RESUMEN
AIMS: To evaluate the efficacy and safety of dulaglutide 1.5 and 0.75 mg in elderly patients (aged ≥65 years) with type 2 diabetes (T2D) in six phase III clinical trials. METHODS: Patients were grouped into two age groups: ≥65 and <65 years. Pooled analysis for glycated haemoglobin (HbA1c) change from baseline, percentage of patients achieving HbA1c targets, and gastrointestinal tolerability were evaluated at 26 weeks for each dulaglutide dose. Change in weight from baseline and rates of hypoglycaemia were evaluated for each individual study. RESULTS: A total of 958 of 5171 (18.5%) patients were aged ≥65 years. The reductions in HbA1c were similar between age groups for dulaglutide 1.5 mg-treated patients {least squares [LS] mean for patients aged ≥65 years: -1.24 [95% confidence interval (CI) -1.36, -1.12] and for patients aged <65 years: -1.29 [95% CI -1.38, -1.20]} and for dulaglutide 0.75 mg-treated patients [LS mean for patients aged ≥65 years: -1.16 (95% CI -1.29, -1.03) and for patients aged <65 years: -1.10 (95% CI -1.19, -1.01)] at 26 weeks. The percentages of patients who achieved HbA1c targets of <7, <8 or <9% were also similar in the two groups with both dulaglutide doses. Patients aged ≥65 years had similar weight change to patients aged <65 years. Severe hypoglycaemic events were infrequent. A similar incidence of gastrointestinal adverse events was observed in each age group with both dulaglutide doses. CONCLUSION: Both dulaglutide doses were well tolerated, with similar efficacy in patients with T2D aged ≥65 years to those aged <65 years. Dulaglutide can be considered a safe and effective treatment option for use in older adults.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Péptidos Similares al Glucagón/análogos & derivados , Hipoglucemiantes/uso terapéutico , Fragmentos Fc de Inmunoglobulinas/uso terapéutico , Proteínas Recombinantes de Fusión/uso terapéutico , Factores de Edad , Anciano , Glucemia/metabolismo , Ensayos Clínicos Fase III como Asunto , Diabetes Mellitus Tipo 2/metabolismo , Diarrea/inducido químicamente , Femenino , Péptidos Similares al Glucagón/uso terapéutico , Hemoglobina Glucada/metabolismo , Humanos , Hipoglucemia/inducido químicamente , Análisis de los Mínimos Cuadrados , Masculino , Persona de Mediana Edad , Náusea/inducido químicamente , Resultado del TratamientoRESUMEN
BACKGROUND: New and innovative concepts of care management have been developed to improve the health of older adults with dementia and depression. AIM: This article describes the American aging brain care (ABC) program and the possible transfer to the German healthcare system is discussed. MATERIAL AND METHODS: The ABC medical home model in Indianapolis incorporates a specialized geriatric healthcare center which is affiliated to the Eskenazi Hospital as well as a program involving home-based domestic visits by healthcare personnel to affected people. The diagnoses are made in the geriatric center where therapy and treatment are also planned. These stages are carried out in a multiprofessional team, which identifies the individual needs of the patients and relatives and discusses these in family conferences as well as in close consultation with the primary care center of the hospital. The care, diagnosis and therapy are coordinated using a self-developed software for the program and via predetermined pathways and procedural instructions on the approach in the healthcare center and in the domestic visit program. RESULTS AND CONCLUSION: From the perspective of the authors the core elements of the program include not only the use of a home-based care model but also the selection and training of a new type of front-line care provider. Models like the program presented here show great promise for meeting the demands of a rapidly expanding population of vulnerable older adults.
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Vías Clínicas/organización & administración , Demencia/terapia , Depresión/terapia , Servicios de Salud para Ancianos/organización & administración , Servicios de Atención de Salud a Domicilio/organización & administración , Programas Nacionales de Salud/organización & administración , Anciano , Anciano de 80 o más Años , Demencia/diagnóstico , Depresión/diagnóstico , Femenino , Humanos , India , Relaciones Interinstitucionales , Cooperación Internacional , Masculino , Modelos OrganizacionalesRESUMEN
As people are living longer, dementia is becoming a significant issue for society. Dementia is now recognised as a major concern in society, and the numbers of people estimated to have dementia in the UK population appear to have stabilised at around 700,000 . Globally, 35.6 million people are estimated to meet criteria for dementia, a number predicted to double every 20 years . Given the absence of treatments that significantly alter the natural history of the clinical syndrome of dementia, there has been increased emphasis on early diagnosis, with research exploring assessment tools and biomarkers that might predict with certainty a particular clinical outcome. At the same time, there has been pressure to focus on biomedical profiles, which assume a very close link between the pathobiology and the manifest clinical syndrome.
