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1.
BMJ Open Qual ; 12(2)2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37328282

RESUMO

BACKGROUND: Throughout the COVID-19 pandemic, many areas of medicine transitioned to virtual care. For patients with diabetes admitted to hospital, this included diabetes education and insulin teaching. Shifting to a virtual model of insulin teaching created new challenges for inpatient certified diabetes educators (CDE). OBJECTIVE: We advanced a quality improvement project to improve the efficiency of safe and effective virtual insulin teaching throughout the COVID-19 pandemic. Our primary aim was to reduce the mean time between CDE referral to successful inpatient insulin teach by 0.5 days. DESIGN, SETTING, PARTICIPANTS: We conducted this initiative at two large academic hospitals between April 2020 and September 2021. We included all admitted patients with diabetes who were referred to our CDE for inpatient insulin teaching and education. INTERVENTION: Alongside a multidisciplinary team of project stakeholders, we created and studied a CDE-led, virtual (video conference or telephone) insulin teaching programme. As tests of change, we added a streamlined method to deliver insulin pens to the ward for patient teaching, created a new electronic order set and included patient-care facilitators in the scheduling process. MAIN OUTCOME AND MEASURES: Our main outcome measure was the mean time between CDE referral and successful insulin teach-back. Our process measure was the percentage of successful insulin pen deliveries to the ward for teaching. As balance measures, we captured the percentage of patients with a successful insulin teach, the time between insulin teach and hospital discharge, and readmissions to hospital for diabetes-related complications. RESULTS: Our tests of change improved the efficiency of safe and effective virtual insulin teaching by 0.27 days. The virtual model appeared less efficient than usual in-person care. CONCLUSIONS: In our centre, virtual insulin teaching supported patients admitted to hospital through the pandemic. Improving the administrative efficiency of virtual models and leveraging key stakeholders remain important for long-term sustainability.


Assuntos
COVID-19 , Diabetes Mellitus , Humanos , Insulina/uso terapêutico , Pandemias , Melhoria de Qualidade , Diabetes Mellitus/tratamento farmacológico , Hospitais
2.
Front Public Health ; 10: 879173, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35812516

RESUMO

Background: Medical schools aim to select and train future physicians representative of and able to serve their diverse population needs. Enhancing equity, diversity, and inclusion (EDI) in admissions processes includes identifying and mitigating barriers for those underrepresented in medicine (URM). Summary of Innovations: In 2017, Schulich School of Medicine and Dentistry (Western University, Ontario, Canada) critically reviewed its general Admissions pathways for the Doctor of Medicine (MD) program. Till that time, interview invitations were primarily based on academic metrics rather than a holistic review as for its Indigenous MD Admissions pathway. To help diversify the Canadian physician workforce, Schulich Medicine utilized a multipronged approach with five key changes implemented over 2 years into the general MD Admissions pathways: 1. A voluntary applicant diversity survey (race, socioeconomic status, and community size) to examine potential barriers within the Admissions process; 2. Diversification of the admissions committee and evaluator pool with the inclusion of an Equity Representative on the admissions committee; 3. A biosketch for applicants' life experiences; 4. Implicit bias awareness training for Committee members, file reviewers and interviewers; and 5. A specific pathway for applicants with financial, sociocultural, and medical barriers (termed ACCESS pathway). Diversity data before (Class of 2022) vs. after (Class of 2024) these initiatives and of the applicant pool vs. admitted class were examined. Conclusion: For the Class of 2024, the percentage of admitted racialized students (55.2%), those with socioeconomic challenges (32.3%), and those from remote/rural/small town communities (18.6%) reflected applicant pool demographics (52.8, 29.9, and 17.2%, respectively). Additionally, 5.3% (vs. 5.6% applicant pool) of admitted students had applied through ACCESS. These data suggest that barriers within the admissions process for these URM populations were potentially mitigated by these initiatives. The initiatives broadly improved representation of racialized students, LGBTQ2S+, and those with disability with statistically significant increases in representation of those with socioeconomic challenges (32.3 vs. 19.3%, p = 0.04), and those with language diversity (42.1 vs. 35.0%, p = 0.04). Thus, these changes within the general MD admissions pathways will help diversify the future Canadian physician workforce and inform future initiatives to address health equity and social accountability within Canada.


