Treatment of De Novo Renal Transplant Recipients With Calcineurin Inhibitor-free, Belatacept Plus Everolimus-based Immunosuppression.

Compared with calcineurin inhibitor-based immunosuppression, belatacept (BELA)-based treatment has been associated with better renal function but higher acute rejection rates. This phase 2 study (NCT02137239) compared the antirejection efficacy of BELA plus everolimus (EVL) with tacrolimus (TAC) plus mycophenolate mofetil (MMF), each following lymphocyte-depleting induction and rapid corticosteroid withdrawal. Methods: Patients who were de novo renal transplant recipients seropositive for Epstein-Barr virus were randomized to receive BELA+EVL or TAC+MMF maintenance therapy after rabbit antithymocyte globulin induction and up to 7 d of corticosteroids. The primary endpoint was the rate of biopsy-proven acute rejection at month 6. Results: Because of an unanticipated BELA supply constraint, enrollment was prematurely terminated at 68 patients, of whom 58 were randomized and transplanted (intention-to-treat [ITT] population: n = 26, BELA+EVL; n = 32, TAC+MMF). However, 25 patients received BELA+EVL' and 33 received TAC+MMF (modified ITT population). In the ITT population, the 6-mo biopsy-proven acute rejection rates were 7.7% versus 9.4% in the BELA+EVL versus TAC+MMF group. The corresponding 24-mo biopsy-proven acute rejection rates were 19.2% versus 12.5% in the ITT population and 16.0% versus 15.2% in the mITT population; all events were Banff severity grade ≤IIA and similar between groups. One patient in each group experienced graft loss unrelated to acute rejection. The 24-mo mean unadjusted estimated glomerular filtration rates were 71.8 versus 68.7 mL/min/1.73 m2 in the BELA+EVL versus TAC+MMF groups. Posttransplant lymphoproliferative disorder was reported for 1 patient in each group. No deaths or unexpected adverse events were observed. Conclusions: A steroid-free maintenance regimen of BELA+EVL may be associated with biopsy-proven acute rejection rates comparable to TAC+MMF.

Impact of the COVID-19 lockdown on liver transplant recipients. A single center observational study

Background: the impact of the COVID-19 outbreak and lockdown on liver transplant (LT) patients remains unknown. The aim of this cross-sectional study was to assess the consequences of the COVID-19 pandemic on the physical and mental health of LT patients during the lockdown period.Methods: a web-based questionnaire was emailed to 238 LT patients undergoing regular follow-up at our unit between August and October 2020. This pseudonymized survey explored demographic and lifestyle variables (i.e., eating and physical habits), disruptions in routine medical care, different dimensions of mental health, COVID-19-related mood and coping (worries/anxiety, depression, insomnia, fear of COVID, resilience, etc.) and health perception using different validated instruments.Results: altogether, 48.7 % (116 of 238) LT recipients accepted to participate in the study, 104 of whom gave their consent to publish the data. The median age was 63 years. Up to 39.4 % presented worrying scores indicating moderate/severe generalized anxiety disorder (GAD), whereas 25.5 % exhibited moderate/severe insomnia and only 10.5 % moderate/severe depression. Forty patients (38.5 %) gained weight, 24 % experienced a worsening in their eating habits and 63.4 % referred to practicing less or much less exercise during the lockdown. Only 25 % perceived a worsening in the control of their chronic comorbidities. Missed medical appointments (0.9 %) or poor adherence to therapy (1.9 %) were exceptional.Conclusions: COVID-19 lockdown has negatively impacted the mental and physical health of LT patients. Long-term consequences remain unclear. (AU)

Impact of the COVID-19 lockdown on liver transplant recipients. A single center observational study.