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Demencia/diagnóstico , Diagnóstico Precoz , Medicina Basada en la Evidencia , Política de Salud , HumanosRESUMEN
BACKGROUND: Anticholinergic properties of certain medications often go unrecognized, and are frequently used by the elderly population. Few studies have yet defined the long-term impact of these medications on the incidence of cognitive impairment. METHODS: We report a 6-year longitudinal, observational study, evaluating 1,652 community-dwelling African American subjects over the age of 70 years who were enrolled in the Indianapolis-Ibadan Dementia Project between 2001 and 2007 and who had normal cognitive function at baseline. The exposure group included those who reported the baseline use of possible or definite anticholinergics as determined by the Anticholinergic Cognitive Burden scale. Our main outcome measure was the incidence of cognitive impairment, defined as either dementia or cognitive impairment not dementia, or poor performance on a dementia screening instrument during the follow-up period. RESULTS: At baseline, 53% of the population used a possible anticholinergic, and 11% used a definite anticholinergic. After adjusting for age, gender, educational level, and baseline cognitive performance, the number of definite anticholinergics was associated with an increased risk of cognitive impairment (odds ratio [OR] 1.46, 95% confidence interval [CI] 1.07-1.99; p = 0.02), whereas the number of possible anticholinergics at baseline did not increase the risk (OR 0.96, 95% CI 0.85-1.09; p = 0.55). The risk of cognitive impairment among definite anticholinergic users was increased if they were not carriers of the APOE epsilon4 allele (OR 1.77, 95% CI 1.03-3.05; p = 0.04). CONCLUSIONS: Limiting the clinical use of definite anticholinergics may reduce the incidence of cognitive impairment among African Americans.
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Antagonistas Colinérgicos/uso terapéutico , Trastornos del Conocimiento/epidemiología , Negro o Afroamericano/genética , Anciano , Anciano de 80 o más Años , Apolipoproteínas E/genética , Distribución de Chi-Cuadrado , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/genética , Femenino , Humanos , Incidencia , Estudios Longitudinales , Masculino , Pruebas Neuropsicológicas , Oportunidad Relativa , Riesgo , Factores de RiesgoRESUMEN
BACKGROUND: The loss of cholinergic, dopaminergic and noradrenergic innervations seen in Parkinson's Disease Dementia (PDD) suggest a potential role for cholinesterase inhibitors. Concerns have been expressed about a theoretical worsening of Parkinson's disease related symptoms particularly movement symptoms. OBJECTIVES: To assess the efficacy, safety, tolerability and health economic data relating to the use of cholinesterase inhibitors in PDD. SEARCH STRATEGY: The trials were identified from the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 19 April 2005 using the search term parkinson*This register contains records from major health care databases and many ongoing trial databases and is updated regularly.Comprehensive searches of abstracts from major scientific meetings were performed. Pharmaceutical companies were approached for information regarding additional and ongoing studies. SELECTION CRITERIA: Randomized, double-blind, placebo-controlled studies assessing the effectiveness of cholinesterase inhibitors in PDD. Inclusion and exclusion criteria were stated to limit bias. DATA COLLECTION AND ANALYSIS: Two reviewers (IM, CF) independently reviewed the quality of the studies utilising criteria from the Cochrane Collaboration Handbook. Medications were examined separately and as a group. The outcome measures assessed were in the following domains: neuropsychiatric features, cognition, global impression, daily living activities, quality of life, burden on caregiver, Parkinsonian related symptoms, treatment acceptability as determined by withdrawal from trials, safety as determined by the frequency of adverse events, institutionalisation, death and health economic factors. MAIN RESULTS: A detailed and systematic search of relevant databases identified one published randomized, double-blind, placebo-controlled study (Emre 2004) involving 541 patients that compared rivastigmine with placebo. Rivastigmine produced statistically significant improvements in several outcome measures. On the primary cognitive measure, the ADAS-Cog, rivastigmine was associated with a 2.80 point ADAS-Cog improvement [WMD -2.80, 95% Cl -4.26 to -1.34, P = 0.0002] and a 2.50 point ADCS-ADL improvement [95% Cl 0.43 to 