Ensayos clínicos. Una asignatura pendiente / Clinical trials. A pending subject

Los ensayos clínicos son una herramienta fundamental para el avance de la medicina clínica en sus vertientes diagnóstica y terapéutica. Desde la aparición del primer ensayo en 1948, que relacionaba el tabaco con el cáncer de pulmón, se han realizado hasta la fecha más de 150.000 en diversas áreas (pediatría, cardiología, oncología, endocrinología, etc.). Este artículo resalta la importancia para todo facultativo de participar, a lo largo de su trayectoria profesional, en algún ensayo clínico por los beneficios inherentes al paciente, al progreso de la medicina, así como al prestigio curricular. Los autores hacen una síntesis de su experiencia sobre ensayos clínicos en hipertensión, diabetes, dislipidemias y cardiopatía isquémica a lo largo de casi 3 décadas. Asimismo, se hace una breve referencia a las características de una unidad en fase i, así como a algunas investigaciones que actualmente se están realizando

Clinical trials are essential tools for the progress of clinical medicine in its diagnostic and therapeutic aspects. Since the first trial in 1948, which related tobacco use with lung cancer, there have been more than 150,000 clinical trials to date in various areas (paediatrics, cardiology, oncology, endocrinology, etc.). This article highlights the importance for all physicians to participate, over the course of their professional career, in a clinical trial, due to the inherent benefits for patients, the progress of medicine and for curricular prestige. The authors have created a synthesis of their experience with clinical trials on hypertension, diabetes, dyslipidaemia and ischaemic heart disease over the course of almost 3 decades. Furthermore, a brief reference has been made to the characteristics of a phase I unit, as well as to a number of research studies currently underway

Clinical trials. A pending subject. / Ensayos clínicos. Una asignatura pendiente.

Clinical trials are essential tools for the progress of clinical medicine in its diagnostic and therapeutic aspects. Since the first trial in 1948, which related tobacco use with lung cancer, there have been more than 150,000 clinical trials to date in various areas (paediatrics, cardiology, oncology, endocrinology, etc.). This article highlights the importance for all physicians to participate, over the course of their professional career, in a clinical trial, due to the inherent benefits for patients, the progress of medicine and for curricular prestige. The authors have created a synthesis of their experience with clinical trials on hypertension, diabetes, dyslipidaemia and ischaemic heart disease over the course of almost 3 decades. Furthermore, a brief reference has been made to the characteristics of a phase I unit, as well as to a number of research studies currently underway.

Blood pressure-lowering effects of nifedipine/candesartan combinations in high-risk individuals: subgroup analysis of the DISTINCT randomised trial.

The DISTINCT study (reDefining Intervention with Studies Testing Innovative Nifedipine GITS-Candesartan Therapy) investigated the efficacy and safety of nifedipine GITS/candesartan cilexetil combinations vs respective monotherapies and placebo in patients with hypertension. This descriptive sub-analysis examined blood pressure (BP)-lowering effects in high-risk participants, including those with renal impairment (estimated glomerular filtration rate<90 ml min-1, n=422), type 2 diabetes mellitus (n=202), hypercholesterolaemia (n=206) and cardiovascular (CV) risk factors (n=971), as well as the impact of gender, age and body mass index (BMI). Participants with grade I/II hypertension were randomised to treatment with nifedipine GITS (N) 20, 30, 60 mg and/or candesartan cilexetil (C) 4, 8, 16, 32 mg or placebo for 8 weeks. Mean systolic BP and diastolic BP reductions after treatment in high-risk participants were greater, overall, with N/C combinations vs respective monotherapies or placebo, with indicators of a dose-response effect. Highest rates of BP control (ESH/ESC 2013 guideline criteria) were also achieved with highest doses of N/C combinations in each high-risk subgroup. The benefits of combination therapy vs monotherapy were additionally observed in patient subgroups categorised by gender, age or BMI. All high-risk participants reported fewer vasodilatory adverse events in the pooled N/C combination therapy than the N monotherapy group. In conclusion, consistent with the DISTINCT main study outcomes, high-risk participants showed greater reductions in BP and higher control rates with N/C combinations compared with respective monotherapies and lesser vasodilatory side-effects compared with N monotherapy.

The enigma of Mozart's death / El enigma de la muerte de Mozart

No disponible

Utility of transcranial sonography in the diagnosis of drug-induced parkinsonism: a prospective study.