Assuntos
Critérios de Admissão Escolar , Faculdades de Medicina , Canadá , Humanos , Grupos Minoritários , Classe Social
3.
Am J Gastroenterol ; 115(7): 1055-1065, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32618656

RESUMO

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is an obesity-related disorder that is rapidly increasing in incidence and is considered the hepatic manifestation of the metabolic syndrome. The gut microbiome plays a role in metabolism and maintaining gut barrier integrity. Studies have found differences in the microbiota between NAFLD and healthy patients and increased intestinal permeability in patients with NAFLD. Fecal microbiota transplantation (FMT) can be used to alter the gut microbiome. It was hypothesized that an FMT from a thin and healthy donor given to patients with NAFLD would improve insulin resistance (IR), hepatic proton density fat fraction (PDFF), and intestinal permeability. METHODS: Twenty-one patients with NAFLD were recruited and randomized in a ratio of 3:1 to either an allogenic (n = 15) or an autologous (n = 6) FMT delivered by using an endoscope to the distal duodenum. IR was calculated by HOMA-IR, hepatic PDFF was measured by MRI, and intestinal permeability was tested using the lactulose:mannitol urine test. Additional markers of metabolic syndrome and the gut microbiota were examined. Patient visits occurred at baseline, 2, 6 weeks, and 6 months post-FMT. RESULTS: There were no significant changes in HOMA-IR or hepatic PDFF in patients who received the allogenic or autologous FMT. Allogenic FMT patients with elevated small intestinal permeability (>0.025 lactulose:mannitol, n = 7) at baseline had a significant reduction 6 weeks after allogenic FMT. DISCUSSION: FMT did not improve IR as measured by HOMA-IR or hepatic PDFF but did have the potential to reduce small intestinal permeability in patients with NAFLD.


Assuntos
Transplante de Microbiota Fecal , Microbioma Gastrointestinal , Intestino Delgado , Hepatopatia Gordurosa não Alcoólica/terapia , Método Duplo-Cego , Duodenoscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Permeabilidade
6.
J Clin Densitom ; 22(1): 125-149, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-28739080

RESUMO

Members of the College of Physicians and Surgeons of Ontario Endocrinology and Metabolism Peer Review Network have been involved in a quality improvement project to help standardize the peer assessment of physicians practicing in endocrinology and metabolism. This has included developing state-of-the-art summaries of common endocrine problems by Canadian experts in endocrinology and metabolism. These tools have been developed in response to the educational needs, as identified by peer reviewers, of practicing endocrinologists in Ontario. These pedagogical tools aim not only to standardize the documentation of the clinical performance of endocrinologists but also to make the process more transparent and to improve the quality of patient care in Ontario. This article summarizes the project and also provides the tools developed for the endocrinology and metabolism section of the College of Physicians and Surgeons of Ontario.


Assuntos
Cuidados Críticos/normas , Doenças do Sistema Endócrino , Endocrinologia/métodos , Doenças Metabólicas , Revisão por Pares/normas , Melhoria de Qualidade , Diagnóstico Diferencial , Doenças do Sistema Endócrino/diagnóstico , Doenças do Sistema Endócrino/terapia , Endocrinologia/normas , Humanos , Doenças Metabólicas/diagnóstico , Doenças Metabólicas/terapia
7.
Can J Cardiol ; 34(12): 1553-1563, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30527143

