Efficacy and safety of dolutegravir/rilpivirine in real-world clinical practice. GeSIDA study 1119.

INTRODUCTION: Dolutegravir/rilpivirine (DTG/RPV) is an effective antiretroviral (ART) regimen endorsed by clinical trials as a switch therapy. The aim of our study was to analyse the efficacy and safety of DTG/RPV in real-world clinical practice. METHODS: Observational, multicentre study of patients who started DTG/RPV. Efficacy, adverse events and metabolic changes at 48 weeks were analysed. RESULTS: A total of 348 patients were included; median time of HIV infection was 21.1 years, 33.7% were AIDS cases; median nadir CD4 was 160 cells/µL; 90.5% had received ≥3 lines of ART and 179 (53.8%) had prior virological failure. Convenience (43.5%), toxicity/intolerance (28.4%) and interactions (17.0%) were the main reasons for starting DTG/RPV. Previous regimens were protease inhibitors (PI) (31.6%), non-nucleoside reverse transcriptase inhibitors (NNRTI) (20.4%) and integrase strand transfer inhibitors (INSTI) (14.9%). Efficacy (HIV-RNA <50 copies/mL) at 48 weeks was 89.7% (95% CI 86.1-92.6) by intention-to-treat (ITT) and 94.2% (95% CI 91.3-96.4) by on treatment (OT); 10 patients (3.1%) were not suppressed (3 had abandoned ART). There was a mean decrease in triglycerides, total cholesterol, low-density lipoprotein-cholesterol, glutamic-pyruvic transaminase (GPT), gamma-glutamyl transferase (GGT) and alkaline phosphatase; creatinine increased with a decrease in glomerular filtration rate. CONCLUSIONS: This study confirms the effectiveness, tolerability and safety of DTG/RPV in real-world clinical practice in a different population from clinical trials, with many years of infection, low CD4 nadir, several previous treatment lines, more than half with virological failures, and one-third diagnosed with AIDS. The switch to DTG/RPV was safe with few discontinuations due to adverse effects. Modifications of the lipid and liver profiles were favourable. There were no relevant changes in kidney function.

Validation of self-reported adherence in chronic patients visiting pharmacies and factors associated with the overestimation and underestimation of good adherence.

BACKGROUND: Studies validating indirect methods to identify nonadherence in chronic patients who visit pharmacies are lacking. The aim of this study was to validate self-reported adherence and assess the variables associated with both overestimation and underestimation of good adherence when using this method. MATERIALS AND METHODS: An observational, cross-sectional study was undertaken to validate self-reported adherence in 132 community pharmacies throughout Spain in 6237 chronic patients. The Morisky-Green test was used as the validation method and through a 2 × 2 table, the validity indicators, predictive values, and likelihood ratios were calculated. To assess the variables associated with both overestimation and underestimation of good adherence, multivariate logistic regression analysis and calculation of the area under the ROC curve were used to evaluate discriminatory capacity. RESULTS: Sensitivity was 27.8% (95% CI: 26.2-29.4) and specificity was 93.9% (95% CI: 93.1-94.7). Discrepancy analysis obtained a significant overestimation of good adherence (p < 0.001). The factors associated with overestimating good adherence were performing a mnemonic trick (p < 0.001), not self-medicating (p < 0.001), a high level of physical activity (p < 0.001), and an older age (p = 0.014). Factors associated with underestimation were self-medication (p < 0.001), desiring more information (p < 0.001), smoking (p = 0.014), not engaging in physical activity in the low (p = 0.006) or high (p < 0.001) categories, having a younger mean age (p = 0.007), and taking two to three (p = 0.029) or four or more (p < 0.001) chronic treatments. CONCLUSION: Self-reported adherence has good specificity but poor sensitivity. The associated profiles of the discrepancies were obtained to identify both good and poor adherence.

Evaluation of Swallowing Related Muscle Activity by Means of Concentric Ring Electrodes.