4.57, P = 0.02] relative to placebo. Clinically meaningful (moderate or marked) improvement occurred in 5.3% more patients on rivastigmine, and meaningful worsening occurred in 10.1% more patients on placebo. Tolerability appeared to be a significant issue. Significantly more patients on rivastigmine dropped out of the study due to adverse events [62/362 versus 14/179, OR 2.44, 95% Cl 1.32 to 4.48, P = 0.004]. Nausea [20/179 versus 105/362, OR 3.25, 95% Cl 1.94 to 5.45, P < 0.00001], tremor [7/179 versus 37/362, OR 2.80, 95% Cl 1.22 to 6.41, P = 0.01] and in particular vomiting [3/179 versus 60/362, OR 11.66, 95% Cl 3.60 to 37.72, P < 0.0001] were significantly more common with rivastigmine. However, significantly fewer patients died on rivastigmine than placebo [4/362 versus 7/179, OR 0.27, 95% CI 0.08 to 0.95, P = 0.04] AUTHORS' CONCLUSIONS: Rivastigmine appears to improve cognition and activities of daily living in patients with PDD. This results in clinically meaningful benefit in about 15% of cases. There is a need for more studies utilising pragmatic measures such as time to residential care facility and both patient and carer quality of life assessments. Future trials should involve other cholinesterase inhibitors, utilise tools to analyse the data that limit any bias and measure health economic factors. It is unlikely that relying solely on the last observation carried forward (LOCF) is sufficient. Publication of the observed case data in the largest trial would assist (Emre 2004). Adverse events were associated with the cholinergic activity of rivastigmine, but may limit patient acceptability as evidenced by the high drop out rate in the active arm.
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Inhibidores de la Colinesterasa/uso terapéutico , Demencia/tratamiento farmacológico , Enfermedad de Parkinson/complicaciones , Fenilcarbamatos/uso terapéutico , Inhibidores de la Colinesterasa/efectos adversos , Demencia/etiología , Humanos , Fenilcarbamatos/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , RivastigminaRESUMEN
OBJECTIVE: To review the literature relating to the use of acetyl cholinesterase inhibitors in Parkinson's disease dementia (PDD). METHOD: MEDLINE (1966--December 2004), PsychINFO (1972--December 2004), EMBASE (1980--December 2004), CINHAL (1982--December 2004), and the Cochrane Collaboration were searched in December 2004. RESULTS: Three controlled trials and seven open studies were identified. Efficacy was assessed in three key domains: cognitive, neuropsychiatric and parkinsonian symptoms. CONCLUSION: Cholinesterase inhibitors have a moderate effect against cognitive symptoms. There is no clear evidence of a noticeable clinical effect against neuropsychiatric symptoms. Tolerability including exacerbation of motor symptoms--in particular tremor--may limit the utility of cholinesterase inhibitors.
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Inhibidores de la Colinesterasa/uso terapéutico , Demencia/complicaciones , Demencia/tratamiento farmacológico , Enfermedad de Parkinson/complicaciones , Anciano , Anciano de 80 o más Años , Inhibidores de la Colinesterasa/clasificación , Humanos , Persona de Mediana Edad , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
We have previously observed that transforming growth factor beta 1 (TGF beta 1) produces a pro-oxidant effect and decreases cellular glutathione (GSH) levels of cultured bovine pulmonary artery endothelial cells (BPAEC) (White A. C., S. K. Das, and B. L. Fanburg. Am. J. Respir. Cell Mol. Biol. 6:364-368, 1992). In the present studies we demonstrate that 2 ng/ml TGF beta 1 reduces the uptake of two GSH precursor amino acids (cystine and glutamate) by 50% (cystine; control 359.35 +/- 100, TGF beta 1 187.7 +/- 26 pmol/10 min/10(6) cells, p < 0.05; glutamate; control 215.15 +/- 18, TGF beta 1 110.2 +/- 16 pmol/10 min/10(6) cells, p < 0.001). The inhibitory effect of TGF beta 1 on the uptake of GSH precursor amino acids persisted in the presence of buthionine sulfoximine (inhibits gamma-glutamyl cysteine synthetase, the rate limiting step in GSH synthesis) or acivicin (inhibits gamma-glutamyl transpeptidase). The uptake of leucine, an amino acid that does not serve as a precursor for GSH, was unaffected by TGF beta 1. In additional experiments TGF beta 1 decreased the levels of cellular and medium GSH-indicating that TGF beta 1 did not increase efflux of GSH from BPAEC. We propose from these observations that TGF beta 1 decreases cellular glutathione, at least in part, through down regulation of precursor amino acid transport and, thereby, its rate of synthesis.