BACKGROUND: the impact of the COVID-19 outbreak and lockdown on liver transplant (LT) patients remains unknown. The aim of this cross-sectional study was to assess the consequences of the COVID-19 pandemic on the physical and mental health of LT patients during the lockdown period. METHODS: a web-based questionnaire was emailed to 238 LT patients undergoing regular follow-up at our unit between August and October 2020. This pseudonymized survey explored demographic and lifestyle variables (i.e., eating and physical habits), disruptions in routine medical care, different dimensions of mental health, COVID-19-related mood and coping (worries/anxiety, depression, insomnia, fear of COVID, resilience, etc.) and health perception using different validated instruments. RESULTS: altogether, 48.7 % (116 of 238) LT recipients accepted to participate in the study, 104 of whom gave their consent to publish the data. The median age was 63 years. Up to 39.4 % presented worrying scores indicating moderate/severe generalized anxiety disorder (GAD), whereas 25.5 % exhibited moderate/severe insomnia and only 10.5 % moderate/severe depression. Forty patients (38.5 %) gained weight, 24 % experienced a worsening in their eating habits and 63.4 % referred to practicing less or much less exercise during the lockdown. Only 25 % perceived a worsening in the control of their chronic comorbidities. Missed medical appointments (0.9 %) or poor adherence to therapy (1.9 %) were exceptional. CONCLUSIONS: COVID-19 lockdown has negatively impacted the mental and physical health of LT patients. Long-term consequences remain unclear.

Failure in all steps of hepatocellular carcinoma surveillance process is frequent in daily practice.

INTRODUCTION AND OBJECTIVES: Failures at any step in the hepatocellular carcinoma (HCC) surveillance process can result in HCC diagnostic delays and associated worse prognosis. We aimed to estimate the prevalence of surveillance failure and its associated risk factors in patients with HCC in Argentina, considering three steps: 1) recognition of at-risk patients, 2) implementation of HCC surveillance, 3) success of HCC surveillance. METHODS: We performed a multi-center cross-sectional study of patients at-risk for HCC in Argentina seen between10.01.2018 and 10.30.2019. Multivariable logistic regression analysis was used to identify correlates of surveillance failure. RESULTS: Of 301 included patients, the majority were male (74.8%) with a mean age of 64 years old. At the time of HCC diagnosis, 75 (25%) patients were unaware of their diagnosis of chronic liver disease, and only 130 (43%) patients were under HCC surveillance. Receipt of HCC surveillance was significantly associated with follow-up by a hepatologist. Of 119 patients with complete surveillance, surveillance failure occurred in 30 (25%) patients. Surveillance failure was significantly associated with alpha fetoprotein ≥20 ng/mL (OR 4.0, CI 95% 1.43-11.55). CONCLUSIONS: HCC surveillance failure was frequent in all the evaluated steps. These data should help guide strategies to improve the implementation and results of HCC surveillance in our country.

Outbreak of hepatitis A in a post-vaccination era: High rate of co-infection with sexually transmitted diseases.

INTRODUCTION AND OBJECTIVES: After hepatitis A (HAV) mandatory immunization in 2005 in Argentina, the incidence of HAV declined drastically. However, several new autochthonous cases of HAV have been reported since 2017. We aimed to evaluate the clinical and epidemiological characteristics and possible transmission routes of affected patients. PATIENTS OR MATERIALS AND METHODS: We performed a cross-sectional study of patients residing in Argentina with acute hepatitis A between 30.06.2017 and 31.12.2018. RESULTS: 66 cases of HAV were registered. Fifty-six patients (86%) were males, with a mean age of 34 ±â€¯12 years old. The most likely routes of transmission were sexual intercourse of men with men, reported by 31 patients. Additionally, 23% and 26% of patients tested positive for HIV and syphilis, respectively. In total, 35% of patients required hospitalization. When assessing outcomes, 79% had a mild presentation and 21% had a severe/fulminant presentation: one patient underwent liver transplantation, and one patient died. CONCLUSIONS: Our study describes that during the study period, HAV infection affected predominantly young adults, particularly men who have sex with men. An elevated proportion of them was diagnosed with a concomitant sexually transmitted disease, and several patients had a severe presentation of the disease.

A Latin American survey on demographic aspects of hospitalized, decompensated cirrhotic patients and the resources for their management.

