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.

Uso de recursos sanitarios y costes asociados al tratamiento antirretroviral de primera línea en España en la era de los inhibidores de la integrasa / Use of health resources and costs associated to first-line antiretroviral therapy in the era of integrase inhibitors

Introducción: El objetivo fue evaluar el uso de recursos sanitarios y costes asociados durante el primer año de tratamiento antirretroviral (TAR) con las pautas de primera línea prescritas más frecuentemente en los pacientes de la cohorte de la Red Española de Investigación en SIDA en la era de los inhibidores de la integrasa. Métodos: Utilizamos un modelo de evaluación de costes en el que el consumo de recursos sanitarios derivados de iniciar tratamiento con cada pauta se estimó utilizando el método Delphi de dos rondas, mediante cuestionario estructurado, en un panel de 35 expertos en VIH. El coste total incluía los costes de TAR, del manejo clínico y del manejo de efectos adversos (EA). Se aplicó la perspectiva del pagador (Sistema Nacional de Salud), considerando solo costes directos. Resultados: En el análisis por intención de tratar, el coste anual varió entre 8.501 Euros para TDF/FTC/EFV y 12.840 Euros para TDF/FTC+RAL. De media, el coste farmacológico supone el 87,6% del coste total, variando entre 83,8 % para TDF/FTC/EFV y 91,1% para TDF/FTC+RAL. El coste del manejo clínico supone el 11,5% del coste total (8,6% para TDF/FTC+RAL y 13,9% para ABC/3TC/DTG). Sólo el 0,9% del coste de la pauta se debe al manejo de EA, más elevados con TDF/FTC/EFV (2,6%) y TDF/FTC+DRV/r (1,1%). Conclusión: El coste para el sistema sanitario del primer año de TAR se debe, fundamentalmente, al precio de los fármacos. Las pautas con menor coste fueron TDF/FTC/EFV, TDF/FTC/RPV y ABC/3TC/DTG, siendo TDF/FTC/EVG/COBI y TDF/FTC+RAL las de coste superior

Introduction: We aimed to evaluate the usage of health resources and the associated costs during the first year of treatment with the most commonly used first-line antiretroviral regimens (ART) in the Cohort of the Spanish AIDS Research Network in the era of integrase inhibitors. Methods: We used a cost evaluation model in which the use of health resources derived from initiating a regimen was estimated using a two-round Delphi method with a structured questionnaire in a pannel of 35 HIV experts. The cost of initiating a regimen included the costs of ART, clinical management and management of adverse effects (AE). The payer perspective (National Health System) was applied. Thus, only direct costs were considered. Results: In an intention-to-treat analysis, the annual cost ranged from 8,501 Euros for TDF/FTC/EFV to 12,840 Euros for TDF / FTC + RAL. On average, the pharmacological cost accounts for 87.6% varying between 83.8% for TDF/FTC/EFV and 91.1% for TDF/FTC+RAL. The cost of clinical management accounts for 11.5% of the total cost, ranging from 8.6% for TDF/FTC+RAL and 13.9% for ABC / 3TC / DTG. Only 0.9% of the total cost is due to management of AE, higher with the use of TDF/FTC/EFV (2.6%) and TDF/FTC+DRV / r (1.1%). Conclusion: The cost for the health system of the first year of antiretroviral treatment is mainly driven by the price of drugs. The regimens with lowest total cost were TDF/FTC/EFV, TDF/FTC/RPV and ABC/3TC/DTG, and the ones with highest total cost were TDF/FTC/EVG/COBI and TDF/FTC+RAL

[Central nervous system lymphoma revealed by lymphocytic meningitis in a patient with systemic lupus erythematosus: An unusual association]. / Méningite lymphocytaire chez une patiente lupique révélant un lymphome cérébral primitif : une association rare.

