How well are we performing the initial assessment of HIV-positive patients? Results from a multicentre cohort in Spain.

OBJECTIVES: The aim of this study was to evaluate adherence to the recommendations of the Spanish guidelines for the initial assessment of patients with HIV infection in the multicentre Cohort of the Spanish HIV/AIDS Network (CoRIS) during the years 2004-2017. METHODS: We calculated the percentage of patients who had each of 11 clinical and analytical recommended examinations performed in their initial evaluation. We evaluated the factors associated with not performing each examination with multivariable logistic regression models. RESULTS: We included 13 612 patients in the study. In the initial assessment, CD4 count and viral load were determined in more than 98.0% of the patients. Serologies for hepatitis A, B and C and syphilis were determined in 55.8%, 66.4%, 89.8% and 81.7% of the patients, respectively. Total cholesterol and creatinine were determined in 78.7% and 78.9% of the patients, respectively. The lowest proportions of examinations were observed for blood pressure, smoking status and latent tuberculosis screening, which were performed in 43.2%, 50.6% and 53.9% of the patients, respectively. Injecting drug users and heterosexual patients (compared to men who have sex with men) and patients with a lower educational level had a higher risk of having an incomplete initial assessment for a substantial number of examinations. Latent tuberculosis screening was less likely in patients with CD4 counts < 200 cells/µL. CONCLUSIONS: The initial assessment of HIV-infected patients is suboptimal for the evaluation of cardiovascular risk, smoking status, screening of syphilis and viral hepatitis, and diagnosis of latent tuberculosis: adherence to the guidelines was low for these examinations.

Compliance with national guidelines for HIV treatment and its association with mortality and treatment outcome: a study in a Spanish cohort.

OBJECTIVES: The aim of the study was to assess the adequacy of initial antiretroviral therapy (ART), in terms of its timing and the choice of regimens, according to the Spanish national treatment guidelines [Spanish AIDS Study Group-National Plan for AIDS (GeSIDA-PNS) Guidelines] for treatment-naïve HIV-infected patients. METHODS: A prospective cohort study of HIV-positive ART-naïve subjects attending 27 centres in Spain from 2004 to 2010 was carried out. Regimens were classified as recommended, alternative or nonrecommended according to the guidelines. Delayed start of treatment was defined as starting treatment later than 12 months after the patient had fulfilled the treatment criteria. Multivariate logistic and Cox regression analyses were performed. RESULTS: A total of 6225 ART-naïve patients were included in the study. Of 4516 patients who started treatment, 91.5% started with a recommended or alternative treatment. The use of a nonrecommended treatment was associated with a CD4 count > 500 cells/µL [odds ratio (OR) 2.03; 95% confidence interval (CI) 1.14-3.59], hepatitis B (OR 2.23; 95% CI 1.50-3.33), treatment in a hospital with < 500 beds, and starting treatment in the years 2004-2006. Fourteen per cent of the patients had a delayed initiation of treatment. Delayed initiation of treatment was more likely in injecting drug users, patients with hepatitis C, patients with higher CD4 counts and during the years 2004-2006, and it was less likely in patients with viral loads > 5 log HIV-1 RNA copies/ml. The use of a nonrecommended regimen was significantly associated with mortality [hazard ratio (HR) 1.61; 95% CI 1.03-2.52; P = 0.035] and lack of virological response. CONCLUSIONS: Compliance with the recommendations of Spanish national guidelines was high with respect to the timing and choice of initial ART. The use of nonrecommended regimens was associated with a lack of virological response and higher mortality.

Mortality due to non-AIDS-defining cancers among people living with HIV in Spain over 18 years of follow-up.

PURPOSE: Our aim was to describe non-AIDS-defining cancer (NADC) mortality among people living with HIV (PLWH), to compare it with that of the general population, and to assess potential risk factors. METHODS: We included antiretroviral-naive PLWH from the multicentre CoRIS cohort (2004-2021). We estimated mortality rates and standardised mortality ratios (SMRs). We used cause-specific Cox models to identify risk factors. RESULTS: Among 17,978 PLWH, NADC caused 21% of all deaths observed during the follow-up. Mortality rate due to NADC was 1.58 (95%CI 1.36, 1.83) × 1000 person-years and lung and liver were the most frequent cancer-related causes of death. PLWH had 79% excess NADC mortality risk compared to the general population with the highest SMR found for Hodgkin lymphoma, anal and liver cancers. The SMRs decreased with age and were the highest in age groups under 50 years. The most important prognostic factor was low CD4 count, followed by smoking, viral hepatitis and HIV transmission through heterosexual contact or injection drug use. CONCLUSION: Non-AIDS cancers are an important cause of death among PLWH. The excess mortality related to certain malignancies and the association with immunodeficiency, smoking, and coinfections highlights the need for early detection and treatment of cancer in this population.