BACKGROUND AND PURPOSE: Drug-induced parkinsonism usually resolves after discontinuation of the causative agent. However, it persists in some patients, who actually have subclinical neurodegenerative parkinsonism. Identification of this condition is important because these patients could benefit from therapeutic measures. The objective of this study was to prove whether transcranial sonography, a technique used in the diagnosis of neurodegenerative parkinsonism, can be used for the said identification. METHODS: In this prospective study, patients with drug-induced parkinsonism were followed for at least 6 months after discontinuation of the causative drug and performance of blinded transcranial sonography. Patients were categorized as having iatrogenic parkinsonism if the clinical presentation had resolved or subclinical drug-exacerbated parkinsonism if it persisted. Once the patient was classified into one of the two groups, an expert assessed the transcranial sonography findings and their agreement with the clinical diagnosis. RESULTS: Twenty patients composed the group for analysis of results. Assessing hyperechogenicity in the substantia nigra >20 mm2 and/or hyperechogenic lentiform nucleus, differences were detected between the iatrogenic parkinsonism and the subclinical drug-exacerbated parkinsonism groups, although they did not reach statistical significance (Fisher's exact test 0.09). Joint assessment of sonographic alterations in both structures had a negative predictive value of 85.7% for diagnosis of drug-induced parkinsonism, with a negative likelihood ratio of 0.3. CONCLUSIONS: Although in our study statistically significant differences were not found between the transcranial sonography characteristics of subclinical drug-exacerbated parkinsonism and iatrogenic parkinsonism patients, we believe that transcranial sonography is a valid technique for diagnosis of drug-induced parkinsonism.

Immediate and late benefits of treating very elderly people with hypertension: results from active treatment extension to Hypertension in the Very Elderly randomised controlled trial.

OBJECTIVE: To assess if very elderly people with hypertension obtain early benefit from antihypertensive treatment. DESIGN: One year open label active treatment extension of randomised controlled trial (Hypertension in the Very Elderly Trial (HYVET)). SETTING: Hospital and general practice based centres mainly in eastern and western Europe, China, and Tunisia. PARTICIPANTS: People on double blind treatment at the end of HYVET were eligible to enter the extension. INTERVENTIONS: Participants on active blood pressure lowering treatment continued taking active drug; those on placebo were given active blood pressure lowering treatment. The treatment regimen was as used in the main trial-indapamide SR 1.5 mg (plus perindopril 2-4 mg if required)-with the same target blood pressure of less than 150/80 mm Hg. MAIN OUTCOME MEASURES: The primary outcome was all stroke; other outcomes included total mortality, cardiovascular mortality, and cardiovascular events. RESULTS: Of 1882 people eligible for entry to the extension, 1712 (91%) agreed to participate. During the extension period, 1682 patient years were accrued. By six months, the difference in blood pressure between the two groups was 1.2/0.7 mm Hg. Comparing people previously treated with active drug and those previously on placebo, no significant differences were seen for stroke (n = 13; hazard ratio 1.92, 95% confidence interval 0.59 to 6.22) or cardiovascular events (n = 25; 0.78, 0.36 to 1.72). Differences were seen for total mortality (47 deaths; hazard ratio 0.48, 0.26 to 0.87; P = 0.02) and cardiovascular mortality (11 deaths; 0.19, 0.04 to 0.87; P = 0.03). CONCLUSION: Very elderly patients with hypertension may gain immediate benefit from treatment. Sustained differences in reductions of total mortality and cardiovascular mortality reinforce the benefits and support the need for early and long term treatment. Trial registration Clinical trials NCT00122811.

Efficacy and safety of extended-release niacin/laropiprant plus statin vs. doubling the dose of statin in patients with primary hypercholesterolaemia or mixed dyslipidaemia.