Surface electromyography (sEMG) can be helpful for evaluating swallowing related muscle activity. Conventional recordings with disc electrodes suffer from significant crosstalk from adjacent muscles and electrode-to-muscle fiber orientation problems, while concentric ring electrodes (CREs) offer enhanced spatial selectivity and axial isotropy. The aim of this work was to evaluate CRE performance in sEMG recordings of the swallowing muscles. Bipolar recordings were taken from 21 healthy young volunteers when swallowing saliva, water and yogurt, first with a conventional disc and then with a CRE. The signals were characterized by the root-mean-square amplitude, signal-to-noise ratio, myopulse, zero-crossings, median frequency, bandwidth and bilateral muscle cross-correlations. The results showed that CREs have advantages in the sEMG analysis of swallowing muscles, including enhanced spatial selectivity and the associated reduction in crosstalk, the ability to pick up a wider range of EMG frequency components and easier electrode placement thanks to its radial symmetry. However, technical changes are recommended in the future to ensure that the lower CRE signal amplitude does not significantly affect its quality. CREs show great potential for improving the clinical monitoring and evaluation of swallowing muscle activity. Future work on pathological subjects will assess the possible advantages of CREs in dysphagia monitoring and diagnosis.

Electrohysterogram for ANN-Based Prediction of Imminent Labor in Women with Threatened Preterm Labor Undergoing Tocolytic Therapy.

Threatened preterm labor (TPL) is the most common cause of hospitalization in the second half of pregnancy and entails high costs for health systems. Currently, no reliable labor proximity prediction techniques are available for clinical use. Regular checks by uterine electrohysterogram (EHG) for predicting preterm labor have been widely studied. The aim of the present study was to assess the feasibility of predicting labor with a 7- and 14-day time horizon in TPL women, who may be under tocolytic treatment, using EHG and/or obstetric data. Based on 140 EHG recordings, artificial neural networks were used to develop prediction models. Non-linear EHG parameters were found to be more reliable than linear for differentiating labor in under and over 7/14 days. Using EHG and obstetric data, the <7- and <14-day labor prediction models achieved an AUC in the test group of 87.1 ± 4.3% and 76.2 ± 5.8%, respectively. These results suggest that EHG can be reliable for predicting imminent labor in TPL women, regardless of the tocolytic therapy stage. This paves the way for the development of diagnostic tools to help obstetricians make better decisions on treatments, hospital stays and admitting TPL women, and can therefore reduce costs and improve maternal and fetal wellbeing.

Consensus on basic conduct during the hospital admission of patients with acute heart failure. / Consenso de actuación básica durante el ingreso hospitalario por insuficiencia cardiaca aguda.

Acute heart failure (AHF) is a highly prevalent clinical entity in individuals older than 45years in Spain. AHF is associated with significant morbidity and mortality and is the leading cause of hospitalisation for individuals older than 65years in Spain, a quarter of whom die within 1year of the hospitalisation. In recent years, there has been an upwards trend in hospitalisations for AHF, which increased 76.7% from 2003 to 2013. Readmissions at 30days for AHF have also increased (from 17.6% to 22.1%), at a relative mean rate of 1.36% per year, with the consequent increase in the use of resources and the economic burden for the healthcare system. The aim of this document (developed by the Heart Failure and Atrial Fibrillation Group of the Spanish Society of Internal Medicine) is to guide specialists on the most important aspects of treatment and follow-up for patients with AHF during hospitalisation and the subsequent follow-up. The main recommendations listed in this document are as follows: (1)At admission, perform a comprehensive assessment, considering the patient's standard treatment and comorbidities, given that these determine the disease prognosis to a considerable measure. (2)During the first few hours of hospital care, decongestive treatment is a priority, and a staged diuretic therapeutic approach based on the patient's response is recommended. (3)To manage patients in the stable phase, consider starting and/or adjusting evidence-based drug treatment (e.g., sacubitril/valsartan or angiotensin-converting enzyme inhibitors/angiotensinII receptor blockers, beta blockers and aldosterone antagonists). (4)At hospital discharge, use a checklist to optimise the patient's management and identify the most efficient options for maintaining continuity of care after discharge.

Evaluation of kidney function in HIV-infected patients receiving an antiretroviral regimen containing one or two inhibitors of the tubular secretion of creatinine.

