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1.
Sci Rep ; 12(1): 7973, 2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35562385

RESUMO

Rapid eye movement (REM) sleep behaviour disorder (RBD) is a REM parasomnia that often predicts the later occurrence of alpha-synucleinopathies. Variants in the gene encoding for the lysosomal enzyme glucocerebrosidase, GBA, strongly increase the risk of RBD. In a GBA1-mouse model recently shown to mimic prodromal stages of α-synucleinopathy, we now demonstrate striking REM and NREM electroencephalographic sleep abnormalities accompanied by distinct structural changes in the more widespread sleep neurocircuitry.

2.
Nat Med ; 2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-35361992

RESUMO

Since its emergence in 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused hundreds of millions of cases and continues to circulate globally. To establish a novel SARS-CoV-2 human challenge model that enables controlled investigation of pathogenesis, correlates of protection and efficacy testing of forthcoming interventions, 36 volunteers aged 18-29 years without evidence of previous infection or vaccination were inoculated with 10 TCID50 of a wild-type virus (SARS-CoV-2/human/GBR/484861/2020) intranasally in an open-label, non-randomized study (ClinicalTrials.gov identifier NCT04865237 ; funder, UK Vaccine Taskforce). After inoculation, participants were housed in a high-containment quarantine unit, with 24-hour close medical monitoring and full access to higher-level clinical care. The study's primary objective was to identify an inoculum dose that induced well-tolerated infection in more than 50% of participants, with secondary objectives to assess virus and symptom kinetics during infection. All pre-specified primary and secondary objectives were met. Two participants were excluded from the per-protocol analysis owing to seroconversion between screening and inoculation, identified post hoc. Eighteen (~53%) participants became infected, with viral load (VL) rising steeply and peaking at ~5 days after inoculation. Virus was first detected in the throat but rose to significantly higher levels in the nose, peaking at ~8.87 log10 copies per milliliter (median, 95% confidence interval (8.41, 9.53)). Viable virus was recoverable from the nose up to ~10 days after inoculation, on average. There were no serious adverse events. Mild-to-moderate symptoms were reported by 16 (89%) infected participants, beginning 2-4 days after inoculation, whereas two (11%) participants remained asymptomatic (no reportable symptoms). Anosmia or dysosmia developed more slowly in 15 (83%) participants. No quantitative correlation was noted between VL and symptoms, with high VLs present even in asymptomatic infection. All infected individuals developed serum spike-specific IgG and neutralizing antibodies. Results from lateral flow tests were strongly associated with viable virus, and modeling showed that twice-weekly rapid antigen tests could diagnose infection before 70-80% of viable virus had been generated. Thus, with detailed characterization and safety analysis of this first SARS-CoV-2 human challenge study in young adults, viral kinetics over the course of primary infection with SARS-CoV-2 were established, with implications for public health recommendations and strategies to affect SARS-CoV-2 transmission. Future studies will identify the immune factors associated with protection in those participants who did not develop infection or symptoms and define the effect of prior immunity and viral variation on clinical outcome.

3.
Vaccine ; 40(20): 2848-2855, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35396165

RESUMO

Vaccines for SARS-CoV-2 have been hugely successful in alleviating hospitalization and deaths caused by the newly emerged coronavirus that is the cause of COVID. However, although the parentally administered vaccines are very effective at reducing severe disease, they do not induce sterilizing immunity. As the virus continues to circulate around the globe, it is still not clear how long protection will last, nor whether variants will emerge that escape vaccine immunity. Animal models can be useful to complement studies of antigenicity of novel variants and inform decision making about the need for vaccine updates. The Syrian golden hamster is the preferred small animal model for SARS-CoV-2 infection. Since virus is efficiently transmitted between hamsters, we developed a transmission challenge model that presents a more natural dose and route of infection than the intranasal challenge usually employed. Our studies demonstrate that an saRNA vaccine based on the earliest Wuhan-like virus spike sequence induced neutralizing antibodies in sera of immunized hamsters at similar titres to those in human convalescent sera or vaccine recipients. The saRNA vaccine was equally effective at abrogating clinical signs in animals who acquired through exposure to cagemates infected either with a virus isolated in summer 2020 or with a representative Alpha (B.1.1.7) variant isolated in December 2020. The vaccine also reduced shedding of infectious virus from the nose, further reinforcing its likely effectiveness at reducing onwards transmission. This model can be extended to test the effectiveness of vaccination in blocking infections with and transmission of novel variants as they emerge.


