Ana Royuela

Immunosuppression With Calcineurin Inhibitors With Respect to the Outcome of HCV Recurrence After Liver Transplantation: Results of a Meta-analysis

A controversy exists over whether the outcome of a hepatitis C virus (HCV)‐infection‐related liver transplant differs based on the calcineurin inhibitor (CNI) used. We have performed a systematic review and a subsequent meta‐analysis evaluating tacrolimus (Tac)‐based vs. cyclosporine A‐based immunosuppression in HCV‐infected liver transplant recipients. Searches were conducted to locate randomized controlled trials comparing Tac vs. cyclosporine A. Data on HCV liver transplant recipients were obtained, independently of whether the study was specifically designed for patients with this disease or not. A fixed effects model was used for statistical pooling of the relative risks (RR) for the different outcomes. A total of 5 articles (366 patients) fulfilled the inclusion criteria. Statistically significant differences between Tac‐based vs. cyclosporine A‐based therapies were not found for mortality (P = 0.11; RR = 0.72; 95% confidence interval [CI], 0.49‐1.08), graft survival (P = 0.37; RR = 0.86; 95% CI, 0.61‐1.21), biopsy‐proven acute rejection (P = 0.65; RR = 0.91; 95% CI, 0.61‐1.36), corticoresistant acute rejection (P = 0.26; RR = 2.25; 95% CI, 0.55‐9.29), and fibrosing cholestatic hepatitis (P = 0.92; RR = 0.96; 95% CI, 0.41‐2.26). In 1 study, no differences were detected regarding severe fibrosis at 1 yr. In conclusion, patient and graft survivals in HCV‐positive liver transplant patients are similar independently of the CNI selected as basic immunosuppressant. Unfortunately, data on the severity of recurrence and effect on viremia are scarce. Well‐designed randomized prospective studies are needed to determine whether there are differences between the 2 CNIs regarding these specific variables. Liver Transpl 13:21–29, 2007.

A systematic review on steroid withdrawal between 3 and 6 months after kidney transplantation.

Background. Steroid withdrawal (SW) after the first posttransplant months in patients receiving a kidney transplant has been recently discouraged in clinical guidelines. Methods. A systematic review and meta-analysis of randomized controlled trials assessing SW (beyond the second week after kidney transplantation) was performed. Only trials using a calcineurin inhibitor plus mycophenolic acid were included. Results. The nine trials (1820 participants) randomly withdrew steroids between 3 and 6 months after transplantation. Death and graft loss were similar in SW and control patients. Including all trials, acute rejection was not more frequent after SW, but stratifying by the drug used, cyclosporine A (CsA) was associated with an increased incidence of overall acute rejection (risk ratio 1.42, 95% confidence interval 1.08–1.87) or biopsy-proven acute rejection (risk ratio 1.61 95% confidence interval 1.20–2.17). Contrarily, tacrolimus allowed SW without increased biopsy-proven acute rejection (P interaction=0.005). Serum cholesterol level was lower after SW than in controls using CsA or tacrolimus. Serum creatinine, blood pressure, serum triglycerides, new-onset diabetes mellitus, infections, or malignancies were similar in SW and control patients. Conclusions. SW after 3 to 6 months of kidney transplantation is associated with increased rates of acute rejection only if CsA is used but not with tacrolimus. Graft function and survival remain stable up to 3 years after transplantation, the longest follow-up reported. The interest for late SW has decreased during the past years in the literature. More trials with carefully designed outcome measures are needed in patients treated with low-exposure tacrolimus and mycophenolic acid derivatives.

Increased Risk of Serious Non-AIDS-Related Events in HIV-Infected Subjects on Antiretroviral Therapy Associated with a Low CD4/CD8 Ratio

