RESUMEN
AIMS: There is high prevalence of hereditary haemochromatosis (HH) in North European populations, yet the diagnosis is often delayed or missed in primary care. Primary care physicians frequently request serum ferritin (SF) estimation but appear uncertain as how to investigate patients with raised SF values. Our aim was to develop a laboratory algorithm with high predictive value for the diagnosis of HH in patients from primary care with raised SF values. METHODS: Transferrin saturation (Tsat) was measured on SF samples sent from primary care; 1657 male and 2077 female patients age ≥ 30 years with SF ≥ 200 µg/L. HFE genotyping was performed on all 878 male and 867 female patients with Tsat >30%. RESULTS: This study identified 402 (206 men; 196 women) C282Y carriers and 132 (58 men; 74 women) C282Y homozygotes. Optimal limits for combined SF and Tsat values for HH recognition were established. The detection rate for homozygous C282Y HH for male patients with both SF ≥ 300 µg/L and Tsat >50% was 18.8% (52/272) and 16.3% (68/415) for female patients with both SF ≥ 200 µg/L and Tsat >40%. CONCLUSIONS: The large number of SF requests received from primary care should be used as a resource to improve the diagnosis of HH in areas of high prevalence.
Asunto(s)
Hemocromatosis/diagnóstico , Adulto , Anciano , Algoritmos , Biomarcadores/sangre , Vías Clínicas , Análisis Mutacional de ADN , Femenino , Ferritinas/sangre , Predisposición Genética a la Enfermedad , Hemocromatosis/genética , Proteína de la Hemocromatosis , Herencia , Heterocigoto , Antígenos de Histocompatibilidad Clase I/genética , Homocigoto , Humanos , Laboratorios de Hospital , Masculino , Proteínas de la Membrana/genética , Persona de Mediana Edad , Mutación , Fenotipo , Valor Predictivo de las Pruebas , Atención Primaria de Salud , Derivación y Consulta , Transferrina/análisis , Regulación hacia ArribaRESUMEN
AIMS: Microvolt T-wave alternans (MTWA) testing identifies beat-to-beat fluctuations in T-wave morphology, which have been linked to ventricular arrhythmias. However, clinical studies have produced conflicting results and data in heart failure (HF) have been limited. The aim of this study was to determine the prevalence and incremental prognostic value of spectral MTWA testing in an unselected cohort of patients recently hospitalized with HF. METHODS AND RESULTS: Consecutive admissions with confirmed HF were recruited, and survivors were invited to attend 1 month post-discharge for MTWA testing. A total of 648 of 1003 enrolled patients returned for MTWA testing (58% male, mean age 71 years). Forty-nine per cent were ineligible due to AF, pacemaker dependency, or inability to exercise. Of the 330 MTWA test results, 30% were positive, 24% negative, and 46% indeterminate. Overall, 268 deaths occurred during a median follow-up of 3.1 (interquartile range 1.9-3.9) years. Of the ineligible patients, 48% died vs. 35% of eligible patients (P < 0.001). Of those patients with positive, negative, and indeterminate tests, 27, 35, and 40%, respectively, died (P = 0.12). Even when analysed as non-negative (positive/indeterminate) vs. negative, there was still no between-group difference in mortality (P = 0.95). MTWA results categorized as positive, negative, or indeterminate showed no incremental prognostic value in a multivariable model, which included BNP. Paradoxically, when compared in a binary fashion with a non-negative result, a negative test was an independent predictor of death, as was ineligibility for MTWA testing. CONCLUSION: Spectral MTWA testing was not widely applicable and failed to predict mortality, and so cannot be endorsed as a risk stratification tool in HF.
