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1.
Nat Rev Cardiol ; 18(3): 153-154, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33408360
2.
Biomater Sci ; 9(4): 1397-1408, 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33393536

RESUMO

Emulsion electrospinning is a versatile technique used to create fibrous meshes for applications in drug delivery and tissue engineering. In this study, the effects of surfactant and increasing internal phase volume fraction on emulsion electrospun fiber morphology were investigated. The fiber diameter, surface topography, internal architecture, mesh hydrophobicity, and fiber volume fraction were all characterized and the resulting effects on model drug release and cell response were determined. Surfactant relocation to the fiber surface resulted in alterations to fiber surface topography and internal morphology, increased rate of water adsorption into the mesh, and reduced burst effects of drug release. Increasing the internal phase volume fraction within the emulsion resulted in minimal change to fiber diameter, surface morphology, fiber volume fraction, and rate of water adsorption illustrating the ability to increase drug loading without affecting fiber properties. Lastly, all meshes promoted cell adhesion and good viability with a trend of increased MTT absorbance from cells on the surfactant and emulsion fibers possibly suggesting that an increase in surface area via smaller fiber diameter and fiber volume fraction increases metabolic activity. Overall, these studies indicate that fiber morphology and mesh hydrophobicity can be tuned by controlling surfactant location within fibers and internal phase volume fraction. Modulating fiber properties within the emulsion electrospun mesh is important to achieve controlled drug release and cell response for tissue engineering applications.

3.
Circ Cardiovasc Qual Outcomes ; 14(1): e006548, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33435730

RESUMO

BACKGROUND: Cardiovascular prevention guidelines use estimated 10-year atherosclerotic cardiovascular disease (CVD) risk based on the pooled cohort equations to guide treatment decisions and engage patients in shared decision-making. We sought to determine patient perceived versus actual risk of atherosclerotic CVD and associations with willingness for preventive therapy. METHODS: We evaluated calculated and perceived CVD risk among 4187 patients across 124 sites in the Patient and Provider Assessment of Lipid Management Registry. Ten-year risk was assessed using the pooled cohort equations; risk relative-to-peers was determined based on age-, sex-, and race-based percentiles; and patient estimates of risk were assessed using patient surveys. Poisson regression models evaluated associations between risk estimates, statin use, and willingness to take prevention therapy. RESULTS: Overall, there was no correlation between patients' estimates of their 10-year CVD risk and calculated 10-year risk (ρ=-0.01, Pcorrelation=0.46), regardless of age, sex, race, or socioeconomic status. The majority (72.2%) overestimated their 10-year CVD risk relative to the pooled cohorts equation (mean perceived 33.3% versus mean calculated 17.1%, Pdifference<0.01). Patients' perceptions of their risk relative-to-peers were slightly correlated with standardized risk percentiles (ρ=0.19, P<0.01), although most had overly optimistic views of how risk compared with their peers. Increasing perceived risk was not associated with current statin use (P=0.18) but was associated with willingness to consider future prevention therapy (P<0.01). Perceived risk relative-to-peers was associated with increased prevalent statin use (risk ratio 1.04 per category increase [95% CI, 1.02-1.06]) and reported willingness for prevention therapy (risk ratio 1.11 [95% CI, 1.07-1.16]). CONCLUSIONS: When asked, most patients overestimate their 10-year risk but hold an optimistic bias of their risk relative to age-, race-, and sex-matched peers. Providing accurate absolute risk assessments to patients without proper context may paradoxically decrease many patients' perceived risk of CVD, thereby disincentivizing initiation of CVD risk reduction therapy.