Background A low CD4/CD8 ratio has been identified in the general population as a hallmark of inmmunosenescence and a surrogate of all-cause mortality. We aimed to investigate in treated HIV-infected individuals the relationship between the CD4/CD8 ratio and serious non-AIDS events. Methods Case-control study within a prospective hospital-based cohort of HIV-infected subjects during at least one year of ART-mediated viral suppression. Cases were patients with serious non-AIDS events (non-AIDS malignancies, cardiovascular disease, and end-stage kidney disease), and controls individuals who did not developed non-AIDS events during follow-up. Data were analyzed using ROC analysis and multivariate logistic regression. Conditional logistic regression was performed in 200 cases/controls matched by age, sex, nadir CD4 and proximal CD4 counts. Results We analyzed 407 subjects (109 cases, 298 controls). The CD4/CD8 ratio was lower in cases (0.44 vs. 0.70, P<0.0001), with higher discriminatory ability for the detection of non-AIDS events than the CD4 count, CD8 count and nadir CD4. Multivariate analyses (adjusted for age, sex, nadir CD4, proximal CD4 count, year of ART initiation and ART duration) confirmed the independent association of a low CD4/CD8 ratio with the risk of non-AIDS morbidity (per CD4/CD8 ratio quartile decrease, OR, 2.9; 95% CI, 1.3–6.2) and non-AIDS mortality (OR, 2.8; 95% CI, 1.5–5.3). Conclusions The CD4/CD8 ratio provides additional information to the CD4 counts and nadir CD4 in treated HIV-infected individuals, since it is independently associated with the risk of non-AIDS-related morbidity and mortality. This association is robust and maintained within different subgroups of patients.

Very early steroid withdrawal or complete avoidance for kidney transplant recipients: a systematic review

BACKGROUND The safety and efficacy of early steroid withdrawal or avoidance in patients receiving a kidney transplant (KT) are controversial. METHODS We performed a systematic review and a meta-analysis of the randomized controlled studies about steroid avoidance or withdrawal after a few days in patients receiving a KT and treated with antibody induction and cyclosporine (CsA) or tacrolimus (Tac) plus mycophenolate mofetil (MMF) (nine available studies and 1934 participants). RESULTS Death and graft loss (including or excluding death with function) were similar in steroid avoidance and control patients, with no differences between CsA and Tac studies. After steroid avoidance, acute rejection was more frequent than conventional steroid use in CsA trials [risk ratios (RR) 1.59, 95% confidence intervals (95% CI) 1.01-2.49] but not when Tac was used (RR 1.06, 95% CI 0.79-1.42). Steroid avoidance was associated with less frequent new-onset diabetes mellitus, but this decrease was only evident with CsA (RR 0.54, 95% CI 0.30-0.98), whereas this difference was not significant analysing Tac studies (RR 0.75, 95% CI 0.32-1.77). Despite this trend, the corresponding interaction tests were not statistically significant (P = 0.140 and P = 0.535, for acute rejection and new-onset diabetes mellitus, respectively). Serum creatinine, creatinine clearance, mean blood pressure, serum cholesterol and serum triglycerides were similar in both groups. CONCLUSIONS Steroid avoidance or early withdrawal within the first 2 weeks is safe in KT recipients receiving induction with anti-interleukin-2 receptor antibodies or thymoglobulin and a drug regimen based on calcineurin inhibitor and MMF. However, the real benefits remain unclear.

Prevalence and Factors Associated With Low Back Pain and Pelvic Girdle Pain During Pregnancy: A Multicenter Study Conducted in the Spanish National Health Service

Study Design. A cross-sectional, multicenter study. Objective. To determine the prevalence of low back pain (LBP), leg pain (LP), and pelvic girdle pain (PGP) in pregnant Spanish women and to identify the factors associated with a higher risk. Summary of Background Data. Previous studies on the prevalence and risk factors for LBP and PGP have shown inconsistent results. Methods. Sixty-one clinicians across 5 regions in Spain recruited 1158 women with a median (interquartile range) pregnancy of 35 (range, 31–38) weeks. Validated methods were used to gather data on the prevalence of LBP, LP, and PGP, anthropometric and sociodemographic characteristics, history of LBP, obstetrical history, physical activity before and during pregnancy, mattress and sleep characteristics, disability, anxiety, and depression. Separate multiple logistic regression models were developed to identify the variables associated with LBP, LP, and PGP. Results. The 4-week prevalence of LBP, LP, and PGP was 71.3%, 46.2%, and 64.7%, respectively. Main factors associated with a higher likelihood of reporting pain for LBP were history of LBP related and unrelated to previous pregnancy and postpartum, pain augmenting with time spent in bed, and anxiety. Previous lumbar surgery was associated with a lower risk. The factors associated with a higher likelihood of reporting LP were reporting LBP, lower academic level, younger age, depression, a lower number of hours of sleep per day, and a higher BMI, and for PGP were higher score for depression, a higher body mass index, and a more advanced stage of pregnancy. Conclusion. Factors associated with a higher risk vary between LBP and PGP. History of LBP, related or not to previous pregnancy or postpartum, LBP surgery, and anxiety were the factors more strongly associated with pregnancy-related LBP. When these variables are taken into account, obstetrical data from current or previous pregnancies and other variables do not show a significant association with LBP. Stage of pregnancy and depression were associated with PGP.