INTRODUCTION & OBJECTIVES: Liver cirrhosis is a major cause of mortality worldwide. Adequate diagnosis and treatment of decompensating events requires of both medical skills and updated technical resources. The objectives of this study were to search the demographic profile of hospitalized cirrhotic patients in a group of Latin American hospitals and the availability of expertise/facilities for the diagnosis and therapy of decompensation episodes. METHODS: A cross sectional, multicenter survey of hospitalized cirrhotic patients. RESULTS: 377 patients, (62% males; 58±11 years) (BMI>25, 57%; diabetes 32%) were hospitalized at 65 centers (63 urbans; 57 academically affiliated) in 13 countries on the survey date. Main admission causes were ascites, gastrointestinal bleeding, hepatic encephalopathy and spontaneous bacterial peritonitis/other infections. Most prevalent etiologies were alcohol-related (AR) (40%); non-alcoholic-steatohepatitis (NASH) (23%), hepatitis C virus infection (HCV) (7%) and autoimmune hepatitis (AIH) (6%). The most frequent concurrent etiologies were AR+NASH. Expertise and resources in every analyzed issue were highly available among participating centers, mostly accomplishing valid guidelines. However, availability of these facilities was significantly higher at institutions located in areas with population>500,000 (n=45) and in those having a higher complexity level (Gastrointestinal, Liver and Internal Medicine Departments at the same hospital (n=22). CONCLUSIONS: The epidemiological etiologic profile in hospitalized, decompensated cirrhotic patients in Latin America is similar to main contemporary emergent agents worldwide. Medical and technical resources are highly available, mostly at great population urban areas and high complexity medical centers. Main diagnostic and therapeutic approaches accomplish current guidelines recommendations.

Intermediate-advanced hepatocellular carcinoma in Argentina: Treatment and survival analysis.

BACKGROUND: Hepatocellular carcinoma (HCC) represents the sixteenth most frequent cancer in Argentina. The rise of new therapeutic modalities in intermediate-advanced HCC opens up a new paradigm for the treatment of HCC. AIM: To describe real-life treatments performed in patients with intermediate-advanced HCC before the approval of new systemic options. METHODS: This longitudinal observational cohort study was conducted between 2009 and 2016 in 14 different regional hospitals from Argentina. Included subjects had intermediate-advanced Barcelona Clinic Liver Cancer (BCLC) HCC stages (BCLC B to D). Primary end point analyzed was survival, which was assessed for each BCLC stage from the date of treatment until last patient follow-up or death. Kaplan Meier survival curves and Cox regression analysis were performed, with hazard ratios (HR) calculations and 95% confidence intervals (95%CI). RESULTS: From 327 HCC patients, 41% were BCLC stage B, 20% stage C and 39% stage D. Corresponding median survival were 15 mo (IQR 5-26 mo), 5 mo (IQR 2-13 mo) and 3 mo (IQR 1-13 mo) (P < 0.0001), respectively. Among BCLC-B patients (n = 135), 57% received TACE with a median number of 2 sessions (IQR 1-3 sessions). Survival was significantly better in BCLC-B patients treated with TACE HR = 0.29 (CI: 0.21-0.40) than those without TACE. After tumor reassessment by RECIST 1.1 criteria following the first TACE, patients with complete response achieved longer survival [HR = 0.15 (CI: 0.04-0.56, P = 0.005)]. Eighty-two patients were treated with sorafenib, mostly BCLC-B and C (87.8%). However, 12.2% were BCLC-D. Median survival with sorafenib was 4.5 mo (IQR 2.3-11.7 mo); which was lower among BCLC-D patients 3.2 mo (IQR 2.0-14.1 mo). A total of 36 BCLC-B patients presented tumor progression after TACE. In these patients, treatment with sorafenib presented better survival when compared to those patients who received sorafenib without prior TACE [HR = 0.26 (CI: 0.09-0.71); P = 0.013]. CONCLUSION: In this real setting, our results were lower than expected. This highlights unmet needs in Argentina, prior to the introduction of new treatments for HCC.

Liver transplantation in adults with acute liver failure: Outcomes from the Argentinean Transplant Registry.