4.
Brain Neurosci Adv ; 4: 2398212820972871, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33294626

RESUMO

Neurophysiological recordings in behaving rodents demonstrate neuronal response properties that may code space and time for episodic memory and goal-directed behaviour. Here, we review recordings from hippocampus, entorhinal cortex, and retrosplenial cortex to address the problem of how neurons encode multiple overlapping spatiotemporal trajectories and disambiguate these for accurate memory-guided behaviour. The solution could involve neurons in the entorhinal cortex and hippocampus that show mixed selectivity, coding both time and location. Some grid cells and place cells that code space also respond selectively as time cells, allowing differentiation of time intervals when a rat runs in the same location during a delay period. Cells in these regions also develop new representations that differentially code the context of prior or future behaviour allowing disambiguation of overlapping trajectories. Spiking activity is also modulated by running speed and head direction, supporting the coding of episodic memory not as a series of snapshots but as a trajectory that can also be distinguished on the basis of speed and direction. Recent data also address the mechanisms by which sensory input could distinguish different spatial locations. Changes in firing rate reflect running speed on long but not short time intervals, and few cells code movement direction, arguing against path integration for coding location. Instead, new evidence for neural coding of environmental boundaries in egocentric coordinates fits with a modelling framework in which egocentric coding of barriers combined with head direction generates distinct allocentric coding of location. The egocentric input can be used both for coding the location of spatiotemporal trajectories and for retrieving specific viewpoints of the environment. Overall, these different patterns of neural activity can be used for encoding and disambiguation of prior episodic spatiotemporal trajectories or for planning of future goal-directed spatiotemporal trajectories.

5.
Neuromodulation ; 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33258531

RESUMO

Objectives Spinal cord stimulation (SCS) is an established treatment of chronic neuropathic pain. Although a temporary SCS screening trial is widely used to determine suitability for a permanent implant, its evidence base is limited. The recent TRIAL-STIM study (a randomized controlled trial at three centers in the United Kingdom) found no evidence that an SCS screening trial strategy provides superior patient outcomes as compared with a no trial approach. As part of the TRIAL-STIM study, we undertook a nested qualitative study to ascertain patients' preferences in relation to undergoing a screening trial or not. Materials and Methods We interviewed 31 patients sampled from all three centers and both study arms (screening trial/no trial) prior to SCS implantation, and 23 of these patients again following implantation (eight patients were lost to follow-up). Interviews were undertaken by telephone and audio-recorded, then transcripts were subject to thematic analysis. In addition, participants were asked to state their overall preference for a one-stage (no screening trial) versus two-stage (screening trial) implant procedure on a five-point Likert scale, before and after implantation. Results Emergent themes favoured the option for a one-stage SCS procedure. Themes identified include: saving time (off work, in hospital, attending appointments), avoiding the worry about having "loose wires" in the two-stage procedure, having only one period of recovery, and saving NHS resources. Participants' rated preferences show similar support for a one-stage procedure without a screening trial. Conclusions Our findings indicate an overwhelming preference among participants for a one-stage SCS procedure both before and after the implant, regardless of which procedure they had undergone. The qualitative study findings further support the TRIAL-STIM RCT results.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33303338

RESUMO

Owing to the extended nature and worldwide exposure of the coronavirus disease (COVID-19) pandemic, it is likely that the presence and impact of behavioral health conditions will increase. For example, it is anticipated that individuals living with a major depressive disorder could reach as high as 60% of the population owing to the ongoing disruption from COVID-19. In 2017, the annual rate of individuals experiencing a major depressive episode was only 7.1%. Pharmacists, specifically community pharmacists, are well positioned to provide needed intervention and triage services to individuals living with, and struggling with, a mental health condition. Pharmacists, therefore, need additional training and support to be effective in serving the community in this way.

7.
PLoS One ; 15(10): e0240166, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33119602

RESUMO

BACKGROUND: The log linear association between on-treatment LDL-C levels and ASCVD events is amplified in higher risk patient subgroups of statin versus placebo trials. OBJECTIVES: Update previous systematic review to evaluate how the log linear association influences the magnitude of cardiovascular risk reduction from intensifying LDL-C lowering therapy. METHODS: MEDLINE/PubMED, Clinical trials.gov, and author files were searched from 1/1/2005 through 10/30/2019 for subgroup analyses of cardiovascular outcomes trials of moderate versus high intensity statin, ezetimibe, and PCSK9 mAbs with an ASCVD endpoint (nonfatal myocardial infarction or stroke, cardiovascular death). Annualized ASCVD event rates were used to extrapolate 5-year ASCVD risk for each treatment group reported in subgroup analyses, which were grouped into a priori risk groups according to annualized placebo/control rates of ≥4%, 3-3.9%, or <3% ASCVD risk. Data were pooled using a random-effects model. Weighted least-squares regression was used to fit linear and log-linear models. RESULTS: Systematic review identified 96 treatment subgroups from 2 trials of moderate versus high intensity statin, 2 trials of a PCSK9 mAb versus placebo, and 1 trial of ezetimibe versus placebo. A log linear association between on-treatment LDL-C and ASCVD risk represents the association between on-treatment LDL-C levels and ASCVD event rates, especially in higher risk subgroups. Greater relative and absolute cardiovascular risk reductions from LDL-C lowering were observed when baseline LDL-C was >100 mg/dl and in extremely high risk ASCVD patient groups. CONCLUSIONS: Greater cardiovascular and mortality risk reduction benefits from intensifying LDL-C lowering therapy may be expected in those with LDL-C ≥100 mg/dl, or in extremely high risk patient groups. When baseline LDL-C <100 mg/dl, the log linear association between LDL-C and event rates suggests that treatment options other than further LDL-C lowering should also be considered for optimal risk reduction.

