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1.
Diabet Med ; 34(7): 916-924, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-27973692

RESUMO

AIMS: To investigate whether the association of severe mental illness with Type 2 diabetes varies by ethnicity and age. METHODS: We conducted a cross-sectional analysis of data from an ethnically diverse sample of 588 408 individuals aged ≥18 years, registered to 98% of general practices (primary care) in London, UK. The outcome of interest was prevalent Type 2 diabetes. RESULTS: Relative to people without severe mental illness, the relative risk of Type 2 diabetes in people with severe mental illness was greatest in the youngest age groups. In the white British group the relative risks were 9.99 (95% CI 5.34, 18.69) in those aged 18-34 years, 2.89 (95% CI 2.43, 3.45) in those aged 35-54 years and 1.16 (95% CI 1.04, 1.30) in those aged ≥55 years, with similar trends across all ethnic minority groups. Additional adjustment for anti-psychotic prescriptions only marginally attenuated the associations. Assessment of estimated prevalence of Type 2 diabetes in severe mental illness by ethnicity (absolute measures of effect) indicated that the association between severe mental illness and Type 2 diabetes was more marked in ethnic minorities than in the white British group with severe mental illness, especially for Indian, Pakistani and Bangladeshi individuals with severe mental illness. CONCLUSIONS: The relative risk of Type 2 diabetes is elevated in younger populations. Most associations persisted despite adjustment for anti-psychotic prescriptions. Ethnic minority groups had a higher prevalence of Type 2 diabetes in the presence of severe mental illness. Future research and policy, particularly with respect to screening and clinical care for Type 2 diabetes in populations with severe mental illness, should take these findings into account.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Transtornos Mentais/complicações , Adolescente , Adulto , Fatores Etários , Idoso , Bangladesh/etnologia , Estudos Transversais , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/etnologia , Diabetes Mellitus Tipo 2/psicologia , Registros Eletrônicos de Saúde , Feminino , Medicina Geral , Disparidades nos Níveis de Saúde , Humanos , Índia/etnologia , Londres/epidemiologia , Masculino , Transtornos Mentais/etnologia , Transtornos Mentais/fisiopatologia , Transtornos Mentais/psicologia , Pessoa de Meia-Idade , Paquistão/etnologia , Prevalência , Risco , Índice de Gravidade de Doença , Medicina Estatal , Adulto Jovem
2.
Diabetes Obes Metab ; 18 Suppl 2: 17-24, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27723226

RESUMO

AIMS: Basal insulin peglispro (BIL), a novel PEGylated basal insulin with a large hydrodynamic size, has a delayed absorption and reduced clearance that prolongs the duration of action. The current study compared the effects of BIL and insulin glargine (GL) on endogenous glucose production (EGP), glucose disposal rate (GDR) and lipolysis in patients with type 1 diabetes. MATERIALS AND METHODS: This was a randomized, open-label, four-period, crossover study. Patients received intravenous infusions of BIL and GL, each at two dose levels selected for partial and maximal suppression of EGP, during an 8 to 10 h euglycemic clamp procedure with d-[3-3 H] glucose. RESULTS: Following correction for equivalent human insulin concentrations (EHIC), low-dose GL infusion resulted in similar EGP at the end of the clamp compared to low-dose BIL infusion (GL/BIL ratio of 1.03) but a higher GDR (GL/BIL ratio of 2.42), indicating similar hepatic activity but attenuated peripheral activity of BIL. Consistent with this, the EHIC-corrected GDR/EGP at the end of the clamp was 1.72-fold greater for GL than BIL following low-dose administration. At the lower dose of BIL and GL (concentrations in the therapeutic range), BIL produced less suppression of lipolysis compared with GL as indicated by free fatty acid and glycerol levels at the end of the clamp. CONCLUSIONS: Compared with GL, BIL restored the hepato-peripheral insulin action gradient seen in normal physiology via its peripherally restricted action on target tissues related to carbohydrate and lipid metabolism.


Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/farmacologia , Insulina Glargina/farmacologia , Insulina Lispro/análogos & derivados , Lipólise/efeitos dos fármacos , Fígado/efeitos dos fármacos , Polietilenoglicóis/farmacologia , Adulto , Glicemia/metabolismo , Estudos Cross-Over , Diabetes Mellitus Tipo 1/metabolismo , Ácidos Graxos não Esterificados/metabolismo , Técnica Clamp de Glucose , Glicerol/metabolismo , Humanos , Hipoglicemiantes/uso terapêutico , Infusões Intravenosas , Insulina Glargina/uso terapêutico , Insulina Lispro/farmacologia , Insulina Lispro/uso terapêutico , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/uso terapêutico , Trítio , Adulto Jovem
3.
Diabetes Obes Metab ; 18 Suppl 2: 3-16, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27723228