INTRODUCTION: We report an unusual observation of central nervous system (CNS) lymphoma in a 60-year-old woman with systemic lupus erythematosus and fatal outcome. OBSERVATION: The patient had systemic erythematosus lupus for 7 years, treated with mycophenolate mofetil and developed lymphocytic meningitis in 2015 associated to the presence of EBV in the cerebrospinal fluid and a necrotic vermis' lesion. Diagnosis of large B-cell lymphoma was histologically confirmed from stereotaxic biopsy, shortly before she died from neurological complications. CONCLUSION: Even though the current association is unusual, lymphocytic meningitis with hypoglycorrachia in patients with systemic lupus erythematosus may reveal CNS lymphoma and diagnosis confirmation requires stereotaxic biopsy in order not to delay specific therapeutic management.

[Prevalence of granulomatous lesions in minor salivary gland biopsy in a case series of 65 patients with tuberculosis]. / Étude de la prévalence des granulomes à la biopsie des glandes salivaires accessoires chez 65 patients atteints de tuberculose.

PURPOSE: The distinction between tuberculosis (TB), a worldwide infectious granulomatosis requiring specific antibiotic therapy, and sarcoidosis, a rare granulomatous disease that may require corticosteroids is not straightforward and may result in diagnostic and therapeutic delay. METHODS: We prospectively and consecutively evaluated the presence of epithelioid granulomas in minor salivary gland biopsy of 65 consecutive patients with TB. RESULTS: In our study, 10.8 % of our TB patients had epithelioid granulomas without caseous necrosis identified in their minor salivary gland biopsy, regardless of the location of TB, HIV status and whether or not the sputum examination was positive for tuberculous bacilli. CONCLUSION: The presence of epithelioid granulomas in minor salivary gland biopsy may not be helpful to the clinician to rule out TB in a patient with suspected sarcoidosis.

Diágnóstico del lenticono en el síndrome de Alport: cálculo del ángulo apical de la cápsula anterior del cristalino mediante imágenes Scheimpflug / Lenticonus diagnosis in Alport's syndrome: Anterior capsule apical angle calculation using Scheimpflug imagery

OBJETIVO: Se describe un método simplificado para detectar lenticono anterior. Realizamos imágenes Scheimpflug del segmento anterior con Pentacam a 3 ojos de 2 pacientes con lenticono anterior y 16 ojos de controles sanos. Se identificó el ángulo del ápex de la cápsula anterior y se midió con AutoCAD. RESULTADOS: El ángulo medio fue 173,06° (DE: 1,91) en los controles sanos y 158,33° (DE: 3,05) en los lenticonos. El ángulo obtenido en los pacientes resultó ser más agudo en más de 3 DE que el de los controles. CONCLUSIONES: El método del cálculo del ángulo apical parece discriminar adecuadamente entre cristalinos normales y lenticono anterior

OBJECTIVE: We describe a simplified method to detect anterior lenticonus. Three eyes of 2 patients with anterior lenticonus, plus 16 eyes from 16 healthy controls underwent Scheimpflug imaging of their anterior segment with Pentacam. The anterior capsule apex angle was manually identified and automatically measured by AutoCAD. RESULTS: The mean angle was 173.06° (SD: 1.91) in healthy subjects, and 158.33° (SD: 3.05) in anterior lenticonus eyes. The angle obtained from patients was more than 3 SD steeper than those from healthy subjects. CONCLUSIONS: The apical angle calculation method seems to discriminate well between normal eyes and eyes suspected of having anterior lenticonus

Increased risk of non-AIDS-related events in HIV subjects with persistent low CD4 counts despite cART in the CoRIS cohort.

