[Antiretroviral therapy and mitochondrial toxicity]. / Tratamiento antirretroviral y toxicidad mitocondrial.

The introduction of highly active antiretroviral therapy for the treatment of human immunodeficiency virus (HIV) infection has led to substantial reduction in morbidity and near-complete suppression of HIV-1 replication. This progress has been tempered by a growing number of new adverse effects. Mitochondrial toxicity is one aspect of these long-term toxicities of antiretroviral drugs, with the role of nucleoside analogs being particularly underlined. Some cases of impaired mitochondrial function have been clearly identified, such as pancreatitis, neuropathy, miopathy and lactic acidosis. Beyond the inhibition of DNA polymerase-g using nucleoside analogs, it appears that several physiopathologic mechanisms interact to explain the observed toxicity. At present there is no reliable method to detect subclinical mitochondrial toxicity. There is no proven effective therapy for antiretroviral therapy-associated mitochondrial toxicity other than ceasing the implicated agent, and even with this strategy, resolution of symptoms may be incomplete. Therefore, investigation of mitochondrial toxicity of new compounds or new combinations is of growing interest for the clinical application of antiretroviral agents.

[Intravenous ferric carboxymaltose-associated hypophosphatemia in patients with iron deficiency anemia. A common side effect]. / Hipofosfatemia asociada a la administración intravenosa de hierro carboximaltosa en pacientes con anemia ferropénica. Un efecto secundario frecuente.

OBJECTIVES: To determine the frequency, severity, time of onset and factors associated with the development of hypophosphatemia (HF) in patients with iron deficiency anemia treated with intravenous ferric carboxymatose (ivFCM). MATERIAL AND METHODS: Retrospective cohort study in patients iron deficiency anemia who received ivFCM and had an a prior and subsequent determination of serum phosphate. We carried out a comparative analysis between baseline and post-ivFCM levels of serum phosphate. In order to identify variables independently associated with HF a logistic regression analysis was also performed. RESULTS: One hundred twenty-five patients were included. HF frequency was 58%. The median time to onset of HF was 18 days. Age, baseline ferritin levels and baseline phosphate levels were independently associated with the development of HF. The risk of HF in patients with baseline phosphate levels ≤ 3.1mg/dl was 67% higher than patients with ≥ 3.7 mg/dl. CONCLUSIONS: ivFCM-associated HF is a frequent, early and, sometimes, prolonged effect in patients with iron deficiency anemia. Serum phosphate levels should be monitored after ivFCM administration, especially in older patients and in those with lower baseline phosphate or ferritin levels.

[Anticoagulation in polypathological patients with atrial fibrillation]. / Anticoagulación en pacientes pluripatológicos con fibrilación auricular.

BACKGROUND AND OBJECTIVES: To determine the use of oral anticoagulants in polypathological patients with atrial fibrillation and its influence on mortality and loss of functionality. PATIENTS AND METHODS: Patients with polypathological patient criteria and atrial fibrillation were included in an observational, prospective and multicenter study. Data on demographic, clinical, functional and sociofamilial characteristics, CHADS2 score, levels of hemoglobin, albumin and creatinine, use of oral anticoagulants and survival and functional status at one year were collected. RESULTS: Five hundred and thirty-two (32.6%) of 1,632 polypathological patients had atrial fibrillation. The stroke risk was high in 505 (94.9%), moderate in 24 (4.5%) and low in 3 (0.6%) patients. Oral anticoagulants were used in 61% of patients with CHADS2 score≥2 and in 37.5% with CHADS2 score=1. Oral anticoagulants were less used in older patients, with more functional and cognitive impairment. Heart failure was associated with more use of oral anticoagulants. There was no difference by the presence of hypertension, diabetes, anemia, renal insufficiency or stroke. In multivariate analysis the use of oral anticoagulants was independently associated with lower age, lower cognitive impairment, absence of hepatic disease and with higher stroke risk. The prescription of oral anticoagulants was independently associated with more survival at one year with no influence on functional status. CONCLUSIONS: Oral anticoagulants are underused in polypathological patients with atrial fibrillation despite being associated with more survival.

Effects of renin-angiotensin blockers/inhibitors and statins on mortality and functional impairment in polypathological patients.

BACKGROUND: Frail and polypathological patients (PP) are often undertreated with evidence-based cardiovascular drugs, as their benefits are uncertain in this population. OBJECTIVES: To determine the effects of treatment with renin-angiotensin system blockers/inhibitors (ACEI/ARB), statins and/or beta-blockers on survival rates and functional decline in PP with evidence-based clinical indications for treatment with any of these drug families. METHOD: Prospective observational multicentre cohort study with a 12-month follow-up period. We selected PP with any condition of the following: chronic heart failure, coronary heart disease, chronic renal disease, cerebrovascular disease, peripheral artery disease, diabetes mellitus with any visceral involvement, hypertension, and dyslipidaemia. Clinical, functional (Barthel index), socio-familial risk data and drug prescriptions were measured at baseline. Multivariate Cox proportional hazards and logistic regression models were used to identify variables independently associated with survival and functional decline. RESULTS: The analysis included 1260 PP. The mean age was 79±9.5 years. The mortality rate was 34.5%. Statin (aHR 0.671; P=0.001), beta-blocker plus statin (aHR 0.645; P=0.007), ACEI/ARB plus statin (aHR 0.680; P=0.002), or combined ACEI/ARB plus statin plus beta-blocker (aHR 0.541; P=0.000) prescriptions were associated with longer survival times. Additionally, PP whose Barthel index was ≥60 showed a lower risk of disability progression if treated with statins (aOR=0.476; P=0.000), or their combinations, mainly with ACEI/ARB plus beta-blockers (aOR 0.563; P=0.031). CONCLUSIONS: The prescription of statins, alone or in combination with other drugs, may impact the survival and functional decline in polypathological patients. Further prospective blinded randomised assays are needed to confirm these observations.