RESUMO

Basal insulin peglispro (BIL) is a novel basal insulin with a flat, prolonged activity profile. BIL has been demonstrated in a dog model, in healthy men and in patients with type 1 diabetes (T1D) to have significant hepato-preferential action resulting from reduced peripheral activity. In the IMAGINE-Phase 3 clinical trial program, more than 6000 patients were included, of whom ~3900 received BIL. Of the 7 pivotal IMAGINE trials, 3 studies were double-blinded and 3 were in T1D patients. BIL consistently demonstrated a greater HbA1c reduction, less glycaemic variability and a clinically relevant reduction in the rates of nocturnal hypoglycaemia across comparator [glargine and isophane insulin (NPH)] studies. Trials using basal/bolus regimens had higher rates of total hypoglycaemia with BIL due to higher rates of daytime hypoglycaemia. Severe hypoglycaemia rates were similar to comparator among both patients with T1D or type 2 diabetes (T2D). T1D patients lost weight compared with glargine (GL). Patients with T2D tended to gain less weight with BIL than with glargine. Compared to glargine, BIL was associated with higher liver fat, triglycerides and alanine aminotransferase (ALT) levels, including a higher frequency of elevation of ALT ≥3 times the upper limit of normal, but without severe, acute drug-induced liver injury. Injection site reactions, primarily lipohypertrophy, were more frequent with BIL. In conclusion, BIL demonstrated better glycaemic control with reduced glucose variability and nocturnal hypoglycaemia but higher triglycerides, ALT and liver fat relative to conventional comparator insulin. The hepato-preferential action of BIL with reduced peripheral activity may account for these findings.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina Lispro/análogos & derivados , Polietilenoglicóis/uso terapêutico , Alanina Transaminase/metabolismo , Glicemia/metabolismo , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Hemoglobina A Glicada/metabolismo , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/farmacologia , Insulina/uso terapêutico , Insulina Glargina/uso terapêutico , Insulina Lispro/farmacologia , Insulina Lispro/uso terapêutico , Insulina Isófana/uso terapêutico , Fígado/efeitos dos fármacos , Fígado/metabolismo , Polietilenoglicóis/farmacologia , Resultado do Tratamento , Triglicerídeos/metabolismo , Perda de Peso
4.
Soc Psychiatry Psychiatr Epidemiol ; 51(4): 627-38, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26846127

RESUMO

PURPOSE: People with severe mental illnesses (SMI) experience a 17- to 20-year reduction in life expectancy. One-third of deaths are due to cardiovascular disease. This study will establish the relationship of SMI with cardiovascular disease in ethnic minority groups (Indian, Pakistani, Bangladeshi, black Caribbean, black African and Irish), in the UK. METHODS: E-CHASM is a mixed methods study utilising data from 1.25 million electronic patient records. Secondary analysis of routine patient records will establish if differences in cause-specific mortality, cardiovascular disease prevalence and disparities in accessing healthcare for ethnic minority people living with SMI exist. A nested qualitative study will be used to assess barriers to accessing healthcare, both from the perspectives of service users and providers. RESULTS: In primary care, 993,116 individuals, aged 18+, provided data from 186/189 (98 %) practices in four inner-city boroughs (local government areas) in London. Prevalence of SMI according to primary care records, ranged from 1.3-1.7 %, across boroughs. The primary care sample included Bangladeshi [n = 94,643 (10 %)], Indian [n = 6086 (6 %)], Pakistani [n = 35,596 (4 %)], black Caribbean [n = 45,013 (5 %)], black African [n = 75,454 (8 %)] and Irish people [n = 13,745 (1 %)]. In the secondary care database, 12,432 individuals with SMI over 2007-2013 contributed information; prevalent diagnoses were schizophrenia [n = 6805 (55 %)], schizoaffective disorders [n = 1438 (12 %)] and bipolar affective disorder [n = 4112 (33 %)]. Largest ethnic minority groups in this sample were black Caribbean [1432 (12 %)] and black African (1393 (11 %)). CONCLUSIONS: There is a dearth of research examining cardiovascular disease in minority ethnic groups with severe mental illnesses. The E-CHASM study will address this knowledge gap.


Assuntos
Transtorno Bipolar/etnologia , Doenças Cardiovasculares/etnologia , Grupos Étnicos/psicologia , Disparidades nos Níveis de Saúde , Grupos Minoritários/psicologia , Transtornos Psicóticos/etnologia , Esquizofrenia/etnologia , Adulto , Grupo com Ancestrais do Continente Africano/psicologia , Grupo com Ancestrais do Continente Africano/estatística & dados numéricos , Grupo com Ancestrais do Continente Asiático/psicologia , Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Região do Caribe/etnologia , Grupos Étnicos/estatística & dados numéricos , Grupo com Ancestrais do Continente Europeu/psicologia , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Grupos Minoritários/estatística & dados numéricos , Prevalência , Pesquisa Qualitativa , Fatores Socioeconômicos , Reino Unido/epidemiologia
5.
Diabetes Obes Metab ; 18(2): 159-68, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26434665