8.
Prog Plann ; : 100513, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33041436

RESUMO

There has been growing interest in the expansion of global investment in urban areas, and the financialisation of urban development, both of which bring new business logics into the production of the built environment and shape urban outcomes. At the same time, mega urban projects have continued and spread as a significant format of urban expansion and renewal, often strongly linked to transnational investors and developers. Nonetheless, the distinctive regulatory and political contexts within which transnational actors must bring such projects to fruition matter greatly to outcomes, with territorialised governance arrangements both shaping and being shaped by transnational dynamics. However, there has been little systematic comparative consideration of these diverse regulatory contexts in their own right, rather than as contributors to wider circulating processes such as neoliberalisation. As a result, the implications of different regulatory regimes for urban outcomes have not been effectively assessed. In this paper we therefore broaden the discussion from globalised processes of "financialisation" to consider three large-scale urban development projects from the perspective of their distinctive "business models", including their place in achieving wider strategic objectives at national and metropolitan scales, their agile and often bespoke institutional configurations, and their different forms of financing, taxation and land value capture. Our cases are Lingang, Shanghai (one of nine planned satellite cities), the Corridors of Freedom project in Johannesburg (a linear transport oriented development seeking to integrate the racially divided city), and Old Oak and Park Royal in north-west London (under a mayoral development corporation, associated with significant new metropolitan and national transport investments). We observe that the business models adopted, notably in relation to financial calculations and income streams associated with the developments, are a result of strongly path dependent formats of governance and income generation in each case. However we want to move beyond seeing these as residual, as contingent and contextual to wider accounts of urban development focussed on globalised financial flows and calculations. Using a comparative approach we initiate a systematic analytical conversation about the implications of different business models for the form and socio-economic potential of mega-urban development projects.

9.
J Am Heart Assoc ; 9(19): e016115, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-32993438

RESUMO

Improvements in cardiovascular disease (CVD) rates among young adults in the past 2 decades have been offset by increasing racial/ethnic and gender disparities, persistence of unhealthy lifestyle habits, overweight and obesity, and other CVD risk factors. To enhance the promotion of cardiovascular health among young adults 18 to 39 years old, the medical and broader public health community must understand the biological, interpersonal, and behavioral features of this life stage. Therefore, the National Heart, Lung, and Blood Institute, with support from the Office of Behavioral and Social Science Research, convened a 2-day workshop in Bethesda, Maryland, in September 2017 to identify research challenges and opportunities related to the cardiovascular health of young adults. The current generation of young adults live in an environment undergoing substantial economic, social, and technological transformations, differentiating them from prior research cohorts of young adults. Although the accumulation of clinical and behavioral risk factors for CVD begins early in life, and research suggests early risk is an important determinant of future events, few trials have studied prevention and treatment of CVD in participants <40 years old. Building an evidence base for CVD prevention in this population will require the engagement of young adults, who are often disconnected from the healthcare system and may not prioritize long-term health. These changes demand a repositioning of existing evidence-based treatments to accommodate new sociotechnical contexts. In this article, the authors review the recent literature and current research opportunities to advance the cardiovascular health of today's young adults.