INTRODUCTION AND AIM: Liver transplantation (LT) for acute liver failure (ALF) still has a high early mortality. We aimed to evaluate changes occurring in recent years and identify risk factors for poor outcomes. MATERIAL AND METHODS: Data were retrospectively obtained from the Argentinean Transplant Registry from two time periods (1998-2005 and 2006-2016). We used survival analysis to evaluate risk of death. RESULTS: A total of 561 patients were listed for LT (69% female, mean age 39.5±16.4 years). Between early and later periods there was a reduction in wait-list mortality from 27% to 19% (p<0.02) and 1-month post-LT survival rates improved from 70% to 82% (p<0.01). Overall, 61% of the patients underwent LT and 22% died on the waiting list. Among those undergoing LT, Cox regression analysis identified prolonged cold ischemia time (HR 1.18 [1.02-1.36] and serum creatinine (HR 1.31 [1.01-1.71]) as independent risk factors of death post-LT. Etiologies of ALF were only available in the later period (N=363) with indeterminate and autoimmune hepatitis accounting for 28% and 26% of the cases, respectively. After adjusting for age, gender, private/public hospital, INR, creatinine and bilirubin, and considering LT as the competing event, indeterminate etiology was significantly associated with death (SHR 1.63 [1.06-2.51] and autoimmune hepatitis presented a trend to improved survival (SHR 0.61 [0.36-1.05]). CONCLUSIONS: Survival of patients with ALF on the waiting list and after LT has significantly improved in recent years. Indeterminate cause and autoimmune hepatitis were the most frequent etiologies of ALF in Argentina and were associated with mortality.

Surveillance for Hepatocellular Carcinoma: Does the Place Where Ultrasound Is Performed Impact Its Effectiveness?

BACKGROUND: Biannual ultrasound (US) is recommended as the clinical screening tool for hepatocellular carcinoma (HCC). The effectiveness of surveillance according to the place where US is performed has not been previously reported. AIMS: To compare the effectiveness of US performed in the center responsible for follow-up as opposed to US proceeding from centers other than that of follow-up. METHODS: This is a multicenter cohort study from Argentina. The last US was categorized as done in the same center or done in a different center from the institution of the patient's follow-up. Surveillance failure was defined as HCC diagnosis not meeting Barcelona Clinic Liver Cancer (BCLC) stages 0-A or when no nodules were observed at HCC diagnosis. RESULTS: From 533 patients with HCC, 62.4% were under routine surveillance with a surveillance failure of 38.8%. After adjusting for a propensity score matching, BCLC stage and lead-time survival bias, surveillance was associated with a significant survival benefit [HR of 0.51 (CI 0.38; 0.69)]. Among patients under routine surveillance (n = 345), last US was performed in the same center in 51.6% and in a different center in 48.4%. Similar rates of surveillance failure were observed between US done in the same or in a different center (32% vs. 26.3%; P = 0.25). Survival was not significantly different between both surveillance modalities [HR 0.79 (CI 0.53; 1.20)]. CONCLUSIONS: Routine surveillance for HCC in the daily practice improved survival either when performed in the same center or in a different center from that of patient's follow-up.

Adherence to Barcelona Clinic Liver Cancer therapeutic algorithm for hepatocellular carcinoma in the daily practice: a multicenter cohort study from Argentina.

BACKGROUND AND AIM: Adherence to the Barcelona Clinic Liver Cancer (BCLC) staging algorithm for the treatment of hepatocellular carcinoma is challenging in the daily practice. We aimed to analyze adherence to BCLC along with its effect on patient survival. PATIENTS AND METHODS: A cohort study was conducted in 14 hospitals from Argentina including patients with newly diagnosed hepatocellular carcinoma (2009-2016). Adherence was considered when the first treatment was the one recommended by the BCLC. RESULTS: Overall, 708 patients were included. At diagnosis, BCLC stages were as follows: stage 0 4%, A 43%, B 22%, C 9% and D 22%. Overall, 53% of the patients were treated according to BCLC, 24% were undertreated, and 23% overtreated. Adherence to BCLC increased to 63% in subsequent treatments. Independent factors associated with adherence to BCLC were the presence of portal hypertension [odds ratio: 1.63; 95% confidence interval (CI): 1.11-2.39] and BCLC stage C (odds ratio: 0.32; 95% CI: 0.12-0.72). In a multivariable model adjusting for portal hypertension and BCLC stages, adherence to BCLC showed improved survival (hazard ratio: 0.67; 95% CI: 0.52-0.87). CONCLUSION: Adherence to BCLC represents a challenge in the daily practice, with almost half of the patients being treated accordingly, showing that the decision-making process should be tailored to each individual patient.