RESUMO

AIMS: To compare the immunogenicity profiles and the potential effects on clinical outcomes of LY2963016 insulin glargine (LY IGlar) and Lantus® insulin glargine (IGlar), products with identical primary amino acid sequences, in patients with type 1 or type 2 diabetes mellitus (T1DM or T2DM). METHODS: To assess immunogenicity, anti-insulin glargine antibodies (measured as percent binding) were compared between treatments in 52-week (open-label) and 24-week (double-blind) randomized studies in total study populations of patients with T1DM (N = 535) and T2DM (N = 756), respectively, and two subgroups of patients with T2DM: insulin-naïve patients and those reporting prestudy IGlar treatment (prior IGlar). Relationships between insulin antibody levels and clinical outcomes were assessed using analysis of covariance and partial correlations. Insulin antibody levels were assessed using Wilcoxon rank sum. Treatment comparisons for treatment-emergent antibody response (TEAR) and incidence of detectable antibodies were analysed using Fisher's exact test. RESULTS: No significant treatment differences were observed for insulin antibody levels, incidence of detectable anti-insulin glargine antibodies, or incidence of TEAR [overall and endpoint, by last-observation-carried-forward (LOCF)] in patients with T1DM or patients with T2DM, including the insulin-naïve subgroup. A statistically significant difference was noted in the overall incidence of detectable antibodies but not at endpoint (LOCF) nor in TEAR for the prior IGlar subgroup of patients with T2DM. Insulin antibody levels were low (<5%) in both treatment groups. Insulin antibody levels or developing TEAR was not associated with clinical outcomes. CONCLUSIONS: LY IGlar and IGlar have similar immunogenicity profiles; anti-insulin glargine antibody levels were low for both treatments, with no observed effect on efficacy and safety outcomes.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipersensibilidade a Drogas/etiologia , Hipoglicemiantes/efeitos adversos , Anticorpos Anti-Insulina/análise , Insulina Glargina/análogos & derivados , Insulina Glargina/efeitos adversos , Doenças Assintomáticas/epidemiologia , Medicamentos Biossimilares/efeitos adversos , Medicamentos Biossimilares/uso terapêutico , Reações Cruzadas , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/imunologia , Método Duplo-Cego , Hipersensibilidade a Drogas/complicações , Hipersensibilidade a Drogas/epidemiologia , Hipersensibilidade a Drogas/imunologia , Humanos , Hiperglicemia/prevenção & controle , Hipoglicemia/induzido quimicamente , Hipoglicemia/prevenção & controle , Hipoglicemiantes/uso terapêutico , Fenômenos Imunogenéticos/efeitos dos fármacos , Incidência , Insulina Glargina/uso terapêutico , Insulina Regular Humana/efeitos adversos , Insulina Regular Humana/análogos & derivados , Insulina Regular Humana/genética , Insulina Regular Humana/uso terapêutico , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico
6.
Braz J Microbiol ; 46(4): 1001-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26691457

RESUMO

A study was performed to investigate the genomic variations in the shrimp farm isolates of Vibrio alginolyticus and V. harveyi when the isolates were subjected to environmental stress. Samples of shrimps, water and sediment were collected from Southern Indian coastal shrimp farms. Vibrio isolates were biochemically identified and confirmed using 16S rDNA and gyrB gene specific PCR. The bacterial strains were genotyped by PCR fingerprinting using GTG(5) and IS (Insertion Sequence) primers. Seven strains each of V. alginolyticus and V. harveyi were subjected to 10 passages through trypticase soya broth (TSB), which contained different NaCl concentrations (3, 6 and 8%) and trypticase soya agar (TSA). V. alginolyticus was also passaged through TSB with a 12% NaCl concentration. PCR fingerprinting, which was performed on the strains that were passaged through different salt concentrations, confirmed that V. alginolyticus and V. harveyi could affect the genomic variations, depending on the environmental conditions of the culture. The study highlights the complex genotypic variations that occur in Vibrio strains of tropical aquatic environment because of varied environmental conditions, which result in genetic divergence and/or probable convergence. Such genetic divergence and/or convergence can lead to the organismal adaptive variation, which results in their ability to cause a productive infection in aquatic organisms or generation of new strains.


Assuntos
Penaeidae/microbiologia , Vibrio alginolyticus/genética , Vibrio/genética , Animais , Aquicultura , Primers do DNA/genética , DNA Bacteriano/genética , Ecossistema , Penaeidae/crescimento & desenvolvimento , Reação em Cadeia da Polimerase , Vibrio/isolamento & purificação , Vibrio alginolyticus/isolamento & purificação
7.
Braz. j. microbiol ; 46(4): 1001-1008, Oct.-Dec. 2015. tab, graf
Artigo em Inglês | LILACS | ID: lil-769644