OBJECTIVES: The aim of this study was to determine the evolution of renal function in patients receiving one or two inhibitors, according to different baseline factors. Some antiretroviral drugs such as rilpivirine (RPV), dolutegravir (DTG), or cobicistat (COBI), interact with the tubular secretion of creatinine, but there are no data about their impact in renal function evaluation in patients with renal disease or when these drugs are used concomitantly. METHODS: A prospective cohort study was carried out in HIV-infected patients who switched to a dual regimen including DTG, RPV or darunavir/COBI, separately or in combination. The primary endpoint was the evolution of the serum creatinine-based estimated glomerular filtration rate (eGFR-scr). A control group not receiving any transporter inhibitor was included. RESULTS: A total of 288 patients on different dual regimens were included (DTG + RPV, 92; DTG + darunavir/COBI, 23; DTG, 26; COBI, 19; control group, 128). In patients receiving two transporter inhibitors, eGFR-scr decreased by a mean of -8.4 mL/min/1.73 m2 , similar to that observed with the separate use of DTG or COBI (mean of both groups, -8.6 mL/min/1.73 m2 ), while eGFR-scr improved in the control group. Similar evolution of proteinuria and tubular dysfunction was observed in all the groups, and there were no significant changes in the cystatin C-based eGFR. Mean eGFR-scr change inversely correlated with baseline eGFR-scr value (r = -0.39; P < 0.01), with a lower eGFR-scr decrease in patients with chronic kidney disease. CONCLUSIONS: Similar eGFR-scr decreases were observed in patients using different antiretroviral drugs inhibiting the tubular transport of creatinine, separately or in combination, with no alterations in proteinuria or cystatin C-based eGFR. The lack of additional changes when the drugs were used in combination, and the lower impact in cases of previous chronic kidney disease, suggest that there are compensatory mechanisms for creatinine secretion.

Switching to dual antiretroviral regimens is associated with improvement or no changes in activation and inflammation markers in virologically suppressed HIV-1-infected patients: the TRILOBITHE pilot study.

OBJECTIVES: While the use of dual antiretroviral therapies could reduce the toxicity of antiretroviral treatment in treatment-experienced HIV-1-infected patients, it is crucial to know if reducing the number of drugs could lead to an adverse increase in inflammation and activation markers. METHODS: This was a cross-sectional pilot study conducted at the HIV-1 Unit at the Tertiary University Hospital in Madrid, Spain, evaluating biomarkers of activation [interferon-γ-induced protein 10 (IP10), high-sensitivity C-reactive protein (hs-CRP), soluble CD14 (sCD14) and sCD163], inflammation [interleukin-6 (IL-6)], blood coagulation (d-dimer), and immune response [interferon (IFN)-γ, tumour necrosis factor (TNF)-α and IL-4] in three groups of suppressed HIV-1-infected patients: patients continuing on triple therapy (26 patients), and patients who switched from triple to dual therapy, at 24 or 48 weeks after switching (13 and 36 patients, respectively). RESULTS: Demographic and immunovirological parameters were similar in the three groups of patients. IL-6 and sCD14 levels were lower in patients at 48 weeks after switching to dual therapy compared with those found in patients who continued to receive triple therapy (P = 0.012 and P = 0.001, respectively), with no differences in the levels of the remaining biomarkers. Among patients with nadir CD4 count ≤ 200 cells/µL, sCD14 levels were lower in patients who had been on dual therapy for 48 weeks (14 patients) compared with those found in patients who received ongoing triple therapy (11 patients; P = 0.029), with no differences in the levels of the other biomarkers. CONCLUSIONS: HIV-1-infected patients receiving dual regimens showed similar or even lower levels of inflammatory and activation markers compared with those found in patients who received ongoing triple therapy. Of note, similar data were obtained in patients with low nadir CD4 count.

Switching to abacavir versus use of a nucleoside-sparing dual regimen for HIV-infected patients with tenofovir-associated renal toxicity.

