[Hepatitis C: New diagnosis and seroconversions in a Madrid sexually transmitted diseases clinic]. / Hepatitis C: nuevos diagnósticos y seroconversiones en una clínica de infecciones de transmisión sexual en Madrid.

OBJECTIVE: The aim of this study was to evaluate the incidence of new hepatitis C virus (HCV) infections, based on their sexual orientation, human immunodeficiency virus (HIV) status, geographical regions and coinfection with other sexually transmitted diseases (STDs). METHODS: This study was carried out at the Sandoval Health Center, reference clinic of Sexually Transmitted Diseases (STDs) in Madrid. All HCV seronegative individuals who were reanalyzed for this virus were included, between January 2010 and December 2016. RESULTS: A total of 59 new diagnoses of HCV were diagnosed. The proportion of men who have sex with men (MSM) diagnosed with HCV was 37% in 2010 and 75% in 2016 and was even higher in the group of coinfected with HIV/HCV (94%). A total of 67 seroconverters for HCV were detected (1.2%) of which 100% were MSM. The proportion of HCV seroconverters with HIV was 89%. CONCLUSIONS: HCV infection continues to be a current health problem, especially in HIV-positive MSM.

Evaluating the addition of bevacizumab to endocrine therapy as first-line treatment for hormone receptor-positive metastatic breast cancer: a pooled analysis from the LEA (GEICAM/2006-11_GBG51) and CALGB 40503 (Alliance) trials.

BACKGROUND: Randomised trials comparing the efficacy of standard endocrine therapy (ET) versus experimental ET + bevacizumab (Bev) in 1st line hormone receptor-positive patients with metastatic breast cancer have thus far shown conflicting results. PATIENTS AND METHODS: We pooled data from two similar phase III randomised trials of ET ± Bev (LEA and Cancer and Leukemia Group B 40503) to increase precision in estimating treatment effect. Primary end-point was progression-free survival (PFS). Secondary end-points were overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR) and safety. Exploratory analyses were performed within subgroups defined by patients with recurrent disease, de novo disease, prior endocrine sensitivity or resistance and reported grades III-IV hypertension and proteinuria. RESULTS: The pooled sample consisted of 749 patients randomised to ET or ET + Bev. Median PFS was 14.3 months for ET versus 19 months for ET + Bev (unadjusted hazard ratio [HR] 0.77; 95% confidence interval [CI] 0.66-0.91; p < 0.01). ORR and CBR with ET and ET + Bev were 40 versus 61% (p < 0.01) and 64 versus 77% (p < 0.01), respectively. There was no difference in OS (HR 0.96; 95% CI 0.77-1.18; p = 0.68). PFS was superior for ET + Bev for endocrine-sensitive patients (HR 0.68; 95% CI 0.53-0.89; p = 0.004). Grade III-IV hypertension (2.2 versus 20.1%), proteinuria (0 versus 9.3%), cardiovascular (0.5 versus 4.2%) and liver events (0 versus 2.9%) were significantly higher for ET + Bev (all p < 0.01). Hypertension and proteinuria were not predictors of efficacy (interaction test p = 0.33). CONCLUSION: The addition of Bev to ET increased PFS overall and in endocrine-sensitive patients but not OS at the expense of significant additional toxicity. TRIALS REGISTRATION: ClinicalTrial.Gov NCT00545077 and NCT00601900.

Implementing pre-exposure prophylaxis could prevent most new HIV infections in transsexual women and men who have sex with men. / La implementación de la profilaxis preexposición podría evitar la mayoría de las nuevas infecciones por el VIH en hombres que tienen sexo con hombres y mujeres transexuales.

