Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 153
Filtrar
1.
Acta Haematol ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38861934

RESUMO

Introduction Promotion of self-efficacy can enhance engagement with healthcare and treatment adherence in patients with cancer. We report the outcomes of a pilot trial of a digital health coach intervention in patients with leukemia with the aim of improving self-efficacy. Methods Adult patients with newly diagnosed acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL) were randomized 1:1 to a digital health coach intervention or standard of care. The primary outcome of self-efficacy was measured by the Cancer Behavior Inventory (CBI) score. Results One-hundred and forty-seven patients (37 AML, 110 CLL) were enrolled from July 2020 to December 2022. In the AML cohort, there was a mean increase in CBI score of 7.03 in the digital health coaching arm compared to a mean decrease of -3.57 in the control arm at 30 days (p=0.219). There were no significant associations between the intervention and other patient reported outcomes for patients with CLL. Conclusion There were numerical, but not statistically significant increases in self-efficacy metrics in AML patients who received digital health coaching. Although this trial was underpowered due to enrollment limitations during a pandemic, digital health coaching may provide benefit to patients with hematologic malignancy and warrants further investigation.

2.
PLoS One ; 19(6): e0305165, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38885220

RESUMO

The objective of this study was to estimate the associations of jail-initiated medication for opioid use disorder (MOUD) and patient navigation (PN) with opioid use disorder (OUD) at 6 months post-release. Three randomized trials (combined N = 330) were combined to assess whether MOUD (extended-release naltrexone or interim methadone) initiated prior to release from jail with or without PN would reduce the likelihood of a DSM-5 diagnosis of OUD 6 months post-release relative to enhanced treatment-as-usual (ETAU). Across the three studies, assignment to MOUD compared to ETAU was not associated with an OUD diagnosis at 6 months post-release (69% vs. 75%, respectively, OR = 0.67, 95% CI: 0.42 to 1.20). Similarly, PN compared to MOUD without PN was not associated with an OUD diagnosis (63% vs 77%, respectively, OR = 0.61, 95% CI: 0.27 to 1.53). Results underscore the need to further optimize the effectiveness of MOUD for patients initiating treatment in jail, beginning with an emphasis on post-release treatment adherence.


Assuntos
Metadona , Naltrexona , Transtornos Relacionados ao Uso de Opioides , Humanos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Masculino , Naltrexona/uso terapêutico , Feminino , Adulto , Metadona/uso terapêutico , Prisões Locais , Tratamento de Substituição de Opiáceos/métodos , Pessoa de Meia-Idade , Antagonistas de Entorpecentes/uso terapêutico , Prisioneiros
3.
Addict Sci Clin Pract ; 19(1): 33, 2024 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-38678216

RESUMO

BACKGROUND: Individuals with substance use disorders (SUDs) frequently use acute hospital services. The Navigation Services to Avoid Rehospitalization (NavSTAR) trial found that a patient navigation intervention for hospitalized patients with comorbid SUDs reduced subsequent inpatient admissions compared to treatment-as-usual (TAU). METHODS: This secondary analysis extends previous findings from the NavSTAR trial by examining whether selected patient characteristics independently predicted hospital service utilization and moderated the effect of the NavSTAR intervention. Participants were 400 medical/surgical hospital patients with comorbid SUDs. We analyzed 30- and 90-day inpatient readmissions (one or more readmissions) and cumulative incidence of inpatient admissions through 12 months using multivariable logistic and negative binomial regression, respectively. RESULTS: Consistent with primary findings and controlling for patient factors, NavSTAR participants were less likely than TAU participants to be readmitted within 30 (P = 0.001) and 90 (P = 0.03) days and had fewer total readmissions over 12 months (P = 0.008). Hospitalization in the previous year (P < 0.001) was associated with cumulative readmissions over 12 months, whereas Medicaid insurance (P = 0.03) and index diagnoses of infection (P = 0.001) and injuries, poisonings, or procedural complications (P = 0.004) were associated with fewer readmissions. None of the selected covariates moderated the effect of the NavSTAR intervention. CONCLUSIONS: Previous findings showed that patient navigation could reduce repeat hospital admissions among patients with comorbid SUDs. Several patient factors were independently associated with readmission. Future research should investigate risk factors for hospital readmission among patients with comorbid SUDs to optimize interventions. TRIAL REGISTRATION: NIH ClinicalTrials.gov NCT02599818, Registered November 9, 2015 https://classic. CLINICALTRIALS: gov/ct2/show/NCT02599818 .