The Influence of Psychological Factors on Low Back Pain‐Related Disability in Community Dwelling Older Persons

OBJECTIVES To assess the influence of fear avoidance beliefs (FAB) and catastrophizing on low back pain (LBP)-related disability in Spanish community dwelling retirees. DESIGN Correlation between variables measured with previously validated instruments. SETTING Majorca, Spain. PATIENTS 1,044 community dwelling subjects attending conferences for retired persons. OUTCOME MEASURES Visual analog scales for LBP and pain referred to the leg (LP), Roland Morris Questionnaire (RMQ) for disability, FAB-Phys questionnaire (FABQ) for FAB, and the Coping Strategies Questionnaire (CSQ) for catastrophizing. RESULTS In subjects without clinically relevant LBP, FAB correlated moderately with catastrophizing (r = 0.535) and disability (r = 0.390), and weakly with LP (r = 0.119) and LBP (r = 0.197). In subjects with LBP, FAB correlated moderately with catastrophizing (r = 0.418) and disability (r = 0.408), and weakly with LP (0.152), but not with LBP. Correlations among CSQ, FABQ, and RMQ were similar in subjects with and without current LBP. In regression models, the coefficient for effect of FAB on disability was 0.14 for participants with no LBP, and 0.28 for those with pain. Corresponding values for catastrophizing were 0.17 and 0.19. CONCLUSION In Spanish community dwelling retirees, the influence of FAB and catastrophizing on LBP-related disability is clinically small.

Fear avoidance beliefs do not influence disability and quality of life in Spanish elderly subjects with low back pain.

Study Design. Correlation between previously validated questionnaires. Objective. To assess the association of fear avoidance beliefs (FAB) with disability and quality of life in elderly Spanish subjects. Summary of Background Data. As opposed to Anglo-Saxon and Northern European patients, in Spanish low back pain (LBP) patients of working age, the influence of FAB on disability and quality of life is sparse and much less than that of pain. The influence of FAB on LBP-related disability and quality of life in the elderly is unknown. Methods. A visual analogue scale (VAS), the Roland Morris Questionnaire (RMQ), the FAB-Phys questionnaire (FABQ), and the SF-12 questionnaire were used to assess LBP, disability, fear avoidance beliefs, and quality of life in 661 institutionalized elderly in Spain, 439 of whom had LBP. Results. In all subjects, FAB correlated with LBP (r = 0.477), disability (r = 0.458), the Physical Component Summary of SF-12 (PCS SF-12) (r = −0.389), and the Mental Component Summary of SF-12 (MCS SF-12) (r = −0.165). In subjects with LBP, FABs only correlated weakly with disability (r = −0.110). The stronger correlations were found between LBP and disability, both in all subjects (r = 0.803) and LBP patients (r = 0.445). Regression models including all the participants showed that the influence of FABs on physical quality of life was sparse and that FABs were not associated with either disability or mental quality of life. In elderly subjects with LBP, FABs were not associated with either disability or quality of life. Conclusion. In Spanish institutionalized elderly subjects, FABs only have a minor influence on physical quality of life, and none on disability or mental quality of life. In elderly subjects with LBP, differences in FABs are not associated with differences in disability or quality of life. Further studies should explore the potential value of FABs in the elderly in other settings.