Fatty liver disease, an emerging etiology of hepatocellular carcinoma in Argentina.

AIM: To investigate any changing trends in the etiologies of hepatocellular carcinoma (HCC) in Argentina during the last years. METHODS: A longitudinal cohort study was conducted by 14 regional hospitals starting in 2009 through 2016. All adult patients with newly diagnosed HCC either with pathology or imaging criteria were included. Patients were classified as presenting non-alcoholic fatty liver disease (NAFLD) either by histology or clinically, provided that all other etiologies of liver disease were ruled out, fatty liver was present on abdominal ultrasound and alcohol consumption was excluded. Complete follow-up was assessed in all included subjects since the date of HCC diagnosis until death or last medical visit. RESULTS: A total of 708 consecutive adults with HCC were included. Six out of 14 hospitals were liver transplant centers (n = 484). The prevalence of diabetes mellitus was 27.7%. Overall, HCV was the main cause of liver disease related with HCC (37%) including cirrhotic and non-cirrhotic patients, followed by alcoholic liver disease 20.8%, NAFLD 11.4%, cryptogenic 9.6%, HBV 5.4% infection, cholestatic disease and autoimmune hepatitis 2.2%, and other causes 9.9%. A 6-fold increase in the percentage corresponding to NAFLD-HCC was detected when the starting year, i.e., 2009 was compared to the last one, i.e., 2015 (4.3% vs 25.6%; P < 0.0001). Accordingly, a higher prevalence of diabetes mellitus was present in NAFLD-HCC group 61.7% when compared to other than NAFLD-HCC 23.3% (P < 0.0001). Lower median AFP values at HCC diagnosis were observed between NAFLD-HCC and non-NAFLD groups (6.6 ng/mL vs 26 ng/mL; P = 0.02). Neither NAFLD nor other HCC etiologies were associated with higher mortality. CONCLUSION: The growing incidence of NAFLD-HCC documented in the United States and Europe is also observed in Argentina, a confirmation with important Public Health implications.

Effectiveness and safety of original and generic sofosbuvir for the treatment of chronic hepatitis C: A real world study.

We report the first real-world prospective multicenter cohort study that evaluated the effectiveness and safety of original or generic sofosbuvir-based regimens in patients with chronic hepatitis C in Latin America. The main endpoints were assessment of sustained virological response and serious adverse events rates. A total of 321 patients with chronic hepatitis C treated with the following regimens were included: sofosbuvir plus daclatasvir for 12 (n = 34) or 24 (n = 135) weeks, sofosbuvir plus daclatasvir plus ribavirin for 12 (n = 84) or 24 (n = 56) weeks, or sofosbuvir plus ribavirin for 12 (n = 8) or 24 (n = 2) weeks. Patients received either original sofosbuvir (Sovaldi® , Gilead Sciences, n = 135) or generic sofosbuvir (Probirase® , Laboratorios RICHMOND, n = 184) which were randomly assigned by the National Ministry of Health. Overall, 292 (91%) patients had cirrhosis, 136 (42%) were treatment experienced, and 240 (75%) genotype 1. The overall sustained virological response was 90% (95% CI 86-93%); 91% (95% CI 84-95%) in patients who received Sovaldi® , and 89% (95% CI 84-93%) in patients who received Probirase® . Anemia was the most common adverse event and was reported in 52 (17%) patients. Bacterial infection, gastrointestinal bleeding, worsening of ascites or encephalopathy occurred in less than 5% of the patients. During the study, seven (2%) patients died, four of whom died of cirrhosis-related complications. In summary, we observed similar sustained virological response rates than prior studies, both in patients who received Sovaldi® or Probirase® . Serious adverse events were infrequent, in line with prior studies that included patients with cirrhosis treated with protease-inhibitor-free regimes.