RESUMO

A study was performed to investigate the genomic variations in the shrimp farm isolates of Vibrio alginolyticus and V. harveyi when the isolates were subjected to environmental stress. Samples of shrimps, water and sediment were collected from Southern Indian coastal shrimp farms. Vibrio isolates were biochemically identified and confirmed using 16S rDNA and gyrB gene specific PCR. The bacterial strains were genotyped by PCR fingerprinting using GTG(5) and IS (Insertion Sequence) primers. Seven strains each of V. alginolyticus and V. harveyi were subjected to 10 passages through trypticase soya broth (TSB), which contained different NaCl concentrations (3, 6 and 8%) and trypticase soya agar (TSA). V. alginolyticus was also passaged through TSB with a 12% NaCl concentration. PCR fingerprinting, which was performed on the strains that were passaged through different salt concentrations, confirmed that V. alginolyticus and V. harveyi could affect the genomic variations, depending on the environmental conditions of the culture. The study highlights the complex genotypic variations that occur in Vibrio strains of tropical aquatic environment because of varied environmental conditions, which result in genetic divergence and/or probable convergence. Such genetic divergence and/or convergence can lead to the organismal adaptive variation, which results in their ability to cause a productive infection in aquatic organisms or generation of new strains.


Assuntos
Animais/genética , Animais/crescimento & desenvolvimento , Animais/isolamento & purificação , Animais/microbiologia , Aquicultura/genética , Aquicultura/crescimento & desenvolvimento , Aquicultura/isolamento & purificação , Aquicultura/microbiologia , Primers do DNA/genética , Primers do DNA/crescimento & desenvolvimento , Primers do DNA/isolamento & purificação , Primers do DNA/microbiologia , DNA Bacteriano/genética , DNA Bacteriano/crescimento & desenvolvimento , DNA Bacteriano/isolamento & purificação , DNA Bacteriano/microbiologia , Ecossistema/genética , Ecossistema/crescimento & desenvolvimento , Ecossistema/isolamento & purificação , Ecossistema/microbiologia , Penaeidae/genética , Penaeidae/crescimento & desenvolvimento , Penaeidae/isolamento & purificação , Penaeidae/microbiologia , Reação em Cadeia da Polimerase/genética , Reação em Cadeia da Polimerase/crescimento & desenvolvimento , Reação em Cadeia da Polimerase/isolamento & purificação , Reação em Cadeia da Polimerase/microbiologia , Vibrio alginolyticus/genética , Vibrio alginolyticus/crescimento & desenvolvimento , Vibrio alginolyticus/isolamento & purificação , Vibrio alginolyticus/microbiologia , Vibrio/genética , Vibrio/crescimento & desenvolvimento , Vibrio/isolamento & purificação , Vibrio/microbiologia
8.
Diabetes Obes Metab ; 17(8): 734-41, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25931141

RESUMO

AIMS: To compare the efficacy and safety of LY2963016 insulin glargine (LY IGlar) and the reference product (Lantus(®)) insulin glargine (IGlar) in combination with oral antihyperglycaemic medications in patients with type 2 diabetes (T2D). METHODS: This phase III, randomized, double-blind, 24-week study enrolled patients with T2D who were insulin-naïve [glycated haemoglobin (HbA1c) ≥7 and ≤11.0%] or previously on IGlar (HbA1c ≤11%) and treated with ≥2 oral antihyperglycaemic medications. Patients were randomized to receive once-daily LY IGlar (n = 376) or IGlar (n = 380) for 24 weeks. The primary efficacy outcome was to test the non-inferiority (0.4% and then 0.3% margin) of LY IGlar to IGlar, as measured by change in HbA1c from baseline to 24 weeks. RESULTS: Both treatment groups had similar and significant (p < 0.001) within-group decreases in mean HbA1c values from baseline. LY IGlar met non-inferiority criteria compared with IGlar for change in HbA1c from baseline [-1.29 vs -1.34%; respectively, least-squares mean difference 0.052% (95% confidence interval -0.070 to 0.175); p > 0.05]. There were no treatment differences (p > 0.05) in fasting plasma glucose, proportion of patients reaching HbA1c <7% or insulin dose at 24 weeks. Adverse events, allergic reactions, weight change, hypoglycaemia and insulin antibodies were similar between treatment groups. Similar findings were observed in patients who were insulin-naïve or previously treated with IGlar at baseline. CONCLUSIONS: Both LY IGlar and IGlar, when used in combination with oral antihyperglycaemic medications, provided effective and similar glucose control with similar safety profiles in patients with T2D.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina Glargina/análogos & derivados , Insulina Glargina/uso terapêutico , Idoso , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/sangue , Método Duplo-Cego , Quimioterapia Combinada/métodos , Jejum/sangue , Feminino , Hemoglobina A Glicada/efeitos dos fármacos , Humanos , Hipoglicemia/induzido quimicamente , Insulina/uso terapêutico , Anticorpos Anti-Insulina/sangue , Masculino , Pessoa de Meia-Idade
9.
Diabetes Obes Metab ; 17(8): 726-33, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25974640