Assuntos
COVID-19 , Vacinas Virais , Animais , COVID-19/prevenção & controle , COVID-19/terapia , Vacinas contra COVID-19 , Cricetinae , Humanos , Imunização Passiva , SARS-CoV-2 , Vacinas Sintéticas
4.
J Clin Invest ; 132(7)2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35362476

RESUMO

The prevalence of metabolic syndrome continues to increase globally and heightens the risk for cardiovascular disease (CVD). Insulin resistance is a core pathophysiologic mechanism that causes abnormal carbohydrate metabolism and atherogenic changes in circulating lipoprotein quantity and function. In particular, dysfunctional HDL is postulated to contribute to CVD risk in part via loss of HDL-associated sphingosine-1-phosphate (S1P). In this issue of the JCI, Izquierdo et al. demonstrate that HDL from humans with insulin resistance contained lower levels of S1P. Apolipoprotein M (ApoM), a protein constituent of HDL that binds S1P and controls bioavailability was decreased in insulin-resistant db/db mice. Gain- and loss-of-function mouse models implicated the forkhead box O transcription factors (FoxO1,3,4) in the regulation of both ApoM and HDL-associated S1P. These data have important implications for potential FoxO-based therapies designed to treat lipid and carbohydrate abnormalities associated with human metabolic disease and CVD.


Assuntos
Apolipoproteínas M , Fatores de Transcrição Forkhead , Resistência à Insulina , Doenças Metabólicas , Animais , Apolipoproteínas M/metabolismo , Fatores de Transcrição Forkhead/genética , Lipoproteínas HDL/metabolismo , Camundongos
5.
Nat Commun ; 13(1): 1609, 2022 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-35338134

RESUMO

Ultrastructural studies of SARS-CoV-2 infected cells are crucial to better understand the mechanisms of viral entry and budding within host cells. Here, we examined human airway epithelium infected with three different isolates of SARS-CoV-2 including the B.1.1.7 variant by transmission electron microscopy and tomography. For all isolates, the virus infected ciliated but not goblet epithelial cells. Key SARS-CoV-2 entry molecules, ACE2 and TMPRSS2, were found to be localised to the plasma membrane including microvilli but excluded from cilia. Consistently, extracellular virions were seen associated with microvilli and the apical plasma membrane but rarely with ciliary membranes. Profiles indicative of viral fusion where tomography showed that the viral membrane was continuous with the apical plasma membrane and the nucleocapsids diluted, compared with unfused virus, demonstrate that the plasma membrane is one site of entry where direct fusion releasing the nucleoprotein-encapsidated genome occurs. Intact intracellular virions were found within ciliated cells in compartments with a single membrane bearing S glycoprotein. Tomography showed concentration of nucleocapsids round the periphery of profiles strongly suggestive of viral budding into these compartments and this may explain how virions gain their S glycoprotein containing envelope.


Assuntos
COVID-19 , SARS-CoV-2 , Epitélio/metabolismo , Humanos , Peptidil Dipeptidase A/metabolismo
6.
Sci Adv ; 8(10): eabj2917, 2022 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-35263131

RESUMO

Circulating corticosteroids orchestrate stress adaptation, including inhibition of inflammation. While pathways governing corticosteroid biosynthesis and intracellular signaling are well understood, less is known about mechanisms controlling plasma corticosteroid transport. Here, we show that hepatocyte KLF15 (Kruppel-like factor 15) controls plasma corticosteroid transport and inflammatory responses through direct transcriptional activation of Serpina6, which encodes corticosteroid-binding globulin (CBG). Klf15-deficient mice have profoundly low CBG, reduced plasma corticosteroid binding capacity, and heightened mortality during inflammatory stress. These defects are completely rescued by reconstituting CBG, supporting that KLF15 works primarily through CBG to control plasma corticosterone homeostasis. To understand transcriptional mechanisms, we generated the first KLF15 cistromes using newly engineered Klf153xFLAG mice. Unexpectedly, liver KLF15 is predominantly promoter enriched, including Serpina6, where it binds a palindromic GC-rich motif, opens chromatin, and transactivates genes with minimal associated direct gene repression. Overall, we provide critical mechanistic insight into KLF15 function and identify a hepatocyte-intrinsic transcriptional module that potently regulates systemic corticosteroid transport and inflammation.

7.
Clin Case Rep ; 10(3): e05624, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35340630

RESUMO

Contrast-induced encephalopathy (CIE) is a rare, reversible complication of coronary angiography that can mimic acute strokes. This case illustrates the diagnostic challenges for a patient presenting with confusion following coronary angiography and raises awareness for CIE as diagnosis of exclusion.