Belatacept and Long-Term Outcomes in Kidney Transplantation.

BACKGROUND: In previous analyses of BENEFIT, a phase 3 study, belatacept-based immunosuppression, as compared with cyclosporine-based immunosuppression, was associated with similar patient and graft survival and significantly improved renal function in kidney-transplant recipients. Here we present the final results from this study. METHODS: We randomly assigned kidney-transplant recipients to a more-intensive belatacept regimen, a less-intensive belatacept regimen, or a cyclosporine regimen. Efficacy and safety outcomes for all patients who underwent randomization and transplantation were analyzed at year 7 (month 84). RESULTS: A total of 666 participants were randomly assigned to a study group and underwent transplantation. Of the 660 patients who were treated, 153 of the 219 patients treated with the more-intensive belatacept regimen, 163 of the 226 treated with the less-intensive belatacept regimen, and 131 of the 215 treated with the cyclosporine regimen were followed for the full 84-month period; all available data were used in the analysis. A 43% reduction in the risk of death or graft loss was observed for both the more-intensive and the less-intensive belatacept regimens as compared with the cyclosporine regimen (hazard ratio with the more-intensive regimen, 0.57; 95% confidence interval [CI], 0.35 to 0.95; P=0.02; hazard ratio with the less-intensive regimen, 0.57; 95% CI, 0.35 to 0.94; P=0.02), with equal contributions from the lower rates of death and graft loss. The mean estimated glomerular filtration rate (eGFR) increased over the 7-year period with both belatacept regimens but declined with the cyclosporine regimen. The cumulative frequencies of serious adverse events at month 84 were similar across treatment groups. CONCLUSIONS: Seven years after transplantation, patient and graft survival and the mean eGFR were significantly higher with belatacept (both the more-intensive regimen and the less-intensive regimen) than with cyclosporine. (Funded by Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00256750.).

Hepatitis C in Argentina: epidemiology and treatment.

Hepatitis C is the leading cause of chronic hepatitis, cirrhosis, and liver cancer in Argentina, where from 1.5% to 2.5% of adults are infected. Most of the infections were acquired 30-50 years ago. It is estimated that more than half of infected individuals are not aware of their infection. Even though the prevalence in blood donors has decreased to 0.45% at present, many high-prevalence populations still exist, where the reported prevalence ranges from 2.2% to 7.1%. Therapy is recommended for patients with fibrosis, in order to prevent disease progression, hepatic decompensation, and hepatocellular carcinoma. Great advances were achieved in the treatment of genotype 1 infection since the development and release of boceprevir and telaprevir. When either of these protease inhibitors is associated with peginterferon plus ribavirin, the sustained virological response (SVR) rate improves from 40%-50% to 67%-75%. For genotype 2 and 3 infection, treatment with peginterferon plus ribavirin is still the standard of care, with SVR rates of 70%-90%. There are significant new antivirals in development, and some of them are close to being released. These drugs will most likely be the future standard of care for all genotypes, and will be incorporated in better-tolerated and highly effective all-oral regimes. The impact that these new therapies might have in health-related economics is unpredictable, especially in developing countries. Each country must carefully evaluate the local situation in order to implement proper screening and treatment programs. Difficult-to-treat patients, such as those with decompensated cirrhosis, patients in hemodialysis, and those with other significant comorbidities, might not be able to receive these new therapeutic approaches and their management will remain challenging.

Expression of HLA-G and MICA mRNA in renal allograft.