OBJECTIVES: We investigated the reversibility of tenofovir disoproxil fumarate (TDF)-associated renal decline and tubular dysfunction using different antiretroviral strategies. METHODS: A successive evaluation of renal [estimated glomerular filtration rate (eGFR)] and tubular (phosphataemia, proteinuria, albuminuria, phosphaturia, uricosuria, glycosuria and tubular proteinuria) parameters was performed in 231 patients, before and after switching from TDF to abacavir (n = 60), using dual therapy (n = 49), or continuing the same regimen including TDF (n = 122). RESULTS: In a successive evaluation after a median of 8.86 months, or less time if treatment was switched (4.8 months vs. 13.3 months to second evaluation; P < 0.01), a significant improvement in eGFR (median change +0.3 vs. -2.91 mL/min/1.73 m2 in patients who did not discontinue TDF; P = 0.04) and tubular dysfunction (median change -40% vs. +30%, respectively; P < 0.01) was observed. Lineal regression showed that age (ß = -0.14; P = 0.04), previous eGFR decline (ß = -0.42; P < 0.01), and time on TDF (ß = -0.19; P = 0.04) were associated with impaired eGFR recovery. There were no differences in eGFR slopes between patients using abacavir instead of TDF and those using a dual therapy, who showed similar improvement in proteinuria (-22% vs. -19%, respectively), phosphaturia (+10.1% vs. +9.4%, respectively), and urinary beta-2-microglobulin (-9% vs. -15%, respectively; P > 0.1 for all), although patients receiving the dual regimen were more heavily pretreated. A eGFR decrease (-6.17 mL/min/1.73 m2 ) was observed in patients taking dolutegravir or rilpivirine, but with similar improvement to that observed in the rest of switching patients in tubular abnormalities. CONCLUSIONS: Tenofovir disoproxil fumarate discontinuation was associated with a rapid and significant improvement in eGFR and tubular abnormalities, regardless of whether abacavir or dual therapy was chosen. Switching to a regimen that included dolutegravir and/or rilpivirine was associated with a eGFR decrease without differences in the rate of tubular dysfunction improvement in comparison with the rest of patients who discontinued tenofovir.

Influence of bladder lithiasis on lower urinary tract dynamics in patients with spinal cord injury.

STUDY DESIGN: A prospective and a case-matched control study. OBJECTIVES: To study the lower urinary tract dysfunction associated with bladder lithiasis in patients with spinal cord injury (SCI). SETTING: Toledo (Spain). METHODS: We have carried out a urodynamic study in 30 patients with SCI with lithiasis in their bladder before and 3 months after bladder endoscopic lithotripsy. This second study was compared with the urodynamic findings of a different group of 30 patients with SCI, without a history of bladder lithiasis, paired with cases by gender and date of urodynamic study. RESULTS: We have found that the prevalence of neurogenic detrusor overactivity (NDO) was significantly different after bladder lithotripsy, although the cystomanometric capacity was significantly increased. A group of patients with lithiasis showed a maximum flow rate, a voiding maximum detrusor pressure and the detrusor contractility parameter Wmax lower than that in controls. On the other hand, a voiding abdominal straining was found to be significantly greater than that in controls. CONCLUSIONS: Bladder lithiasis affects the presence of NDO in patients with SCI. Patients with SCI who develop bladder lithiasis present a lower detrusor contractility power compared with those who do not.

Liver toxicity and risk of discontinuation in HIV/hepatitis C virus-coinfected patients receiving an etravirine-containing antiretroviral regimen: influence of liver fibrosis.

OBJECTIVES: The aim of the study was to establish the risk of liver toxicity in HIV/hepatitis C virus (HCV)-coinfected patients receiving etravirine, according to the degree of liver fibrosis. METHODS: A prospective cohort study of 211 HIV-infected patients initiating an etravirine-containing regimen was carried out. HCV coinfection was defined as a positive HCV RNA test, and baseline liver fibrosis was assessed by transient elastography. Hepatotoxicity was defined as clinical symptoms, or an aspartate aminotransferase (AST) or alanine aminotransferase (ALT) value > 5-fold higher than the upper limit of normal if baseline values were normal, or 3.5-fold higher if values were altered at baseline. RESULTS: Overall, 145 patients (69%) were HCV coinfected, with a lower nadir (165 versus 220 cells/µL, respectively; p = 0.03) and baseline (374 versus 498 cells/µL, respectively; p = 0.04) CD4 count than monoinfected patients. Etravirine was mainly used with two nucleoside reverse transcriptase inhibitors (129; 61%) or with a boosted protease inhibitor (PI) (28%), with no significant differences according to HCV serostatus. Transient elastography in 117 patients (81%) showed a median (range) stiffness value of 8.25 (3.5-69) kPa, with fibrosis stage 1 in 43 patients (37%) and fibrosis stage 4 in 28 patients (24%). During an accumulated follow-up time of 449.3 patient-years (median 548 days), only one patient with advanced fibrosis (50.8 kPa) had grade 3-4 liver toxicity (0.7%). Transaminases changed slightly, with no significant differences compared with baseline fibrosis, and nine and six patients had grade 1 and 2 transaminase increases, respectively. Also, HCV coinfection was not associated with a higher risk of discontinuation (25% discontinued versus 21% of monoinfected patients; p = 0.39, log-rank test) or virological failure (8% versus 12%, respectively; p = 0.4). CONCLUSIONS: Our data suggest that etravirine is a safe option for HIV/HCV-coinfected patients, including those with significant liver fibrosis.