BACKGROUND: Pre-exposure prophylaxis (PrEP) consists of administering antiretroviral drugs to HIV-seronegative individuals who engage in high-risk practices, with the aim of reducing the probability of acquiring the infection. Despite its safety and efficacy, PrEP is still not available within Spain's public healthcare system. The aim of this study was to estimate the preventive impact of adding PrEP to the other preventive measures. We estimated the number of HIV seroconversions that could have been prevented (if PrEP had been available) among initially seronegative transsexual women and men who have sex with men. METHODS: We conducted a descriptive study of recent HIV seroconverters between 2014-2016 in a reference HIV/sexually transmitted infection clinic in Madrid. We analysed the individuals who were indicated PrEP, according to the guidelines of the 2016 AIDS Study Group. The statistical analysis to estimate the HIV infections that could have been prevented (if PrEP had been available) was conducted using Stata 14. RESULTS: We estimated that 195 of the 228 men who have sex with men and transsexual women, with documented HIV seroconversion, were indicated for PrEP. Considering the preventive efficacy reported in European studies, we estimated that 168 HIV seroconversions could have been prevented, which represents 73.7% of the diagnosed infections. CONCLUSIONS: The results confirm the need to promote combined preventive programs against HIV that integrate all possible measures, including PrEP.

[Reason for consultation: Weight loss]. / Motivo de consulta: pérdida de peso.

BACKGROUND AND OBJECTIVE: Unintentional weight loss is frequent reason to visit a doctor and it has multiple diagnostic possibilities. The objective of this study is to examine the background of the patients who seek consultation for weight loss and to establish the relationship between weight loss and neoplasia. METHOD: An analysis was performed on the demographic data, quantified weight loss, accompanying symptomatology, and diagnosis of patients who sought medical advice for unintentional weight loss during the year 2015. RESULTS: A total of 226 patients were included, of whom 44.2% of them had an intentional weight loss ≥ 5% in 6 months. The most frequent diagnosis in this group was a neoplasia, whereas in the rest of patients the most common diagnosis was a gastrointestinal disease. In light of this study we can conclude that there is a relationship between unintentional weight loss≥5% and the presence of neoplasia. CONCLUSION: An unintentional weight loss greater than 5% in the previous 6 months is associated with the presence of neoplastic diseases, and therefore requires further diagnostic study.

[Identifying gaps between guidelines and clinical practice in Clostridium difficile infection]. / Diferencias entre las recomendaciones y la práctica clínica en la infección por Clostridium difficile.

OBJECTIVES: The first aim was to determine whether patients are being treated in accordance with the Society for Healthcare Epidemiology of America and the Infectious Diseases Society of America (IDSA/SHEA) Clostridium difficile guidelines and whether adherence impacts patient outcomes. The second aim was to identify specific action items in the guidelines that are not being translated into clinical practice, for their subsequent implementation. MATERIAL AND METHODS: A retrospective, descriptive study was conducted over a 36 month period, on patients with compatible clinical symptoms and positive test for C. difficile toxins A and/or B in stool samples, in an internal medicine department of a tertiary medical centre. Patient demographic and clinical data (outcomes, comorbidity, risk factors) and compliance with guidelines, were examined RESULTS: A total of 77 patients with C. difficile infection were identified (87 episodes). Stratified by disease severity criteria, 49.3% of patients were mild-moderate, 35.1% severe, and 15.6% severe-complicated. Full adherence with the guidelines was observed in only 40.2% of patients, and was significantly better for mild-moderate (71.0%), than in severe (7.4%) or severe-complicated patients (16.6%) (P<.003). Adherence was significantly associated with clinical cure (57% vs 42%), fewer recurrences (22.2% vs 77.7%), and mortality (25% vs 75%) (P<.01). The stratification of severity of the episode, and the adequacy of antibiotic to clinical severity, need improvement. CONCLUSIONS: Overall adherence with the guidelines for management of Clostridium difficile infection was poor, especially in severe and severe-complicated patients, being associated with worse clinical outcomes. Educational interventions aimed at improving guideline adherence are warranted.

Phase I clinical trial of nintedanib plus paclitaxel in early HER-2-negative breast cancer (CNIO-BR-01-2010/GEICAM-2010-10 study).

