Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

Clínica y genética de la hipercolesterolemia familiar en Mallorca

Familial hypercholesterolemia (FH) is the best known monogenic disorder from the fat metabolism. This disease is characterized by xanthomas , increased serum levels of cLDL and premature cardiovascular disease. We carry out the genetical diagnosis from the DNA study, from selected patients who present clinical symptomps for FH in Mallorca Island. Thanks to molecular tecnics applied to this study we can have unequivocal results in those patients, we are able to start a treatment as soon as posible in order to delay the complications from this illness such as atherosclerosis. The objetives we persue are: study prevalence of mutaciones on coronary LRDR gene, on those patients with clinical criteria for FH in Mallorca population. To know the typus and characteristic from the different mutations of gen LRDR resulting on FH. Detect the effects on the different mutations. To study the frecuency of clinical symptoms (xanthomas tendinosos, arco corneal, xanthelasma, Achilles tendinitis , Hypertension and DM) in order to start correct and early treatment on patients with FH. We collect 212 cases with clinical criteria for FH, 65 cases (CI) were selected by Med Ped holandes for FH. 23% develop premature cardiovascular disease. Those results compared to the rest of the mainland were smaller. First complication was ischaemic heart disease, twice in number on males and middle age population. Coronary disease (17%) was first followed by brain disease (4.6%). We found 24 mutations, 4 of them were new finding on this study. We found that HF prevalence is 1/474 and HF by genetical diagnosis is 1/780. Resulting from this study we have realized a proposal for the diagnosis for FH.La hipercolesterolemia familiar (HF) es la enfermedad monogénica del metabolismo lipídico mejor conocida. La enfermedad se caracteriza por la presencia de xantomas, elevados niveles plasmáticos de cLDL y cardiopatía isquémica prematura debida al desarrollo de arteriosclerosis coronaria. En este trabajo realizamos el diagnóstico genético, a través de estudio del DNA, de los pacientes que presentaban características clínicas de HF de la Isla de Mallorca. La aplicación de las técnicas de biología molecular al estudio de la HF permite realizar un diagnóstico inequívoco en estos pacientes, iniciar un tratamiento precoz para intentar evitar las complicaciones ateroscleróticas de la enfermedad. Los objetivos que se plantean son: estudiar la prevalencia de mutaciones en el gen del LDLR, en los pacientes con criterios clínicos de HF en la población de Mallorca. Conocer el tipo y características de las distintas mutaciones en el gen LDLR responsables de HF en la Isla. Evaluar la repercusión de las distintas mutaciones. Conocer la frecuencia de manifestaciones clínicas (xantomas tendinosos, arco corneal, xantelasmas, tendinitis aquilea, HTA y DM) y conseguir el tratamiento adecuado y precoz de los individuos con HF. De la población de Mallorca se recogieron 212 casos con criterios clínicos de HF, de éstos se seleccionaron 65 casos índices (CI) que cumplían los criterios del MedPed holandés para HF. Un 23% presentaron enfermedad cardiovascular prematura (ECVP) ( 11 varones y 3 mujeres) resultados inferiores a los descritos en otras provincias españolas. La primera manifestación fue la cardiopatía isquémica (CI) que fue el doble en varones y más frecuente en las edades medias de la vida. El territorio más afectado fue el conorario (17%) seguido del cerebral (4,6%). Se han encontrado 24 mutaciones y de éstas 4 han sido descritas por primera vez en este trabajo. Del mismo, se deduce una prevalencia de HF clínica de 1/474 y de HF con diagnostico genético de 1/780. De este estudio ha derivado una propuesta de diagnóstico de HF

100 años investigando el mar. El IEO en su centenario (1914-2014).

Se trata de un libro que pretende divulgar a la sociedad las principales investigaciones multidisciplinares llevadas a cabo por el Instituto Español de Oceanografía durante su primer siglo de vida, y dar a conocer la historia del organismo, de su Sede Central y de los nueve centros oceanográficos repartidos por los litorales mediterráneo y atlántico, en la península y archipiélagos.Kongsberg 200Postprin

Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients

BACKGROUN

Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients

Bococizumab is a humanized monoclonal antibody that inhibits proprotein convertase subtilisin- kexin type 9 (PCSK9) and reduces levels of low-density lipoprotein (LDL) cholesterol. We sought to evaluate the efficacy of bococizumab in patients at high cardiovascular risk. METHODS In two parallel, multinational trials with different entry criteria for LDL cholesterol levels, we randomly assigned the 27,438 patients in the combined trials to receive bococizumab (at a dose of 150 mg) subcutaneously every 2 weeks or placebo. The primary end point was nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina requiring urgent revascularization, or cardiovascular death; 93% of the patients were receiving statin therapy at baseline. The trials were stopped early after the sponsor elected to discontinue the development of bococizumab owing in part to the development of high rates of antidrug antibodies, as seen in data from other studies in the program. The median follow-up was 10 months. RESULTS At 14 weeks, patients in the combined trials had a mean change from baseline in LDL cholesterol levels of -56.0% in the bococizumab group and +2.9% in the placebo group, for a between-group difference of -59.0 percentage points (P<0.001) and a median reduction from baseline of 64.2% (P<0.001). In the lower-risk, shorter-duration trial (in which the patients had a baseline LDL cholesterol level of ≥70 mg per deciliter [1.8 mmol per liter] and the median follow-up was 7 months), major cardiovascular events occurred in 173 patients each in the bococizumab group and the placebo group (hazard ratio, 0.99; 95% confidence interval [CI], 0.80 to 1.22; P = 0.94). In the higher-risk, longer-duration trial (in which the patients had a baseline LDL cholesterol level of ≥100 mg per deciliter [2.6 mmol per liter] and the median follow-up was 12 months), major cardiovascular events occurred in 179 and 224 patients, respectively (hazard ratio, 0.79; 95% CI, 0.65 to 0.97; P = 0.02). The hazard ratio for the primary end point in the combined trials was 0.88 (95% CI, 0.76 to 1.02; P = 0.08). Injection-site reactions were more common in the bococizumab group than in the placebo group (10.4% vs. 1.3%, P<0.001). CONCLUSIONS In two randomized trials comparing the PCSK9 inhibitor bococizumab with placebo, bococizumab had no benefit with respect to major adverse cardiovascular events in the trial involving lower-risk patients but did have a significant benefit in the trial involving higher-risk patients