8.
J Athl Train ; 57(2): 158-164, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35201302

RESUMO

CONTEXT: Altered knee moments are common during gait in patients after anterior cruciate ligament reconstruction (ACLR). Modifiable factors that influence knee moments and are feasible to record in clinical settings such as strength and spatiotemporal values (eg, step length, step width) have not been identified in persons after ACLR. OBJECTIVE: To identify strength and spatiotemporal gait values that can predict knee moments in persons after ACLR. DESIGN: Cross-sectional study. SETTING: Laboratory. PATIENTS OR OTHER PARTICIPANTS: Twenty-three individuals with ACLR (14.4 ± 17.2 months post-ACLR). MAIN OUTCOME MEASURE(S): Peak knee-flexion and -adduction moments were measured while the participants walked at self-selected speeds. Peak isokinetic knee-extensor strength (60°/s) was recorded on a dynamometer, and spatiotemporal gait values were recorded using a pressure walkway. Pearson coefficients were calculated to examine the association of peak knee moments with strength and gait values. Variables correlated with peak knee-flexion and -adduction moments were entered into a stepwise regression model. RESULTS: Knee-extensor strength and step width were the strongest predictors of knee-flexion moment, accounting for 44% of the variance, whereas stance-phase time and step width were the strongest predictors of knee-adduction moment, explaining 62% of the variance. CONCLUSIONS: The identified spatiotemporal variables could be clinically feasible targets for biofeedback to improve gait after ACLR.


Assuntos
Lesões do Ligamento Cruzado Anterior , Reconstrução do Ligamento Cruzado Anterior , Lesões do Ligamento Cruzado Anterior/cirurgia , Fenômenos Biomecânicos , Estudos Transversais , Marcha , Humanos , Articulação do Joelho/cirurgia
9.
Elife ; 112022 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-35084335

RESUMO

There is mounting evidence that microbes residing in the human intestine contribute to diverse alcohol-associated liver diseases (ALD) including the most deadly form known as alcohol-associated hepatitis (AH). However, mechanisms by which gut microbes synergize with excessive alcohol intake to promote liver injury are poorly understood. Furthermore, whether drugs that selectively target gut microbial metabolism can improve ALD has never been tested. We used liquid chromatography tandem mass spectrometry to quantify the levels of microbe and host choline co-metabolites in healthy controls and AH patients, finding elevated levels of the microbial metabolite trimethylamine (TMA) in AH. In subsequent studies, we treated mice with non-lethal bacterial choline TMA lyase (CutC/D) inhibitors to blunt gut microbe-dependent production of TMA in the context of chronic ethanol administration. Indices of liver injury were quantified by complementary RNA sequencing, biochemical, and histological approaches. In addition, we examined the impact of ethanol consumption and TMA lyase inhibition on gut microbiome structure via 16S rRNA sequencing. We show the gut microbial choline metabolite TMA is elevated in AH patients and correlates with reduced hepatic expression of the TMA oxygenase flavin-containing monooxygenase 3 (FMO3). Provocatively, we find that small molecule inhibition of gut microbial CutC/D activity protects mice from ethanol-induced liver injury. CutC/D inhibitor-driven improvement in ethanol-induced liver injury is associated with distinct reorganization of the gut microbiome and host liver transcriptome. The microbial metabolite TMA is elevated in patients with AH, and inhibition of TMA production from gut microbes can protect mice from ethanol-induced liver injury.


Assuntos
Bactérias/metabolismo , Doença Hepática Crônica Induzida por Substâncias e Drogas/metabolismo , Microbioma Gastrointestinal , Hepatite/metabolismo , Metilaminas/metabolismo , Animais , Etanol/efeitos adversos , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Distribuição Aleatória
10.
Elife ; 112022 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-35072627

RESUMO

Obesity has repeatedly been linked to reorganization of the gut microbiome, yet to this point obesity therapeutics have been targeted exclusively toward the human host. Here, we show that gut microbe-targeted inhibition of the trimethylamine N-oxide (TMAO) pathway protects mice against the metabolic disturbances associated with diet-induced obesity (DIO) or leptin deficiency (Lepob/ob). Small molecule inhibition of the gut microbial enzyme choline TMA-lyase (CutC) does not reduce food intake but is instead associated with alterations in the gut microbiome, improvement in glucose tolerance, and enhanced energy expenditure. We also show that gut microbial CutC inhibition is associated with reorganization of host circadian control of both phosphatidylcholine and energy metabolism. This study underscores the relationship between microbe and host metabolism and provides evidence that gut microbe-derived trimethylamine (TMA) is a key regulator of the host circadian clock. This work also demonstrates that gut microbe-targeted enzyme inhibitors have potential as anti-obesity therapeutics.