RESUMO

Familial hypercholesterolemia (FH) is the most common monogenic disorder causing premature atherosclerotic cardiovascular disease. It affects 1 in 250 individuals worldwide, and of the approximately 145,000 Canadians estimated to have FH, most are undiagnosed. Herein, we provide an update of the 2014 Canadian Cardiovascular Society position statement on FH addressing the need for case identification, prompt recognition, and treatment with statins and ezetimibe, and cascade family screening. We provide a new Canadian definition for FH and tools for clinicians to make a diagnosis. The risk of atherosclerotic cardiovascular disease in patients with "definite" FH is 10- to 20-fold that of a normolipidemic individual and initiating treatment in youth or young adulthood can normalize life expectancy. Target levels for low-density lipoprotein cholesterol are proposed and are aligned with the Canadian Cardiovascular Society guidelines on dyslipidemia. Recommendation for the use of inhibitors of proprotein convertase kexin/subtilisin type 9 are made in patients who cannot achieve therapeutic low-density lipoprotein cholesterol targets on maximally tolerated statins and ezetimibe. The writing committee used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology in the preparation of the present document, which offers guidance for practical evaluation and management of patients with FH. This position statement also aims to raise awareness of FH nationally, and to mobilize patient support, promote knowledge translation, and availability of treatment and health care resources for this under-recognized, but important medical condition.


Assuntos
Hiperlipoproteinemia Tipo II , Programas de Rastreamento , Anticolesterolemiantes/uso terapêutico , Valva Aórtica/diagnóstico por imagem , Remoção de Componentes Sanguíneos , Canadá , Artérias Carótidas/diagnóstico por imagem , Contraindicações de Medicamentos , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/prevenção & controle , Diabetes Mellitus Tipo 2/complicações , Feminino , Testes Genéticos , Comportamentos Relacionados com a Saúde , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/genética , Hiperlipoproteinemia Tipo II/terapia , Estilo de Vida , Lipídeos/sangue , Gravidez , Prevenção Primária , Sistema de Registros , Medição de Risco , Calcificação Vascular/diagnóstico por imagem
8.
Can J Cardiol ; 33(5): 666-673, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28449837

RESUMO

BACKGROUND: Statin-associated muscle symptoms (SAMS) are common. Rechallenge with the same statin (same-statin rechallenge) has recently been included as part of a proposed scoring index for diagnosing SAMS, but data regarding tolerability and efficacy of same-statin rechallenge, compared with other strategies, is minimal. In this study we evaluated the tolerability, percent change in low-density lipoprotein cholesterol (LDL-C), and proportion of patients achieving their LDL-C targets among 3 common management strategies-same-statin rechallenge, switching to a different statin (statin switch), and use of nonstatin medications only. METHODS: We performed a retrospective analysis of 118 patients referred to our tertiary care centre for management of SAMS, defined as development of muscle-related symptoms with 2 or more statins. Baseline and last follow-up lipid parameters were documented. Patients were classified as tolerant of a strategy if, at their last follow-up, they remained on that strategy. RESULTS: After a median follow-up of 17 months, most (n = 79; 67%) patients were able to tolerate a statin. Tolerability was similar among the 3 treatment strategies (71% same-statin rechallenge vs 53% statin switch vs 57% for nonstatin therapy only; P = 0.11). Those in the same-statin rechallenge and statin switch groups achieved greater LDL-C reductions compared with those who only tolerated nonstatins (-38.8 ± 3.4% vs -36.4 ± 2.9% vs -17.3 ± 4.5%; P = 0.0007). A greater proportion of patients in the same-statin rechallenge group achieved their target LDL-C compared with those in the nonstatin therapy only group (50% vs 15%; odds ratio, 6.8; 95% confidence interval, 1.5-40.7; P = 0.04). CONCLUSIONS: Among individuals with a history of SAMS, most will tolerate statin therapy. Same-statin rechallenge was highly tolerable and efficacious. Thus, same-statin rechallenge might warrant increased utilization.