Assuntos
Comorbidade , Readmissão do Paciente , Transtornos Relacionados ao Uso de Substâncias , Humanos , Masculino , Feminino , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/terapia , Readmissão do Paciente/estatística & dados numéricos , Pessoa de Meia-Idade , Adulto , Hospitalização/estatística & dados numéricos , Navegação de Pacientes , Estados Unidos/epidemiologia
4.
J Struct Biol X ; 9: 100096, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38318529

RESUMO

Milk contains high concentrations of amyloidogenic casein proteins and is supersaturated with respect to crystalline calcium phosphates such as apatite. Nevertheless, the mammary gland normally remains unmineralized and free of amyloid. Unlike κ-casein, ß- and αS-caseins are highly effective mineral chaperones that prevent ectopic and pathological calcification of the mammary gland. Milk invariably contains a mixture of two to five different caseins that act on each other as molecular chaperones. Instead of forming amyloid fibrils, several thousand caseins and hundreds of nanoclusters of amorphous calcium phosphate combine to form fuzzy complexes called casein micelles. To understand the biological functions of the casein micelle its structure needs to be understood better than at present. The location in micelles of the highly amyloidogenic κ-casein is disputed. In traditional hydrophobic colloid models, it, alone, forms a stabilizing surface coat that also determines the average size of the micelles. In the recent multivalent-binding model, κ-casein is present throughout the micelle, in intimate contact with the other caseins. To discriminate between these models, a range of biomimetic micelles was prepared using a fixed concentration of the mineral chaperone ß-casein and nanoclusters of calcium phosphate, with variable concentrations of κ-casein. A biomimetic micelle was also prepared using a highly deuterated and in vivo phosphorylated recombinant ß-casein with calcium phosphate and unlabelled κ-casein. Neutron and X-ray scattering experiments revealed that κ-casein is distributed throughout the micelle, in quantitative agreement with the multivalent-binding model but contrary to the hydrophobic colloid models.

6.
JAMA ; 330(22): 2200-2208, 2023 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-37943553

RESUMO

Importance: In the US, the prevalence of hepatitis C virus (HCV) is 1.8% among people who are Black and 0.8% among people who are not Black. Mortality rates due to HCV are 5.01/100 000 among people who are Black and 2.98/100 000 among people who are White. Observations: While people of all races and ethnicities experienced increased rates of incident HCV between 2015 and 2021, Black individuals experienced the largest percentage increase of 0.3 to 1.4/100 000 (367%) compared with 1.8 to 2.7/100 000 among American Indian/Alaska Native (50%), 0.3 to 0.9/100 000 among Hispanic (200%), and 0.9 to 1.6/100 000 among White (78%) populations. Among 47 687 persons diagnosed with HCV in 2019-2020, including 37 877 (79%) covered by Medicaid (7666 Black and 24 374 White individuals), 23.5% of Black people and 23.7% of White people with Medicaid insurance initiated HCV treatment. Strategies to increase HCV screening include electronic health record prompts for universal HCV screening, which increased screening tests from 2052/month to 4169/month in an outpatient setting. Awareness of HCV status can be increased through point-of-care testing in community-based settings, which was associated with increased likelihood of receiving HCV test results compared with referral for testing off-site (69% on-site vs 19% off-site, P < .001). Access to HCV care can be facilitated by patient navigation, in which an individual is assigned to work with a patient to help them access care and treatments; this was associated with greater likelihood of HCV care access (odds ratio, 3.7 [95% CI, 2.9-4.8]) and treatment initiation within 6 months (odds ratio, 3.2 [95% CI, 2.3-4.2]) in a public health system providing health care to individuals regardless of their insurance status or ability to pay compared with usual care. Eliminating Medicaid's HCV treatment restrictions, including removal of a requirement for advanced fibrosis or a specialist prescriber, was associated with increased treatment rates from 2.4 persons per month to 72.3 persons per month in a retrospective study of 10 336 adults with HCV with no significant difference by race (526/1388 [37.8%] for Black vs 2706/8277 [32.6%] for White patients; adjusted odds ratio, 1.02 [95% CI, 0.8-1.3]). Conclusions and Relevance: In the US, the prevalence of HCV is higher in people who are Black than in people who are not Black. Point-of-care HCV tests, patient navigation, electronic health record prompts, and unrestricted access to HCV treatment in community-based settings have potential to increase diagnosis and treatment of HCV and improve outcomes in people who are Black.