RESUMO

AIMS: To compare the efficacy and safety of LY2963016 insulin glargine (LY IGlar) and the reference product (Lantus®) insulin glargine (IGlar) in patients with type 1 diabetes (T1D). METHODS: This phase III, randomized, open-label, 52-week study enrolled patients with T1D [glycated haemoglobin (HbA1c) ≤11%] being treated with basal (once-daily) and bolus insulin. Patients were randomized to receive once-daily LY IGlar (n = 268) or IGlar (n = 267) in combination with mealtime insulin lispro for 52 weeks. The primary efficacy outcome was to test the non-inferiority (0.4% and then 0.3% margin) of LY IGlar to IGlar as measured by change in HbA1c from baseline to 24 weeks. RESULTS: Both treatment groups had similar and significant (p < 0.001) within-group decreases in mean HbA1c values from baseline. LY IGlar met the non-inferiority criteria compared with IGlar for change in HbA1c from baseline to 24 weeks [-0.35 vs -0.46%, least-squares mean difference 0.108% (95% confidence interval -0.002 to 0.219), p > 0.05]. There were no significant (p > 0.05) treatment differences in other efficacy measures, including proportion of patients reaching HbA1c <7%, daily mean blood glucose, and insulin dose at 24 and 52 weeks. At 52 weeks, similar findings were observed between LY IGlar and IGlar for safety outcomes, including adverse events, allergic reactions, hypoglycaemia, weight change and insulin antibodies. CONCLUSIONS: Both LY IGlar and IGlar, when used in combination with mealtime insulin lispro, provided effective and similar glucose control and similar safety profiles.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina Glargina/análogos & derivados , Insulina Glargina/uso terapêutico , Insulina Lispro/administração & dosagem , Adulto , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 1/sangue , Esquema de Medicação , Quimioterapia Combinada/métodos , Feminino , Hemoglobina A Glicada/efeitos dos fármacos , Humanos , Hipoglicemia/induzido quimicamente , Anticorpos Anti-Insulina/sangue , Masculino , Refeições , Pessoa de Meia-Idade , Resultado do Tratamento
10.
Diabetes Obes Metab ; 17(4): 414-22, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25656305

RESUMO

AIM: To describe the clinical effects of single and multiple doses of a potent, selective, orally administered, small-molecule antagonist of the human glucagon receptor, LY2409021, in healthy subjects and in patients with type 2 diabetes. METHODS: LY2409021 was administered in dose-escalation studies to healthy subjects (n = 23) and patients with type 2 diabetes (n = 9) as single doses (Study 1) and daily to patients with type 2 diabetes (n = 47) for 28 days (Study 2). Safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) assessments were made after single doses and in patients receiving once-daily doses of LY2409021 (5, 30, 60 or 90 mg) for 28 days. RESULTS: LY2409021 was well tolerated at all dose levels in both studies. Fasting and postprandial glucose were reduced and glucagon levels increased after single and multiple dosing, with reductions in fasting serum glucose of up to ∼1.25 mmol/l on day 28. Serum aminotransferases increased in a dose-dependent manner with multiple dosing and reversed after cessation of dosing. Significant glucose-lowering was observed with LY2409021 at dose levels associated with only minor aminotransferase increases. CONCLUSION: Blockade of glucagon signalling in patients with type 2 diabetes is well tolerated and results in substantial reduction of fasting and postprandial glucose with minimal hypoglycaemia, but with reversible increases in aminotransferases. Inhibition of glucagon signalling by LY2409021 is a promising potential treatment for patients with type 2 diabetes and should be evaluated in longer clinical trials to better evaluate benefits and risks.


Assuntos
Compostos de Bifenilo/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hiperglicemia/prevenção & controle , Hipoglicemia/prevenção & controle , Hipoglicemiantes/uso terapêutico , Terapia de Alvo Molecular , Receptores de Glucagon/antagonistas & inibidores , Adulto , Idoso , Compostos de Bifenilo/administração & dosagem , Compostos de Bifenilo/sangue , Compostos de Bifenilo/farmacocinética , Estudos de Coortes , Estudos Cross-Over , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Glucagon/agonistas , Glucagon/sangue , Glucagon/metabolismo , Hemoglobina A Glicada/análise , Meia-Vida , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/sangue , Hipoglicemiantes/farmacocinética , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular/efeitos adversos , Risco , Método Simples-Cego
11.
Acta Psychiatr Scand ; 131(3): 213-22, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25311084

RESUMO

OBJECTIVE: To investigate the association between acute myocardial infarction (AMI) and recent exposure to antipsychotic agents in people with serious mental illness (SMI), and modifying influences. METHOD: A case-crossover design was applied using the Taiwan National Health Insurance Research Database (NHIRD) to compare the exposure frequency of antipsychotic agents within individuals of schizophrenia or bipolar disorder between 60-day case and control periods prior to their first AMI episode during 1996-2007. RESULTS: A sample of 834 patients with incident AMI was analysed. AMI was significantly associated with more recent antipsychotic exposure in schizophrenia after adjustment (OR 1.87, 95% confidence interval 1.15-3.03) bipolar disorder (OR 1.06, 0.51-2.21). This association in schizophrenia was significantly stronger in men and in patients without previous diagnoses of cardiovascular risk factors. CONCLUSION: These findings are consistent with a short-term risk effect of antipsychotic exposure on risk of AMI and identify potentially vulnerable groups. Further research is required to clarify underlying biological mechanisms.