Assuntos
Colina/análogos & derivados , Ritmo Circadiano/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Obesidade/metabolismo , Animais , Colina/administração & dosagem , Colina/metabolismo , Dieta Hiperlipídica , Inibidores Enzimáticos/farmacologia , Leptina/deficiência , Liases/efeitos dos fármacos , Masculino , Metilaminas/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/genética , Obesidade/microbiologia
11.
Cell Rep ; 38(6): 110344, 2022 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-35093235

RESUMO

SARS-CoV-2 has a broad mammalian species tropism infecting humans, cats, dogs, and farmed mink. Since the start of the 2019 pandemic, several reverse zoonotic outbreaks of SARS-CoV-2 have occurred in mink, one of which reinfected humans and caused a cluster of infections in Denmark. Here we investigate the molecular basis of mink and ferret adaptation and demonstrate the spike mutations Y453F, F486L, and N501T all specifically adapt SARS-CoV-2 to use mustelid ACE2. Furthermore, we risk assess these mutations and conclude mink-adapted viruses are unlikely to pose an increased threat to humans, as Y453F attenuates the virus replication in human cells and all three mink adaptations have minimal antigenic impact. Finally, we show that certain SARS-CoV-2 variants emerging from circulation in humans may naturally have a greater propensity to infect mustelid hosts and therefore these species should continue to be surveyed for reverse zoonotic infections.


Assuntos
Adaptação Biológica/imunologia , SARS-CoV-2/genética , Zoonoses Virais/genética , Animais , COVID-19 , Furões/imunologia , Aptidão Genética/genética , Humanos , Vison/imunologia , Mutação , Pandemias , Sistema Respiratório/virologia , SARS-CoV-2/patogenicidade , Glicoproteína da Espícula de Coronavírus/imunologia
12.
Hisp Health Care Int ; 20(1): 4-9, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33882734

RESUMO

INTRODUCTION: Reliable and valid measures are needed to assess the patient-centeredness of clinical care among Latino populations. METHODS: We translated the Consultation and Relational Empathy (CARE) measure from English to Spanish and assessed its psychometric properties using data from 349 Latino parents/guardians visiting a pediatric clinic. Using confirmatory factor analysis, we examined the psychometric properties of the Spanish CARE measure. RESULTS: Internal reliability of the Spanish CARE measure was high (Omega coefficient = 0.95). Similar to the English-language CARE measure, factor analysis of the Spanish CARE measure yielded a single domain of patient-centeredness with high item loadings (factor loadings range from 0.79 to 0.96). CONCLUSION: This preliminary analysis supports the reliability and validity of the Spanish version of the CARE measure among Latinos in pediatric care settings. With further testing, the Spanish CARE measure may be a useful tool for tracking and improving the health care delivered to Latino populations.


Assuntos
Empatia , Idioma , Criança , Humanos , Assistência Centrada no Paciente , Psicometria , Encaminhamento e Consulta , Reprodutibilidade dos Testes , Inquéritos e Questionários
13.
Psychiatr Serv ; 73(5): 584-587, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34496629

RESUMO

Initiatives that support and incentivize the integration of behavioral health and general medical care have become a focus of government strategies to achieve the triple aim of improved health, better patient experience, and reduced costs. The authors describe the components of four large-scale national initiatives aimed at integrating care for a wide range of behavioral health needs. Commonalities across these national initiatives highlight health care and social services needs that must be addressed to improve care for people with co-occurring behavioral health and general medical conditions. These findings can inform how to design, test, select, and align the most promising strategies for integrated care in a variety of settings.

14.
Res Sq ; 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34816257

RESUMO

Cell penetrating peptides are unique, 5-30 amino acid long peptides that are able to breach cell membrane barriers and carry cargoes intracellularly in a functional form. Our prior work identified a synthetic, non-naturally occurring 12-amino acid long peptide that we termed cardiac targeting peptide (CTP: APWHLSSQYSRT) due to its ability to transduce cardiomyocytes in vivo. Studies looking into its mechanism of transduction identified two lung targeting peptides (LTPs), S7A (APWHLSAQYSRT) and R11A (APWHLSSQYSAT). These peptides robustly transduced human bronchial epithelial cell lines in vitro and mouse lung tissue in vivo. This uptake occurred independently of clathrin mediated endocytosis. Biodistribution studies of R11A showed peak uptake at 15 minutes with uptake in liver but not kidneys, indicating primarily a hepatobiliary mode of excretion. Cyclic version of both peptides was ~100-fold more efficient in permeating cells than their linear counterparts. As proof of principle, we conjugated anti-spike and anti-envelope SARS-CoV-2 siRNAs to cyclized R11A and demonstrate anti-viral efficacy in vitro. Our work presented here identifies two novel lung-specific cell penetrating peptides that could potentially deliver myriad therapeutic cargoes to lung tissue.