The influence of patient beliefs and treatment satisfaction on the discontinuation of current first-line antiretroviral regimens.

OBJECTIVES: Large cohort studies have shown a high rate of first-line combination antiretroviral therapy (cART) regimen discontinuation in HIV-infected patients, attributed to characteristics of the cART regimen or toxicity. METHODS: A cohort study of 274 patients receiving a first-line regimen was carried out. Patients' perceptions and beliefs prior to initiation were assessed using an attitude towards medication scale (0-15 points), and their satisfaction during therapy was assessed using an HIV treatment satisfaction questionnaire (HIVTSQ). Treatment discontinuation was defined as any switch in the cART regimen. RESULTS: During 474.8 person-years of follow-up, 63 (23%) patients changed their cART regimen, mainly because of toxicity/intolerance (42; 67%). The overall rate of change was 13.2 per 100 patient-years [95% confidence interval (CI) 11.1-16.4 per 100 patient-years]. An efavirenz (EFV)-based single tablet regimen showed the highest rate of adverse events (27%), but the lowest rate of change (16%; 7.44 per 100 patient-years). Cox regression revealed a decreased hazard of first regimen termination with better initial attitude towards drugs [hazard ratio (HR) 0.76; 95% CI 0.62-0.93; P < 0.01] and higher satisfaction (HR 0.94; 95% CI 0.89-0.99; P = 0.01), and an increased hazard of termination with the presence of adverse events (HR 7.7; 95% CI 2.4-11.6; P < 0.01). One-third of patients (18 of 59; 31%) with mild/moderate adverse events (which were mainly central nervous system symptoms) continued the regimen; these patients, compared with those discontinuing therapy, showed better perception of therapy (mean score 14.4 versus 12.1, respectively; P = 0.05) and greater satisfaction during therapy (mean score 50.6 versus 44.6, respectively; P = 0.04). CONCLUSIONS: Patients' beliefs and satisfaction with therapy influence the durability of the first antiretroviral regimen. These patient-related factors modulate the impact of mild adverse events, and could explain differences in the rate of discontinuation.

Incidence and prognosis of immune reconstitution inflammatory syndrome in HIV-associated progressive multifocal leucoencephalopathy.

BACKGROUND AND PURPOSE: Progressive multifocal leucoencephalopathy-associated immune reconstitution inflammatory syndrome (PML-IRIS) is the paradoxical worsening or unmasking of preexisting infection with JC virus attributable to a rapid recovery of the immune system after highly active antiretroviral therapy (HAART) initiation. We investigated the incidence and factors associated with PML-IRIS in HIV-infected patients. We also studied its influence on mortality of PML and the effect of corticosteroid therapy. METHODS: Single-center retrospective analysis of HIV-infected patients diagnosed with PML from 1996 to 2012 who received HAART. RESULTS: Among 59 PML patients treated with HAART, 18 (30.51%) developed PML-IRIS (five delayed PML-IRIS, 13 simultaneous PML-IRIS). Patients who developed IRIS had lower CD4 counts prior to treatment (102 vs. 68.5, P < 0.05) and experienced a greater decline in HIV-RNA levels in response to HAART (2.5log vs. 2.95log, P < 0.05). Gadolinium enhancement on MRI was observed in 31.25% of PML-IRIS cases versus 2.56% of PML non-IRIS (P < 0.01). Survival rates were higher in patients with PML-IRIS compared to those with PML non-IRIS. Eight patients received corticosteroids, five of which had a good outcome. Patients who died were severely ill when treatment was initiated whereas patients who survived were treated before major neurological deterioration occurred. CONCLUSIONS: Nearly one-third of HIV-infected patients with PML develop IRIS after initiating HAART. Patients severely immunocompromised who experience a rapid virological response to HAART have a higher risk for PML-IRIS. There was a trend for lower mortality in patients with IRIS. Early treatment with corticosteroids might be useful.

Other radiological lesions of the Lower Urinary Tract in patients after isolated pelvic radiotherapy and combined with surgery. / Otras lesiones radiológicas del tracto urinario inferior (TUI) en pacientes sometidos a radioterapia pélvica en monoterapia y combinada con cirugía.