Assuntos
Hepacivirus , Hepatite C , Adulto , Estados Unidos/epidemiologia , Humanos , Estudos Retrospectivos , Hepatite C/diagnóstico , Hepatite C/epidemiologia , Etnicidade , População Negra
7.
Int J Drug Policy ; 121: 104191, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37740989

RESUMO

BACKGROUND: Substance use disorder (SUD) and infectious disease (ID) care integration may lead to improvements in SUD and ID outcomes. We assessed implementation of integrating peer-supported SUD care in an outpatient ID setting. METHODS: In this implementation study, we describe REcovery in Specialty care Through medication and OutREach (RESTORE), a low-threshold SUD program implemented in a Baltimore outpatient ID clinic. Key program components were clinician training and support in SUD care, prescription of SUD treatment medications, and peer-based psychosocial support provided by peer recovery specialists. We assessed clinician adoption of RESTORE and compared patient outcomes from baseline to 6 months. RESULTS: Between January 2019 and January 2022, the number of ID clinicians (N=61) who prescribed buprenorphine increased eightfold from 3 (5%) to 24 (39%). Of 258 ID patients referred to RESTORE, 182 (71%) engaged, 137 consented to study participation. Mean age in the study sample was 52.1 (SD=10.4), 63% were male, 84% were Black/African-American. Among 127 (93%) who completed 6-month follow-up, fewer participants reported illicit/non-prescribed opioid use in the past 30 days at follow-up (32%) compared to baseline (52%; p<0.001). Similar reductions were noted for cocaine use (47% to 34%; p=0.006), emergency department visits (23% to 9%; p=0.002), and inpatient hospitalizations (15% to 7%; p=0.025). CONCLUSION: SUD care integration into an outpatient ID care setting using a peer-supported implementation strategy was adopted by clinicians and improved clinical outcomes for patients. This strategy is a promising approach to treating people with infectious diseases and SUD.


Assuntos
Buprenorfina , Transtornos Relacionados ao Uso de Cocaína , Transtornos Relacionados ao Uso de Opioides , Transtornos Relacionados ao Uso de Substâncias , Humanos , Masculino , Feminino , Pacientes Ambulatoriais , Transtornos Relacionados ao Uso de Substâncias/terapia , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Transtornos Relacionados ao Uso de Opioides/terapia , Hospitalização
8.
FEBS J ; 289(7): 1876-1896, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34817923

RESUMO

ZAG is a multifunctional glycoprotein with a class I MHC-like protein fold and an α1-α2 lipid-binding groove. The intrinsic ZAG ligand is unknown. Our previous studies showed that ZAG binds the dansylated C11 fatty acid, DAUDA, differently to the boron dipyrromethane C16 fatty acid, C16 -BODIPY. Here, the molecular basis for this difference was elucidated. Multi-wavelength analytical ultracentrifugation confirmed that DAUDA and C16 -BODIPY individually bind to ZAG and compete for the same binding site. Molecular docking of lipid-binding in the structurally related Cluster of differentiation 1 proteins predicted nine conserved ligand contact residues in ZAG. Twelve mutants were accordingly created by alanine scanning site directed mutagenesis for characterisation. Mutation of Y12 caused ZAG to misfold. Mutation of K147, R157 and A158 abrogated C16 -BODIPY but not DAUDA binding. L69 and T169 increased the fluorescence emission intensity of C16 -BODIPY but not of DAUDA compared to wild-type ZAG and showed that C16 -BODIPY binds close to T169 and L69. Distance measurements of the crystal structure revealed K147 forms a salt bridge with D83. A range of bioactive bulky lipids including phospholipids and sphingolipids displaced DAUDA from the ZAG binding site but unexpectedly did not displace C16 -BODIPY. We conclude that the ZAG α1-α2 groove contains separate but overlapping sites for DAUDA and C16 -BODIPY and is involved in binding to a bulkier and wider repertoire of lipids than previously reported. This work suggested that the in vivo activity of ZAG may be dictated by its lipid ligand.