Assuntos
LDL-Colesterol , Substituição de Medicamentos/métodos , Inibidores de Hidroximetilglutaril-CoA Redutases , Hipercolesterolemia/tratamento farmacológico , Conduta do Tratamento Medicamentoso , Doenças Musculares , Idoso , Canadá/etnologia , LDL-Colesterol/análise , LDL-Colesterol/metabolismo , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Hipercolesterolemia/epidemiologia , Hipercolesterolemia/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Doenças Musculares/induzido quimicamente , Doenças Musculares/diagnóstico , Doenças Musculares/epidemiologia , Doenças Musculares/prevenção & controle , Nível de Efeito Adverso não Observado , Estudos Retrospectivos , Resultado do Tratamento
9.
World J Gastroenterol ; 23(1): 141-150, 2017 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-28104990

RESUMO

AIM: To evaluate the effect of sitagliptin vs placebo on histologic and non-histologic parameters of non-alcoholic steatohepatitis (NASH). METHODS: Twelve patients with biopsy-proven NASH were randomized to sitagliptin (100 mg daily) (n = 6) or placebo (n = 6) for 24 wk. The primary outcome was improvement in liver fibrosis after 24 wk. Secondary outcomes included evaluation of changes in NAFLD activity score (NAS), individual components of NAS (hepatocyte ballooning, lobular inflammation, and steatosis), glycemic control and insulin resistance [including measurements of glycated hemoglobin (HbA1C) and adipocytokines], lipid profile including free fatty acids, adipose distribution measured using magnetic resonance imaging (MRI), and thrombosis markers (platelet aggregation and plasminogen activator inhibitor 1 levels). We also sought to determine the correlation between changes in hepatic fat fraction (%) [as measured using the Iterative Decomposition of water and fat with Echo Asymmetry and Least-squares estimation (IDEAL) MRI technique] and changes in hepatic steatosis on liver biopsy. RESULTS: Sitagliptin was not significantly better than placebo at reducing liver fibrosis score as measured on liver biopsy (mean difference between sitagliptin and placebo arms, 0.40, P = 0.82). There were no significant improvements evident with the use of sitagliptin vs placebo for the secondary histologic outcomes of NAS total score as well as for the individual components of NAS. Compared to baseline, those patients who received sitagliptin demonstrated improved HbA1C (6.7% ± 0.4% vs 7.9% ± 1.0%, P = 0.02), and trended towards improved adiponectin levels (4.7 ± 3.5 µg/mL vs 3.9 ± 2.7 µg/mL, P = 0.06) and triglyceride levels (1.26 ± 0.43 mmol/L vs 2.80 ± 1.64 mmol/L, P = 0.08). However, when compared with placebo, sitagliptin did not cause a statistically significant improvement in HbA1C (mean difference, -0.7%, P = 0.19) nor triglyceride levels (mean difference -1.10 mmol/L, P = 0.19) but did trend towards improved adiponectin levels only (mean difference, 0.60 µg/mL, P = 0.095). No significant changes in anthropometrics, liver enzymes, other adipocytokines, lipid profile, thrombosis parameters, or adipose distribution were demonstrated. The MRI IDEAL procedure correlated well with steatosis scores obtained on liver biopsy in both groups at baseline and post-treatment, and the Spearman correlation coefficients ranged from r = 0.819 (baseline) to r = 0.878 (post-treatment), P = 0.002. CONCLUSION: Sitagliptin does not improve fibrosis score or NAS after 24 wk of therapy. The MRI IDEAL technique may be useful for non-invasive measurement of hepatic steatosis.