15.
Water Res ; 205: 117718, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34619607

RESUMO

SARS-CoV-2 transmission remains a global problem which exerts a significant direct cost to public health. Additionally, other aspects of physical and mental health can be affected by limited access to social and exercise venues as a result of lockdowns in the community or personal reluctance due to safety concerns. Swimming pools reopened in the UK on April 12th 2021, but the effect of swimming pool water on inactivation of SARS-CoV-2 has not yet been directly demonstrated. Here we demonstrate that chlorinated water which adheres to UK swimming pool guidelines is sufficient to reduce SARS-CoV-2 infectious titre by at least 3 orders of magnitude.


Assuntos
COVID-19 , Desinfetantes , Piscinas , Cloro , Controle de Doenças Transmissíveis , Humanos , SARS-CoV-2 , Natação , Água
16.
Nature ; 599(7883): 114-119, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34488225

RESUMO

The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era.


Assuntos
Evasão da Resposta Imune , SARS-CoV-2/crescimento & desenvolvimento , SARS-CoV-2/imunologia , Replicação Viral/imunologia , Anticorpos Neutralizantes/imunologia , Vacinas contra COVID-19/imunologia , Fusão Celular , Linhagem Celular , Feminino , Pessoal de Saúde , Humanos , Índia , Cinética , Masculino , Glicoproteína da Espícula de Coronavírus/metabolismo , Vacinação
19.
J Athl Train ; 2021(preprint): 0, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34329453

RESUMO

CONTEXT: Altered knee moments are common during gait in patients following anterior cruciate ligament reconstruction (ACLR). Modifiable factors that influence knee moments and are feasible to record in clinical settings such as strength and spatiotemporal parameters (e.g. step length, step width) have not been identified in persons after ACLR. OBJECTIVE: The objective was to identify strength and spatiotemporal gait parameters that can predict knee moments in persons after ACLR. DESIGN: Cross-Sectional Study Setting: Laboratory Patients: Twenty-three participants with ACLR (14.4 ± 17.2 months post-ACLR) participated. MAIN OUTCOME MEASURES: Peak knee flexion and adduction moments were measured while walking at self-selected speeds. Spatiotemporal gait parameters were recorded with a pressure walkway, and peak isokinetic knee extensor strength (60°/s) was recorded on a dynamometer. Pearson coefficients were used to examine the association of peak knee moments with strength and gait parameters. Variables correlated with peak knee flexion and adduction moments were entered into a stepwise regression model. RESULTS: Step width and knee extensor strength were the strongest predictors of knee flexion moment accounting for 44% of data variance, whereas stance phase time and step width were the strongest predictors of knee adduction moment explaining 62% of data variance. CONCLUSIONS: The spatiotemporal variables that were identified could be clinically feasible targets for biofeedback to improve gait after ACLR.


Assuntos
Lesões do Ligamento Cruzado Anterior , Reconstrução do Ligamento Cruzado Anterior , Marcha , Força Muscular , Lesões do Ligamento Cruzado Anterior/cirurgia , Fenômenos Biomecânicos , Estudos Transversais , Humanos , Articulação do Joelho/cirurgia , Amplitude de Movimento Articular
20.
Psychiatr Serv ; 72(11): 1301-1310, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34074150

RESUMO

People with serious mental illness die 10-20 years earlier, compared with the overall population, and the excess mortality is driven by undertreated physical health conditions. In the United States, there is growing interest in models integrating physical health care delivery, management, or coordination into specialty mental health programs, sometimes called "reverse integration." In November 2019, the Johns Hopkins ALACRITY Center for Health and Longevity in Mental Illness convened a forum of 25 experts to discuss the current state of the evidence on integrated care models based in the specialty mental health system and to identify priorities for future research, policy, and practice. This article summarizes the group's conclusions. Key research priorities include identifying the active ingredients in multicomponent integrated care models and developing and validating integration performance metrics. Key policy and practice recommendations include developing new financing mechanisms and implementing strategies to build workforce and data capacity. Forum participants also highlighted an overarching need to address socioeconomic risks contributing to excess mortality among adults with serious mental illness.


Assuntos
Transtornos Mentais , Saúde Mental , Adulto , Humanos , Transtornos Mentais/epidemiologia , Transtornos Mentais/terapia , Estados Unidos , Recursos Humanos
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