Past and future of HIV infection. A document based on expert opinion.

HIV infection is now almost 40 years old. In this time, along with the catastrophe and tragedy that it has entailed, it has also represented the capacity of modern society to take on a challenge of this magnitude and to transform an almost uniformly lethal disease into a chronic illness, compatible with a practically normal personal and relationship life. This anniversary seemed an ideal moment to pause and reflect on the future of HIV infection, the challenges that remain to be addressed and the prospects for the immediate future. This reflection has to go beyond merely technical approaches, by specialized professionals, to also address social and ethical aspects. For this reason, the Health Sciences Foundation convened a group of experts in different aspects of this disease to discuss a series of questions that seemed pertinent to all those present. Each question was presented by one of the participants and discussed by the group. The document we offer is the result of this reflection.

SARS-CoV-2 infection among healthcare workers in a hospital in Madrid, Spain.

BACKGROUND: Healthcare workers (HCWs) are especially vulnerable to infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). AIM: The aim of this study was to describe the epidemiological and clinical characteristics of coronavirus disease 2019 (COVID-19) among HCWs from February 24th to April 30th, 2020, in a hospital in Madrid, Spain. METHODS: This was a retrospective cohort study. Cumulative COVID-19 incidence was calculated for all HCWs and categorized according to presumed level of COVID-19 exposure (high, medium, and low). FINDINGS: Among 1911 HCWs, 213 (11.1%) had COVID-19 during the study period. Cases increased gradually from March 8th, peaking on March 17th and declining thereafter. The peak of cases among HCWs was reached 14 days before the peak in admitted COVID-19 cases in the hospital. There were no significant differences in the proportion of COVID-19 cases according to level of occupational exposure (P = 0.123). There were five departments and two professions in which >20% of the workers had confirmed COVID-19. Temporal clusters were identified in three of these departments and one profession, with most of the cases occurring over a period of less than five days. The prevalence of comorbidities was low and 91.5% of patients had mild or moderate symptoms. Eleven patients were admitted to the hospital and one patient needed intensive care. None of the patients died. The median time of sick leave was 20 (interquartile range: 15-26) days. CONCLUSION: The results suggest that HCW-HCW transmission accounted for part of the cases. In spite of a low prevalence of comorbidities and a mild clinical course in most cases, COVID-19 caused long periods of sick leave.

Risk factors for multidrug-resistant tuberculosis in a tuberculosis unit in Madrid, Spain.

The setting for this retrospective cohort study was a specialised tuberculosis unit in Madrid, Spain. The objective was to describe the risk factors for multidrug-resistant tuberculosis (MDR-TB). The medical records of all patients admitted to the unit were reviewed retrospectively to identify factors associated with multidrug resistance. Patients with positive culture for M. tuberculosis and with available drug-susceptibility tests were included. The variables assessed were age, gender, country of origin, homelessness, alcohol consumption, intravenous drug use, methadone substitution therapy, contact with a tuberculosis patient, sputum smear, site of disease, previous tuberculosis treatment, HIV infection, history of imprisonment, diabetes mellitus and chronic obstructive pulmonary disease. Thirty patients with MDR-TB and 666 patients with non-MDR-TB were included from the years 1997 to 2006. The only factors associated with MDR-TB in multivariate analysis were previous tuberculosis treatment (OR: 3.44; 95% CI: 1.58-7.50; p = 0.003), age group 45-64 years (OR: 3.24; 95% CI: 1.34-7.81; p = 0.009) and alcohol abuse (OR: 0.12; 95% CI: 0.03 to 0.55; p = 0.003). In our study, patients who had had previous treatment for tuberculosis, who were 45-64 years of age or who had no history of alcohol abuse were more likely to have MDR-TB.

Mortality due to injuries by place of occurrence in the European region: analysis of data quality in the WHO mortality database.

BACKGROUND AND OBJECTIVE: The 10th revision of the International Classification of Diseases (ICD-10) has codes for the place of occurrence of external causes of mortality. The purpose of this study was to investigate the quality of data available in the World Health Organization (WHO) mortality database on the place of occurrence of fatal injuries in the European region. METHODS: Data on external causes of mortality from countries in the European region according to the ICD-10 with four-character subdivision, between the years 1998 and 2003, were analysed. The quality of ICD-10 place of occurrence data was analysed for each country, based on the completeness, coverage and percentage of unspecified place of injury occurrence. RESULTS: Only three countries in the European region (Hungary, Iceland and Lithuania) had high quality of data on place of occurrence of injuries, and six had medium-quality data. CONCLUSIONS: Few countries in the European region have injury mortality data of adequate quality by place of occurrence.