Assuntos
Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Fosfato de Sitagliptina/uso terapêutico , Idoso , Biomarcadores/análise , Biópsia , Inibidores da Dipeptidil Peptidase IV/administração & dosagem , Ácidos Graxos não Esterificados/sangue , Feminino , Fibrose , Hemoglobinas Glicadas/análise , Humanos , Fígado/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/patologia , Placebos/administração & dosagem , Agregação Plaquetária , Fosfato de Sitagliptina/administração & dosagem , Resultado do Tratamento
12.
Ann Intern Med ; 160(5): 301-10, 2014 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-24737272

RESUMO

BACKGROUND: Statin-related myalgia is difficult to distinguish from other conditions causing myalgia and may often lead to statin discontinuation. OBJECTIVE: To compare the effect of statin rechallenge with placebo in patients with prior statin-related myalgia and to determine whether patients resumed statin therapy after evaluating the results. DESIGN: N-of-1 trial with 3 double-blind, crossover comparisons separated by 3-week washout periods. (Clinicaltrials.gov: NCT01259791) SETTING: Tertiary care lipid clinic. PATIENTS: Patients with prior statin-related myalgia with or without mild elevation of creatine kinase levels. INTERVENTION: Rechallenge with the statin that was previously associated with myalgia within 3 weeks of open-label use versus matching placebo. MEASUREMENTS: Weekly visual analogue scale (VAS) scores for myalgia and specific symptoms (VAS myalgia score and symptom-specific VAS score, respectively), pain interference scores, and pain severity scores were recorded during the 3-week periods when patients were receiving placebo or statin. The primary outcome was the VAS myalgia score (range, 0 to 100 mm). RESULTS: Eight patients (mean age, 66 years [SD, 8 years]; 88% women, all with high 10-year Framingham cardiovascular risk) participated in n-of-1 trials. Seven patients completed 3 treatment pairs, and 1 completed 2 treatment pairs. For each n-of-1 trial, no statistically significant differences were seen between statin and placebo in the VAS myalgia score, symptom-specific VAS score, pain interference score, and pain severity score. Five patients resumed open-label statin treatment, with a median posttrial follow-up of 10 months. LIMITATION: Results are limited by the small sample size and cannot be extended to patients with longer onset of myalgia after statin initiation. CONCLUSION: In selected patients with a history of statin-related myalgia whose symptoms are difficult to evaluate, n-of-1 trials may be a useful method for determining statin tolerability. PRIMARY FUNDING SOURCE: Western University, London, Ontario, Canada.


Assuntos
Fluorbenzenos/efeitos adversos , Ácidos Heptanoicos/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Hipercolesterolemia/tratamento farmacológico , Mialgia/induzido quimicamente , Pirimidinas/efeitos adversos , Pirróis/efeitos adversos , Sulfonamidas/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Atorvastatina , Método Duplo-Cego , Feminino , Fluorbenzenos/uso terapêutico , Ácidos Heptanoicos/uso terapêutico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Masculino , Pirimidinas/uso terapêutico , Pirróis/uso terapêutico , Projetos de Pesquisa , Rosuvastatina Cálcica , Sulfonamidas/uso terapêutico
13.
Philos Ethics Humanit Med ; 8: 16, 2013 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-24165577

RESUMO

Good nutrition plays an important role in the optimal growth, development, health and well-being of individuals in all stages of life. Healthy eating can reduce the risk of chronic diseases, such as heart disease, stroke, diabetes and some types of cancer. However, the capitalist mindset that shapes the food environment has led to the commoditization of food. Food is not just a marketable commodity like any other commodity. Food is different from other commodities on the market in that it is explicitly and intrinsically linked to our human existence. While possessing another commodity allows for social benefits, food ensures survival. Millions of people in United States of America are either malnourished or food insecure. The purpose of this paper is to present a critique of the current food system using four meanings of the common good--as a framework, rhetorical device, ethical concept and practical tool for social justice. The first section of this paper provides a general overview of the notion of the common good. The second section outlines how each of the four meanings of the common good helps us understand public practices, social policies and market values that shape the distal causal factors of nutritious food inaccessibility. We then outline policy and empowerment initiatives for nutritious food access.