HLA-G is a nonclassical MHC class I antigen that displays tolerogenic functions; MICA is a stress-regulated molecule recognized by NKG2D cytotoxicity-activating receptor expressed by NK and T cells subsets. We evaluated HLA-G isoforms and MICA mRNA levels in peripheral blood mononuclear cells (PBMCs) and in biopsies from kidney allograft recipients with acute rejection (AR), chronic rejection (CR), and stable graft evolution (SE). HLA-G1 was the only transcript resulted from amplification, both in PBMCs as in biopsy samples. HLA-G1 mRNA levels in PBMCs from 9/10 patients with CR, 7/9 with AR and 8/10 healthy volunteers were below the median value of SE patients. The analysis of biopsies revealed that patients with AR (n=6), who overcame rejection had a tendency towards higher HLA-G1 levels than those with nephrotoxic acute tubular necrosis (ATN) (n=3). Similar levels of MICA expression were observed in PBMCs from AR, CR, SE and C groups; MICA expression levels were similar also in biopsy specimens from AR and nephrotoxic ATN patients. No correlation was found between MICA expression and the graft state. These preliminary results suggest that HLA-G1 isoforms, but not MICA mRNA levels, may provide a marker for measuring the state of kidney allograft, and be the basis for further studies that may establish the influence of these molecules in renal allograft rejection or acceptance.

Gastrointestinal (GI)-Specific patient reported outcomes instruments differentiate between renal transplant patients with or without GI symptoms: results from a South American cohort.

BACKGROUND: Immunosuppressive therapies have burdensome side effects which may lead to sub-therapeutic dosing and non-compliance. Patients on different immunosuppressant regimens may feel less bothered by Gastrointestinal (GI) side effects or report better health-related quality of life (HRQL). We evaluated the reliability and validity of two GI-specific outcome instruments (Gastrointestinal Symptom Rating Scale (GSRS; higher scores = increased severity) and Gastrointestinal Quality of Life Index (GIQLI; higher scores = better GI-specific HRQL)) in renal transplant patients in South America. METHODS: Data from 5 South American centers participating in an international, longitudinal, observational study were analyzed. Patients were > or = 1 month post transplant and on mycophenolate mofetil (MMF) and a calcineurin inhibitor. Patients completed the GSRS, GIQLI, and Psychological General Well-Being (PGWB; higher scores = better HRQL) Index at baseline and at 4-6 weeks. Internal consistency, test-retest reliability and construct and discriminant validity were assessed. RESULTS: Sixty-two participants were enrolled. Mean age was 42 years; mean time since transplant was 3.3 years; 57% were male; 65% received a deceased organ transplant and 68%had GI events. The GSRS and GIQLI demonstrated high internal consistency (Cronbach's alphas 0.72-0.96). Test-retest reliability was adequate (intraclass correlation coefficient > 0.6) for all GIQLI subscales and all GSRS subscales except Diarrhea and Reflux syndrome. Correlations between the GSRS and PGWB were moderate (range: -0.21 to -0.53, all p < 0.001 except 6 correlations with p < 0.05); correlations between the GIQLI and PGWB were higher (range: 0.36 to 0.71 p < 0.001), indicating good construct validity. The GSRS and GIQLI demonstrated good discriminant validity, as they clinically and statistically distinguished between patients with and without GI complaints and among patients with varying GI complication severity. Patients with GI complaints reported higher GSRS scores than patients without complaints (all p < 0.001). GIQLI scores were lower in patients with GI complaints than patients without complaints (all p < 0.001). The GSRS and GIQLI differentiated among patients with four GI severity levels (overall Kruskall-Wallis test p < 0.001, except for one scale). The GSRS and GIQLI are acceptable for use in South American renal transplant patients. These two instruments demonstrate adequate reliability and validity. Patients with GI complaints reported poor HRQL and strategies are needed to improve patients' HRQL.

Main determinants of Global Assessment of Functioning score in schizophrenia: a European multicenter study.

BACKGROUND: The Global Assessment of Functioning (GAF) scale is a measure widely used to assess the outcome of patients with schizophrenia. However, little is known about the importance of clinical and psychosocial variables in determining its final score. The aim of this paper is to identify which factors predict GAF scores of patients with schizophrenia and their variability in 5 different European settings. METHOD: A representative sample of 404 patients with schizophrenia was assessed with the GAF. A multiple regression analysis was performed to identify predictors of the GAF scores. RESULTS: Clinical factors are the main determinants of GAF score. However, the analysis also showed that social and functioning factors were also significantly associated with GAF scores. Finally, the study showed the presence of intercenter differences in the factors, mainly in social functioning. CONCLUSIONS: The GAF is a useful and easy-to-apply measure of global functioning, independent of cross-cultural differences. Clinical factors are the main determinants of its score, although social functioning variables also have a lesser effect.