10.
J Spec Pediatr Nurs ; : e12313, 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32970924

RESUMO

PURPOSE: The purpose of this study was to examine the feasibility and preliminary effectiveness of using wearable activity tracker technology, integrated with altruistic motivation in children to increase physical activity (PA), fitness, and prosocial behavior. DESIGN AND METHODS: A quasiexperimental design was employed in two 4th grade classrooms in a rural southern state. The intervention was a wearable PA tracker and a web-based curriculum with activities to earn power points redeemable to provide life-saving food to undernourished kids internationally. Seventeen children in the intervention group participated in the 10-week PA program and 18 children were in the wait listed control group. Three measures were assessed in both groups at baseline and postintervention: (a) PA measured with accelerometers, (b) fitness levels measured with shuttle run, and (c) prosocial behavior measured with Strengths and Difficulties questionnaire. RESULTS: Of the 35 children enrolled, the majority were nine years old (n = 28), black (n = 31) and female (n = 23). An overall enrollment rate of 88%, attrition rate of 9%, and an accelerometer noncompliance rate of 25% was determined to assess feasibility. There was no statistical significance between the control and intervention group outcome variables. The average minutes of PA in the control group decreased 8 min from baseline to postintervention (p = .05). In the intervention group, PA decreased by 10 min from baseline to postintervention (p = .12). In both the control and intervention groups, prosocial behavior scores decreased (p = .09 control; p = .62 intervention). The fitness scores, VO2 max, did not significantly change (intervention p = .21; control p = .35). PRACTICE IMPLICATIONS: Developing effective interventions that foster PA and dissuade sedentary behaviors are essential to enhancing PA and fitness levels. The recruitment, retention, and accelerometer wear adherence suggest this setting, with this population is feasible. The intervention is deliverable, however, the potential of wearable activity trackers and the effect of prosocial behavior that benefits others in increasing PA and improving cardiorespiratory fitness, should be further researched by building on the successful elements of this study.

11.
J Clin Lipidol ; 14(5): 707-719, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32928709

RESUMO

BACKGROUND: The ODYSSEY CHOICE I study (NCT01926782) evaluated alirocumab 300 mg every 4 weeks (Q4W) in patients with hypercholesterolemia receiving maximally tolerated statin or no statin. OBJECTIVE: The objective of the study was to assess the relationship between alirocumab, proprotein convertase subtilisin/kexin type 9 (PCSK9), and low-density lipoprotein cholesterol (LDL-C) concentrations with the CHOICE I alirocumab dosing regimen. METHODS: This analysis included 803 patients (547 statin-treated, 256 without statin) who were randomized to alirocumab 300 mg Q4W, alirocumab 75 mg every 2 weeks (Q2W), or placebo. 300 mg Q4W and 75 mg Q2W doses were adjusted to 150 mg Q2W at Week 12 if Week 8 LDL-C was >70 or >100 mg/dL, depending on cardiovascular risk, or if LDL-C reduction was <30% from baseline. RESULTS: Most patients remained on 300 mg Q4W without dose adjustment as they achieved study-defined LDL-C goals at Week 8 (statin-treated: 80.7%; no statin: 85.3%). LDL-C was reduced by 60.5%-71.9% over Weeks 20-24 in patients on 300 mg Q4W and 57.2%-63.0% in patients with dose adjustment from 300 mg Q4W to 150 mg Q2W. Statin-treated patients had higher cardiovascular risk as well as higher free PCSK9 and lower alirocumab concentrations (vs no statin), suggesting increased target-mediated clearance. Regardless of statin status, the most common adverse events in alirocumab-treated patients were injection-site reaction and headache. CONCLUSIONS: Data provide further insight on alirocumab's mode of action in terms of relationship between alirocumab, PCSK9, and LDL-C, and disease severity, and support the use of alirocumab 300 mg Q4W as an efficacious dosing regimen for clinically meaningful LDL-C reductions.

12.
Am J Pharm Educ ; 84(8): ajpe847813, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32934394

RESUMO

Objective. To determine whether students gained knowledge, confidence, and skills in identifying and preventing suicide in patients, peers, friends, and family after receiving training in suicide prevention. Methods. Student pharmacists participated in a 3.5-hour suicide prevention training program. A pre- and post- intervention assessment and pre- and post-intervention survey were administered before and after completion of the training program. Questions were designed to assess knowledge of, comfort with, and confidence in assessing and intervening with individuals at risk of suicide. A standardized patient prescription counseling session was conducted two weeks after the training session. Videos of the counseling sessions were reviewed to determine whether student pharmacists assessed the patient for suicide risk. Additionally, a post-counseling reflection was completed asking students to reflect on incorporation of the suicide prevention training into their prescription counseling session. Results. One-hundred seventy-one student pharmacists participated in the training. Knowledge increased across all areas as evidenced by improved scores on the post-intervention knowledge assessment. Students' comfort level with asking about suicidal ideation and their confidence with intervening significantly increased from the pre- to post-intervention survey. After the training, 40% stated they knew someone who may need help and 21% said they had decided to seek help for themselves. Conclusion. The training program increased student pharmacists' knowledge of and confidence in assessing and counseling individuals considering suicide. Encouraging student pharmacists to participate in prevention training may aid future providers in preventing death by suicide.