Assuntos
Abastecimento de Alimentos , Valor Nutritivo , Saúde Pública/ética , Classe Social , Humanos , Formulação de Políticas , Justiça Social , Estados Unidos
14.
J Cardiovasc Magn Reson ; 15: 77, 2013 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-24020829

RESUMO

BACKGROUND: Visceral adiposity is increased in those with Metabolic Syndrome (MetS) and atherosclerotic disease burden. In this study we evaluate for associations between intra-thoracic fat volume (ITFV) and myocardial infarction (MI) in patients with MetS. METHODS: Ninety-four patients with MetS, MI or both were identified from a cardiovascular CMR clinical registry. MetS was defined in accordance to published guidelines; where-as MI was defined as the presence of subendocardial-based injury on late gadolinium enhancement imaging in a coronary vascular distribution. A healthy control group was also obtained from the same registry. Patients were selected into the following groups: MetS+/MI- (N = 32), MetS-/MI + (N = 30), MetS+/MI + (N = 32), MetS-/MI- (N = 16). ITFV quantification was performed using signal threshold analysis of sequential sagittal CMR datasets (HASTE) and indexed to body mass index. RESULTS: The mean age of the population was 59.8 ± 12.5 years. MetS+ patients (N=64) demonstrated a significantly higher indexed ITFV compared to MetS- patients (p = 0.05). Patients in respective MetS-/MI-, MetS+/MI-, MetS-/MI+, and MetS+/MI + study groups demonstrated a progressive elevation in the indexed ITFV (22.3 ± 10.6, 28.6 ± 12.6, 30.6 ± 12.3, and 35.2 ± 1.4 ml/kg/m(2), (p = 0.002)). Among MetS+ patients those with MI showed a significantly higher indexed ITFV compared to those without MI (p = 0.02). CONCLUSIONS: ITFV is elevated in patients with MetS and incrementally elevated among those with evidence of prior ischemic myocardial injury. Accordingly, the quantification of ITFV may be a valuable marker of myocardial infarction risk among patients with MetS and warrants further investigation.


Assuntos
Adiposidade , Gordura Intra-Abdominal/patologia , Imagem Cinética por Ressonância Magnética , Síndrome Metabólica/diagnóstico , Infarto do Miocárdio/diagnóstico , Adulto , Idoso , Meios de Contraste , Feminino , Humanos , Masculino , Síndrome Metabólica/patologia , Pessoa de Meia-Idade , Infarto do Miocárdio/patologia , Compostos Organometálicos , Valor Preditivo dos Testes , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco
15.
Pharmacol Ther ; 135(1): 18-30, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22465158

RESUMO

Reduction in low-density lipoprotein cholesterol (LDL-C) levels has been associated with a 25-30% reduction in cardiovascular disease risk. However, there still remains a significant and quantifiable risk. Since epidemiologic data have demonstrated that low levels of high-density lipoprotein cholesterol (HDL-C) are associated with an increased risk for cardiovascular disease, novel therapeutic agents are currently being developed to either raise HDL-C levels or enhance HDL functionality. This review will highlight some of these therapeutic agents including cholesteryl ester transfer protein inhibitors, apolipoprotein A-I mimetics, RVX-208, and apolipoprotein A-I based infusion therapies. For each therapeutic class, an overview of the mechanism of action, pharmacokinetic data, and efficacy/safety evidence will be provided.


Assuntos
Doenças Cardiovasculares/prevenção & controle , HDL-Colesterol/sangue , Dislipidemias/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Animais , Apolipoproteína A-I/uso terapêutico , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Proteínas de Transferência de Ésteres de Colesterol/antagonistas & inibidores , Proteínas de Transferência de Ésteres de Colesterol/sangue , LDL-Colesterol/sangue , Dislipidemias/sangue , Dislipidemias/complicações , Humanos , Hipolipemiantes/efeitos adversos , Hipolipemiantes/farmacocinética , Mimetismo Molecular , Quinazolinas/uso terapêutico , Quinazolinonas , Resultado do Tratamento
16.
Pharmacol Ther ; 135(1): 31-43, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22465160