The aim was to analyze clinical complications in HIV-infected subjects who persistently maintain low CD4 levels despite virological response to cART in the Spanish CoRIS cohort. The main inclusion criteria were CD4 counts <200cells/mm(3) at cART-initiation and at least 2years under cART achieving a viral load <500copies/mL. Those patients with CD4 counts <250cells/mm(3) 2years after cART were classified as the Low-CD4 group, and clinical events were collected from this time-point. Poisson regression models were used to calculate incidence rate ratios of death, AIDS-defining events, serious non-AIDS-defining events (NAE) and of each specific NAE category (non-AIDS-defining malignancies (non-ADM), cardiovascular, kidney- and liver-related events). Of 9667 patients in the cohort, a total of 1128 met the criteria and 287 (25.4%) were classified in the Low-CD4 group. A higher risk of death (aIRR: 4.71; 95% CI: 1.88-11.82; p-value=0.001) and of non-ADM were observed in this group (aIRR: 2.23; 95% CI: 1.07-4.63; p=0.03). Our results stress the need to control accelerated aging in this population to counter their increased risk of non-AIDS-defining diseases, particularly cancer, and are consistent with the concept that clinical complications are potentially affected by genetics and lifestyle.

Lenticonus diagnosis in Alport's syndrome: Anterior capsule apical angle calculation using Scheimpflug imagery.

OBJECTIVE: We describe a simplified method to detect anterior lenticonus. Three eyes of 2 patients with anterior lenticonus, plus 16 eyes from 16 healthy controls underwent Scheimpflug imaging of their anterior segment with Pentacam. The anterior capsule apex angle was manually identified and automatically measured by AutoCAD. RESULTS: The mean angle was 173.06° (SD: 1.91) in healthy subjects, and 158.33° (SD: 3.05) in anterior lenticonus eyes. The angle obtained from patients was more than 3 SD steeper than those from healthy subjects. CONCLUSIONS: The apical angle calculation method seems to discriminate well between normal eyes and eyes suspected of having anterior lenticonus.

Interpreting the reasons for the choice and changing of two drug regimens in an observational cohort: comparison of a ritonavir-boosted protease inhibitor-based versus a nonnucleoside reverse transcriptase inhibitor-based first-line regimen.

OBJECTIVES: We compared reasons for the choice of regimen, time to and reasons for third drug modification, virological response and change in CD4 T-cell counts in patients started on atazanavir/ritonavir (ATV/r)- vs. efavirenz (EFV)-based first-line regimens. METHODS: We included patients from the Cohort of the Spanish HIV Research Network (CoRIS), a multicentre cohort of HIV-positive treatment-naïve subjects, in the study. We used logistic regression to assess factors associated with choosing ATV/r vs. EFV, proportional hazards models on the subdistribution hazard to estimate subdistribution hazard ratios (sHRs) for third drug modification, logistic regression to estimate odds ratios (ORs) for virological response and linear regression to assess mean differences in CD4 T-cell count increase from baseline. RESULTS: Of 2167 patients, 10.7% started on ATV/r. ATV/r was more likely than EFV to be prescribed in injecting drug users [adjusted OR 1.85; 95% confidence interval (CI) 1.03-3.33], in 2009-2010 (adjusted OR 1.63; 95% CI 1.08-2.47) and combined with abacavir plus lamivudine (adjusted OR 1.53; 95% CI 0.98-2.43). Multivariate analyses showed no differences, comparing ATV/r vs. EFV, in the risk of third drug modification (sHR 1.04; 95% CI 0.74-1.46) or in virological response (OR 0.81; 95% CI 0.46-1.41); differences in mean CD4 T-cell count increase from baseline were at the limit of statistical significance (mean difference 29.8 cells/µL; 95% CI -4.1 to 63.6 cells/µL). In patients changing from EFV, 48% of changes were attributable to toxicity/adverse events, 16% to treatment failure/resistance, 3% to simplification, and 8 and 12%, respectively, to patients' and physicians' decisions; these percentages were 24, 6, 12, 14 and 24%, respectively, in those changing from ATV/r. CONCLUSIONS: ATV/r- and EFV-based regimens meet the requirements of both efficacy and safety for initial combination antiretroviral regimen, which relate to better durability.