Calidad de vida en pacientes con obesidad mórbida sometidos a gastroplastia vertical bandeada / Quality of life in patients with morbid obesity undergoing vertical banded gastroplasty

Introducción. Los pacientes con obesidad mórbida que son sometidos a técnicas quirúrgicas para perder peso constituyen una población referencial para analizar la calidad de vida ya que, generalmente, el tratamiento quirúrgico provoca una importante y duradera pérdida de peso. Métodos. La muestra está formada por 100 pacientes con obesidad mórbida (85 mujeres, 15 varones) que han sido sometidos a tratamiento quirúrgico (gastroplastia vertical anillada) para perder peso. Cuarenta pacientes (40 por ciento) cumplieron criterios CIE-10 para el diagnóstico de trastornos psiquiátricos y fueron incluidos en el grupo de "obesos mórbidos psiquiátricos". Los 60 pacientes restantes (60 por ciento) no cumplieron criterios diagnósticos CIE-10 y fueron incluidos en el grupo de "obesos mórbidos sanos". Cada paciente completó le escala de calidad de vida del Lancashire Quality of Life Profile-European Version (LQOLP-EU). Resultados. La calidad de vida del grupo con trastornos psiquiátricos está más deteriorada que en el grupo carente de ellos. Hemos encontrado diferencias estadísticamente significativas para los dos grupos en las subescalas de relaciones familiares (p < 0,001), salud (p < 0,002), bienestar general (p < 0,001), afectividad positiva (p < 0,0001), afectividad negativa (p < 0,0001), autoestima negativa (p < 0,0001), opinión del paciente (p < 0,002) y opinión del clínico (p < 0,001). La pérdida de peso no se relaciona con el diagnóstico psiquiátrico. Conclusiones. La calidad de vida de los pacientes con obesidad mórbida sometidos a cirugía bariátrica está más deteriorada si presentan trastornos psiquiátricos. La pérdida de peso es independiente del diagnóstico psiquiátrico. Hacemos hincapié en la necesidad de realizar una evaluación psiquiátrica en los pacientes con obesidad mórbida sometidos a cirugía bariátrica, antes y después de la intervención, ya que nos hemos encontrado con una peor calidad de vida que podría ensombrecer el pronóstico a largo plazo. (AU)

Psychopathological status and interpersonal functioning following weight loss in morbidly obese patients undergoing bariatric surgery.

BACKGROUND: We questioned whether differences in psychopathological status and interpersonal relations exist in a group of morbidly obese patients 18 months after bariatric surgery, as related to extent of weight loss. METHODS: The study group consisted of 100 morbidly obese patients (85 female, 15 male) who had undergone surgical treatment (vertical banded gastroplasty) for weight reduction. Each patient completed the Lancashire Quality of Life Profile European version, the Eating Disorder Inventory, the Symptom Check List-90-Revised, and the Millon Clinical Multiaxial Inventory-II. The sample was divided into 2 groups according to the percentage of excess weight loss 18 months after surgery: a greater weight loss group (weight loss > 30%) and a lesser weight loss group (weight loss < 30%). RESULTS: Significant differences were found between the 2 groups in percentage of weight loss (P < 0.0001), negative self-esteem (P < 0.001), drive for thinness (P < 0.001), body dissatisfaction (P < 0.001), global EDI (P < 0.002), anxiety (P < 0.003), GSI (P < 0.002), avoidant (P < 0.001), borderline (P < 0.0001), and passive-aggressive (P < 0.002). CONCLUSION: Greater weight loss strongly correlates with improved quality of life, less disturbed eating behavior, and lower psychopathology. These results justify the clinical use of surgical procedures and demonstrate that weight loss has powerful psychological and psychosocial implications.