INTRODUCTION: The cystographic study of patients who have undergone radiotherapy (RT) and pelvic surgeries is uncommon in the literature, not described in patients without complications, and mostly related to urinary fistulae. OBJECTIVE: The study of the lower urinary tract (LUT) by cystography in these patients, with a description of some other types of radiation lesions. METHODS: 127 cystographies have been performed (88 men and 39 women) in consecutive patients undergoing radiotherapy (RT) (48 monotherapy and 79 cases combined with surgery), with a mean age of 69.6 years, and a mean time from radiation of 215 months (17 years). A General Electric X ray equipment has been used. We studied: behavior of the bladder neck at rest and during micturition, assessment of vesicoureteral reflux (VUR), bladder morphology (BM), urethral strictures (UE) and fistulas (F). RESULTS: We observed: Filling phase bladder neck incompetence (BNI) (37.8%), bladder smooth morphology (60.6%), coughing urinary incontinence (UI) (26.4%), basal cystocele (64.7%) and Valsalva cystocele (96.6%), a normal opening bladder neck (96,1%), reduction of the urethral diameter during voiding (41.3%), and vesicoureteral reflux (VUR) (13.2%). Five cases of filling BNI, were all related to prostate cancer (PC) (one of them with colon cancer as well). There were six cases of fistulae (4.14%), five of them women. Forty two patients (28.96%) had reduced urethral lumen, thirty five of them affecting the posterior urethra (83%), five (11.9%) the anterior and, finally, two cases of mixed lesion (5%). 95% were patients with PC without concurrent interventions (67%). Significant differences were found regarding the gender and the background of pelvic surgery. The filling BNI (p=0.007), the irregular bladder morphology (p=0.004) and the reduction of the urethral lumen (p<0.001) have been found to be more common in male patients, while the coughing UI was more common in women (p=0.007). The study shows that BNI (p=0.046), VUR (p=0.02) and the IU due to cough (p=0.03) were more frequent in operated patients, while reduced urethral lumen was less common (p<0.01). Patients with VUR present more time from radiotherapy, but not in other cystography variables. There was a relationship between RT and the BNI, stress urinary incontinence, anterior urethral stricture and VUR. The risk factor was increased by surgery. CONCLUSIONS: Bladder neck incompetence, stress UI, anterior urethral stricture and VUR have been related to radiotherapy. Surgery increased the risk factor in operated patients.

Visceral leishmaniasis as an independent cause of high immune activation, T-cell senescence, and lack of immune recovery in virologically suppressed HIV-1-coinfected patients.

OBJECTIVES: Different immune alterations have been described in HIV-infected patients with visceral leishmaniasis (VL). We aimed to identify the immunological factors involved in the lack of immunological recovery and VL relapses in HIV-infected patients with VL, by comparison with other HIV-infected patients. METHODS: We carried out a cross-sectional study of 55 patients receiving suppressive combination antiretroviral therapy (cART) for at least 1 year: nine with previous relapsing VL, 20 with an immunodiscordant response (IDR) to cART (CD4 count < 200 cells/µL) and no previous VL, and 26 with a concordant response (CR) to cART (CD4 count > 350 cells/µL) without VL. Immunosenescence was investigated by analysing CD57(+) CD28(-) levels, immune activation by analysing CD38(+) HLA-DR(+) levels, inflammation by analysing interleukin (IL)-6 levels, and microbial translocation by analysing lipopolysaccharide (LPS) and soluble CD14 (sCD14) levels. RESULTS: In VL patients, the median time since VL diagnosis was 42 months, and all patients had had at least one relapse despite suppressive cART for a median time of 43 months. Patients with previously diagnosed VL had a higher CD8 T-cell activation level (P < 0.001) than those with IDR. Also, levels of IL-6, LPS and especially sCD14, associated with bacterial translocation and additional monocyte activation, were significantly increased in patients with previous VL compared with patients with IDR (P = 0.048, P = 0.049 and P < 0.001, respectively). In addition, patients with previous VL had higher levels of CD8 T-cell senescence. Notably, the levels of immune activation and inflammation in patients with previous VL were not related to the time of VL diagnosis, the number of VL relapses, or hepatitis C virus (HCV) coinfection. CONCLUSIONS: Our data demonstrate that VL patients had an even worse immunological status than patients with IDR, which was probably associated with increased microbial translocation and additional monocyte/macrophage activation. These data explain the observed lack of immunological recovery and the occurrence of VL relapses in HIV-infected patients with previous VL.