Assuntos
Zinco , Glicoproteína Zn-alfa-2 , Ácidos Graxos/metabolismo , Glicoproteínas/metabolismo , Simulação de Acoplamento Molecular , Zinco/metabolismo
9.
J Org Chem ; 87(1): 258-270, 2022 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-34913698

RESUMO

The (+) and (-) enantiomers of a new turn-inducing cyclopropyl dipeptide mimic have been synthesized and evaluated. The mimic derives its turn-inducing capabilities solely from the cyclopropyl group and without the conformational biasing that would be provided by side-chain substituents. The mimic and peptide-mimic hybrids prepared from it have been studied using a combination of spectroscopic techniques (NMR, IR, and CD). The dipeptide mimic itself displays intramolecular hydrogen bonding in organic solvents, which differs from that observed in natural peptide turns. In contrast, more elaborate peptide-mimic hybrids exhibit hydrogen bonding characteristics that vary with solvent but are consistent with structures found in the tetrapeptide portion (i → i + 3) of a native ß-turn.


Assuntos
Dipeptídeos , Peptídeos , Ligação de Hidrogênio , Conformação Molecular , Estereoisomerismo
11.
J Subst Abuse Treat ; 127: 108351, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34134868

RESUMO

BACKGROUND: Patient navigation has potential for assisting patients who initiate methadone during pretrial detention to enter and remain in treatment following release, but we know little about participants' experiences with this service. METHODS: This study drew a purposive sample of male and female participants (N = 17) from participants enrolled in a randomized trial of initiating methadone with vs. without patient navigation while in the Baltimore City Detention Center. The study interviewed participants in the community at 1 and 3 months following release and asked them about their experiences of reentry, methadone treatment continuation, drug use, and interactions with the patient navigator. The study recorded, transcribed, coded using Atlas.ti, and analyzed thematically the interviews. RESULTS: Participants reported encountering four key challenges in the community: getting to treatment following release, assembling basic supports, managing criminal justice system demands, and staying in treatment. Participants' experiences of the patient navigator's support to address these challenges fell into six thematic groups: showing nonjudgmental caring and persistence, advocating within programs, brokering resources, managing interactions with the criminal justice system, balancing encouragement and self-determination, and offering genuine and familial-type support. CONCLUSION: Nearly all participants appreciated the navigator's support and deemed it helpful. The previously reported randomized trial found that participants assigned to initiate methadone treatment with navigation had higher rates of receiving their first "guest" methadone dose in the community but did not have significantly different rates of treatment enrollment or of illicit opioid use compared to those assigned to begin methadone treatment without navigation. Treatment programs should work to improve retention and postrelease outcomes among this population.


Assuntos
Transtornos Relacionados ao Uso de Opioides , Navegação de Pacientes , Analgésicos Opioides/uso terapêutico , Feminino , Humanos , Prisões Locais , Masculino , Metadona/uso terapêutico , Tratamento de Substituição de Opiáceos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico
12.
Eur Biophys J ; 50(3-4): 411-427, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33881594

RESUMO

Microscale thermophoresis (MST), and the closely related Temperature Related Intensity Change (TRIC), are synonyms for a recently developed measurement technique in the field of biophysics to quantify biomolecular interactions, using the (capillary-based) NanoTemper Monolith and (multiwell plate-based) Dianthus instruments. Although this technique has been extensively used within the scientific community due to its low sample consumption, ease of use, and ubiquitous applicability, MST/TRIC has not enjoyed the unambiguous acceptance from biophysicists afforded to other biophysical techniques like isothermal titration calorimetry (ITC) or surface plasmon resonance (SPR). This might be attributed to several facts, e.g., that various (not fully understood) effects are contributing to the signal, that the technique is licensed to only a single instrument developer, NanoTemper Technology, and that its reliability and reproducibility have never been tested independently and systematically. Thus, a working group of ARBRE-MOBIEU has set up a benchmark study on MST/TRIC to assess this technique as a method to characterize biomolecular interactions. Here we present the results of this study involving 32 scientific groups within Europe and two groups from the US, carrying out experiments on 40 Monolith instruments, employing a standard operation procedure and centrally prepared samples. A protein-small molecule interaction, a newly developed protein-protein interaction system and a pure dye were used as test systems. We characterized the instrument properties and evaluated instrument performance, reproducibility, the effect of different analysis tools, the influence of the experimenter during data analysis, and thus the overall reliability of this method.