Gene expression differences in primary colorectal tumors and matched liver metastases: chemotherapy related or tumoral heterogeneity?

BACKGROUND: Treatment of metastatic colorectal cancer (mCRC) is generally based on genetic testing performed in primary tumor biopsies, but whether the genomic status of primary tumors is identical to that of metastases is not well known. We compared the gene expression profiles of formalin-fixed paraffin-embedded (FFPE) biopsies of colorectal primary tumors and matched liver metastases. PATIENTS AND METHODS: We compared the expression of 18 genes in FFPE CRC tumors and their matched liver metastases from 32 patients. The expression of each gene in CRC primary tumors and their matched liver metastases was tested using Student's t test for paired samples. Pairwise correlations of each gene in the primary tumors and matched liver metastases were evaluated by Pearson's correlation coefficient. RESULTS: The expression of six genes was significantly different in primary tumors compared with their matched liver metastases [CXCR4 (p < 0.001), THBS1 (p = 0.007), MMP 9 (p = 0.048), GST Pi (p = 0.050), TYMP (p = 0.042) and DPYD (p < 0.001)]. For the remaining genes, where no significant differences were observed, only SMAD4 (r s = 0.447, p = 0.010), ERCC1 (r s = 0.423, p = 0.016) and VEGF A (r s = 0.453, p = 0.009) showed significant correlation in expression between the two tissues. Therefore, we only detected similar gene expression levels between the tumor and the metastases in these three markers. CONCLUSIONS: We only found similar gene expression levels between the tumor and the metastases in three genes (SMAD4, ERCC1, and VEGF A). However, our study could not assess whether the differences in gene expression were secondary to tumoral heterogeneity or to molecular changes induced by previous chemotherapy.

SMAD4 and TS expression might predict the risk of recurrence after resection of colorectal liver metastases.

PURPOSE: Colorectal liver metastases (CLM) have significant molecular heterogeneity, which contributes to the risk of recurrence following surgery. Most of the traditional scores intended to predict recurrence is based on clinicopathological variables and it is unclear whether incorporating molecular biomarkers might improve our assessment of the risk of recurrence. Our aim was to determine if molecular biomarkers might be associated with the risk of recurrence after surgery of CLM. PATIENTS AND METHODS: A total of 121 patients diagnosed with colorectal cancer (CRC) with resected liver metastases were included. The role of several clinicopathological variables to predict patient's outcome after resection of liver metastases was analyzed. Eighteen genes related to CRC pathogenesis were also included in the analyses. Univariate and multivariate stepwise Cox regression analyses were performed to identify factors associated with recurrence and the risk of death. RESULTS: Eight prognostic factors for progression-free survival and nine factors for overall survival were identified in the univariate analyses. After adjusting for other risk factors, only the expression of two molecular factors was associated with the risk of recurrence: TS (HR 0.631, 95 % CI 0.422-0.944) and SMAD4 (HR 1.680, 95 % CI 1.047-2.695). None of the variables was significantly associated with the risk of death in the multivariate analyses. CONCLUSIONS: The prognostic significance of most traditional clinicopathological variables might be insufficient to define patients at risk for recurrence after liver metastases resection. Molecular biomarkers might improve the identification of patients with higher risk of recurrence.

[Homocysteine. The cardiovascular risk factor of the next millennium?]. / La homocisteína. El factor de riesgo cardiovascular del próximo milenio?

Several epidemiologic studies have demonstrated that hyperhomocysteinemia is a risk factor for arteriosclerosis in coronary, cerebral, peripheral and aortic arteries. This risk is independent of other cardiovascular risk factors, and it is dose related. However, prospective studies show contradictory findings. Hyperhomocysteinemia is also associated with a higher risk of venous thrombosis to which other coagulation disorders, such as factor V Leiden, could contribute. Hyperhomocysteinemia can be due to genetic defects in the enzymes that control homocysteine metabolism, and also to other factors, mainly nutritional (deficiencies in vitamin B6, vitamin B12, or folic acid). Dietary supplements of these vitamins reduce plasma homocysteine levels. Randomized clinical trials are still needed to demonstrate that reducing plasma homocysteine levels will reduce the risk for cardiovascular disease.