High levels of CD4⁺ CTLA-4⁺ Treg cells and CCR5 density in HIV-1-infected patients with visceral leishmaniasis.

Visceral leishmaniasis (VL) in HIV-1-infected patients has been associated with poor immunological recovery and frequent disease relapses. The aim of this study was to analyse the role of T cell populations, Treg cells and CCR5 density in patients with VL compared to HIV-1-infected patients without leishmaniasis. A cross-sectional study of nine Leishmania-HIV-1-coinfected (LH) patients with VL receiving suppressive cART for at least 1 year were compared to 16 HIV-1-infected patients with non-immunological response (NIR, CD4 count below 250 cells/mm(3)) and 26 HIV-1-infected patients with immunological response (IR, CD4 count above 500 cells/mm(3)) without leishmaniasis. LH patients had a deep depletion of naïve T cells (p = 0.002), despite similar levels of effector T cells compared to NIR patients. CD4 Treg cells were similar compared to NIR patients, but higher compared to IR patients (p < 0.001). Interestingly, CD4 Treg CTLA-4(+) cells were higher in LH patients compared to either NIR or IR patients (p = 0.022 and p < 0.001, respectively), and the CD4 Treg/TEM ratio was similar to NIR patients, but higher compared to IR patients (p = 0.017). CCR5(+) T cell levels were higher compared to IR patients (p < 0.001), while CCR5 density on T cells were higher compared to both NIR and IR patients (p < 0.005 in both cases). Higher levels of CD4(+) CTLA-4(+) Treg cells and CCR5 density on CD8(+) T cells are strongly associated with VL in HIV-1-infected patients. Also, these patients have a poor immunological profile that might explain the persistence and relapse of the pathogen.

Risk factors of urethral diverticula in male patients with spinal cord injury.

STUDY DESIGN: A case-control study in a series of 55 males with urethral diverticula (UD) and their correspondent control, matched by age and time of radiological assessments. OBJECTIVES: To evaluate the risk factors to develop UD in males with spinal cord injury (SCI) and the place in the urethra where they are, most commonly, allocated. SETTING: Toledo, Spain. METHODS: Clinical histories and urodynamic studies, of all patients, were reviewed. The study was completed with a telephone survey according to an established protocol. RESULTS: The univariate analysis study showed the following risk factors: the age of onset of the spinal injury, the sphincterotomy procedure, personal history of lower urinary tract infections (LUTIs) and the chronic need of either indwelling catheter (IC) or the external condom drainage (ECD). Regarding the location of the UD, we have found the stress urinary incontinence as the only risk factor to develop UD in the prostatic urethra.On the other hand, we can conclude that the sphincterotomy, the ECD, the personal history of LUTIs and the detrusor external sphincter dyssynergia seem to be risk factors to develop diverticula in the bulbo-membranous urethra. Finally, we could point out the IC as the only risk factor for penile UD. Multivariate analysis showed that all of these risk factors were independent among them except the age of the onset of the injury and the ECD for UD in the bulbo-membranous urethra. CONCLUSION: According to our study, there is evidence of some specific risk factors for the development of UD in male patients with SCI, and therefore we should adopt the appropriate preventive measures to prevent them.

Identifying physical activity type in manual wheelchair users with spinal cord injury by means of accelerometers.

STUDY DESIGN: This was a cross-sectional study. OBJECTIVES: The main objective of this study was to develop and test classification algorithms based on machine learning using accelerometers to identify the activity type performed by manual wheelchair users with spinal cord injury (SCI). SETTING: The study was conducted in the Physical Therapy department and the Physical Education and Sports department of the University of Valencia. METHODS: A total of 20 volunteers were asked to perform 10 physical activities, lying down, body transfers, moving items, mopping, working on a computer, watching TV, arm-ergometer exercises, passive propulsion, slow propulsion and fast propulsion, while fitted with four accelerometers placed on both wrists, chest and waist. The activities were grouped into five categories: sedentary, locomotion, housework, body transfers and moderate physical activity. Different machine learning algorithms were used to develop individual and group activity classifiers from the acceleration data for different combinations of number and position of the accelerometers. RESULTS: We found that although the accuracy of the classifiers for individual activities was moderate (55-72%), with higher values for a greater number of accelerometers, grouped activities were correctly classified in a high percentage of cases (83.2-93.6%). CONCLUSIONS: With only two accelerometers and the quadratic discriminant analysis algorithm we achieved a reasonably accurate group activity recognition system (>90%). Such a system with the minimum of intervention would be a valuable tool for studying physical activity in individuals with SCI.