Assuntos
Benchmarking , Laboratórios , Calorimetria , Reprodutibilidade dos Testes , Temperatura
13.
Diving Hyperb Med ; 51(1): 68-71, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33761543

RESUMO

INTRODUCTION: Idiopathic sudden sensorineural hearing loss (ISSHL) is an otolaryngologic emergency. The Undersea and Hyperbaric Medicine Society (UHMS) revised practice guidelines in 2014 adding ISSHL to approved indications. This study investigated whether the UHMS guidelines influenced referral and practice in Australia and New Zealand. METHODS: Retrospective review of 319 patient referrals in two time periods (five years prior to addition of ISSHL to indications (T-PRE) and three years post (T-POST)). RESULTS: Seven of eight participating hyperbaric facilities provided data down to the level of the indication for HBOT for analysis. In T-PRE 136 patients were treated with HBOT for ISSHL, representing between 0% and 18% of the total cases to each facility. In the T-POST period 183 patients were treated for ISSHL, representing from 0.35% to 24.8% of the total patients in each facility. Comparison between the two periods shows the proportion of patients treated with ISSHL among all indications increased from 3.2% to 12.1% (P < 0.0009). One facility accounted for 74% (101/136) of ISSHL patients receiving HBOT in T-PRE and 63% (116/183) in T-POST. ISSHL case load at that facility increased from 18% to 24.8% (P = 0.009) after the UHMS guideline publication. Three of the seven units had a significant increase in referrals after the guideline change. CONCLUSION: There remains equipoise regarding HBOT in the management of ISSHL. Only three out of seven units had a significant increase in ISSHL patients after the UHMS guidelines publication. Without well controlled RCTs to develop guidelines based on good evidence this is unlikely to change and practice variation will continue.


Assuntos
Perda Auditiva Neurossensorial , Perda Auditiva Súbita , Oxigenoterapia Hiperbárica , Austrália , Perda Auditiva Neurossensorial/terapia , Perda Auditiva Súbita/terapia , Humanos , Nova Zelândia , Estudos Retrospectivos
14.
Drug Alcohol Depend ; 218: 108392, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33187759

RESUMO

BACKGROUND: We report on the 24-month post-release outcomes of arrestees with opioid use disorder (OUD) enrolled in a randomized trial comparing three treatment approaches initiated in jail. METHODS: Adults (N = 225) receiving medically supervised withdrawal from opioids in the Baltimore Detention Center within a few days of arrest were randomly assigned to: (1) interim methadone treatment plus patient navigation (IM + PN) started in the Detention Center; (2) IM; or (3) Enhanced Treatment-as-Usual (ETAU) consisting of detoxification with methadone and referral to treatment in the community. Participants in both methadone conditions could transfer to standard methadone treatment following release. Participants were interviewed at baseline, and 1, 3, 6, 12, and 24 months post-release. Urine was drug tested at follow-up and official arrest records were obtained. RESULTS: On an intention-to-treat basis, there were no significant differences among the three conditions over the 24-month post-release period in terms of opioid- or cocaine-positive urine test results or self-reported opioid or cocaine use, meeting opioid or cocaine use disorder criteria, self-reported criminal behavior, or the number of official arrests. There were 9 fatal overdoses, none occurring during methadone treatment, and 109 hospitalizations unrelated to the study. CONCLUSIONS: Given the high morbidity and mortality found in this population of arrestees and costs to society associated with their health care utilization and continued crime and arrests, research aimed at finding more effective interventions should be continued. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT02334215.


Assuntos
Analgésicos Opioides/uso terapêutico , Metadona/uso terapêutico , Tratamento de Substituição de Opiáceos/métodos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Adulto , Baltimore/epidemiologia , Transtornos Relacionados ao Uso de Cocaína/tratamento farmacológico , Custos e Análise de Custo , Crime , Overdose de Drogas/tratamento farmacológico , Feminino , Humanos , Masculino , Aceitação pelo Paciente de Cuidados de Saúde
15.
J Vis Commun Med ; 43(4): 184-189, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32967479

RESUMO

This article provides an overview of how long COVID-19 (SARS-CoV-2) survives on the built environment, and reviews currently available resources to provide recommendations on effective decontamination of photographic equipment based within a secondary care setting.