BACKGROUND: Co-administration of niacin with statin offers the potential for additional lipid management and cardiovascular risk reduction. However, niacin is underutilised because of the side effects of flushing, mediated primarily by prostaglandin D(2) (PGD(2)). A combination tablet containing extended-release niacin and laropiprant (ERN/LRPT), a PGD(2) receptor (DP1) antagonist, offers improved tolerability. This study assessed the efficacy and safety of ERN/LRPT added to statin vs. doubling the dose of statin in patients with primary hypercholesterolaemia or mixed dyslipidaemia who were not at their National Cholesterol Education Program Adult Treatment Panel III low-density lipoprotein cholesterol (LDL-C) goal based on their coronary heart disease risk category (high, moderate or low). METHODS: After a 2- to 6-week run-in statin (simvastatin 10 or 20 mg or atorvastatin 10 mg) period, 1216 patients were randomised equally to one of two treatment groups in a double-blind fashion: group 1 received ERN/LRPT (1 g) plus the run-in statin dose and advanced to ERN/LRPT (2 g) after 4 weeks for an additional 8 weeks, with no adjustments to the run-in statin dose; group 2 received simvastatin or atorvastatin at twice their run-in statin dose and remained on this stable dose for 12 weeks. RESULTS: ERN/LRPT added to statin (pooled across statin and statin dose) significantly improved key lipid parameters vs. the doubled statin dose (pooled): the between-treatment group difference in least squares mean per cent change [95% confidence interval (CI)] from baseline to week 12 in LDL-C (primary end-point) was -4.5% (-7.7, -1.3) and in high-density lipoprotein cholesterol (HDL-C) was 15.6% (13.4, 17.9) and in median per cent change for triglyceride (TG) was -15.4% (-19.2, -11.7). Treatment-related adverse experiences (AEs) related to flushing, pruritis, rash, gastrointestinal upset and elevations in liver transaminases and fasting serum glucose occurred more frequently with ERN/LRPT added to statin vs. statin dose doubled. CONCLUSIONS: The addition of ERN/LRPT to ongoing statin treatment produced significantly improved lipid-modifying benefits on LDL-C, HDL-C and TG and all other lipid parameters compared with doubling the statin dose in patients with primary hypercholesterolaemia or mixed dyslipidaemia. The types of AEs that occurred at a greater frequency in the ERN/LRPT group were those typically associated with niacin.

Influencia de los antecedentes familiares sobre la edad de aparición de la hipertensión. Implicación de la impronta genética / The influence of family history on the age of onset of hypertension: possible role of genetic imprinting

Objetivo. El objetivo de este trabajo ha sido estudiarla influencia de la historia familiar de hipertensión enla edad de aparición de la enfermedad en los pacientesestudiados.Pacientes y métodos. Analizamos un grupo de poblaciónhipertensa española de 528 pacientes (302 mujeresy 226 hombres) de edades comprendidas entre16 y 89 años. Se hizo un estudio descriptivo y transversal.Resultados. Nuestros resultados muestran que la edadde aparición de la hipertensión fue más temprana enhombres (43,32±11,74) que en mujeres (47,84±10,92). Encontramos diferencias estadísticamente significativasen la edad de aparición de la hipertensiónentre sujetos con padre hipertenso (independientementede tener madre hipertensa o normotensa) y elgrupo control (ambos padres normotensos), edad quefue más temprana en sujetos con padre hipertenso.Conclusión. Aunque la enfermedad se transmite normalmentepor vía materna, ésta aparece antes cuandoocurre por vía paterna, lo que puede indicar quealgunos de los genes implicados podría estar afectadopor el fenómeno de impronta genética (AU)

Objective. We aimed to study the influence of familyhistory on the age of onset of hypertension.Patients and methods. We analyzed 528 (302 womenand 226 men; age range, 16-89 years) hypertensivepatients in a descriptive cross-sectional study.Results. Onset was earlier in men (43.32±11.74 years)than in women (47.84±10.92). Age of onset was significantlylower in subjects with a hypertense father(regardless of whether the mother was hypertensiveor normotensive) than in the control group (with bothparents normotensive).Conclusion. Although hypertension is usually transmittedmaternally, it appears early when transmittedpaternally; this indicates that one of the genes involvedmight be affected by genetic imprinting (AU)

¿Debemos tratar la hipertensión arterial en el muy anciano? / No disponible

No disponible

Tratando a nuestros octogenarios / No disponible

No disponible

Paciente con disnea progresiva de un mes de evolución / Patient with one-month long progressive dyspnea

No disponible

[Some reflections and findings of a Hypertension [corrected] Unit in Spain]. / Algunas reflexiones y hallazgos de una Unidad de Hipertensión en España.

The Hypertension Unit, University Hospital San Cecilio of Granada, on fulfilling 15 years and after the experience acquired in this extended period, wants to stress various "facts": 1) the importance of correctly measuring blood pressure, avoiding rounding off "numbers" and making three consecutive measurements, taking the mean value of the last two; 2) carefully using the concept of "white coat" hypertension; the continuous follow-up of these cases and the use of ambulatory blood pressure monitoring reveal that they are really hypertensive; 3) using those values less than 130/85 mmHg as normality values; 4) the high rate of risk factors (obesity, diabetes, hyperuricemia, smoking, etc.) accompanying recently diagnosed hypertension; and 5) the need to give an intensive treatment in many cases (high doses, greater number of drugs, etc.). The experience of more than fifteen years and thousands of patients seen support the ideas included herein.