Prevalence of causes of secondary osteoporosis and contribution to lower bone mineral density in HIV-infected patients.

SUMMARY: Eighty-one percent of human immunodeficiency virus (HIV)-infected patients had one or more of seven evaluated causes of secondary osteoporosis, and this rate increases with age. The type and number of causes were associated with a lower bone mineral density (BMD), and with an increased rate of osteopenia/osteoporosis, regardless of age and body mass index. INTRODUCTION: The objective of this study was to determine whether factors of secondary osteoporosis were associated with lower BMD in HIV. METHODS: This was a cross-sectional study of 285 HIV-infected patients (25 % females) evaluating the impact of seven different factors of reduced BMD: hyperthyroidism, diabetes, chronic viral hepatitis, chronic kidney disease (CKD), hypovitaminosis D, secondary hyperparathyroidism, and hypogonadism. Dual-energy X-ray absorptiometry scan of the femoral neck was obtained at the clinical visit. RESULTS: Mean age was 45.7 years; osteopenia and osteoporosis were diagnosed in 38 and 6 %, respectively. Overall, 230 patients (81 %) had secondary factors; 107 (38 %) had only 1 cause, 94 (33 %) had 2, and 28 (10 %) had 3 or more, predominantly vitamin D deficiency in 61 %, hepatitis C virus coinfection in 45 %, and secondary hyperparathyroidism in 27 %. The number of secondary factors was closely related to a lower BMD, which is statistically significant for patients having ≥2 causes (0.77 vs 0.73 g/cm(2), p = 0.02). The rate of osteopenia ranged from 36 % without any cause to 57 % with three or more, osteoporosis from 0 to 19 %, and Z-score <-2 SD from 0 to 27 %, respectively. In a multivariate linear regression, adjusting by age, body mass index, and HIV-related factors, the number of secondary factors was independently associated with a lower BMD (ß coefficient -0.134; p = 0.02), mainly due to patients with hepatitis C virus (HCV) coinfection, secondary hyperparathyroidism, and CKD. CONCLUSIONS: A high prevalence of secondary causes of osteoporosis is observed in HIV-infected patients, and its type and cumulative number determine a lower BMD, after adjusting by age and body mass index.

Continued declining incidence and improved survival of progressive multifocal leukoencephalopathy in HIV/AIDS patients in the current era.

To evaluate the situation and perspectives of progressive multifocal leukoencephalopathy (PML) in human immunodeficiency virus (HIV)-infected patients, we investigated changes in the incidence, causes, and long-term outcome of this disease in 72 acquired immunodeficiency syndrome (AIDS) patients who were diagnosed with PML from 1996 to 2011. Patients were classified according to the date of diagnosis in the first (1996-2000, n = 35), second (2001-2006, n = 26), and recent or third highly active antiretroviral therapy (HAART) period (2007-2011, n = 11). Overall, the incidence of PML decreased from 14.8 cases/1,000 patients/year in 1996 to 2.6 in 2005 and 0.8 in 2011, and nearly two-thirds of recent cases (64 %) were observed in HIV patients not attending clinical visits. The baseline median CD4+ count was higher in recently PML-diagnosed patients (77 vs. 86 vs. 101 cells/mm(3); p < 0.01), and this fact was associated with a cerebrospinal fluid (CSF) inflammatory profile (from 11 to 31 to 55 %, p = 0.007) and with a significantly longer survival (attributable death, 54 vs. 35 vs. 36 %, respectively, p < 0.01). Thus, the overall 1-year and 3-year survival rates were 55 and 50 %, respectively, increasing to 79 % at 1 year for patients with CD4+ count above 100 cells/mm(3) at diagnosis. In a Cox regression analysis, an older age (hazard ratio, HR 0.76), a baseline CD4+ count above 100 cells/mm(3) (HR 0.33), and a CSF inflammatory profile (HR 0.12) were significantly associated with a longer survival. The clinical presentation and outcome of PML in AIDS patients continue to change dramatically. Now, a declining incidence and long-term survival is observed.