La Epidemiología en la Salud Pública del futuro

El paso desde una investigación epidemiológica de factores de riesgo a una investigación de carácter poblacional, centrada en las teorías etiológicas y más ligada al contexto social y ambiental podría aportar conocimientos que favorezcan la implantación de políticas públicas dirigidas a mejorar la salud de la población, pero no lo garantizan.

Intravascular ultrasound and virtual histology of basilar artery atherosclerotic lesion. A case report.

To our knowledge, this paper presents the first intravascular ultrasound and virtual histology (IVUS-VH) study in the basilar artery. IVUS-VH serves to characterize and determine the extension of the plaque and we also to check stent placement.

Description of liver disease in a cohort of HIV/HBV coinfected patients.

BACKGROUND: Factors associated with advanced liver disease have been incompletely explored in HIV/HBV coinfected patients. OBJECTIVES: To describe liver-related morbidity, mortality, and related risk factors, in HIV/HBV coinfected patients. STUDY DESIGN: We followed-up 107 consecutive HIV/HBV coinfected patients. Clinical, biological and virological data were collected every 3 months. Liver-related mortality and a composite score were used to define advanced liver disease. RESULTS: The patients were mainly sub-Saharan Africans (61%) or Europeans (33%). Forty-four percent of patients had liver biopsy, 78% of patients received lamivudine. Advanced liver disease (ALD) was diagnosed in 19/107 patients during follow-up (mean 4.8 years): 10 extensive fibrosis, 5 cirrhosis, 3 hepatocellular carcinoma resulting from cirrhosis, and 1 fulminant hepatitis following lamivudine withdrawal. Eleven patients died, 4 from HBV-related liver disease. In univariate analysis, male gender, mean HIV and HBV viral loads, and raised AST/ALT transaminases were associated with increased risk of ALD. The strongest associations, in a multivariate model, were mean AST transaminase and cumulated time receiving lamivudine, with a favourable effect. 39% of patients with increased mean AST presented with ALD, versus 7% when normal mean AST (Relative Risk 5.5). CONCLUSIONS: During HIV/HBV coinfection, transaminase levels are strongly associated with ALD. Normal mean AST has a high negative predictive value, contrary to previously reported data in HIV/HCV patients.

Discrimination and mental health in Ecuadorian immigrants in Spain.

BACKGROUND: The aim of this study was to examine the effects of ethnic discrimination on the mental health of Ecuadorian immigrants in Spain and to assess the roles of material and social resources. METHODS: Data were taken from the "Neighbourhood characteristics, immigration and mental health" survey conducted in 2006 in Spain. Psychological distress measured as "Possible Psychiatric Case" (PPC) was measured by the GHQ-28. A logistic regression was fitted to assess the association between PPC and discrimination. Interactions of discrimination with social and material resources were tested using product terms. RESULTS: Some 28% of the participants met our definition of PPC. About 20% of those who reported no discrimination were PPCs, rising to 30% of those who sometimes felt discriminated against and 41% of those who continually perceived discrimination. The OR for continuous discrimination was 12 (95% CI 3.5 to 40.3) among those with high financial strain, and 10 (2.4 to 41.7) when there was lack of economic support. Emotional support had an independent effect on PPC (OR 1.8, 95% CI 1.0 to 3.6, for those who reported having no friends). Social integration through a community group or association was positively related to the probability of being a PPC (OR 1.7, 95% CI 1.0 to 2.9). CONCLUSION: Ethnic discrimination is associated with psychological distress in these Ecuadorian immigrants in Spain. Discrimination effects may be exacerbated among those facing economic stress and those without economic support. These particularly vulnerable immigrants should be the subject of social and health interventions.

Incidence and risk factors for tuberculosis in HIV-positive subjects by HAART status.