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Arritmias Cardíacas/diagnóstico , Electrocardiografía/métodos , Insuficiencia Cardíaca/diagnóstico , Medición de Riesgo/métodos , Anciano , Anciano de 80 o más Años , Arritmias Cardíacas/complicaciones , Estudios de Cohortes , Femenino , Insuficiencia Cardíaca/complicaciones , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Análisis EspectralRESUMEN
BACKGROUND: Antiplatelet therapy is recommended as part of a strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. However, compliance with these guideline-recommended therapies appears to be less than ideal. OBJECTIVE: To assess the effect of adding pharmacists to primary care teams on initiation of guideline-concordant antiplatelet therapy in type 2 diabetic patients. METHODS: Prespecified secondary analysis of randomized trial data. In the main study, the pharmacist intervention included a complete medication history, limited physical examination, provision of guideline-concordant recommendations to the physician to optimize drug therapy, and 1-year follow-up. Controls received usual care without pharmacist interactions. Patients with an indication for antiplatelet therapy, but not using an antiplatelet drug at randomization were included in this substudy. The primary outcome was the proportion of patients using an antiplatelet drug at 1 year. RESULTS: At randomization, 257 of 260 study patients had guideline-concordant indications for antiplatelet therapy, but less than half (121; 47%) were using an antiplatelet drug. Overall, 136 patients met inclusion criteria for the substudy (71 intervention and 65 controls): 60% were women, with mean (SD) age 58.0 (11.9) years, diabetes duration 5.3 (6.0) years, and hemoglobin A(1c) 7.6% (1.5). Sixteen (12%) had established cardiovascular disease at enrollment. At 1 year, 43 (61%) intervention patients and 15 (23%) controls were using an antiplatelet drug (38% absolute difference; number needed to treat, 3; relative increase, 2.6; 95% CI 1.5-4.7; p < 0.001). Of these 58 patients, 52 (90%) were using aspirin 81 mg daily. CONCLUSIONS: Adding pharmacists to primary care teams significantly and substantially increased the proportion of type 2 diabetic patients using guideline-concordant antiplatelet therapy.
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Enfermedades Cardiovasculares/prevención & control , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Farmacéuticos/organización & administración , Inhibidores de Agregación Plaquetaria/uso terapéutico , Anciano , Enfermedades Cardiovasculares/etiología , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Estudios de Seguimiento , Adhesión a Directriz , Humanos , Masculino , Persona de Mediana Edad , Grupo de Atención al Paciente/organización & administración , Servicios Farmacéuticos/organización & administración , Inhibidores de Agregación Plaquetaria/administración & dosificación , Guías de Práctica Clínica como Asunto , Atención Primaria de Salud/organización & administración , Rol Profesional , Factores de TiempoRESUMEN
B-type natriuretic peptide (BNP) response early after a tetralogy of Fallot's repair remains unclear. BNP was measured pre- and post-operatively (immediately, day 1) in 18 children undergoing corrective repair with concurrent echocardiography (pre-, post-op day 1) to assess right ventricular (RV) systolic dysfunction, restrictive physiology, wall motion and pulmonary regurgitation (PR). In the first 24 h postoperatively, BNP rose acutely in all patients (mean 34.9 vs 144.4 vs 716.9 pg/ml at pre-op, days 0 and 1; P < 0.001). Immediate postoperative BNP correlated with preoperative haematocrit (rho = 0.52, P = 0.03) and inversely with preoperative oxygen saturation (rho = -0.63, P = 0.007). All patients showed reduced RV systolic function and abnormal wall motion with at least moderate PR in six patients (33.3%) and restrictive physiology in four (24%). Subsequent BNP expression (post-op day 1) correlated with a low RV fractional area change (rho = -0.51, P = 0.04), high oxygen extraction ratio (rho = 0.56, P = 0.02) and high central venous pressure (rho = 0.79, P < 0.001). The LV function and wall motion remained preserved in all patients. The mechanism of BNP expression is likely to be multi-factorial in the presence of a complex postoperative RV physiology in tetralogy of Fallot. An acute BNP response in the early postoperative period reflects an important physiological role and may be used as an adjunct biomarker to assess the RV function.
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Ventrículos Cardíacos/fisiopatología , Péptido Natriurético Encefálico/sangre , Tetralogía de Fallot/sangre , Función Ventricular Derecha/fisiología , Biomarcadores/sangre , Preescolar , Ecocardiografía Doppler , Prueba de Esfuerzo , Femenino , Estudios de Seguimiento , Ventrículos Cardíacos/diagnóstico por imagen , Humanos , Lactante , Masculino , Contracción Miocárdica , Periodo Posoperatorio , Pronóstico , Estudios Prospectivos , Sístole , Tetralogía de Fallot/fisiopatología , Tetralogía de Fallot/cirugía , Factores de TiempoRESUMEN
Poor warfarin control with resultant high International Normalized Ratios (INRs) and bleeding events is most common during the first months of treatment. The effects of genetic polymorphisms at the vitamin K epoxide reductase [VKORC1] and cytochrome P450 2C9 [CYP2C9] loci have been increasingly acknowledged as contributory factors of enhanced warfarin sensitivity. In our prospective, blinded study, 557 patients (49·1% male, mean age 65·4 years, range 18-91 years) commencing warfarin (target INR 2·5) were genotyped and monitored through the first 3 months of anticoagulation. Homozygosity for the -1639 G>A single nucleotide functional promoter polymorphism of the VKORC1 gene (genotype AA; 14·5% of cases) was associated with a significantly shortened time to therapeutic INR ≥ 2 (P < 0·01), reduced stable warfarin dose (P < 0·01), and an increased number of INRs > 5 (P < 0·001) and occurrence of bleeding events (P < 0·01) during the first month, as compared to the GG genotype. CYP2C9 genetic variations *2 and *3 were not associated with significant effect on these factors. Neither VKORC1 nor CYP2C9 polymorphisms influenced these parameters beyond the first month of treatment. These findings imply possible benefits of assessing VKORC1 polymorphisms prior to anticoagulation, particularly as a low dose induction regime in VKORC1 AA individuals appears to reduce the incidence of high INRs.