Assuntos
Antipsicóticos/administração & dosagem , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/epidemiologia , Infarto do Miocárdio/epidemiologia , Esquizofrenia/tratamento farmacológico , Esquizofrenia/epidemiologia , Adulto , Idoso , Antipsicóticos/efeitos adversos , Estudos de Casos e Controles , Estudos Cross-Over , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/induzido quimicamente , Fatores de Risco , Taiwan/epidemiologia
12.
Diabetes Obes Metab ; 16(4): 351-6, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24719911

RESUMO

AIMS: The basal insulin analogue LY2605541, a PEGylated insulin lispro with prolonged duration of action, was previously shown to be associated with modest weight loss in Phase 2, randomized, open-label trials in type 2 (N=288) and type 1 (N=137) diabetes mellitus (T2DM and T1DM), compared with modest weight gain with insulin glargine. Exploratory analyses were conducted to further characterize these findings. METHODS: Pearson correlations between change in body weight and other variables were calculated. Continuous variables were analysed using a mixed linear model with repeated measurements. Proportions of subjects with weight loss were analysed using Fisher's exact test for T2DM and Nagelkerke's method for T1DM. RESULTS: Weight loss was more common in LY2605541-treated patients than in patients treated with insulin glargine (T2DM: 56.9 vs. 40.2%, p=0.011; T1DM: 66.1 vs. 40.3%, p<0.001). More LY2605541-treated patients experienced ≥5% weight loss compared to patients treated with glargine (T2DM: 4.8 vs. 0%, p=0.033; T1DM: 11.9 vs. 0.8%, p<0.001). In both the T1DM and T2DM studies, weight change did not correlate with baseline body mass index (BMI), or change in HDL-cholesterol in either treatment group. No consistent correlations were found across both studies between weight change and any of the variables assessed; however, weight change was significantly correlated with hypoglycaemia rate in glargine-treated T2DM patients. CONCLUSION: In two Phase 2 trials, improved glycaemic control with long-acting basal insulin analogue LY2605541 is associated with weight loss in previously insulin-treated patients. This weight change is independent of baseline BMI or hypoglycaemia.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina Lispro/uso terapêutico , Insulina de Ação Prolongada/uso terapêutico , Polietilenoglicóis/uso terapêutico , Ganho de Peso , Perda de Peso , Adulto , Glicemia , Índice de Massa Corporal , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Insulina Glargina , Insulina Lispro/efeitos adversos , Insulina de Ação Prolongada/efeitos adversos , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/efeitos adversos , Resultado do Tratamento , Ganho de Peso/efeitos dos fármacos , Perda de Peso/efeitos dos fármacos
13.
J Public Health (Oxf) ; 36(1): 92-103, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23596193

RESUMO

BACKGROUND: Worldwide, the Irish diaspora experience health inequalities persisting across generations. The present study sought to establish the prevalence of psychological morbidity in the children of migrant parents from Ireland, and reasons for differences. METHODS: Data from two British birth cohorts were used for analysis. Each surveyed 17 000 babies born in one week in 1958 and 1970 and followed up through childhood. Validated scales assessed psychological health. RESULTS: Relative to the rest of the cohort, second-generation Irish children grew up in material hardship and showed greater psychological problems at ages 7, 11 (1958 cohort) and 16 (both cohorts). Adjusting for material adversity and maternal psychological distress markedly reduced differences. Relative to non-Irish parents, Irish-born parents were more likely to report chronic health problems (odds ratio [OR]: 1.29; 95% confidence interval [CI]: 1.08-1.54), and Irish-born mothers were more likely to be psychologically distressed (OR: 1.44; 95% CI: 1.13-1.84, when child was 10). Effect sizes diminished once material adversity was taken into account. CONCLUSIONS: Second-generation Irish children experienced high levels of psychological morbidity, but this was accounted for through adverse material circumstances in childhood and psychological distress in parents. Public health initiatives focusing on settlement experiences may reduce health inequalities in migrant children.


Assuntos
Transtornos Mentais/epidemiologia , Estresse Psicológico/epidemiologia , Adolescente , Fatores Etários , Criança , Pré-Escolar , Estudos de Coortes , Emigrantes e Imigrantes/psicologia , Emigrantes e Imigrantes/estatística & dados numéricos , Nível de Saúde , Disparidades nos Níveis de Saúde , Humanos , Irlanda/etnologia , Transtornos Mentais/etiologia , Pais/psicologia , Pobreza/psicologia , Pobreza/estatística & dados numéricos , Reino Unido/epidemiologia
14.
Ethn Health ; 17(1-2): 17-53, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22074468

