forms the driving force for excitation. Because the frequent sodium transients from glutamate receptor activity need to be efficiently extruded, a functional coupling between NKA and AMPARs should be a necessary cellular device for synapse physiology. We show that NKA is enriched at synapses and associates with AMPARs. NKA dysfunction induces a rapid reduction in AMPAR cell-surface expression as well as total protein abundance, leading to a long-lasting depression in synaptic transmission. AMPAR proteolysis requires sodium influx, proteasomal activity and receptor internalization. These data elucidate a novel mechanism by which NKA regulates AMPAR turnover and thereby synaptic strength and brain function.


Assuntos
Complexo de Endopeptidases do Proteassoma/fisiologia , Receptores de AMPA/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismo , Animais , Células Cultivadas , Hidrólise , Ouabaína/farmacologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Ratos , Receptores de AMPA/fisiologia , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores , Sinapses/efeitos dos fármacos , Sinapses/enzimologia , Sinapses/metabolismo
14.
Microb Pathog ; 40(6): 261-70, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16626926

RESUMO

Neisseria gonorrhoeae is an obligate human pathogen that represents a significant health concern, particularly in the developing world. Although generally associated with an acute inflammatory infection of urogenital epithelia cells, infections have been noted in multiple tissues and many infected individuals can become asymptomatic carriers. Few studies of immune response to N. gonorrhoeae infection in peripheral blood have evaluated the production of T helper cytokines (TH1/TH2) induced early after infection. We developed a quantitative realtime PCR assay based on the gonococcal rmpIII gene to monitor dose-response effects of infection on cytokine release from peripheral blood mononuclear cells (PBMCs). We observed upregulation of CD69 transcription and surface CD25 expression on lymphocytes, consistent with early T-cell activation. We observed dosage-dependent transcription of the chemotactic factor IL-8 and previously unreported activation of the chemoattractant MCP-2. Multiplex analysis of broad cytokine protein production revealed a differential increase in the TH1 and TH2 associated cytokines: IL-2, IL-4, IL-8, IL-10, IL-12, IFN-gamma, TNF-alpha and MCP-1. Markov models of protein accumulation implicated a cross-regulated response to infection, notably for IL-8, IL-10 and IL-12. Taken together, the cytokine profile we observed early in response to whole gonococcal bacteria was broader than has been previously described and may have relevance for the contribution of antagonistic signaling events early in infection and in understanding peripheral immune mechanisms engaged to control infection.


Assuntos
Citocinas/imunologia , Gonorreia/imunologia , Leucócitos Mononucleares/imunologia , Neisseria gonorrhoeae/imunologia , Células Th1/imunologia , Células Th2/imunologia , Quimiocina CCL8 , Gonorreia/sangue , Humanos , Interleucinas/imunologia , Leucócitos Mononucleares/microbiologia , Proteínas Quimioatraentes de Monócitos/imunologia
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