RESUMO

Elevated low density lipoprotein cholesterol (LDL-C) levels have been associated with an increased risk for cardiovascular disease (CVD). Despite a 25-30% reduction in CVD risk with LDL-C reducing strategies, there is still a significant residual risk. Moreover, achieving target LDL-C values in individuals at high CVD risk is sometimes limited because of tolerability and/or efficacy. Thus, novel therapeutic agents are currently being developed to lower LDL-C levels further. This review will highlight some of these therapeutic agents including anti-sense oligonucleotides focused on apolipoprotein B, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, microsomal triglyceride transfer protein inhibitors, and thyromimetics. For each therapeutic class, an overview of the mechanism of action, pharmacokinetic data, and efficacy/safety evidence will be provided.


Assuntos
Anticolesterolemiantes/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , LDL-Colesterol/sangue , Hipercolesterolemia/tratamento farmacológico , Animais , Anticolesterolemiantes/efeitos adversos , Anticolesterolemiantes/farmacocinética , Apolipoproteínas B/sangue , Apolipoproteínas B/genética , Biomarcadores/sangue , Materiais Biomiméticos/uso terapêutico , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/genética , Proteínas de Transporte/antagonistas & inibidores , Proteínas de Transporte/metabolismo , Regulação para Baixo , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/complicações , Hipercolesterolemia/genética , Oligonucleotídeos Antissenso/uso terapêutico , Pró-Proteína Convertase 9 , Pró-Proteína Convertases/antagonistas & inibidores , Pró-Proteína Convertases/metabolismo , Inibidores de Proteínas Quinases/uso terapêutico , Serina Endopeptidases/metabolismo , Hormônios Tireóideos/metabolismo , Resultado do Tratamento
17.
Nat Rev Endocrinol ; 8(9): 517-28, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22349076

RESUMO

Niacin, or water-soluble vitamin B(3), when given at pharmacologic doses, is a powerful lipid-altering agent. This drug, which lowers the levels of atherogenic, apolipoprotein-B-containing lipoproteins, is one of few medications that can raise the levels of atheroprotective HDL cholesterol. Niacin also has beneficial effects on other cardiovascular risk factors, including lipoprotein(a), C-reactive protein, platelet-activating factor acetylhydrolase, plasminogen activator inhibitor 1 and fibrinogen. Many clinical trials have confirmed the lipid effects of niacin treatment; however, its effects on cardiovascular outcomes have been called into question owing to the AIM-HIGH trial, which showed no benefit of niacin therapy on cardiovascular endpoints. Furthermore, use of niacin has historically been limited by tolerability issues. In addition to flushing, worsened hyperglycaemia among patients with diabetes mellitus has also been a concern with niacin therapy. This article reviews the utility of niacin including its mechanism of action, clinical trial data regarding cardiovascular outcomes, adverse effect profile and strategies to address these effects and improve compliance.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Niacina/uso terapêutico , Padrões de Prática Médica/estatística & dados numéricos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Química Farmacêutica , HDL-Colesterol/sangue , Ensaios Clínicos como Assunto/métodos , Ensaios Clínicos como Assunto/estatística & dados numéricos , Feminino , Humanos , Masculino , Modelos Biológicos
18.
Philos Ethics Humanit Med ; 6: 16, 2011 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-22177365

RESUMO

Bernard Lonergan's cognitive theory challenges us to raise questions about both the cognitive process through which obesity is perceived as a behaviour change issue and the objectivity of such a moral judgment. Lonergan's theory provides the theoretical tools to affirm that anti-fat discrimination, in the United States of America and in many industrialized countries, is the result of both a group bias that resists insights into the good of other groups and a general bias of anti-intellectualism that tends to set common sense against insights that require any thorough scientific analyses. While general bias diverts the public's attention away from the true aetiology of obesity, group bias sustains an anti-fat culture that subtly legitimates discriminatory practices and policies against obese people. Although anti-discrimination laws may seem to be a reasonable way of protecting obese and overweight individuals from discrimination, obesity bias can be best addressed by reframing the obesity debate from an environmental perspective from which tools and strategies to address both the social and individual determinants of obesity can be developed. Attention should not be concentrated on individuals' behaviour as it is related to lifestyle choices, without giving due consideration to the all-encompassing constraining factors which challenge the social and rational blindness of obesity bias.