Assuntos
Betacoronavirus/isolamento & purificação , Ambiente Construído , Infecções por Coronavirus/prevenção & controle , Descontaminação/métodos , Pandemias/prevenção & controle , Fotografação/instrumentação , Pneumonia Viral/prevenção & controle , COVID-19 , Humanos , SARS-CoV-2
16.
Drug Alcohol Depend ; 217: 108292, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-32992151

RESUMO

BACKGROUND: Individuals with opioid use disorder (OUD) who are released from pre-trial detention in jail have a high risk of opioid relapse. While several interventions for OUD initiated during incarceration have been studied, few have had an economic evaluation. As part of a three-group randomized trial, we estimated the cost and cost-effectiveness of a negative urine opioid test. Detainees were assigned to interim methadone (IM) in jail with continued methadone treatment post-release with and without 3 months of post-release patient navigation (PN) compared to an enhanced treatment-as-usual group. METHODS: We implemented a micro-costing approach from the provider's perspective to estimate the cost per participant in jail and over the 12 months post-release from jail. Economic data included jail-based and community-based service utilization, self-reported healthcare utilization and justice system involvement, and administrative arrest records. Our outcome measure is the number of participants with a negative opioid urine test at their 12-month follow-up. We calculated incremental cost-effectiveness ratios (ICERs) for intervention costs only and costs from a societal perspective. RESULTS: The average cost of providing patient navigation services per individual beginning in jail and continuing in the community was $283. We find that IM is dominated by ETAU and IM + PN. Per additional participant with a negative opioid urine test, the ICER for IM + PN including intervention costs only is $91 and $305 including societal costs. CONCLUSIONS: IM + PN is almost certainly the cost-effective choice from both an intervention provider and societal perspective.


Assuntos
Análise Custo-Benefício , Prisões Locais/economia , Metadona/economia , Tratamento de Substituição de Opiáceos/economia , Transtornos Relacionados ao Uso de Opioides/economia , Navegação de Pacientes/economia , Adulto , Analgésicos Opioides/economia , Analgésicos Opioides/uso terapêutico , Análise Custo-Benefício/métodos , Feminino , Humanos , Masculino , Metadona/uso terapêutico , Pessoa de Meia-Idade , Tratamento de Substituição de Opiáceos/métodos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Aceitação pelo Paciente de Cuidados de Saúde , Navegação de Pacientes/métodos , Resultado do Tratamento
17.
Cancers (Basel) ; 12(7)2020 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-32664705

RESUMO

Treatment of chronic lymphocytic leukemia has advanced substantially as our understanding of the kinase signal transduction pathways driven by the B cell receptor (BcR) has developed. Particularly, understanding the role of Bruton tyrosine kinase and phosphatidyl inositol 3 kinase delta in driving prosurvival signal transduction in chronic lymphocytic leukemia (CLL) cells and their targeting with pharmacological inhibitors (ibrutinib and idelalisib, respectively) has improved patient outcomes significantly. The kinase signaling pathway induced by the BcR is highly complex and has multiple interconnecting branches mediated by tyrosine and serine/threonine kinases activated downstream of the BcR. There is a high level of redundancy in the biological responses, with several BcR-signaling kinases driving nuclear factor kappa B activation or inducing antiapoptotic Bcl-2 genes. Accordingly, common gene targets of BcR-signaling kinases may serve as biomarkers indicating enhanced BCR-signaling and aggressive disease progression. This study used a gene expression correlation analysis of malignant B cell lines and primary CLL cells to identify genes whose expression correlated with BCR-signaling kinases overexpressed and/or overactivated in CLL, namely: AKT1, AKT2, BTK, MAPK1, MAPK3, PI3KCD and ZAP70. The analysis identified a 32-gene signature with a strong prognostic potential and DNPEP, the gene coding for aspartic aminopeptidase, as a predictor of aggressive CLL. DNPEP gene expression correlated with MAPK3, PI3KCD, and ZAP70 expression and, in the primary CLL test dataset, showed a strong prognostic potential. The inhibition of DNPEP with a pharmacological inhibitor enhanced the cytotoxic potential of idelalisib and ibrutinib, indicating a biological functionality of DNPEP in CLL. DNPEP, as an aminopeptidase, contributes to the maintenance of the free amino acid pool in CLL cells found to be an essential process for the survival of many cancer cell types, and thus, these results warrant further research into the exploitation of aminopeptidase inhibitors in the treatment of drug-resistant CLL.