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Anticoagulantes/farmacología , Hidrocarburo de Aril Hidroxilasas/genética , Oxigenasas de Función Mixta/genética , Polimorfismo de Nucleótido Simple , Warfarina/farmacología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Coagulación Sanguínea/efectos de los fármacos , Coagulación Sanguínea/genética , Citocromo P-450 CYP2C9 , Esquema de Medicación , Monitoreo de Drogas/métodos , Femenino , Genotipo , Hemorragia/inducido químicamente , Hemorragia/genética , Humanos , Relación Normalizada Internacional , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Método Simple Ciego , Factores de Tiempo , Resultado del Tratamiento , Vitamina K Epóxido Reductasas , Warfarina/administración & dosificación , Warfarina/efectos adversos , Adulto JovenRESUMEN
AIMS: Observational studies in selected populations have suggested that microvolt T-wave alternans (MTWA) testing may identify patients with heart failure (HF) at risk of sudden cardiac death. The aims of this study were to investigate the utility of MTWA testing in an unselected population of patients with HF and to evaluate the clinical characteristics associated with the MTWA results. METHODS AND RESULTS: A total of 1003 patients hospitalized with decompensated HF were enrolled. MTWA testing was planned 1 month post-discharge; 648 patients returned for MTWA testing. Mean age was 70.8 ± 10.6 years and 58% were male. Of these patients who returned, 318 (49%) were ineligible for MTWA testing due to atrial fibrillation (AF), pacemaker dependency, or physical inability to undertake the test. Of the MTWA tests, 100 (30%) were positive, 78 (24%) were negative, and 152 (46%) were indeterminate; 112/152 indeterminate tests (74%) occurred because of failure to achieve target heart rate (HR) due to chronotropic incompetence or physical limitations. There were differences in patient characteristics according to MTWA result. Independent predictors of a negative result included younger age and higher left ventricular ejection fraction (LVEF). Independent predictors of a positive result included higher HR during MTWA testing and lower LVEF. Independent predictors of an indeterminate result included older age and history of previous/paroxysmal AF. CONCLUSIONS: Only half of patients with HF are eligible for MTWA testing and the most common result is an indeterminate test. Patients with positive and indeterminate tests have different clinical characteristics. MTWA treadmill testing is not widely applicable in typical HF patients and is unlikely to refine risk stratification for sudden death on a population level.
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Arritmias Cardíacas/patología , Insuficiencia Cardíaca/patología , Anciano , Análisis de Varianza , Distribución de Chi-Cuadrado , Desfibriladores Implantables , Prueba de Esfuerzo , Femenino , Humanos , Masculino , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Medición de Riesgo/métodos , Volumen Sistólico , Función Ventricular IzquierdaRESUMEN
OBJECTIVE: To evaluate the effect of adding pharmacists to primary care teams on the management of hypertension and other cardiovascular risk factors in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted a randomized controlled trial with blinded ascertainment of outcomes within primary care clinics in Edmonton, Canada. Pharmacists performed medication assessments and limited history and physical examinations and provided guideline-concordant recommendations to optimize medication management. Follow-up contact was completed as necessary. Control patients received usual care. The primary outcome was a ≥10% decrease in systolic blood pressure at 1 year. RESULTS: A total of 260 patients were enrolled, 57% were women, the mean age was 59 years, diabetes duration was 6 years, and blood pressure was 129/74 mmHg. Forty-eight of 131 (37%) intervention patients and 30 of 129 (23%) control patients achieved the primary outcome (odds ratio 1.9 [95% CI 1.1-3.3]; P = 0.02). Among 153 patients with inadequately controlled hypertension at baseline, intervention patients (n = 82) were significantly more likely than control patients (n = 71) to achieve the primary outcome (41 [50%] vs. 20 [28%]; 2.6 [1.3-5.0]; P = 0.007) and recommended blood pressure targets (44 [54%] vs. 21 [30%]; 2.8 [1.4-5.4]; P = 0.003). The 10-year risk of cardiovascular disease, based on changes to the UK Prospective Diabetes Study Risk Engine, were predicted to decrease by 3% for intervention patients and 1% for control patients (P = 0.005). CONCLUSIONS: Significantly more patients with type 2 diabetes achieved better blood pressure control when pharmacists were added to primary care teams, which suggests that pharmacists can make important contributions to the primary care of these patients.