INTRODUCTION: Previous small-molecule antiangiogenics have compromised chemotherapy dose intensity in breast cancer. We present a phase I trial of a novel selective agent, nintedanib, plus standard chemotherapy in early breast cancer. METHODS: Her-2-negative breast cancer patients with tumours larger than 2 cm were eligible for dose-escalation trial (classic 3+3 method). RESULTS: The recommended phase II dose (RP2D) was 150 mg BID of nintedanib combined with standard dose of weekly paclitaxel followed by adriamycin plus cyclophosphamide. The dose-limiting toxicity was transaminase elevation. At the RP2D, the dose intensity was ∼100%. The pathologic complete response was 50%. CONCLUSIONS: The combination allows the delivery of full-dose intensity, while efficacy seems promising.

A randomized phase II trial of platinum salts in basal-like breast cancer patients in the neoadjuvant setting. Results from the GEICAM/2006-03, multicenter study.

Chemotherapy remains as the only systemic treatment option available for basal-like breast cancer (BC) patients. Preclinical models and several phase II studies suggested that platinum salts are active drugs in this BC subtype though there is no randomized study supporting this hypothesis. This study investigates if the addition of carboplatin to a combination of an alkylating agent together with anthracyclines and taxanes is able to increase the efficacy in the neoadjuvant treatment context. Patients with operable breast cancer and immunophenotypically defined basal-like disease (ER-/PR-/HER2- and cytokeratin 5/6+ or EGFR+) were recruited. Patients were randomized to receive EC (epirubicin 90 mg/m(2) plus cyclophosphamide 600 mg/m(2) for 4 cycles) followed either by D (docetaxel 100 mg/m(2) × 4 cycles; EC-D) or DCb (docetaxel 75 mg/m(2) plus carboplatin AUC 6 × 4 cycles; EC-DCb). The primary end point was pathological complete response (pCR) in the breast following the Miller and Payne criteria. Ninety-four patients were randomized (46 EC-D, 48 EC-DCb). pCR rate in the breast was seen in 16 patients (35 %) with EC-D and 14 patients (30 %) with EC-DCb (P value = 0.61). pCR in the breast and axilla was seen in 30 % of patients in both arms. The overall clinical response rate was 70 % (95 % CI 56-83) in the EC-D arm and 77 % (95 % CI 65-87) in the EC-DCb arm. Grade 3/4 toxicity was similar in both arms. The addition of carboplatin to conventional chemotherapy with EC-D in basal-like breast cancer patients did not improve the efficacy probably because they had already received an alkylating agent. These findings should be taken into consideration when developing new agents for this disease.

Pegylated liposomal doxorubicin in combination with cyclophosphamide and trastuzumab in HER2-positive metastatic breast cancer patients: efficacy and cardiac safety from the GEICAM/2004-05 study.

BACKGROUND: In order to determine the feasibility of substituting pegylated liposomal doxorubicin (PLD) for doxorubicin in combination with cyclophosphamide and trastuzumab as adjuvant therapy, we conducted a phase II study of the combination as first-line therapy in human epidermal growth factor receptor 2 (HER2) overexpressing metastatic breast cancer (MBC). METHODS: PLD 50 mg/m(2) and cyclophosphamide 600 mg/m(2) were administered every 4 weeks for six cycles; trastuzumab (4 mg/kg loading dose, then 2 mg/kg) was administered weekly for 24 weeks. The primary end point was objective response rate (ORR), and the secondary end points included time to progression (TTP), overall survival (OS), and safety. RESULTS: Among the 48 evaluable patients, ORR was 68.8% [95% confidence interval (CI) 55.69% to 81.91%], with 6 patients (12.5%) achieving a complete response and 27 (56.2%) a partial response. The median TTP was 12 months (95% CI 9-15.1 months), and the median OS was 34.2 months (95% CI 27.2-41.2 months). Febrile neutropenia was seen in three patients, grade 3 hand-foot syndrome in 29.2% of patients, and grade 3-4 mucositis in 22.9% of patients. Symptomatic congestive heart failure was not observed, and 16.7% of patients experienced grade 2 asymptomatic left ventricular systolic dysfunction. CONCLUSION: The combination of PLD-cyclophosphamide-concurrent trastuzumab is a feasible, safe, and effective first-line regimen for HER2-overexpressing MBC.