13.
Cancer ; 126(20): 4602-4613, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32780430

RESUMO

BACKGROUND: To the authors' knowledge, the empiric identification of agents and interventions to mitigate chemotherapy-induced peripheral neuropathy (CIPN) has resulted in only 1 agent that modestly mitigates it and no agents or interventions that prevent its development. This speaks to the need for a mechanistic understanding of CIPN to develop effective interventions. METHODS: To understand the extent to which mechanistic understanding of CIPN is being translated into the development of interventions, the National Cancer Institute conducted a review of the National Institutes of Health (NIH)'s portfolio of investigator-initiated grants, the literature regarding CIPN mechanisms, and the clinical trials listed in the ClinicalTrials.gov database from January 1, 2011, to May 22, 2019. RESULTS: A total of 69 NIH-supported grants and 95 published articles were identified that evaluated mechanistic pathways of 7 different chemotherapy agents that cause CIPN. The review also identified 35 clinical trials that investigated agents or devices with which to treat CIPN. Only 3 trials incorporated a mechanistic rationale to support the choice of the intervention. CONCLUSIONS: To the authors' knowledge, very little of the mechanistic understanding of the development of CIPN is being translated into intervention rationale in clinical trials that evaluate interventions to mitigate CIPN. Efforts to incentivize this translation are needed.

14.
Pain ; 161(12): 2820-2829, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32618875

RESUMO

Spinal cord stimulation (SCS) is an established treatment of chronic neuropathic pain. Although a temporary SCS screening trial is widely used to determine whether a patient should receive permanent SCS implant, its evidence base is limited. We aimed to establish the clinical utility, diagnostic accuracy, and cost-effectiveness of an SCS screening trial. A multicentre single-blind, parallel two-group randomised controlled superiority trial was undertaken at 3 centres in the United Kingdom. Patients were randomised 1:1 to either SCS screening trial strategy (TG) or no trial screening strategy (NTG). Treatment was open label, but outcome assessors were masked. The primary outcome measure was numerical rating scale (NRS) pain at 6-month follow-up. Between June 2017 and September 2018, 105 participants were enrolled and randomised (TG = 54, NTG = 51). Mean numerical rating scale pain decreased from 7.47 at baseline (before SCS implantation) to 4.28 at 6 months in TG and from 7.54 to 4.49 in NTG (mean group difference: 0.2, 95% confidence interval [CI]: -1.2 to 0.9, P = 0.89). We found no difference between TG and NTG in the proportion of pain responders or other secondary outcomes. Spinal cord stimulation screening trial had a sensitivity of 100% (95% CI: 78-100) and specificity of 8% (95% CI: 1-25). The mean incremental cost-effectiveness ratio of TG vs NTG was £78,895 per additional quality-adjusted life-year gained. In conclusion, although the SCS screening trial may have some diagnostic utility, there was no evidence that an SCS screening TG provides superior patient outcomes or is cost-effective compared to a no trial screening approach.

15.
AMIA Jt Summits Transl Sci Proc ; 2020: 664-673, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32477689

RESUMO

Simvastatin is a commonly used medication for lipid management and cardiovascular disease, however, the risk of adverse events (AEs) with its use increases via drug-drug interaction (DDI) exposures. Patients were extracted if initially diagnosed with cardiovascular disease and newly initiated simvastatin therapy. The cohort was divided into a DDI-exposed group and a non-DDI exposed group. The DDI-exposed group was further divided into gemfibrozil, clarithromycin, and erythromycin exposure groups. The outcome was defined as a composite of predefined AEs. Our results show that the simvastatin-DDI group had a higher illness burden with longer simvastatin exposure time and more medical care follow-up compared with the simvastatin-non-DDI exposed group. AEs occurred more frequently in subjects exposed to interacting drugs with a higher risk for clarithromycin and erythromycin exposed subjects than for gemfibrozil subjects.