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Presión Sanguínea/fisiología , Diabetes Mellitus Tipo 2/fisiopatología , Farmacéuticos , Atención Primaria de Salud/organización & administración , Anciano , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Hemochromatosis causes iron overload by enhanced intestinal absorption. This study examined erythropoietin and intravenous (i.v.) iron requirements in hemodialysis (HD) patients with HFE mutations. Patients on HD for > 90 days with no cause of anemia except chronic kidney disease were tested for HFE mutations (H63D and C282Y). Intravenous iron and erythropoietin doses were adjusted to achieve recommended targets. Monthly hemoglobin (Hb), ferritin, mean corpuscular volume, mean cell hemoglobin, erythropoietin, and i.v. iron doses for 3 consecutive months were averaged. Of 172 patients, 71 (41.3%) had > or = 1 HFE mutation: 24 (14%) C282Y heterozygotes, 40 (23.3%) H63D heterozygotes, 5 compound heterozygotes, and 2 homozygotes. Comparing patients with > or = 1 HFE mutation to those without mutations showed no significant difference in Hb or serum ferritin. There was a trend toward lower median weekly erythropoietin dose in patients with > or = 1 HFE mutation (94.0 vs. 135.4 U/kg body weight; P=0.13). There was no difference in median weekly i.v. iron dose (1.0 vs. 0.9 mg/kg body weight; P=0.56). Comparing the 30 patients with a C282Y mutation to patients without HFE mutations produced similar results. Comparing the 47 patients with an H63D mutation, with those without HFE mutations, no discernable trend was observed. In this study, patients with HFE gene mutations on HD for established renal failure do not require less iron supplementation to achieve recommended Hb targets. We observed a trend toward lower erythropoietin requirement in patients possessing C282Y mutations. Larger studies may clarify the role of HFE mutations, regulators of iron metabolism and erythropoiesis in chronic kidney disease.
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Anemia/genética , Anemia/terapia , Hemocromatosis/genética , Antígenos de Histocompatibilidad Clase I/genética , Proteínas de la Membrana/genética , Mutación/genética , Diálisis Renal , Femenino , Genotipo , Proteína de la Hemocromatosis , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: HFE-related genetic haemochromatosis (GH) is the commonest inherited genetic disorder in Caucasian populations with approximately one in 180 of individuals in the west of Scotland homozygous for the common C282Y mutation. The clinical diagnosis of GH, however, remains relatively uncommon - suggesting either under diagnosis or low clinical penetrance. AIM: We aimed to assess the biochemical and clinical penetrance of GH in first-degree relatives of patients with known GH, who subsequently themselves screened positive for the common GH mutations. METHODS: Individuals were identified from two large teaching hospitals in North Glasgow from July 1997 to July 2005 diagnosed with GH after predictive genetic testing after a relative was found to have GH. Details of patient history, biochemistry and known comorbidity at diagnosis and results of related further investigations were collected. RESULTS: Sixty-three individuals were identified, 31 (49%) of whom were males. Fifty-five individuals (87%) were C282Y homozygous and the remaining eight were compound heterozygotes for C282Y and H63D. All 31 male patients were found to have evidence of iron overload as opposed to 63% of females. Elevated liver enzyme levels were encountered in 15 patients (24%). All except one had evidence of iron overload. Four individuals underwent a liver biopsy, two of whom had hepatic fibrosis. Four patients were found to be diabetic. A full clinical history was obtained from 54 of 63 individuals, 38 (70%) of whom were entirely asymptomatic. Thirteen individuals complained of joint pains and a further nine complained of fatigue. CONCLUSION: This study suggests that although biochemical penetrance of GH is high, the clinical penetrance is low.