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Cistina/metabolismo , Endotelio Vascular/metabolismo , Ácido Glutámico/metabolismo , Glutatión/metabolismo , Factor de Crecimiento Transformador beta/farmacología , Animales , Transporte Biológico , Butionina Sulfoximina/farmacología , Bovinos , Recuento de Células , Células Cultivadas , Endotelio Vascular/citología , Inhibidores Enzimáticos/farmacología , Glutamato-Cisteína Ligasa/antagonistas & inhibidores , Isoxazoles/farmacología , Arteria Pulmonar , gamma-Glutamiltransferasa/antagonistas & inhibidoresRESUMEN
Nitric oxide (NO) has been demonstrated to play a protective role in cell injury. In this study, we have explored the effect of NO and two NO donors (sodium nitroprusside [SNP] and isosorbide dinitrate [ISDN]) on cellular glutathione (GSH) levels in a rat lung fibroblast cell line (RFL6 cells). SNP and ISDN significantly increased cellular GSH in RFL6 cells (5 x 10(-4) M SNP: 21.9 +/- 3.6 nmol/10(6) cells and 5 x 10(-3) M ISDN: 27.6 +/- 1.7 nmol/10(6) cells versus control: 13.2 +/- 0.4 nmol/10(6) cells; P < 0.05). The stimulatory effect of SNP and ISDN on GSH was first seen at 6 h and peaked at 12 to 24 h. A similar increase in GSH was observed in RFL6 cells exposed to 400 ppm NO for 7.5 h (NO: 20.5 +/- 3.4 nmol/10(6) cells versus control: 11.9 +/- 2.4; P < 0.05). SNP and ISDN also increased cellular GSH in bovine pulmonary artery smooth muscle cells (BPSMC) and bovine pulmonary artery endothelial cells (BPAEC). Buthionine sulfoximine (BSO) (0.01 mM), an inhibitor of the GSH synthetic enzyme gamma-glutamyl cysteine synthetase, blocked the increase in GSH in RFL6 cells seen with both SNP and ISDN. In BPAEC, exposure to NO donors for 24 h stimulated glutamate uptake (SNP: 441 +/- 19 pmol/10 min/10(6) cells and ISDN: 677 +/- 48 pmol/10 min/10(6) min/10(6) cells versus control: 222 +/- 9 pmol/10 min/10(6); P < 0.05). This effect paralleled the increase in GSH. In RFL6 cells, only SNP increased glutamate uptake after 24 h of incubation. In summary, NO and NO donors increase cellular GSH in RFL6 cells, BPAEC, and BPSMC. The mechanism of this effect is unclear but may involve upregulation of the normal GSH synthetic pathways. This observation may explain in part the protective effect of NO seen in some cell culture systems and may contribute to a protective effect against oxidant injury in vivo.
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Fibroblastos/metabolismo , Glutatión/metabolismo , Óxido Nítrico/farmacología , Animales , Arginina/farmacología , Butionina Sulfoximina , Bovinos , Línea Celular , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/metabolismo , Inhibidores Enzimáticos/farmacología , Fibroblastos/efectos de los fármacos , Glutamato-Cisteína Ligasa/antagonistas & inhibidores , Ácido Glutámico/metabolismo , Dinitrato de Isosorbide/farmacología , Pulmón , Metionina Sulfoximina/análogos & derivados , Metionina Sulfoximina/farmacología , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/metabolismo , Nitroprusiato/farmacología , Arteria Pulmonar , Ratas , Vasodilatadores/farmacologíaRESUMEN
Babesiosis is a tick-borne protozoal disease with infrequent clinical complications. We report three cases of noncardiogenic pulmonary edema in patients from Nantucket Island, MA, with a history of Lyme disease and review the clinical presentation of babesiosis and its treatment. Respiratory complications in our patients, as well as in the four previously reported cases in the literature, occurred a few days after initiation of medical therapy. We hypothesize that the pathophysiology of the pulmonary edema is multifactorial, due to decreased deformability of the infected erythrocytes, increased cytoadherence of red blood cells in capillaries and venules, and a possible role of excessive production of certain cytokines, such as tumor necrosis factor and interleukin-1.