16.
PLoS Med ; 17(6): e1003102, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32530938

RESUMO

BACKGROUND: De novo lipogenesis (DNL) is the primary metabolic pathway synthesizing fatty acids from carbohydrates, protein, or alcohol. Our aim was to examine associations of in vivo levels of selected fatty acids (16:0, 16:1n7, 18:0, 18:1n9) in DNL with incidence of type 2 diabetes (T2D). METHODS AND FINDINGS: Seventeen cohorts from 12 countries (7 from Europe, 7 from the United States, 1 from Australia, 1 from Taiwan; baseline years = 1970-1973 to 2006-2010) conducted harmonized individual-level analyses of associations of DNL-related fatty acids with incident T2D. In total, we evaluated 65,225 participants (mean ages = 52.3-75.5 years; % women = 20.4%-62.3% in 12 cohorts recruiting both sexes) and 15,383 incident cases of T2D over the 9-year follow-up on average. Cohort-specific association of each of 16:0, 16:1n7, 18:0, and 18:1n9 with incident T2D was estimated, adjusted for demographic factors, socioeconomic characteristics, alcohol, smoking, physical activity, dyslipidemia, hypertension, menopausal status, and adiposity. Cohort-specific associations were meta-analyzed with an inverse-variance-weighted approach. Each of the 4 fatty acids positively related to incident T2D. Relative risks (RRs) per cohort-specific range between midpoints of the top and bottom quintiles of fatty acid concentrations were 1.53 (1.41-1.66; p < 0.001) for 16:0, 1.40 (1.33-1.48; p < 0.001) for 16:1n-7, 1.14 (1.05-1.22; p = 0.001) for 18:0, and 1.16 (1.07-1.25; p < 0.001) for 18:1n9. Heterogeneity was seen across cohorts (I2 = 51.1%-73.1% for each fatty acid) but not explained by lipid fractions and global geographical regions. Further adjusted for triglycerides (and 16:0 when appropriate) to evaluate associations independent of overall DNL, the associations remained significant for 16:0, 16:1n7, and 18:0 but were attenuated for 18:1n9 (RR = 1.03, 95% confidence interval (CI) = 0.94-1.13). These findings had limitations in potential reverse causation and residual confounding by imprecisely measured or unmeasured factors. CONCLUSIONS: Concentrations of fatty acids in the DNL were positively associated with T2D incidence. Our findings support further work to investigate a possible role of DNL and individual fatty acids in the development of T2D.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Ácidos Graxos/metabolismo , Lipogênese , Idoso , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Ácidos Graxos/sangue , Feminino , Humanos , Incidência , Masculino , Redes e Vias Metabólicas , Pessoa de Meia-Idade , Estudos Prospectivos
17.
Nat Commun ; 11(1): 3026, 2020 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-32541860

RESUMO

Survival in complex environments necessitates a flexible navigation system that incorporates memory of recent behavior and associations. Yet, how the hippocampal spatial circuit represents latent information independent of sensory inputs and future goals has not been determined. To address this, we image the activity of large ensembles in subregion CA1 via wide-field fluorescent microscopy during a novel behavioral paradigm. Our results demonstrate that latent information is represented through reliable firing rate changes during unconstrained navigation. We then hypothesize that the representation of latent information in CA1 is mediated by pattern separation/completion processes instantiated upstream within the dentate gyrus (DG) and CA3 subregions. Indeed, CA3 ensemble recordings reveal an analogous code for latent information. Moreover, selective chemogenetic inactivation of DG-CA3 circuitry completely and reversibly abolishes the CA1 representation of latent information. These results reveal a causal and specific role of DG-CA3 circuitry in the maintenance of latent information within the hippocampus.


Assuntos
Região CA3 Hipocampal/fisiologia , Giro Denteado/fisiologia , Animais , Região CA1 Hipocampal/fisiologia , Masculino , Memória , Camundongos Endogâmicos C57BL , Modelos Neurológicos , Reconhecimento Fisiológico de Modelo
18.
Cardiol Ther ; 9(2): 447-465, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32564340