RESUMO

OBJECTIVE: Changes in socio-economic position in people who migrate may have adverse associations with mental health. The main objective of this review was to assess the association of social mobility with common mental disorders in migrant and second-generation groups, to inform future research. DESIGN: Systematic review and meta-analysis of English-language studies assessing the association of social mobility in migrant or second-generation groups with common mental disorders. Approaches to operationalise 'social mobility' were reviewed. RESULTS: Twelve studies (n=18,548) met criteria for retrieval. Very few included second-generation groups, and most studies were cross-sectional in design. Approaches to operationalise 'social mobility' varied between studies. Downward intragenerational social mobility was associated with migration in the majority of studies. Random effects meta-analysis (n=5179) suggested that migrants to higher income countries who experienced downward mobility or underemployment were more likely to screen positive for common mental disorders, relative to migrants who were upwardly mobile or experienced no changes to socio-economic position. Conclusions on second-generation groups were limited by the lack of research highlighted for these groups. Downward intragenerational mobility associated with migration may be associated with vulnerability to common mental disorders in some migrant groups. CONCLUSION: Given the increasing scale of global migration, further research is needed to clarify how changes to socio-economic position associated with international migration may impact on the mental health of migrants, and in their children.


Assuntos
Emigração e Imigração/estatística & dados numéricos , Disparidades nos Níveis de Saúde , Transtornos Mentais/epidemiologia , Refugiados/estatística & dados numéricos , Mobilidade Social/economia , Intervalos de Confiança , Saúde Global , Humanos , Renda , Pobreza , Classe Social , Mobilidade Social/estatística & dados numéricos , Fatores Socioeconômicos , Estatística como Assunto
15.
Neuroepidemiology ; 31(4): 243-51, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18931519

RESUMO

BACKGROUND: We aimed to estimate the prevalence, correlates and impact of dementia in Havana and Matanzas, Cuba. METHODS: A 1-phase catchment area survey of all over 65-year-old residents of 7 catchment areas in Havana and 1 in Matanzas was conducted. Dementia diagnosis was established according to DSM-IV and our own, pre-validated 10/66 criteria. The impact of dementia was assessed through associations with needs for care, cutting back on work to care and caregiver psychological morbidity. RESULTS: We interviewed 2,944 older people, a response proportion of 96.4%. The prevalence of DSM-IV dementia was 6.4% and that of 10/66 dementia 10.8%. Both dementia outcomes were associated with older age, less education, a family history of dementia, shorter leg length and smaller skull circumference. Dementia, rather than physical health problems or depression, was the main contributor to needs for care (population-attributable prevalence fraction = 64.6%) and caregiver cutting back on work (population-attributable prevalence fraction = 57.3%). CONCLUSION: The prevalence of dementia in Cuba is similar to Europe. Among health conditions, dementia is the major contributor to dependency and caregiver economic and psychological strain. More attention needs to be given to it and other chronic diseases associated more with disability than premature mortality.


Assuntos
Doença de Alzheimer/epidemiologia , Demência/epidemiologia , Inquéritos Epidemiológicos , Idoso , Idoso de 80 Anos ou mais , Comorbidade/tendências , Efeitos Psicossociais da Doença , Cuba/epidemiologia , Demência/diagnóstico , Depressão/epidemiologia , Europa (Continente)/epidemiologia , Feminino , Saúde Global , Humanos , Entrevistas como Assunto , Masculino , Prevalência , Fatores Socioeconômicos
16.
Neuroepidemiology ; 31(4)2008. tab
Artigo em Inglês | CUMED | ID: cum-41394

RESUMO

We aimed to estimate the prevalence, correlates and impact of dementia in Havana and Matanzas, Cuba. Methods: A 1-phase catchment area survey of all over 65-year-old residents of 7 catchment areas in Havana and 1 in Matanzas was conducted. Dementia diagnosis was established according to DSM-IV and our own, pre-validated10/66 criteria. The impact of dementia was assessed through associations with needs for care, cutting back on work to care and caregiver psychological morbidity...(AU)


Assuntos
Humanos , Adulto , Demência/epidemiologia , Demência/etiologia , Prevalência
17.
Acta Psychiatr Scand ; 116(2): 125-8, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17650274

RESUMO

OBJECTIVE: This study attempted to evaluate sensitivity, specificity and predictive values of the diagnosis of dementia made by trained community health workers. METHOD: A total of 1,000 subjects over the age of 65 years were recruited for the study. The community health workers identified nine subjects as having dementia. This was compared against an education adjusted diagnosis of dementia made in accordance with the 10/66 dementia research group protocol. RESULTS: The sensitivity and specificity of the community health worker diagnosis was 3.8% and 99.4% respectively. The false positive rate and positive predictive values were 55.6% and 44.4%, respectively. The false negative rate and negative predictive value were 10.3% and 89.7% respectively. Similar values were obtained against a DSM IV diagnosis. Subjects with dementia who were correctly diagnosed by the community health workers and those whose condition was missed did not differ significantly on socio-demographic and clinical variables. CONCLUSION: Informal screening by community health workers resulted in low sensitivity and positive predictive values. Screening strategies in situations of low prevalence are not effective.


