Increase of 10% in the Rate of Adverse Drug Reactions for Each Drug Administered in Hospitalized Patients

OBJECTIVE: To assess the risk factors, incidence and severity of adverse drug reactions in in-patients. METHODS: This prospective study evaluated 472 patients treated at a teaching hospital in Brazil between 2010 and 2013 by five medical specialties: Internal Medicine, General Surgery, Geriatrics, Neurology, and Clinical Immunology and Allergy. The following variables were assessed: patient age, gender, comorbidities, family history of hypersensitivity, personal and family history of atopy, number of prescribed drugs before and during hospitalization, hospital diagnoses, days of hospitalization. The patients were visited every other day, and medical records were reviewed by the investigators to detect adverse drug reactions. RESULTS: There were a total of 94 adverse drug reactions in 75 patients. Most reactions were predictable and of moderate severity. The incidence of adverse drug reactions was 16.2%, and the incidence varied, according to the medical specialty; it was higher in Internal Medicine (30%). Antibiotics were the most commonly involved medication. Chronic renal failure, longer hospital stay, greater number of diagnoses and greater number of medications upon admission were risk factors. For each medication introduced during hospitalization, there was a 10% increase in the rate of adverse drug reaction. In the present study, the probability of observing an adverse drug reaction was 1 in 104 patients per day. CONCLUSIONS: Adverse drug reactions are frequent and potentially serious and should be better monitored in patients with chronic renal failure or prolonged hospitalization and especially in those on ‘polypharmacy’ regimens. The rational use of medications plays an important role in preventing adverse drug reactions

Identification of immunodominant epitopes of Schistosoma mansoni vaccine candidate antigens using human T cells

Paramyosin and Sm14 are two of the six antigens selected by the World Health Organization as candidates to compose a subunit vaccine against schistosomiasis. Both antigens are recognized by individuals naturally resistant to Schistosoma mansoni infection and induced protective immunity in the murine model. Three Sm14 epitopes and eleven paramyosin epitopes were selected by their ability to bind to different HLA-DR molecules using the TEPITOPE computer program, and these peptides were synthetically produced. The cellular recognition of Sm14 and paramyosin epitopes by peripheral blood mononuclear cells of individuals living in endemic area for schistosomiasis was tested by T cell proliferation assay. Among all Sm14 and paramyosin epitopes studied, Sm14-3 was preferentially recognized by individuals naturally resistant to S. mansoni infection while Para-5 was preferentially recognized by individuals resistant to reinfection. These two peptides represent promising antigens to be used in an experimental vaccine against schistosomiasis, since their preferential recognition by resistant individuals suggest their involvement in the induction of protective immunity

Papel do Marcapasso Atrioventricular Seqüencial no Tratamento da Miocardiopatia Hipertrófica Obstrutiva

Este trabalho apresenta os resultados da estimulaçao DDD em pacientes com miocardiopatia hipertrófica obstrutiva (MHO), relativos à evoluçao clínica tardia e às modificaçoes na obstruçao na via de saída do ventrículo esquerdo (OVSVE), quantificados pelo gradiente sistólico instantâneo máximo obtido no Doppler ecocardiograma (ECO). Vinte e oito pacientes receberam o implante de um marcapasso DDD para tratar MHO refratária ao tratamento clínico e associada à OSVSVE crescente ou superior a 50 mmHg. O marcapasso foi programado com freqüência cardíaca capaz de manter o controle elétrico atrial e ventricular e o intervalo atrioventricular (AV) reduzido (+ 30,2 mmHg e passou para 44,8 + 22,0 mmHg após a programaçao do marcapasso (P+ 23,4 mmHg. Atualmente 12 (42,9%) pacientes apresentam OVSVE inferior a 30 mmHg no ECO. Em (25,0%), OVSVE situa-se entre 31 e 50 mmHg, e em 9 (32,1%), supera os 50 mmHg. A reprogramaçao do marcapasso foi necessária na maioria dos pacientes para permitir uma maior reduçao da OVSVE. Houve melhora na sintomatologia em todos os pacientes, embora 6 (21,4%) ainda apresentem sintomas significativos. Houve um caso (3,6%) de morte súbita. As complicaçoes relativas ao marcapasso, observadas individualmente, foram um episódio de fibrilaçao atrial e a necessidade de reposicionamento do eletrodo atrial. A utilizaçao de marcapasso DDD pode resultar em acentuada melhora clínica e reduçao no gradiente da VSVE na maioria dos pacientes com MHO