18.
J Subst Abuse Treat ; 113: 108006, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32359668

RESUMO

BACKGROUND: There are limited data from randomized trials about the impact of starting methadone treatment in jail on subsequent arrest after release for adults with opioid use disorder (OUD). METHODS: Official arrest records were obtained for 212 participants with OUD who were enrolled in a three-group randomized controlled trial of initiating methadone treatment in jail either with or without patient navigation vs. enhanced treatment-as-usual in Baltimore, Maryland. Participants treated for opioid withdrawal in jail were assigned to: 1) interim methadone (IM) with patient navigation (PN; IM + PN); 2) IM without PN (IM); or 3) enhanced treatment-as-usual (ETAU). Participants in both IM groups were able to continue treatment at a community-based methadone treatment program with counseling upon release, while ETAU participants received overdose information and a city-wide treatment assessment/referral number. Likelihood of arrest, time to first subsequent arrest, and severity of arrest charges in the 12 months following release were examined for: 1) combined IM + PN and IM groups compared to ETAU; and 2) IM + PN compared to IM. RESULTS: Within 12 months of release from the index incarceration, 50.5% of the sample had been arrested. The majority of arrest charges (71%) were for low-level, nonviolent crimes. On an intention-to-treat basis, there were no significant differences between the combined IM + PN and IM groups vs. ETAU or IM + PN vs. IM in the likelihood of arrest, time to first subsequent arrest, or severity of arrest charges. CONCLUSION: Initiating IM with or without PN during pretrial detention did not have a significant effect on subsequent arrest during a 12-month post-release follow-up compared to not starting methadone maintenance during detention, despite the high rate of methadone treatment entry in the community following release. This finding may be attributable to the considerable attrition from treatment in the community or other systematic factors. Additional interventions may be needed to reduce the likelihood of subsequent arrest.


Assuntos
Prisões Locais , Transtornos Relacionados ao Uso de Opioides , Adulto , Analgésicos Opioides/uso terapêutico , Baltimore , Humanos , Metadona/uso terapêutico , Tratamento de Substituição de Opiáceos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico
19.
AIDS Behav ; 24(6): 1776-1783, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31748939

RESUMO

Adults entering pre-trial detention who inject drugs are at high risk for acquiring HIV/AIDS. In the current study, we examined pre-incarceration HIV risk behaviors among 114 people with opioid use disorder who inject drugs. Participants were recruited from the Baltimore City Detention Center as part of a randomized controlled trial of pre-release methadone treatment. Using latent class analysis, we found three separate latent classes, which we identified as the sex exchange class (14.2%), drug equipment sharing class (36.8%) and lower risk class (49.0%). Women in the sex exchange class (n = 16) reported having multiple male partners and selling sex for money or drugs; however, this group also reported more consistent condom use and less frequent injection drug and equipment sharing than participants in the drug equipment sharing class. Our findings highlight distinct profiles of jail detainees with OUD based on their risks for HIV, and could inform more targeted interventions for each group.Clinical Trials Registration: Clinicaltrials.gov NCT02334215.


Assuntos
Infecções por HIV/prevenção & controle , Transtornos Relacionados ao Uso de Opioides/psicologia , Assunção de Riscos , Sexo Seguro , Parceiros Sexuais , Adulto , Baltimore , Preservativos , Direito Penal , Feminino , Humanos , Análise de Classes Latentes , Masculino , Pessoa de Meia-Idade , Prisões , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco
20.
Chemistry ; 25(33): 7881-7887, 2019 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-30945773

RESUMO

The possibility of using differential pre-heating prior to supramolecular gelation to control the balance between hydrogen-bonding and aromatic stacking interactions in supramolecular gels and obtain consequent systematic regulation of structure and properties is demonstrated. Using a model aromatic peptide amphiphile, Fmoc-tyrosyl-leucine (Fmoc-YL) and a combination of fluorescence, infrared, circular dichroism and NMR spectroscopy, it is shown that the balance of these interactions can be adjusted by temporary exposure to elevated temperatures in the range 313-365 K, followed by supramolecular locking in the gel state by cooling to room temperature. Distinct regimes can be identified regarding the balance between H-bonding and aromatic stacking interactions, with a transition point at 333 K. Consequently, gels can be obtained with customizable properties, including supramolecular chirality and gel stiffness. The differential supramolecular structures also result in changes in proteolytic stability, highlighting the possibility of obtaining a range of supramolecular architectures from a single molecular structure by simply controlling the pre-assembly temperature.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...