RESUMO

INTRODUCTION: Clinicians, payers, guideline committees, and policymakers support the use of high-intensity statins in patients at high risk for complications of cardiovascular disease (CVD). Guidelines and recommendations provide guidance on next steps for patients with inadequate low-density lipoprotein cholesterol (LDL-C) control on maximally tolerated statin or for those who are statin-intolerant. Ezetimibe and evolocumab improve CV outcomes when added to statins in high-CV-risk populations. The aim of the study was to compare evolocumab and ezetimibe for lipid-lowering efficacy and safety. METHODS: We summarized data from 1427 patients from three phase 3 evolocumab studies comparing double-blinded evolocumab vs. ezetimibe. These studies evaluated four distinct populations: those free of CVD receiving each agent as monotherapy, patients with CVD receiving add-on therapy to low- or high-intensity statin, and statin-intolerant patients. Lipid efficacy and safety were reported at week 12. RESULTS: Across the studies, evolocumab reduced LDL-C by a mean 55-61% from baseline to week 12; ezetimibe lowered LDL-C by 18-20% from baseline (mean difference = 38-43% favoring evolocumab; p < 0.0001). This corresponded to absolute reductions in LDL-C of 60-104 mg/dL with evolocumab vs. 17-35 mg/dL with ezetimibe. Evolocumab also significantly improved other lipids and led to a higher percentage of patients achieving LDL-C goals vs. ezetimibe. Adverse events and discontinuation rates (oral and parenteral therapy) were balanced across groups, suggesting good tolerance and acceptance of both treatments. CONCLUSIONS: Evolocumab outperformed ezetimibe in efficacy and lipid goal attainment. Both products demonstrated good safety/tolerability. These data may help guide access decisions for high-risk patients with inadequate treatment response or intolerance to statin therapy.

19.
Am Heart J ; 225: 88-96, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32485329

RESUMO

Intensive lipid management is critical to reduce cardiovascular (CV) risk for patients with diabetes mellitus (DM). METHODS: We performed an observational study of 7628 patients with (n = 2943) and without DM (n = 4685), enrolled in the Provider Assessment of Lipid Management (PALM) registry and treated at 140 outpatient clinics across the United States in 2015. Patient self-estimated CV risk, patient-perceived statin benefit and risk, observed statin therapy use and dosing were assessed. RESULTS: Patients with DM were more likely to believe that their CV risk was elevated compared with patients without DM (39.1% vs 29.3%, P < .001). Patients with DM were more likely to receive a statin (74.2% vs 63.5%, P < .001) but less likely to be treated with guideline-recommended statin intensity (36.5% vs 46.9%, P < .001), driven by the low proportion (16.5%) of high risk (ASCVD risk ≥7.5%) primary prevention DM patients treated with a high intensity statin. Patients with DM treated with guideline-recommended statin intensity were more likely to believe they were at high CV risk (44.9% vs 38.4%, P = .005) and that statins can reduce this risk (41.1% vs 35.6%, P = .02), compared with patients treated with lower than guideline-recommended statin intensity. Compared with patients with an elevated HgbA1c, patients with well-controlled DM were no more likely to be on a statin (77.9% vs 79.3%, P = .43). CONCLUSIONS: In this nationwide study, the majority of patients with DM were treated with lower than guideline-recommended statin intensity. Patient education and engagement may help providers improve lipid therapy for these high-risk patients.


Assuntos
Atitude Frente a Saúde , Complicações do Diabetes/tratamento farmacológico , Diabetes Mellitus , Fidelidade a Diretrizes , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Idoso , Doenças Cardiovasculares/prevenção & controle , Colesterol/sangue , Diabetes Mellitus/sangue , Feminino , Hemoglobina A Glicada/análise , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Sistema de Registros , Fatores de Risco , Estados Unidos
20.
Curr Pharm Teach Learn ; 12(7): 885-892, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32540052

RESUMO

BACKGROUND AND PURPOSE: A mental health first aid elective course was developed at a four-year doctor of pharmacy program. The objectives of the course were to de-stigmatize the attitudes of enrolled student pharmacists and provide tools to triage and manage mental health crises. The purpose of this work is to investigate the impact of a newly developed mental health first aid elective course. EDUCATIONAL ACTIVITY AND SETTING: Student pharmacists enrolled in a two-credit mental health first aid elective course and electronically completed the Opening Minds Scale for Health Care Providers (OMS-HC) pre-course, post-course, and months post-course to quantitatively measure changes in attitudes around stigma in various domains. Students also submitted a guided reflection post-course to collect self-perceived changes in attitudes. The reflection evaluated the changes in perceptions, confidence, and willingness to practice mental health first aid. FINDINGS: Forty-second and third-year student pharmacists participated and 31 were included in the pre-protocol analysis for pre- and post-course paired comparisons. Improvements in the OMS-HC domains of "disclosure and help-seeking" and "attitudes of health care providers" at post-course were observed. Self-reflections submitted post-course supported the quantitative analysis results of the OMS-HC scores. Improvements were noted in attitudes towards individuals with mental health disorders and in confidence and willingness to initiate conversations on mental health. SUMMARY: The implementation of a mental health first aid elective course positively influenced student pharmacists' attitudes on mental health and improved confidence and willingness to provide mental health related interventions.

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