Assuntos
Doença de Alzheimer/diagnóstico , Agentes Comunitários de Saúde , Serviços Comunitários de Saúde Mental , Países em Desenvolvimento , Programas de Rastreamento , Adulto , Idoso , Doença de Alzheimer/epidemiologia , Agentes Comunitários de Saúde/educação , Estudos Transversais , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Índia , Capacitação em Serviço , Masculino , Programas de Rastreamento/estatística & dados numéricos , Pessoa de Meia-Idade , Vigilância da População , Encaminhamento e Consulta/estatística & dados numéricos , Sensibilidade e Especificidade
18.
Int Psychogeriatr ; 19(4): 669-78, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17433119

RESUMO

BACKGROUND: Different interview schedules and diagnostic criteria for dementia have contributed to differing incidence and prevalence rates. AIM: This study aimed to examine the effect of different diagnostic criteria on the prevalence of dementia in the community. METHODS: Some 1000 subjects (>65 years) were recruited in Kaniyambadi Block, Vellore, India, using a one-stage assessment procedure. RESULTS: The prevalence of dementia by Diagnostic and Statistical Manual IV standard, the Community Screening instrument for Dementia DF Score, the education adjusted 10/66 Dementia Research Group criteria, and the Geriatric Mental State was 0.8%, 6.2%, 10.6%, 63.2% respectively. CONCLUSION: Differences in information, interview schedules, diagnostic criteria and settings contribute to variation in identification of people with dementia. Minor variations in criteria have a significant impact on diagnosis. The assessment of the clinical state is influenced by education, level of baseline function, impairment in current functioning, life style and demands on the person, tolerance of impairment and expectation by relatives and by differences between patients attending hospitals and those living in the community. The variation in rates demands a debate on the criteria for dementia in the community in general and for less literate populations in particular.


Assuntos
Serviços Comunitários de Saúde Mental/estatística & dados numéricos , Demência/diagnóstico , Demência/epidemiologia , Idoso , Algoritmos , Relações Comunidade-Instituição , Feminino , Humanos , Índia/epidemiologia , Masculino , Prevalência
19.
Br J Psychiatry ; 187: 35-42, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15994569

RESUMO

BACKGROUND: Associations between physical health and depression are consistent across cultures among adults up to 65 years of age. In later life, the impact of physical health on depression is much more substantial and may depend on sociocultural factors. AIMS: To examine cross-national differences in the association between physical health and depressive symptoms in elderly people across western Europe. METHOD: Fourteen community-based studies on depression in later life in nine western European countries contributed to a total study sample of 22 570 respondents aged 65 years and older. Measures were harmonized for depressive symptoms (EURO-D scale), functional limitations and chronic physical conditions. RESULTS: In the majority of the participating samples, the association of depressive symptoms with functional disability was stronger than with chronic physical conditions. Associations were slightly more pronounced in the UK and Ireland. CONCLUSIONS: The association between physical health and depressive symptoms in later life is consistent across western Europe.


Assuntos
Depressão/etiologia , Nível de Saúde , Idoso , Idoso de 80 Anos ou mais , Doença Crônica/epidemiologia , Cognição , Comparação Transcultural , Depressão/epidemiologia , Avaliação da Deficiência , Europa (Continente)/epidemiologia , Feminino , Indicadores Básicos de Saúde , Humanos , Masculino , Escalas de Graduação Psiquiátrica
20.
Diabetes Obes Metab ; 6(2): 133-56, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-14746579

RESUMO

AIM: Patients with type 2 diabetes often have dyslipidaemia, putting them at risk of cardiovascular disease, and are frequently treated with oral anti-hyperglycaemic medications (OAMs). This review compares the effects of OAMs on serum lipids [total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs) and free fatty acids (FFAs)] in patients with type 2 diabetes. METHODS: medline was searched for entries indexed from January 1966 to November 2002; search terms included the names of OAMs and serum lipids, limited to English language and human subjects. We selected clinical studies in type 2 diabetes of OAM monotherapy that included serum lipid data, treated all patients in a treatment group with the same drug, used therapeutic OAM doses not higher than the maximum recommended in the USA, compared therapy with baseline or placebo and specified statistical tests used. One unblinded investigator selected studies for inclusion. Data reported include number of patients, study length, OAM dose, serum lipid data at baseline and endpoint, p-values and statistical tests. RESULTS: Data on the serum lipid effects of sulphonylureas, repaglinide, nateglinide and miglitol were inconclusive. Acarbose increased HDL-C and decreased LDL-C and voglibose reduced TC. Metformin at higher doses reduced TC; data on its effects on other lipids were inconclusive. Rosiglitazone increased LDL-C, HDL-C and TC and reduced FFAs but had no effect on TGs. Pioglitazone increased HDL-C and reduced TGs and FFAs but did not affect LDL-C or TC. CONCLUSIONS: Lipid changes as a result of improved glycaemic control are not uniform findings associated with anti-diabetic therapy. Only metformin, acarbose, voglibose, rosiglitazone and pioglitazone had significant effects on the lipid profile. These effects should be considered when selecting OAMs for patients with type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Lipídeos/sangue , Administração Oral , Humanos , Hipoglicemiantes/uso terapêutico
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