OBJECTIVE: To estimate incidence rates and risk factors for tuberculosis (TB) in human immunodeficiency virus seroprevalent subjects. METHODS: Multicentre, hospital-based cohort study of patients presenting to 10 Spanish hospitals from 1 January 1997 to 31 December 2003. Poisson regression was used and highly active antiretroviral treatment (HAART) was modelled as a time-dependent covariate. RESULTS: A total of 4268 patients were followed for a median of 3.8 years; 221 TB cases were diagnosed over 16 464 person-years (py). TB rates were higher in HAART-naïve subjects (1.56 per 100 py, 95%CI 1.36-1.79) than those on HAART (0.5/100 py, 95%CI 0.31-0.80). Among HAART-naïves, TB risk factors were: being male, being an injecting drug user (IDU) (RR 2.01, 95%CI 1.28-3.16), having low CD4 counts (P < 0.001) and high viral loads (P < 0.001). HAART was protective (RR 0.26, 95%CI 0.16-0.40) and reductions in TB rates were observed in the last calendar period (RR 0.74, 95%CI 0.55-1.00). For patients on HAART, no differences were observed by category of transmission. Low CD4 counts at entry were associated with higher TB rates (P < 0.001). CONCLUSIONS: HAART was associated with lower TB rates, and TB risk factors differed according to whether or not patients had received HAART. To further reduce TB rates, additional strategies are needed, such as timely access and adherence to HAART, especially in IDUs.

Effect of education on overall and cause-specific mortality in injecting drug users, according to HIV and introduction of HAART.

BACKGROUND: We assessed the impact of education on long-term overall and cause-specific mortality among 6575 injecting drug users (IDUs) according to HIV status and introduction of highly active antiretroviral therapy (HAART). METHODS: Community-based cohort study of IDUs recruited in three AIDS prevention centres (1987-1996). Causes of death were ascertained in clinical centres and Mortality Registry and classified as AIDS, drug use related, injuries, or liver diseases. Poisson regression models including education and calendar period interaction and adjusted by sex, age, and HIV were used. RESULTS: In 73 901 person-years of follow-up, there were 1493 deaths (20.2/1000 person-years): 761 related to AIDS, 234 to drug use, 179 to injuries, and 93 to liver diseases. IDUs with university studies had a lower risk of death (RR 0.52; 95% CI 0.36-0.77) than those without studies: this difference was higher after (RR 0.45; 95% CI 0.25-0.80) than before 1997 (RR 0.68; 95% CI 0.41-1.13). Compared to before 1997, while decreases in the risk of AIDS mortality were seen during 1997-2004 for both lower (RR 0.49; 95% CI 0.41-0.58) and higher (RR 0.33; 95% CI 0.23-0.48) educated, only those higher educated experienced a reduction in drug-use mortality (RR 0.54; 95% CI 0.28-1.05) and death from injuries (RR 0.52; 95% CI 0.23-1.21). CONCLUSIONS: Independently of HIV status, lower education predicts a higher risk of death in IDUs and its impact is stronger after 1997. Education has a protective effect on most causes of death and it cannot be entirely attributable to the access or use of HAART.

Higher prevalence of human papillomavirus infection in migrant women from Latin America in Spain.

OBJECTIVES: To estimate prevalence and determinants of high risk (HR) human papillomavirus (HPV) by country of origin in women attending a family planning centre (FPC) in Alicante, Spain. METHODS: Cross sectional study of all women attending a FPC from May 2003 to January 2004. An ad hoc questionnaire was designed and data were collected prospectively. HR HPV infection was determined through the Digene HPV test, Hybrid Capture II, and positive samples for PCR were directly sequenced. Data were analysed through multiple logistic regression. RESULTS: HR HPV prevalence in 1011 women was 10% (95% CI: 8.2 to 12). Compared to Spaniards (prevalence 8.2%) HR HPV prevalence in Colombians was 27.5% (OR: 4.24 95% CI: 2.03 to 8.86), 23.1% in Ecuadoreans (OR: 3.35 95% CI: 1.30 to 8.63), and 22.73% in women from other Latin American countries (OR: 3.29 95% CI: 1.17 to 9.19). Women with more than three lifetime sexual partners had an increased risk of HR HPV infection (OR 3.21 95% CI: 2.02 to 5.10). The higher risk of HR HPV infection was maintained in Latin American women in multivariate analyses that adjusted for age, number of lifetime sexual partners, and reason for consultation. The commonest HPV types in women with normal cervical smears were HPV-18 (20%), HPV-16 (14%) and HPV-33 (11%). CONCLUSIONS: Prevalence of HR HPV is more than three times higher in Latin Americans than in Spaniards. Latin American women's HPV prevalence resembles more that of their countries of origin. It is essential that health service providers identify these women as a priority group in current cervical screening programmes.