Papel do Marcapasso Atrioventricular Seqüencial no Tratamento da Miocardiopatia Hipertrófica Obstrutiva

Este trabalho apresenta os resultados da estimulaçao DDD em pacientes com miocardiopatia hipertrófica obstrutiva (MHO), relativos à evoluçao clínica tardia e às modificaçoes na obstruçao na via de saída do ventrículo esquerdo (OVSVE), quantificados pelo gradiente sistólico instantâneo máximo obtido no Doppler ecocardiograma (ECO). Vinte e oito pacientes receberam o implante de um marcapasso DDD para tratar MHO refratária ao tratamento clínico e associada à OSVSVE crescente ou superior a 50 mmHg. O marcapasso foi programado com freqüência cardíaca capaz de manter o controle elétrico atrial e ventricular e o intervalo atrioventricular (AV) reduzido (+ 30,2 mmHg e passou para 44,8 + 22,0 mmHg após a programaçao do marcapasso (P+ 23,4 mmHg. Atualmente 12 (42,9%) pacientes apresentam OVSVE inferior a 30 mmHg no ECO. Em (25,0%), OVSVE situa-se entre 31 e 50 mmHg, e em 9 (32,1%), supera os 50 mmHg. A reprogramaçao do marcapasso foi necessária na maioria dos pacientes para permitir uma maior reduçao da OVSVE. Houve melhora na sintomatologia em todos os pacientes, embora 6 (21,4%) ainda apresentem sintomas significativos. Houve um caso (3,6%) de morte súbita. As complicaçoes relativas ao marcapasso, observadas individualmente, foram um episódio de fibrilaçao atrial e a necessidade de reposicionamento do eletrodo atrial. A utilizaçao de marcapasso DDD pode resultar em acentuada melhora clínica e reduçao no gradiente da VSVE na maioria dos pacientes com MHO

Unexpected Diversity of Cellular Immune Responses against Nef and Vif in HIV-1-Infected Patients Who Spontaneously Control Viral Replication

Background: HIV-1-infected individuals who spontaneously control viral replication represent an example of successful containment of the AIDS virus. Understanding the anti-viral immune responses in these individuals may help in vaccine design. However, immune responses against HIV-1 are normally analyzed using HIV-1 consensus B 15-mers that overlap by 11 amino acids. Unfortunately, this method may underestimate the real breadth of the cellular immune responses against the autologous sequence of the infecting virus. Methodology and Principal Findings: Here we compared cellular immune responses against nef and vif-encoded consensus B 15-mer peptides to responses against HLA class I-predicted minimal optimal epitopes from consensus B and autologous sequences in six patients who have controlled HIV-1 replication. Interestingly, our analysis revealed that three of our patients had broader cellular immune responses against HLA class I-predicted minimal optimal epitopes from either autologous viruses or from the HIV-1 consensus B sequence, when compared to responses against the 15-mer HIV-1 type B consensus peptides. Conclusion and Significance: This suggests that the cellular immune responses against HIV-1 in controller patients may be broader than we had previously anticipated.National Institutes of Health (NIH)[R24 RR015371]Ministry of Health[914/BRA/3014-UNESCO]Sao Paulo City Health Department[2004-0.168.922-7]Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)[04/15856-9]Coordenacao de Aperfeicoamento de Pessoal de Ni-vel Superior (CAPES), Brazilian Ministry of Educatio

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402