Assuntos
Países Desenvolvidos , Conhecimentos, Atitudes e Prática em Saúde , Julgamento/ética , Obesidade , Preconceito , Cultura , Feminino , Humanos , Masculino , Modelos Teóricos
19.
J Magn Reson Imaging ; 34(2): 474-9, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21780238

RESUMO

PURPOSE: To validate iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) for adipose tissue volume quantification. IDEAL allows MRI images to be produced only from adipose-containing tissues; hence, quantifying adipose tissue should be simpler and more accurate than with current methods. MATERIALS AND METHODS: Ten healthy controls were imaged with 1.5 Tesla (T) Spin Echo (SE), 3.0T T1-weighted spoiled gradient echo (SPGR), and 3.0T IDEAL-SPGR. Images were acquired from the abdomen, pelvis, mid-thigh, and mid-calf. Mean subcutaneous and visceral adipose tissue volumes were compared between the three acquisitions for each subject. RESULTS: There were no significant differences (P>0.05) between the three acquisitions for subcutaneous adipose tissue volumes. However, there was a significant difference (P=0.0002) for visceral adipose tissue volumes in the abdomen. Post hoc analysis showed significantly lower visceral adipose tissue volumes measured by IDEAL versus 1.5T (P<0.0001) and 3.0T SPGR (P<0.002). The lower volumes given by IDEAL are due to its ability to differentiate true visceral adipose tissue from other bright structures like blood vessels and bowel content that are mistaken for adipose tissue in non-fat suppressed images. CONCLUSION: IDEAL measurements of adipose tissue are equivalent to established 1.5T measurement techniques for subcutaneous depots and have improved accuracy for visceral depots, which are more metabolically relevant.


Assuntos
Tecido Adiposo/patologia , Imageamento por Ressonância Magnética/métodos , Adulto , Artefatos , Índice de Massa Corporal , Água Corporal , Feminino , Humanos , Processamento de Imagem Assistida por Computador/métodos , Masculino
20.
Cardiovasc Ther ; 29(5): 327-39, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20406242

RESUMO

Inhibition of cholesteryl ester transfer protein (CETP), a key protein involved in reverse cholesterol transport, can lead to increases in high-density lipoprotein cholesterol (HDL-C) levels and thus, is under evaluation as an antiatherogenic strategy. Several CETP inhibitors have been under development including anacetrapib, dalcetrapib, and torcetrapib. To date, anacetrapib demonstrates the greatest HDL-C raising and low-density lipoprotein cholesterol (LDL-C) lowering potential. Phase I and phase II trials with anacetrapib have revealed that anacetrapib is well-tolerated and does not seem to possess the pressor effects associated with torcetrapib. This article will briefly review the HDL-C raising through CETP inhibition as an antiatherogenic strategy with a specific focus on anacetrapib.


Assuntos
Anticolesterolemiantes/uso terapêutico , Aterosclerose/tratamento farmacológico , Proteínas de Transferência de Ésteres de Colesterol/antagonistas & inibidores , Oxazolidinonas/uso terapêutico , Animais , Anticolesterolemiantes/efeitos adversos , Anticolesterolemiantes/farmacocinética , Aterosclerose/metabolismo , Biomarcadores/sangue , Proteínas de Transferência de Ésteres de Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Humanos , Oxazolidinonas/efeitos adversos , Oxazolidinonas/farmacocinética , Resultado do Tratamento
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