Cardiac variability in critically ill adults: influence of sepsis.

OBJECTIVE: To evaluate, in critically ill adults, factors associated with impaired sympathovagal balance. DESIGN: One-month inception cohort study. SETTING: Twenty-six-bed medical intensive care unit of a teaching hospital. PATIENTS: Critically ill adults with an expected duration of intensive care unit stay of > or =48 hrs were enrolled. Patients with permanent arrhythmia or cardiac pacing were not included. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Sympathovagal balance was assessed on the day after intensive care unit admission by the low-frequency/high-frequency ratio obtained from spectral components of heart rate signal: overall variability, low frequency, and high frequency. RESULTS: Forty-one patients, 13 with sepsis and 28 without sepsis, were assessed. Predictors of low-frequency/high-frequency ratio with the automatic interaction detection method were sepsis and age. Binary logit analysis adjusted for age showed that sepsis remained a strong and independent factor of a low-frequency/high-frequency ratio of <1.50, with an odds ratio of 3.63 (95% confidence interval, 1.47-9.01, p =.005). Use of mechanical ventilation, catecholamines, or sedation did not add any information. The use of the low-frequency/high-frequency ratio in diagnosing sepsis may be supported by a likelihood ratio for low frequency/high frequency <1 at 6.47. CONCLUSIONS: This work suggests that impaired cardiac variability and notably sympathovagal balance (i.e., a low-frequency/high-frequency ratio <1.0) may be a diagnostic test for sepsis.

Inappropriate sympathetic activation at onset of septic shock: a spectral analysis approach.

The autonomic cardiovascular control was investigated in 10 patients with septic shock, 10 patients with sepsis syndrome, and six tilted healthy subjects. Overall variability, high- and low-frequency components (AUC, HF, and LF, beats/min(2)/Hz or mm Hg(2)/Hz) from heart rate (HR), systolic (SBP) and diastolic (DBP) blood pressures spectra were obtained from 5-min recordings. LF(HR)/HF(HR) and the square root of LF(SBP)/LF(HR) (alpha) were used as indices of sympathovagal interaction and baroreflex control of the heart, respectively. Compared with tilted control subjects and patients with sepsis syndrome, septic shock is characterized by reduction in: (1) HR variability, i.e., decreased AUC(HR) (p = 0.007), LF(HR) (p = 0.002), and LF(HR)/HF(HR) (p = 0.0002); (2) DBP variability, i.e., decreased AUC(DBP) (p = 0.003) and LF(DBP) (p = 0.001), (3) alpha (p = 0.003). In septic shock, LF(HR)/HF(HR), alpha, and LF(DBP) correlated with mean blood pressure (r = 0.67, p = 0.04, r = 0.64, p = 0.03, and r = 0.88, p = 0.0008, respectively), and with plasma norepinephrine levels (r = -0.65, p = 0.03, r = -0.79, p = 0.006, and r = -0.69, p = 0.03, respectively). In conclusion, onset of septic shock is characterized by high concentrations of circulating catecholamines but impaired sympathetic modulation on heart and vessels, suggesting that central autonomic regulatory impairment contributes to circulatory failure.