Agreement in the Interpretation of Magnetic Resonance Images of the Lumbar Spine

Background: Correlation between clinical features and magnetic resonance imaging (MRI) findings is essential in low-back-pain patients. Most previous studies have analyzed concordance in the interpretation of lumbar MRI among a few radiologists who worked together. This may have overestimated concordance. Purpose: To evaluate intra- and interobserver agreement in the interpretation of lumbar MRI performed in an open 0.2T system. Material and Methods: Seven radiologists from two different geographic settings in Spain interpreted the lumbar MRIs of 50 subjects representative of the general Danish population aged 40 years. The radiologists interpreted the images in routine clinical practice, having no knowledge of the clinical and demographic characteristics of the subjects and blinded to their colleagues’ assessments. Six of the radiologists evaluated the same MRIs 14 days later, having no knowledge of the previous results. Data on the existence of disc degeneration, high-intensity zones, disc contour, Schmorl nodes, Modic changes, osteophytes, spondylolisthesis, and spinal stenosis were collected in the Nordic Modic Consensus Group Classification form. Intra- and interobserver agreement was analyzed for variables with a prevalence ≥10% and ≤90% by means of the kappa statistic. Results: Intra- and interobserver agreement was excellent for variables related to Modic changes, and fair to good for disc contour, high-intensity zones, and Schmorl nodes. The evaluations for disc degeneration and osteophytes were found to have fair to good intraobserver agreement and poor interobserver agreement. The agreement for the evaluations of spondylolisthesis and spinal stenosis was not analyzed because they were observed in <10% of reports. Conclusion: Images from 0.2T MRIs appear to lead to good agreement in the reporting of disc contour, high-intensity zones, Schmorl nodes, and, in particular, Modic changes, suggesting that they can possibly be reliably used for clinical research purposes. In contrast, assessment of osteophytes and disc degeneration is not reliable.

Catastrophizing, State Anxiety, Anger, and Depressive Symptoms Do Not Correlate with Disability when Variations of Trait Anxiety Are Taken into Account. A Study of Chronic Low Back Pain Patients Treated in Spanish Pain Units [NCT00360802]

OBJECTIVES To assess the influence of pain severity, catastrophizing, anger, anxiety, and depression on nonspecific low back pain (LBP)-related disability in Spanish patients with chronic LBP. Study Design.  Cross-sectional correlation between psychological variables and disability. Methods.  One hundred twenty-three patients treated for chronic LBP in pain units within nine Spanish National Health Service Hospitals, in eight cities, were included in this study. Intensity of LBP and pain referred to the leg, disability, catastrophizing, anger, state anxiety, trait anxiety, and depression were assessed through previously validated questionnaires. The association of disability with these variables, as well as gender, age, academic level, work status, and use of antidepressants, was analyzed through linear regression models. RESULTS Correlations between LBP, referred pain, disability, catastrophizing, anger, state anxiety, trait anxiety, and depression were significant, except for the ones between anger and LBP and between anger and referred pain. The multivariate regression model showed that when variations of trait anxiety were taken into account, the association of the other psychological variables with disability was no longer significant. The final model explained 49% of the variability of disability. Standardized coefficients were 0.452 for trait anxiety, 0.362 for intensity of LBP, 0.253 for failed back surgery, and -0.140 for higher academic level. CONCLUSION Among Spanish chronic LBP patients treated at pain units, the correlation of catastrophizing, state anxiety, anger, and depression with disability ceases to be significant when variations of trait anxiety are taken into account. Further studies with LBP patients should determine whether anxiety trait mediates the effects of the other variables, explore its prognostic value, and assess the therapeutic effect of reducing it.

The correlation between pain, catastrophizing, and disability in subacute and chronic low back pain: a study in the routine clinical practice of the Spanish National Health Service.

Study Design. Correlation between variables measured with previously validated instruments. Objective. To explore the association between catastrophizing and disability in patients treated for subacute or chronic low back pain (LBP) within routine clinical practice in Spain. Summary of Background Data. The influence of psychological variables on LBP-related disability in Southern Europe is different to the one in the Anglo-Saxon and Northern European cultural environments. In Spanish LBP patients, the influence of fear avoidance beliefs on disability is negligible, and catastrophizing does not mediate the improvement of disability caused by active education. The association between catastrophizing and disability is unknown. Methods. Thirty-three clinicians working for the Spanish National Health Service in 6 primary care and 8 specialty centers, recruited 1461 patients seeking care for subacute and chronic LBP. Patients were assessed only once. A linear regression model was developed to assess the percentage of the variance of disability explained by gender, age, chronicity status, severity of LBP, severity of referred pain (referred pain down to the leg), catastrophizing, eligible for workers’ compensation (yes/no), failed back surgery (yes/no), radiologic findings, and treatments. Results. Correlations among LBP, referred pain down to the leg, disability, and catastrophizing were moderate, but significant. The strongest one was between disability and catastrophizing (r ∇ 0.520). Catastrophizing explained 28% of disability, whereas severity of LBP only 3%. Global adjusted R2 of the model was 0.387. There was an association between some radiologic findings and treatments, and slightly higher levels of disability. Conclusion. In Southern European subacute and chronic LBP patients, catastrophizing correlates with disability and explains approximately one-fourth of its variance. Further studies should assess its value as a prognostic factor in subacute and chronic patients.