[Cost-effectiveness of computerized axial tomography in the diagnosis of traditional clinical picture of fever of unknown origin]. / Rentabilidad de la tomografía axial computarizada en el diagnóstico de la fiebre de origen desconocido clásica.

Diagnostic strategy in fever of unknown origin has been changing in recent decades. The objective of this study is to define the role of thoracoabdominal computerized axial tomography in the first diagnostic stage. A sample of 24 patients with classical fever of unknown origin from our hospital Internal Medicine department was selected between January 1995 and December 2002. Cost-effectiveness of diagnostic thoracoabdominal computerized axial tomography compared to that of abdominal echography was analyzed; the information obtained with both diagnostic techniques for the final diagnosis was also evaluated. Computerized axial tomography contributed data suggestive of the diagnosis in 10 of 24 patients (41.7%); abdominal echography only gave orienting information to the diagnosis in 2 cases (8%). In 9 (90%) of the 10 patients with computerized axial tomography specific alterations, a conclusive definitive diagnosis (with analysis of biological sample) was possible. Accordingly, the use of this technique is justified at the beginning of the study of the classical fever unknown origin in order to orient the clinician to resort to other more directed and specific diagnostic techniques and with higher diagnostic cost-effectiveness.

[Clinical-biological and radiological study of Wegener's granulomatosis in a university hospital]. / Estudio clínico-biológico y radiológico de la granulomatosis de Wegener en un hospital universitario.

UNLABELLED: Wegener's granulomatosis is a rare systemic vasculitis that fundamentally affects the kidney and respiratory tract. Although the histological findings are very characteristic, they do not occur in all cases, which makes diagnosis difficult. METHODS: The main clinical, biological and radiological characteristics of 13 cases of Wegener's granulomatosis diagnosed in a university hospital of the center of Spain are collected in this present paper. RESULTS: The majority of the patients were men in their 50's. Fever and general syndrome were usual presentations of the disease. Upper respiratory tract (10 cases) and lung involvement (9), followed by renal involvement (8), were the most common. Alveolar infiltrates and bilateral nodules were the most common findings in the X-ray and thoracic CT scan, although the latter permits a greater definition of the lesions. Measurement of antibodies against cytoplasma of the neutrophils (ANCA) was positive in 8 patients (6 cANCA and 2 pANCA). Renal biopsy was used most for the histologic diagnosis, where focal and segmental glomerulonephritis was the most common finding. The majority of the patients received steroids plus cyclophosphamide as induction treatment. CONCLUSIONS: Wegener's disease is a rare systemic vasculitis. The existence of hematuria or respiratory tract involvement in a patient with fever suggests the diagnosis. Conducting a CT scan and ANCAs measurement are useful tools for its diagnosis, since the histology is not definitive.

[Churg-Strauss syndrome. Our experience in 2 decades]. / Síndrome de Churg-Strauss. Nuestra experiencia en dos décadas.

BACKGROUND: Since 1951, the year when the Churg-Strauss syndrome was reported, several isolated cases have been reported in the literature but works containing a high number of cases are exceptional. The features of the syndrome as well as diagnostic criteria have not been contrasted in large series. We therefore tried to analyze these parameters in 16 patients diagnosed of Churg-Strauss syndrome at our hospital. METHODS: A retrospective analysis was made of 16 patients diagnosed of Churg-Strauss syndrome at Hospital Universitario La Paz from 1978 at 1998. Data regarding personal antecedents, clinical manifestations, analytical parameters, histology and clinical course were collected. Also, the main diagnostic criteria reported in the literature were applied to each case. RESULTS: Of the 16 cases, thirteen (81%) were women, six were diagnosed at an age between 21 and 40 years; other six cases from 51 to 70 years. All patients had antecedents of bronchial asthma. Among clinical manifestations, 60% had fever and 50% a general syndrome. The main involved organs by decreasing frequency were lung (100%), nervous system (63%), and heart (44%). The mean eosinophilic count was 7,640/mm3. The histological diagnosis was obtained in 14 out of the 16 patients (88%). The most efficient biopsies corresponded to muscle and nerve. After therapy, no relapse was noted of vasculitis although bronchial asthma persisted in most patients (12). Twelve cases (75%) fulfilled the Lanham diagnostic criteria. CONCLUSIONS: Churg-Strauss syndrome affects mainly women with severe eosinophilia. Electromyogram and muscle and peripheral nerve biopsy are useful tools for diagnosis. The Lanham criteria lead to the diagnosis in most patients.